FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sarna, L Cooley, ME Brown, JK Chernecky, C Elashoff, D Kotlerman, J AF Sarna, Linda Cooley, Mary E. Brown, Jean K. Chernecky, Cynthia Elashoff, David Kotlerman, Jenny TI SYMPTOM SEVERITY 1 TO 4 MONTHS AFTER THORACOTOMY FOR LUNG CANCER SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID QUALITY-OF-LIFE; ASSISTED THORACIC-SURGERY; LONG-TERM SURVIVORS; BRONCHOGENIC-CARCINOMA; PULMONARY-FUNCTION; EXERCISE CAPACITY; CLINICAL-TRIALS; UNITED-STATES; SCALE LCSS; RESECTION AB Background Information about the severity of symptoms during recovery from surgery for lung cancer can be useful in planning and anticipating needs for recovery. Objectives To describe symptom severity during the first 4 months after thoracotomy for non -small cell lung cancer and factors associated with overall symptom severity at 1 and 4 months. Methods Ninety-four patients were assessed at 1, 2, and 4 months after thoracotomy by using the Lung Cancer Symptom Scale, Brief Pain Inventory, Schwartz Fatigue Scale, Dyspnea Index, and Center for Epidemiology Studies -Depression Scale (CES-D). Clinically meaningful changes, decrease in the proportion of patients with severe symptoms, and relationships among symptoms were determined. Mixed effects models for repeated measures were used to evaluate changes in severity. Multiple regression models were used to examine correlates of overall symptoms. Results Mean symptom severity significantly decreased over time for most symptoms. Only disrupted appetite, pain, and dyspnea had clinically meaningful improvement at 4 months. Severe symptoms included fatigue (57%), dyspnea (49%), cough (29%), and pain (20%). Prevalence of depressed mood decreased at 4 months. Most patients (77%) had comorbid conditions. Number of comorbid conditions and CES-D explained 54% of the variance in symptom severity at 1 month; comorbid conditions, male sex, neoadjuvant treatment, and CES-D score explained 50% of the variance at 4 months. Conclusions Severe symptoms continued 4 months after surgery for some patients, indicating the need for support during recovery, especially for patients with multiple comorbid conditions and depressed mood. C1 [Sarna, Linda] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Res Nursing & Patient Care Serv, Boston, MA 02115 USA. [Brown, Jean K.] SUNY Buffalo, Buffalo, NY 14260 USA. [Chernecky, Cynthia] Med Coll Georgia, Sch Nursing, Augusta, GA 30912 USA. [Elashoff, David; Kotlerman, Jenny] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Elashoff, David] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. RP Sarna, L (reprint author), Univ Calif Los Angeles, Sch Nursing, 700 Tiverton Ave, Los Angeles, CA 90095 USA. EM lsarna@sonnet.ucla.edu FU Oncology Nursing Foundation [03018863] FX This study was funded by grant 03018863 from the Oncology Nursing Foundation. NR 64 TC 35 Z9 37 U1 2 U2 2 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 J9 AM J CRIT CARE JI Am. J. Crit. Care PD SEP 1 PY 2008 VL 17 IS 5 BP 455 EP 467 PG 13 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 366SK UT WOS:000260503500011 PM 18776002 ER PT J AU Comer, G Kum-Nji, P Mahomedy, S Kierkus, J Hinz, M Li, HH Maguire, M Winter, H AF Comer, Gail Kum-Nji, Philip Mahomedy, Suleman Kierkus, Jaroslaw Hinz, Michelle Li, Huihua Maguire, Mary Winter, Harland TI Efficacy and tolerability of pantoprazole delayed-release granules for oral suspension in a placebo-controlled treatment-withdrawal study in infants 1 through 11 months of age with symptomatic GERD SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 03-08, 2008 CL Orlando, FL SP Amer Coll Gastroenterol C1 Wyeth Ayerst Res, Collegeville, PA USA. Virginia Commonwealth Univ, Richmond, VA USA. Westville Med Ctr, Hiway Med Ctr, Durban, South Africa. Childrens Mem Hlth Inst, Dept Gastroenterol Hepatol & Immunol, Warsaw, Poland. MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2008 VL 103 SU S MA 1357 BP S532 EP S533 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 347MH UT WOS:000259145201345 ER PT J AU Ford, A Chey, W Talley, N Malhotra, A Spiegel, B Moayyedi, P AF Ford, Alexander Chey, William Talley, Nicholas Malhotra, Ashish Spiegel, Brennan Moayyedi, Paul TI Utility of diagnostic tests for Celiac disease in irritable bowel syndrome: Systematic review and meta-analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 03-08, 2008 CL Orlando, FL SP Amer Coll Gastroenterol C1 McMaster Univ, Med Ctr, Div Gastroenterol, Hamilton, ON, Canada. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. Mayo Clin Florida, Dept Med, Jacksonville, FL USA. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. Univ Calif Los Angeles, Sch Publ Hlth, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst,VA Ctr Ou, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2008 VL 103 SU S MA 1185 BP S463 EP S463 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 347MH UT WOS:000259145201174 ER PT J AU Ford, A Talley, N Spiegel, B Foxx-Orenstein, A Schiller, L Quigley, E Moayyedi, P AF Ford, Alexander Talley, Nicholas Spiegel, Brennan Foxx-Orenstein, Amy Schiller, Lawrence Quigley, Eamonn Moayyedi, Paul TI Efficacy of antispasmodics and peppermint oil in irritable bowel syndrome: Systematic review and meta-analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 03-08, 2008 CL Orlando, FL SP Amer Coll Gastroenterol C1 McMaster Univ, Med Ctr, Div Gastroenterol, Hamilton, ON, Canada. Mayo Clin Florida, Dept Med, Jacksonville, FL USA. Univ Calif Los Angeles, Sch Publ Hlth, David Geffen Sch Med, VA Greater Angeles Healthcare Syst,VA Ctr Outcome, Los Angeles, CA 90024 USA. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. Baylor Univ, Med Ctr, Digest Hlth Associates Texas, Dallas, TX USA. Cork Univ Hosp, Dept Med, Cork, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2008 VL 103 SU S MA 1177 BP S459 EP S459 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 347MH UT WOS:000259145201166 ER PT J AU Ford, A Talley, N Spiegel, B Foxx-Orenstein, A Schiller, L Quigley, E Moayyedi, P AF Ford, Alexander Talley, Nicholas Spiegel, Brennan Foxx-Orenstein, Amy Schiller, Lawrence Quigley, Eamonn Moayyedi, Paul TI Efficacy of fiber in irritable bowel syndrome: Systematic review and meta-analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 03-08, 2008 CL Orlando, FL SP Amer Coll Gastroenterol C1 McMaster Univ, Med Ctr, Div Gastroenterol, Hamilton, ON, Canada. Mayo Clin, Dept Med, Jacksonville, FL 32224 USA. Univ Calif Los Angeles, Sch Publ Hlth, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst,VA Ctr Out, Los Angeles, CA 90024 USA. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. Baylor Univ, Med Ctr, Digest Hlth Associates Texas, Dallas, TX USA. Cork Univ Hosp, Dept Med, Cork, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2008 VL 103 SU S MA 1176 BP S459 EP S459 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 347MH UT WOS:000259145201165 ER PT J AU Rao, S Paulson, J Kuo, B McCallum, R Sitrin, M Chey, W Lackner, J Semler, J Wilding, G Parkman, H AF Rao, Satish Paulson, Jessica Kuo, Braden McCallum, Richard Sitrin, Michael Chey, William Lackner, Jeffrey Semler, John Wilding, Greg Parkman, Henry TI Relationship between the colonic transit of wireless capsule (Smartpill (R)) and radio opaque markers in constipation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 03-08, 2008 CL Orlando, FL SP Amer Coll Gastroenterol C1 Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Univ Kansas, Med Ctr, Ctr GI Nerve & Muscle Funct & GI Motil, Kansas City, KS 66103 USA. Univ Michigan, Ann Arbor, MI 48109 USA. SUNY Buffalo, Sch Med, Buffalo, NY 14260 USA. SmartPill Corp, Buffalo, NY USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. SUNY Buffalo, Western NewYork VA Med Ctr, Buffalo, NY 14260 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2008 VL 103 SU S MA 1215 BP S475 EP S475 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 347MH UT WOS:000259145201204 ER PT J AU Rao, S Paulson, J Kuo, B McCallum, R Sitrin, M Chey, W Lackner, J Semler, J Wilding, G Parkman, H AF Rao, Satish Paulson, Jessica Kuo, Braden McCallum, Richard Sitrin, Michael Chey, William Lackner, Jeffrey Semler, John Wilding, Greg Parkman, Henry TI Assessment of inter-observer agreement of colonic transit time (Ctt) with radiopaque markers SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 03-08, 2008 CL Orlando, FL SP Amer Coll Gastroenterol C1 Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. SmartPill Corp, Buffalo, NY USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Univ Kansas, Med Ctr, Ctr GI Nerve & Muscle Funct & GI Motil, Kansas City, KS 66103 USA. Univ Michigan, Ann Arbor, MI 48109 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. SUNY Buffalo, Sch Med, Buffalo, NY 14260 USA. SUNY Buffalo, Western New York VA Med Ctr, Buffalo, NY 14260 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2008 VL 103 SU S MA 502 BP S194 EP S194 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 347MH UT WOS:000259145200498 ER PT J AU Sands, B Wolf, D Panjabi, S Niecko, T Hass, S Lacey, L AF Sands, Bruce Wolf, Douglas Panjabi, Sumeet Niecko, Timothy Hass, Steven Lacey, Loretto TI Cost-effectiveness of natalizumab in patients with Crohn's disease who have failed Anti-TNF alpha therapy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 03-08, 2008 CL Orlando, FL SP Amer Coll Gastroenterol C1 Massachusetts Gen Hosp, Gastrointestinal Unit, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Atlanta Gastroenterol Associates, Atlanta, GA USA. Elan Pharmaceut Inc, San Francisco, CA USA. LLC, Niecko Hlth Econ, Escondido, CA USA. Elan Pharmaceut Ltd, Pharmacoecon, Dublin, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2008 VL 103 SU S MA 1025 BP S401 EP S402 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 347MH UT WOS:000259145201017 ER PT J AU Siegel, C Siegel, L Sands, B Wrobel, I Wahbeh, G Quiros, A Silber, G Bahar, R Dubinsky, M AF Siegel, Corey Siegel, Lori Sands, Bruce Wrobel, Iwona Wahbeh, Ghassan Quiros, Antonio Silber, Gary Bahar, Ron Dubinsky, Marla TI A prototype system dynamics model to communicate the risk of Crohn's disease complications to patients and their predicted treatment response SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 03-08, 2008 CL Orlando, FL SP Amer Coll Gastroenterol C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Siegel Environm Dynam LLC, Hanover, NH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. Seattle Childrens Hosp, Seattle, WA USA. Calif Pacific Med Ctr, San Francisco, CA USA. Phoenix Childrens Hosp, Phoenix, AZ USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2008 VL 103 SU S MA 1154 BP S451 EP S451 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 347MH UT WOS:000259145201143 ER PT J AU Tukey, M Falchuk, K Cheifetz, A Moss, A AF Tukey, Melissa Falchuk, Kenneth Cheifetz, Adam Moss, Alan TI A patient support program (PSP) to enhance medication adherence and quality-of-life in patients prescribed mesalamine for ulcerative colitis - a pilot study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 73rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 03-08, 2008 CL Orlando, FL SP Amer Coll Gastroenterol C1 [Tukey, Melissa; Falchuk, Kenneth; Cheifetz, Adam; Moss, Alan] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2008 VL 103 SU S MA 1059 BP S414 EP S414 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 347MH UT WOS:000259145201050 ER PT J AU West, R Beeri, MS Schmeidler, J Hannigan, CM Angelo, G Grossman, HT Rosendorff, C Silverman, JM AF West, Rebecca Beeri, Michal Schnaider Schmeidler, James Hannigan, Christine M. Angelo, Gary Grossman, Hillel T. Rosendorff, Clive Silverman, Jeremy M. TI Better memory functioning associated with higher total and low-density lipoprotein cholesterol levels in very elderly subjects without the apolipoprotein e4 allele SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE dementia; cognitive performance; apolipoprotein E; cholesterol ID ALZHEIMER-DISEASE; OLDEST-OLD; DEMENTIA; RISK; DECLINE AB Objective: To examine the association of cholesterol with cognitive functioning in oldest old community dwelling individuals with and without the apolipoprotein e4 (APOE4) allele. Method: One hundred eighty-five nondemented, community dwelling individuals (>= 85) were assessed with a broad neuropsychological battery. Bloods were drawn to assess total, low-density lipoprotein (LDL), and high-density lipoprotein cholesterol, as well as for APOE genotyping. Results: In contrast to our expectations, high total cholesterol and high LDL cholesterol were associated with higher memory scores for noncarriers of the APOE4 allele. No significant associations between cognitive performance and lipid profile were found for carriers of the APOE4 allele. Conclusions: In oldest old nondemented noncarriers of the APOE4 allele, high cholesterol is associated with better memory function. Further examination of the role of APOE genotype on the association between cholesterol and cognitive performance, especially in the oldest old is warranted. C1 [West, Rebecca; Beeri, Michal Schnaider; Schmeidler, James; Hannigan, Christine M.; Angelo, Gary; Grossman, Hillel T.; Rosendorff, Clive; Silverman, Jeremy M.] Mt Sinai Sch Med, New York, NY USA. [Grossman, Hillel T.; Rosendorff, Clive; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP West, R (reprint author), 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM rebecca.west@mssm.edu FU National Institutes of Health [AG002219, AG023515]; United States Department of Veterans Affairs; Berkman Charitable Trust FX This work was supported by National Institutes of Health AG002219 ( to JMS), AG023515 ( to MSB), United States Department of Veterans Affairs, Berkman Charitable Trust. NR 18 TC 36 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SEP PY 2008 VL 16 IS 9 BP 781 EP 785 DI 10.1097/JGP.0b013e3181812790 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 343KL UT WOS:000258852200011 PM 18757771 ER PT J AU Rahman, M Baimbridge, C Davis, BR Barzilay, J Basile, JN Henriquez, MA Huml, A Kopyt, N Louis, GT Pressel, SL Rosendorff, C Sastrasinh, S Stanford, C AF Rahman, Mahboob Baimbridge, Charles Davis, Barry R. Barzilay, Joshua Basile, Jan N. Henriquez, Mario A. Huml, Anne Kopyt, Nelson Louis, Gail T. Pressel, Sara L. Rosendorff, Clive Sastrasinh, Sithiporn Stanford, Carol CA ALLHAT Collaborative Res Grp TI Progression of kidney disease in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin versus usual care: A report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hyperlipidemia; glomerular filtration rate; pravastatin ID RENAL-FUNCTION; SIMVASTATIN TREATMENT; NEPHROTIC SYNDROME; DIABETIC-NEPHROPATHY; ALBUMIN EXCRETION; CLINICAL-TRIAL; STATINS; PROTEINURIA; DYSLIPIDEMIA; METAANALYSIS AB Background: Dyslipidemia is common in patients with chronic kidney disease. The role of statin therapy in the progression of kidney disease is unclear. Study Design: Prospective randomized clinical trial, post hoc analyses. Setting & Participants: 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) stratified by baseline estimated glomerular filtration rate (eGFR): less than 60, 60 to 89, and 90 or greater mL/min/1.73 m(2). Mean follow-up was 4.8 years. Intervention: Randomized; pravastatin, 40 mg/d, or usual care. Outcomes & Measurements: Total, high-density lipoprotein, and low-density lipoprotein cholesterol; end-stage renal disease (ESRD), eGFR. Results: Through year 6, total cholesterol levels decreased in the pravastatin (-20.7%) and usual-care groups (-11.2%). No significant differences were seen between groups for rates of ESRD (1.36 v 1.45/100 patient-years; P = 0.9), composite end points of ESRD and 50% or 25% decrease in eGFR, or rate of change in eGFR. Findings were consistent across eGFR strata. In patients with eGFR of 90 mL/min/1.73 m(2) or greater, the pravastatin arm tended to have a higher eGFR. Limitations: Proteinuria data unavailable, post hoc analyses, unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range, statin drop-in rate in usual-care group with small cholesterol differential between groups. Conclusions: In hypertensive patients with moderate dyslipidemia and decreased eGFR, pravastatin was not superior to usual care in preventing clinical renal outcomes. This was consistent across the strata of baseline eGFR. However, benefit from statin therapy may depend on the degree of the cholesterol level decrease achieved. C1 [Rahman, Mahboob; Huml, Anne] Case Western Reserve Univ, Univ Hosp Cleveland Case Med Ctr, Louis Stokes Cleveland VA Med Ctr, Cleveland, OH 44106 USA. [Baimbridge, Charles; Davis, Barry R.; Pressel, Sara L.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Barzilay, Joshua] Kaiser Permanente Georgia, Tucker, GA USA. [Basile, Jan N.] VAMC Charleston, Charleston, SC USA. [Henriquez, Mario A.] Bronx Nephrol Hypertens, Bronx, NY USA. [Kopyt, Nelson] Lehigh Valley Hosp, Allentown, PA USA. [Louis, Gail T.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Rosendorff, Clive] Mt Sinai Sch Med, New York, NY USA. [Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY USA. [Sastrasinh, Sithiporn] VA New Jersey Hlth Care Syst, E Orange, NJ USA. [Stanford, Carol] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. RP Pressel, SL (reprint author), 1200 Herman Pressler St,Ste E801, Houston, TX 77030 USA. EM sara.l.pressel@uth.tmc.edu FU NHLBI NIH HHS [N01 HC035130, N01-HC-35130, N01HC35130] NR 37 TC 47 Z9 53 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2008 VL 52 IS 3 BP 412 EP 424 DI 10.1053/j.ajkd.2008.05.027 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 343ML UT WOS:000258857900008 PM 18676075 ER PT J AU Rosenthal, ES Schwamm, LH Roccatagliata, L Coutts, SB Demchuk, AM Schaefer, PW Gonzalez, RG Hill, MD Halpern, EF Lev, MH AF Rosenthal, E. S. Schwamm, L. H. Roccatagliata, L. Coutts, S. B. Demchuk, A. M. Schaefer, P. W. Gonzalez, R. G. Hill, M. D. Halpern, E. F. Lev, M. H. TI Role of recanalization in acute stroke outcome: Rationale for a CT angiogram-based "Benefit of Recanalization" model SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE ISCHEMIC-STROKE; PERFUSION COMPUTED-TOMOGRAPHY; 3-DIMENSIONAL FUNCTIONAL CT; FINAL INFARCT EXTENT; SOURCE IMAGES; INTRAARTERIAL THROMBOLYSIS; ARTERIAL-OCCLUSION; HYPERACUTE STROKE; BLOOD-VOLUME AB BACKGROUND AND PURPOSE: In acute middle cerebral artery (MCA) stroke, CT angiographic (CTA) source images (CTA-SI) identify tissue likely to infarct despite early recanalization. This pilot study evaluated the impact of recanalization status on clinical and radiologic predictors of patient outcomes. MATERIALS AND METHODS: Of 44 patients undergoing CT/CTA within 6 hours of developing symptoms of proximal MCA ischemia, 19 patients achieved complete proximal MCA (MCA M1) recanalization. Admission National Institutes of Health Stroke Scale (NIHSS) score, onset-to-imaging time, CTA-SI Alberta Stroke Program Early CT Score, MCA M1 occlusion, cerebrovascular collaterals score, and CTA-SI lesion volume were correlated with 3- to 6-month follow-up modified Rankin Scale (mRS). We developed 2 stepwise regression models: one for patients with complete MCA M1 recanalization and one for patients without complete recanalization. RESULTS: Complete and incomplete recanalization groups had similar median admission NIHSS scores (19 versus 19) and mean onset-to-imaging times (2.3 versus 1.9 hours) but different proportions of patients achieving mRS scores 0-2 (74% versus 40%; P =.04). The only independent predictors of clinical outcome in patients with complete recanalization were onset-to-imaging time and admission CTA-SI lesion volume (total model R-2 = 0.75; P = .01). The only independent predictors of outcome in patients with incomplete recanalization were admission CTA-SI lesion volume and NIHSS score (total model R-2 = 0.66; P = .007). CONCLUSION: Regardless of recanalization status, admission CTA-SI lesion volume was associated with clinical outcome. Recanalization status did, however, affect which variables in addition to CTA-SI volume significantly impacted clinical outcome: time with complete recanalization and NIHSS with incomplete recanalization. This finding may support the development of a model predicting the potential clinical benefit expected with early successful recanalization. C1 [Schwamm, L. H.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Schaefer, P. W.; Gonzalez, R. G.; Halpern, E. F.; Lev, M. H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Roccatagliata, L.] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. [Coutts, S. B.; Demchuk, A. M.; Hill, M. D.] Univ Calgary, Dept Clin Neurosci, Foothills Hosp, Calgary, AB, Canada. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, 55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org RI Demchuk, Andrew/E-1103-2012; OI Demchuk, Andrew/0000-0002-4930-7789; Schwamm, Lee/0000-0003-0592-9145; Rosenthal, Eric/0000-0003-3900-356X; Hill, Michael/0000-0002-6269-1543 NR 51 TC 40 Z9 41 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2008 VL 29 IS 8 BP 1471 EP 1475 DI 10.3174/ajnr.A1153 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 355DH UT WOS:000259688700011 PM 18599577 ER PT J AU Stefancyk, AL AF Stefancyk, Amanda L. TI Transforming Care at Mass General SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stefancyk, AL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM astefancyk@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD SEP PY 2008 VL 108 IS 9 BP 71 EP 72 PG 2 WC Nursing SC Nursing GA 359EC UT WOS:000259968200024 PM 18756163 ER PT J AU Friedman, E AF Friedman, Ephraim TI The pathogenesis of age-related macular degeneration SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material C1 [Friedman, Ephraim] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Friedman, Ephraim] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Friedman, E (reprint author), 45 West St 22, Beverly, MA 01915 USA. EM ephraimfriedman@mac.com NR 5 TC 13 Z9 13 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2008 VL 146 IS 3 BP 348 EP 349 DI 10.1016/j.ajo.2008.05.017 PG 2 WC Ophthalmology SC Ophthalmology GA 343VR UT WOS:000258883900005 PM 18724980 ER PT J AU Berisha, F Feke, GT Hirose, T McMeel, JW Pasquale, LR AF Berisha, Fatmire Feke, Gilbert T. Hirose, Tatsuo McMeel, J. Wallace Pasquale, Louis R. TI Retinal blood flow and nerve fiber layer measurements in early-stage open-angle glaucoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; NITRIC-OXIDE SYNTHASE; SCANNING LASER OPHTHALMOSCOPY; VESSEL DIAMETER; OCULAR HYPERTENSION; HEAD; EYES; HEMODYNAMICS; CIRCULATION; PRESSURE AB PURPOSE: To evaluate the relationship between retinal circulatory abnormalities and retinal nerve fiber layer (RNFL) thinning in early,stage open angle glaucoma (OAG) to help elucidate the mechanisms underlying the development of glaucomatous optic neuropathy. DESIGN: Prospective cross-sectional. METHODS: Twelve patients with early OAG and a known maximum untreated intraocular pressure less than 22 mm Hg (age, 61.4 +/- 9.7 years; Humphrey visual field mean deviation -2.7 +/- 2.1) and eight age,matched healthy control subjects (age, 58.5 +/- 8.3 years) were included in the study. Blood column diameter, centerline blood speed, and retinal blood flow were measured in the major inferior temporal retinal artery using a Canon laser Doppler blood flow instrument (CLBF 100; Canon, Tokyo, Japan). Peripapillary RNFL thickness was mea, sured using a Stratus optical coherence tomography instrument. RESULTS: On average, there were significant reductions in retinal blood speed (P = .009) and flow (P = .010) in OAG patients compared to controls. The RNFL was significantly thinner in the OAG patients compared to controls (P = .002). There were significant inverse correlations between retinal blood flow and average RNFL thickness and RNFL thickness in the inferior quadrant within the glaucoma group (Rsq = 0.50, P = .01; Rsq = 0.62, P = .003). CONCLUSION: The results showed that a thinner RNFL was associated with a higher retinal blood flow in patients with early-stage OAG. The mechanisms under, lying this phenomenon remain to be elucidated. C1 [Berisha, Fatmire; Feke, Gilbert T.; Hirose, Tatsuo; McMeel, J. Wallace] Schepens Retina Associates Fdn, Boston, MA 02215 USA. [Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Feke, Gilbert T.; Hirose, Tatsuo; McMeel, J. Wallace; Pasquale, Louis R.] Schepens Eye Res Inst, Boston, MA USA. [Berisha, Fatmire; Feke, Gilbert T.; Hirose, Tatsuo; McMeel, J. Wallace; Pasquale, Louis R.] Harvard Univ, Sch Med, Boston, MA USA. RP Feke, GT (reprint author), Schepens Retina Associates Fdn, 1 Autumn St,6th Floor, Boston, MA 02215 USA. EM feke@schepens.com NR 27 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2008 VL 146 IS 3 BP 466 EP 472 DI 10.1016/j.ajo.2008.04.034 PG 7 WC Ophthalmology SC Ophthalmology GA 343VR UT WOS:000258883900023 PM 18571616 ER PT J AU Noubade, R del Rio, R McElvany, B Zachary, JF Millward, JM Wagner, DD Offner, H Blankenhorn, EP Teuscher, C AF Noubade, Rajkumar del Rio, Roxana McElvany, Benjamin Zachary, James F. Millward, Jason M. Wagner, Denisa D. Offner, Halina Blankenhorn, Elizabeth P. Teuscher, Cory TI Von-willebrand factor influences blood brain barrier permeability and brain inflammation in experimental allergic encephalomyelitis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID WEIBEL-PALADE BODIES; CELL PERTUSSIS-VACCINE; ENDOTHELIAL-CELLS; MULTIPLE-SCLEROSIS; BORDETELLA-PERTUSSIS; WHOLE-CELL; AUTOIMMUNE ENCEPHALOMYELITIS; G-PROTEINS; MICE; DISEASE AB Weibel-Palade bodies within endothelial cells are secretory granules known to release von Witlebrand Factor (VWF), P-selectin, chemokines, and other stored molecules following histamine exposure. Mice with a disrupted VWF gene (VWFKO) have endothetial cells that are deficient in Weibel-Palade bodies. These mice were used to evaluate the role of VWF and/or Weibel-Palade bodies in Bordetella perfussis toxin-induced hypersensitivity to histamine, a subphenotype of experimental allergic encephalomyelitis, the principal autoimmune model of multiple sclerosis. No significant differences in susceptibility to histamine between wild-type and VWFKO mice were detected after 3 days; however, histamine sensitivity persisted significantly longer in VWFKO mice. Correspondingly, encephalomyelitis onset was earlier, disease was more severe, and blood brain barrier (BBB) permeability was significantly increased in VWFKO mice, as compared with wild-type mice. Moreover, inflammation was selectively increased in the brains, but not spinal cords, of VWFKO mice as compared with wild-type mice. Early increases in BBB permeability in VWFKO mice were not due to increased encephalitogenic T-cell activity since BBB permeability did not differ in adjuvant-treated VWFKO mice as compared with littermates immunized with encephalitogenic peptide plus adjuvant. Taken together, these data indicate that VWF and/or Weibel-Palade bodies negatively regulate BBB permeability changes and autoimmune inflammatory lesion formation within the brain elicited by peripheral inflammatory stimuli. C1 [Teuscher, Cory] Univ Vermont, Immunobiol Program, Dept Med, Burlington, VT 05405 USA. [Zachary, James F.] Univ Illinois, Dept Pathobiol, Urbana, IL 61801 USA. [Millward, Jason M.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Cambridge, MA 02138 USA. [Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. [Blankenhorn, Elizabeth P.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Teuscher, Cory] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. RP Teuscher, C (reprint author), Univ Vermont, Immunobiol Program, Dept Med, C317 Given Med Bldg, Burlington, VT 05405 USA. EM c.teuscher@uvm.edu OI Millward, Jason/0000-0003-4484-2798 FU NHLBI NIH HHS [R01 HL041002, HL041002, R37 HL041002]; NIAID NIH HHS [P01 AI045666, AI45105, AI41747, R01 AI041747, AI45666]; NINDS NIH HHS [R01 NS036526, NS36526] NR 52 TC 21 Z9 22 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2008 VL 173 IS 3 BP 892 EP 900 DI 10.2353/ajpath.2008.080001 PG 9 WC Pathology SC Pathology GA 344JD UT WOS:000258921900027 PM 18688020 ER PT J AU Sweadner, KJ AF Sweadner, Kathleen J. TI A third mode of ouabain signaling. Focus on "Regulation of ERK1/2 by ouabain and Na-K-ATPase-dependent energy utilization and AMPK activation in parotid acinar cells" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material ID ROLES C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Thier 415,55 Fuirt St, Boston, MA 02114 USA. EM sweadner@helix.mgh.harvard.edu NR 9 TC 3 Z9 3 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 2008 VL 295 IS 3 BP C588 EP C589 DI 10.1152/ajpcell.00388.2008 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 345KJ UT WOS:000258995000003 PM 18684986 ER PT J AU Miedlich, SU Abou-Samra, AB AF Miedlich, Susanne U. Abou-Samra, Abdul B. TI Eliminating phosphorylation sites of the parathyroid hormone receptor type 1 differentially affects stimulation of phospholipase C and receptor internalization SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE G protein-coupled receptor kinases; phosphorylation ID PROTEIN-COUPLED RECEPTOR; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; N-TERMINAL REGION; PTH/PTHRP RECEPTOR; HOMOLOGY DOMAIN; BONE-FORMATION; KINASE; PTH; DESENSITIZATION; CONFORMATIONS AB The parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTH1R) belongs to family B of seven-transmembrane-spanning receptors and is activated by PTH and PTHrP. Upon PTH stimulation, the rat PTH1R becomes phosphorylated at seven serine residues. Elimination of all PTH1R phosphorylation sites results in prolonged cAMP accumulation and impaired internalization in stably transfected LLC-PK1 cells. The present study explores the role of individual PTH1R phosphorylation sites in PTH1R signaling through phospholipase C, agonist-dependent receptor internalization, and regulation by G protein-coupled receptor kinases. By means of transiently transfected COS-7 cells, we demonstrate that the phosphorylation-deficient (pd) PTH1R confers dramatically enhanced coupling to Gq/11 proteins upon PTH stimulation predominantly caused by elimination of Ser491/492/493, Ser501, or Ser504. Reportedly, impaired internalization of the pd PTH1R, however, is not dependent on a specific phosphorylation site. In addition, we show that G protein-coupled receptor kinase 2 interferes with pd PTH1R signaling to Gq/11 proteins at least partially by direct binding to Gq/11 proteins. C1 [Miedlich, Susanne U.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Miedlich, Susanne U.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Abou-Samra, Abdul B.] Wayne State Univ, Sch Med, Detroit, MI USA. RP Miedlich, SU (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1101,50 Blossom St, Boston, MA 02114 USA. EM smiedlich@partners.org OI Abou-Samra, Abdul/0000-0001-8735-1142 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-063211, DK-11794] FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-063211 and DK-11794. NR 41 TC 10 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 2008 VL 295 IS 3 BP E665 EP E671 DI 10.1152/ajpendo.00036.2008 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 344MA UT WOS:000258930100017 PM 18577695 ER PT J AU Wu, SV Harikumar, KG Burgess, RJ Reeve, JR Miller, LJ AF Wu, S. Vincent Harikumar, Kaleeckal G. Burgess, Rebecca J. Reeve, Joseph R. Miller, Laurence J. TI Effects of cholecystokinin-58 on type 1 cholecystokinin receptor function and regulation SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE bioluminescence resonance energy transfer ID DIFFERENT CONFORMATIONS; FOOD-INTAKE; CCK-58; RATS; OLIGOMERIZATION; PEPTIDES; BLOOD; FORM; LOOP AB Cholecystokinin, like many peptide hormones, is present as multiple molecular forms. CCK-58 has been identified as the dominant form in the circulation, whereas most of the studies of CCK-receptor interactions have been performed with CCK-8. Despite both sharing the pharmacophoric region of CCK, representing its carboxy terminal heptapeptide amide, studies in vivo have demonstrated biological diversity of action of the two peptides, with CCK-58, but not CCK-8, stimulating pancreatic fluid secretion and lengthening the interval between meals. Here, we have directly studied the ability of these two CCK peptides to bind to the type 1 CCK receptor and to stimulate it to elicit an intracellular calcium response. The calcium response relative to receptor occupation was identical for CCK-58 and CCK-8, with the longer peptide binding with approximately fivefold lower affinity. We also examined the ability of the two peptides to elicit receptor internalization using morphological techniques and to disrupt the constitutive oligomerization of the CCK receptor using receptor bioluminescence resonance energy transfer. Here, both full agonist peptides had similar effects on these regulatory processes. These data suggest that both molecular forms of CCK act at the CCK1 receptor quite similarly and elicit similar regulatory processes for that receptor, suggesting that the differences in biological activity observed in vivo most likely reflect differences in the clearance and/or metabolism of these long and short forms of CCK peptides. C1 [Harikumar, Kaleeckal G.; Burgess, Rebecca J.; Miller, Laurence J.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Scottsdale, AZ 85259 USA. [Wu, S. Vincent; Reeve, Joseph R.] Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst &, Digest Dis Res Ctr,CURE, Los Angeles, CA USA. RP Miller, LJ (reprint author), Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM miller@mayo.edu FU National Institutes of Health [DK- 32878, DK- 33850, DK-41301]; Peptidomic, Radioimmunoassay, and Proteomic Core of the CURE Digestive Diseases [P50-AA011999]; Research Center for Alcoholic Liver and Pancreatic Diseases; Veterans Affairs Research Administration at Veterans Affairs Greater Los Angeles Healthcare System; Fiterman Foundation; Mayo Clinic FX This work was supported by grants from the National Institutes of Health, DK-32878 (L. J. Miller), DK-33850 (J. R. Reeve), DK-41301 (Peptidomic, Radioimmunoassay, and Proteomic Core of the CURE Digestive Diseases Center, J. R. Reeve), and P50-AA011999 (a pilot study supported by the Research Center for Alcoholic Liver and Pancreatic Diseases, S. V. Wu), as well as by the Veterans Affairs Research Administration at Veterans Affairs Greater Los Angeles Healthcare System (J. R. Reeve), the Fiterman Foundation (L. J. Miller), and the Mayo Clinic (L. J. Miller). NR 28 TC 10 Z9 10 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP PY 2008 VL 295 IS 3 BP G641 EP G647 DI 10.1152/ajpgi.90390.2008 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 345HD UT WOS:000258986100025 PM 18776046 ER PT J AU Baggish, AL Yared, K Wang, F Weiner, RB Hutter, AM Picard, MH Wood, MJ AF Baggish, Aaron L. Yared, Kibar Wang, Francis Weiner, Rory B. Hutter, Adolph M., Jr. Picard, Michael H. Wood, Malissa J. TI The impact of endurance exercise training on left ventricular systolic mechanics SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE athlete's heart; left ventricle; strain; ventricular interdependence ID HYPERTROPHIC CARDIOMYOPATHY; DOPPLER-ECHOCARDIOGRAPHY; MYOCARDIAL-FUNCTION; VOLUME-OVERLOAD; STRAIN-RATE; 2-DIMENSIONAL STRAIN; FILLING PRESSURES; CARDIAC STRUCTURE; ATHLETES HEART; BLOOD-PRESSURE AB Although exercise training-induced changes in left ventricular (LV) structure are well characterized, adaptive functional changes are incompletely understood. Detailed echocardiographic assessment of LV systolic function was performed on 20 competitive rowers (10 males and 10 females) before and after endurance exercise training (EET; 90 days, 10.7 +/- 1.1 h/wk). Structural changes included LV dilation (end-diastolic volume = 128 +/- 25 vs. 144 +/- 28 ml, P < 0.001), right ventricular (RV) dilation (end-diastolic area = 2,850 +/- 550 vs. 3,260 +/- 530 mm(2), P < 0.001), and LV hypertrophy (mass = 227 +/- 51 vs. 256 +/- 56 g, P < 0.001). Although LV ejection fraction was unchanged (62 +/- 3% vs. 60 +/- 3%, P = not significant), all direct measures of LV systolic function were altered. Peak systolic tissue velocities increased significantly (basal lateral S'Delta = 0.9 +/- 0.6 cm/s, P = 0.004; and basal septal S'Delta = 0.8 +/- 0.4 cm/s, P = 0.008). Radial strain increased similarly in all segments, whereas longitudinal strain increased with a base-to-apex gradient. In contrast, circumferential strain (CS) increased in the LV free wall but decreased in regions adjacent to the RV. Reductions in septal CS correlated strongly with changes in RV structure (Delta RV end-diastolic area vs. Delta LV septal CS; r(2) = 0.898, P < 0.001) and function (Delta peak RV systolic velocity vs. Delta LV septal CS, r(2) = 0.697, P < 0.001). EET leads to significant changes in LV systolic function with regional heterogeneity that may be secondary to concomitant RV adaptation. These changes are not detected by conventional measurements such as ejection fraction. C1 [Baggish, Aaron L.; Yared, Kibar; Weiner, Rory B.; Hutter, Adolph M., Jr.; Picard, Michael H.; Wood, Malissa J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Wang, Francis] Harvard Univ, Univ Hlth Serv, Cambridge, MA 02138 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Sutie 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 46 TC 52 Z9 52 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2008 VL 295 IS 3 BP H1109 EP H1116 DI 10.1152/ajpheart.00395.2008 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 344TC UT WOS:000258949200027 PM 18621855 ER PT J AU Feng, Y Zhao, H Xu, X Buys, ES Raher, MJ Bopassa, JC Thibault, H Scherrer-Crosbie, M Schmidt, U Chao, W AF Feng, Yan Zhao, Huailong Xu, Xinhua Buys, Emmanuel S. Raher, Michael J. Bopassa, Jean C. Thibault, Helene Scherrer-Crosbie, Marielle Schmidt, Ulrich Chao, Wei TI Innate immune adaptor MyD88 mediates neutrophil recruitment and myocardial injury after ischemia-reperfusion in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardial infarction; inflammation; echocardiography; innate immune system ID TOLL-LIKE RECEPTOR-4; NITRIC-OXIDE SYNTHASE; ISCHEMIA/REPERFUSION INJURY; TNF-ALPHA; RAT-HEART; DELAYED PROTECTION; CARDIAC MYOCYTES; INFARCT SIZE; IN-VIVO; ENDOTOXIN AB MyD88 is an adaptor protein critical for innate immune response against microbial infection and in certain noninfectious tissue injury. The present study examined the role of MyD88 in myocardial inflammation and injury after ischemia-reperfusion (I/R). I/R was produced by coronary artery ligation for 30 min followed by reperfusion. The ratios of area at risk to left ventricle (LV) were similar between wild-type (WT) and MyD88-deficient (MyD88(-/-)) mice. However, 24 h after I/R, the ratios of myocardial infarction to area at risk were 58% less in MyD88(-/-) than in WT mice (14 +/- 2% vs. 33 +/- 6%, P = 0.01). Serial echocardiographic studies demonstrated that there was no difference in baseline LV contractile function between the two groups. Twenty-four hours after I/R, LV ejection fraction (EF) and fractional shortening (FS) in WT mice were reduced by 44% and 62% (EF, 51 +/- 2%, and FS, 22 +/- 1%, P < 0.001), respectively, and remained depressed on the seventh day after I/R. In comparison, EF and FS in MyD88(-/-) mice were 67 +/- 3% and 33 +/- 2%, respectively, after I/R (P < 0.001 vs. WT). Similarly, LV function, as demonstrated by invasive hemodynamic measurements, was better preserved in MyD88(-/-) compared with WT mice after I/R. Furthermore, when compared with WT mice, MyD88(-/-) mice subjected to I/R had a marked decrease in myocardial inflammation as demonstrated by attenuated neutrophil recruitment and decreased expression of the proinflammatory mediators keratinocyte chemoattractant, monocyte chemoattractant protein-1, and ICAM-1. Taken together, these data suggest that MyD88 modulates myocardial inflammatory injury and contributes to myocardial infarction and LV dysfunction during I/R. C1 [Feng, Yan; Zhao, Huailong; Xu, Xinhua; Buys, Emmanuel S.; Raher, Michael J.; Bopassa, Jean C.; Schmidt, Ulrich; Chao, Wei] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Thibault, Helene; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Thibault, Helene; Scherrer-Crosbie, Marielle] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chao, W (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, GRJ-4-462,55 Fruit St, Boston, MA 02114 USA. EM wchao@partners.org RI Feng, Yan/H-5808-2012 FU National Institutes of Health [HL-04336, GM-080906]; William Milton Foundation of Harvard University; American Heart Association FX This study was supported in part by National Institutes of Health Grants HL-04336 and GM-080906 (to W. Chao) and grants from the William Milton Foundation of Harvard University Grant (to W. Chao) and the American Heart Association (to E. S. Buys and W. Chao). NR 52 TC 58 Z9 62 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2008 VL 295 IS 3 BP H1311 EP H1318 DI 10.1152/ajpheart.00119.2008 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 344TC UT WOS:000258949200051 PM 18660455 ER PT J AU Phillips, KA Didie, ER Feusner, J Wilhelm, S AF Phillips, Katharine A. Didie, Elizabeth R. Feusner, Jamie Wilhelm, Sabine TI Body dysmorphic disorder: Treating an underrecognized disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID OBSESSIVE-COMPULSIVE DISORDER; IMAGINED UGLINESS; OPEN-LABEL; CLINICAL-FEATURES; CONTROLLED-TRIAL; PREVALENCE; THERAPY; DYSMORPHOPHOBIA; FLUVOXAMINE; POPULATION C1 [Phillips, Katharine A.] Butler Hosp, Providence, RI 02906 USA. Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Phillips, KA (reprint author), Butler Hosp, 345 Blackstone Blvd, Providence, RI 02906 USA. EM katharine_phillips@brown.edu RI Feusner, Jamie/K-2312-2012 OI Feusner, Jamie/0000-0002-0391-345X FU NIMH NIH HHS [K23 MH-079212, K23 MH076934, K23 MH079212, K23 MH079212-02, K24 MH-063975, K24 MH063975, K24 MH063975-07] NR 42 TC 30 Z9 31 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2008 VL 165 IS 9 BP 1111 EP 1118 DI 10.1176/appi.ajp.2008.08040500 PG 8 WC Psychiatry SC Psychiatry GA 344BF UT WOS:000258899500010 PM 18765493 ER PT J AU Wrase, J Makris, N Braus, DF Mann, K Smolka, MN Kennedy, DN Caviness, VS Hodge, SM Tang, L Albaugh, M Ziegler, DA Davis, OC Kissling, C Schumann, G Breiter, HC Heinz, A AF Wrase, Jana Makris, Nicos Braus, Dieter F. Mann, Karl Smolka, Michael N. Kennedy, David N. Caviness, Verne S. Hodge, Steven M. Tang, Lena Albaugh, Matthew Ziegler, David A. Davis, Orin C. Kissling, Christian Schumann, Gunter Breiter, Hans C. Heinz, Andreas TI Amygdala volume associated with alcohol abuse relapse and craving SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FEAR-POTENTIATED STARTLE; HIPPOCAMPAL VOLUME; ORBITOFRONTAL CORTEX; USE DISORDERS; BRAIN; DEPENDENCE; EXPRESSION; DRINKING; DEFICITS; INDEXES AB Objective: Amygdala volume has been associated with drug craving in cocaine addicts, and amygdala volume reduction is observed in some alcohol-dependent subjects. This study sought an association in alcohol-dependent subjects between volumes of reward-related brain regions, alcohol craving, and the risk of relapse. Method: Besides alcohol craving, the authors assessed amygdala, hippocampus, and ventral striatum volumes in 51 alcohol-dependent subjects and 52 age- and education-matched healthy comparison subjects after detoxification. After imaging and clinical assessment, patients were followed for 6 months and alcohol intake was recorded. Results: Alcohol-dependent subjects showed reduced amygdala, hippocampus, and ventral striatum volumes and reported stronger craving in relation to healthy comparison subjects. However, only amygdala volume and craving differentiated between subsequent relapsers and abstainers. A significant decrease of amygdala volume in alcohol-dependent subjects was associated with increased alcohol craving before imaging and an increased alcohol intake during the 6-month follow-up period. Conclusions: These findings suggest a relationship between amygdala volume reduction, alcohol craving, and prospective relapse into alcohol consumption. C1 [Heinz, Andreas] Charite Univ Med Berlin, Dept Psychiat, D-10117 Berlin, Germany. Cent Inst Mental Hlth, D-6800 Mannheim, Germany. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. Clin Psychiat & Psychotherapy, Wiesbaden, Germany. Tech Univ Dresden, Dept Psychol, Dresden, Germany. Univ Wales Swansea, Sch Med, Swansea, W Glam, Wales. Kings Coll London, Inst Psychiat, Sect Addict Biol, London WC2R 2LS, England. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Heinz, A (reprint author), Charite Univ Med Berlin, Dept Psychiat, Charite Campus Mitte,Charitepl 1, D-10117 Berlin, Germany. EM andreas.heinz@charite.de RI Smolka, Michael/B-4865-2011; Kennedy, David/H-3627-2012; Albaugh, Matthew/R-4349-2016 OI Smolka, Michael/0000-0001-5398-5569; FU German Research Foundation [He2597/4-3]; Bernstein Centre for Computational Neuroscience Berlin [01GQ0411]; National Institute on Drug Abuse [00265, 09467, 14118]; Office of National Drug Control Policy-Counterdrug Technology Assessment Center [DABK39-03-C-0098]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery (MIND) Institute FX Dr. Heinz is supported by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft number He2597/4-3) and the Bernstein Centre for Computational Neuroscience Berlin (01GQ0411). Further support for this study was provided by grants to Dr. Breiter (numbers 00265, 09467, and 14118) from the National Institute on Drug Abuse and a grant (DABK39-03-C-0098 from the Phenotype Genotype Project in Addiction and Depression) from the Office of National Drug Control Policy-Counterdrug Technology Assessment Center. Further support, in part, was provided to Dr. Breiter by the Massachusetts General Hospital Department of Radiology, the National Center for Research Resources (P41RR14075), and the Mental Illness and Neuroscience Discovery (MIND) Institute. NR 40 TC 96 Z9 97 U1 4 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2008 VL 165 IS 9 BP 1179 EP 1184 DI 10.1176/appi.ajp.2008.07121877 PG 6 WC Psychiatry SC Psychiatry GA 344BF UT WOS:000258899500019 PM 18593776 ER PT J AU Wise, SK Ahn, CN Lathers, DMR Mulligan, RM Schlosser, RJ AF Wise, Sarah K. Ahn, Chadwick N. Lathers, Deanne M. R. Mulligan, Ryan M. Schlosser, Rodney J. TI Antigen-specific IgE in sinus mucosa of allergic fungal rhinosinusitis patients SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article; Proceedings Paper CT Spring Meeting of the American-Rhinologic-Society CY MAY 01, 2008 CL Orlando, FL SP Amer Rhinol Soc DE Allergic fungal sinusitis; allergic rhinitis; allergy; chronic rhinosinusitis; immunoglobulin E; local production; nasal polyps; specific IgE ID STAPHYLOCOCCUS-AUREUS ENTEROTOXINS; NASAL POLYP TISSUE; IMMUNOGLOBULIN-E; SOCIOECONOMIC-FACTORS; LOCAL PRODUCTION; BONE EROSION; IMMUNOTHERAPY; INFLAMMATION; ANTIBODIES; DIAGNOSIS AB Background: Local tissue production of antigen-specific immunoglobulin E (IgE) has been shown in patients With allergic rhinitis and in patients with chronic rhinosinusitis (CRS) With nasal polyps. In allergic fungal rhinosinusitis (AFRS), specific IgE has been established in nasal lavage fluid and eosinophilic mucin. In this stud, local production of antigen-specific IgE within sinus mucosa of AFRS patients was evaluated. Methods: Sinus mucosa homogenates front 11 AFRS patients, 8 patients with CRS without nasal polyps (CRSsNP), and 9 nonrhinosinusitis control patients were assessed for IgE localization by immunohistochemistry. AFRS and control tissue homogenates were also evaluated for antigen-specific IgE to 14 common antigens by ImmunoCAP testing (Phadia AB, Portage, MI). Results: There was a significant increase in IgE staining in AFRS sinus epithelium and subepithelium compared with controls and with patients with CRSsNP (p <= 0.012 for all group differences). AFRS patients showed increased IgE staining in the subepithelium when compared with epithelium (p < 0.001). AFRS sinus tissue had significantly more IgE measured by ImmunoCAP when compared with control shuts tissue for 7 of 14 specific antigens (p < 0.05) and for total IgE (p = 0.004). Antigens with a significant difference on ImmunoCAP included Cladosporium, Aspergillus, Timothy grass, red maple, cockroach, ragweed, and cocklebur. Conclusion: AFRS patients showed significantly more IgE in sinus mucosa tissue specimens, with increased IgE in subepithelial sites when compared with epithelium. The increased expression of antigen-specific IgE is not limited to fungal antigens. These findings support the role of type I hypersensitivity and local manifestations of allergy in AFRS patients. C1 [Wise, Sarah K.; Ahn, Chadwick N.; Lathers, Deanne M. R.; Mulligan, Ryan M.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Wise, Sarah K.] Emory Univ, Dept Otolaryngol Head & Neck Surg, Atlanta, GA 30322 USA. [Lathers, Deanne M. R.] Res Serv, Ralph H Johnson VAMC, Charleston, SC USA. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Suite 1130,POB 250550, Charleston, SC 29425 USA. EM schlossr@musc.edu NR 27 TC 26 Z9 27 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD SEP-OCT PY 2008 VL 22 IS 5 BP 451 EP 456 DI 10.2500/ajr.2008.22.3227 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 364UQ UT WOS:000260361300001 PM 18954501 ER PT J AU Lewis, CM Lin, DT Curry, WT Barker, FG Deschler, DG AF Lewis, Carol M. Lin, Derrick T. Curry, William T., Jr. Barker, Fred G., II Deschler, Daniel G. TI The use of nasopharyngeal airways for airway diversion in anterior craniofacial resection SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the North-American-Skull-Base-Society CY MAY 26, 2007 CL Chicago, IL SP N Amer Skull Base Soc DE Airway diversion; complication; craniofacial resection; morbidity; nasal trumpet; nasopharyngeal airway; retrospective; tension pneumocephalus ID SKULL BASE SURGERY; TENSION PNEUMOCEPHALUS; PARANASAL SINUSES; COMPLICATIONS; TUMORS; MANAGEMENT AB Background: Tension pneumocephalus is an uncommon, but life-threatening, postoperative complication associated with craniofacial resection. This study was performed to evaluate our institution's experience using nasal trumpets for airway diversion. Methods: A retrospective chart review was performed of patients who underwent anterior craniofacial resection (ACR) from 2000 to 2006. After Institutional Review Board approval, charts were reviewed with specific attention to short- and long-term complications. Results: Twenty-two patients have undergone ACR since 2000 and had nasopharyngeal airways postoperatively. Nineteen patients (86.4%) were extubated on the day of surgery. Fourteen patients (63.6%) spent 1 day in an intensive care unit for observation. Nasal trumpets remained in place for an average of 7.3 days and patients had an average hospital stay of 7.4 days. Complications occurred in 14 patients (63.6%), with infection as the most common cause. No cases of tension pneumocephalus, meningitis, epidural abscess, or bone flap loss occurred in this group of patients. Conclusion: We present the use of nasopharyngeal airways in postoperative ACR patients as a successful method of airway diversion, which can significantly reduce the incidence of postoperative pneumocephalus and related morbidity. C1 [Lewis, Carol M.; Lin, Derrick T.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Div Head & Neck Surg, Dept Otolaryngol, Boston, MA 02114 USA. [Lewis, Carol M.; Lin, Derrick T.; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Curry, William T., Jr.; Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Curry, William T., Jr.; Barker, Fred G., II] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Div Head & Neck Surg, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM daniel_deschler@meei.harvard.edu NR 20 TC 1 Z9 2 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD SEP-OCT PY 2008 VL 22 IS 5 BP 529 EP 532 DI 10.2500/ajr.2008.22.3219 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 364UQ UT WOS:000260361300017 PM 18954515 ER PT J AU Ma, XZ Samir, AE Holalkere, NS Sahani, DV AF Ma, Xiaozhou Samir, Anthony E. Holalkere, Nagaraj-Setty Sahani, Dushyant V. TI Optimal arterial phase imaging for detection of hypervascular hepatocellular carcinoma determined by continuous image capture on 16-MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE hepatocellular carcinoma; liver; MDCT; MRI; peak enhancement; rapid bolus injection ID ROW HELICAL CT; CONTRAST-ENHANCED CT; TO-LIVER CONTRAST; HEPATIC ENHANCEMENT; BOLUS-TRACKING; IODINE CONCENTRATION; CIRRHOTIC LIVERS; MULTIDETECTOR CT; INJECTION RATE; SPIRAL CT AB OBJECTIVE. The purpose of this study is to estimate the optimal time delay before the initiation of arterial phase scanning for detection of hypervascular hepatocellular carcinoma (HCC) on 16-MDCT when a rapid bolus injection of contrast medium is administered. SUBJECTS AND METHODS. In this prospective study, 25 patients ( 19 men and six women; mean age, 63.5 years; age range, 50-81 years) with pathologically confirmed HCC were included. Dynamic 16-MDCT imaging was performed in cine mode using 70 mL of nonionic iodinated contrast medium (300 mg I/mL) at an injection rate of 7 mL/s. Four consecutive 5-mm-thick slices at the maximum diameter of the HCC were selected as the region of interest. Time-attenuation curves were generated by region of interest drawn on the aorta, tumor, and liver. Qualitative assessments of conspicuity for contrast medium wash-in, peak, and wash-out of aorta and tumor were performed. RESULTS. There were 108 arterial phase enhancing lesions (mean [+/- SD], 4.9 +/- 2.4 cm; range, 0.7-12.9 cm) in the 25 patients. The maximum Hounsfield value of aorta, tumor, and background liver parenchyma were 463.8 +/- 98 HU, 106.5 +/- 19 HU, and 98.3 +/- 14 HU, respectively. At the time of onset of peak tumor enhancement, the difference between tumor density and background liver density was 38.2 +/- 19 HU. The time-attenuation curve showed that the mean times of contrast enhancement start, peak, and end were 9.2 +/- 2.7 seconds, 19.4 +/- 2.1 seconds, and 38 +/- 13.5 seconds, respectively, for the aorta, and 15.5 +/- 2.6 seconds, 26.3 +/- 2.9 seconds, and 57.7 +/- 14.4 seconds, respectively, for 25 pathologically confirmed hepatocellular carcinomas. Qualitatively, the mean times of contrast enhancement wash-in, peak, and washout were 10.2 +/- 2.8 seconds, 19.9 +/- 3 seconds, and 39.9 +/- 9.2 seconds, respectively for the aorta, and 18 +/- 4.2 seconds, 27 +/- 3 seconds, and 55.7 +/- 21 seconds, respectively, for tumor. There were no differences between quantitative and qualitative measurements of wash-in and peak time for the aorta (p = 0.00017, p = 0.00016) and tumor (p = 0.00163, p = 0.00040). CONCLUSION. When using 70 mL of 300 mg I/mL of contrast medium with an injection rate of 7 mL/s in 16-MDCT scanning, the optimal time to initiate scanning for HCC is 26.3 +/- 2.9 seconds (range, 24.0-34.5 seconds) after contrast medium administration. C1 [Ma, Xiaozhou; Samir, Anthony E.; Holalkere, Nagaraj-Setty; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Ma, Xiaozhou; Samir, Anthony E.; Holalkere, Nagaraj-Setty; Sahani, Dushyant V.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, WHT 2-270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org OI Samir, Anthony/0000-0002-7801-8724; Holalkere, Nagaraj/0000-0001-6324-7682 NR 33 TC 8 Z9 10 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2008 VL 191 IS 3 BP 772 EP 777 DI 10.2214/AJR.07.3452 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 339UG UT WOS:000258602200024 PM 18716108 ER PT J AU Dodd, JD Kalva, S Pena, A Bamberg, F Shapiro, MD Abbara, S Cury, RC Brady, TJ Hoffmann, U AF Dodd, Jonathan D. Kalva, Sanjeeva Pena, Antonio Bamberg, Fabien Shapiro, Michael D. Abbara, Suhny Cury, Ricardo C. Brady, Thomas J. Hoffmann, Udo TI Emergency cardiac CT for suspected acute coronary syndrome: Qualitative and quantitative assessment of coronary, pulmonary, and aortic image quality SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE aortic disease; chest pain; coronary angiography; CT; pulmonary embolism; radiography ID ACUTE CHEST-PAIN; MULTIDETECTOR COMPUTED-TOMOGRAPHY; MYOCARDIAL-INFARCTION; SPIRAL CT; ANGIOGRAPHY; DIAGNOSIS; DISSECTION; EMBOLISM; ISCHEMIA; 64-MDCT AB OBJECTIVE. The purpose of this study was to determine whether a dedicated coronary CT protocol provides adequate contrast enhancement and artifact-free depiction of coronary, pulmonary, and aortic circulation. MATERIALS AND METHODS. Dedicated coronary 64-MDCT data sets of 50 patients ( 27 men; mean age, 54 +/- 12.4 years) consecutively admitted from the emergency department with suspected acute coronary syndrome were analyzed. Two independent observers graded overall coronary arterial image quality and qualitative and quantitative contrast opacification, motion, and streak artifacts within the pulmonary arteries and aorta. RESULTS. Coronary image quality was excellent in 48 patients (96%) and moderate in two patients (4%). Eleven left main and 22 left upper lobar pulmonary arteries were not visualized. Qualitative evaluation showed pulmonary arterial tree opacification to be excellent except for the right and left lower lateral and posterior segmental branches (52-54% rate of poor opacification). Quantitative evaluation showed four central (8%), six lobar ( 8%), and 206 segmental (29%) branches had poor contrast opacification (< 200 HU). Nineteen right upper lobar arteries (38%) were slightly and one was severely affected by streak artifact. At the segmental pulmonary artery level, marked differences in contrast enhancement were detected between the upper (292 +/- 72 HU) and both the middle (249 +/- 85 HU) and the lower lobes (248 +/- 76 HU) (p < 0.01). Mean aortic opacification was 300 +/- 34 HU with excellent contrast homogeneity without severe motion or streak artifacts. CONCLUSION. In the evaluation of patients presenting to the emergency department with suspected acute coronary syndrome, a dedicated coronary CT protocol enables excellent assessment of the coronary arteries and proximal ascending aorta but does not depict the pulmonary vasculature well enough for exclusion of pulmonary embolism. C1 [Dodd, Jonathan D.; Kalva, Sanjeeva; Pena, Antonio; Bamberg, Fabien; Shapiro, Michael D.; Abbara, Suhny; Cury, Ricardo C.; Brady, Thomas J.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Dodd, Jonathan D.; Pena, Antonio; Bamberg, Fabien; Shapiro, Michael D.; Abbara, Suhny; Cury, Ricardo C.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MRI PET CT Program, Boston, MA 02114 USA. [Dodd, Jonathan D.; Kalva, Sanjeeva; Abbara, Suhny; Cury, Ricardo C.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Dodd, JD (reprint author), St Vincents Univ Hosp, Cardiac CT MRI Program, Elm Pk, Dublin 4, Ireland. FU NHLBI NIH HHS [T32 HL076136, T32 HL076136-05] NR 31 TC 26 Z9 27 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2008 VL 191 IS 3 BP 870 EP 877 DI 10.2214/AJR.07.3387 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 339UG UT WOS:000258602200037 PM 18716121 ER PT J AU Hall, JF Berger, D AF Hall, Jason F. Berger, David TI Outcome of colectomy for Clostridium difficile colitis: a plea for early surgical management SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Clostridium difficile; Clostridium difficile colitis; toxic megacolon; Fulminant colitis; subtotal colectomy ID PSEUDOMEMBRANOUS COLITIS; DIARRHEA AB BACKGROUND: Fulminant Clostridium difficile colitis is a common nosocomial infection that occurs with increasing frequency. METHODS: A total of 3,237 consecutive cases of C difficile cytotoxin-positive stool samples from 1998 to 2006 were reviewed. Commonly referenced indicators for surgical intervention were gathered on the day of surgery. The preoperative characteristics of patients surviving subtotal colectomy were compared with those who did not survive. RESULTS: Thirty-six patients underwent colectomy. Twenty-three patients (64%) were discharged from the hospital alive. Preoperative intubation and vasopressor requirement were risk factors for in-hospital mortality (odds ratio [OR], 7.15; 95% confidence interval [95% CI]. 1.28-39.8 and OR, 6.0; CI, 1.08-33, respectively). Patients who had a recent surgical procedure had a lower in-hospital mortality rate (OR,.11: 95% CI,.02-.52). CONCLUSIONS: Fulminant C difficile colitis is associated with a high mortality rate. Development of a vasopressor requirement or need for intubation are ominous signs and should lead to rapid surgical intervention. (c) 2008 Elsevier Inc. All rights reserved. C1 [Hall, Jason F.; Berger, David] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Hall, JF (reprint author), Massachusetts Gen Hosp, Dept Surg, WANG ACC 455, Boston, MA 02115 USA. EM jfhall13@gmail.com NR 15 TC 60 Z9 61 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD SEP PY 2008 VL 196 IS 3 BP 384 EP 388 DI 10.1016/j.amjsurg.2007.11.017 PG 5 WC Surgery SC Surgery GA 343ET UT WOS:000258836400013 PM 18519126 ER PT J AU Staats, PN McCluggage, WG Clement, PB Young, RH AF Staats, Paul N. McCluggage, W. Glenn Clement, Philip B. Young, Robert H. TI Luteinized thecomas (Thecomatosis) of the type typically associated with sclerosing peritonitis - A clinical, histopathologic, and immunohistochemical analysis of 27 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; luteinized thecoma; sclerosing peritonitis; immunohistochemistry ID CORD-STROMAL TUMORS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GRANULOSA-CELL TUMORS; EXPRESS KIT PROTEIN; OVARIAN FIBROMATOSIS; CLINICOPATHOLOGICAL ANALYSIS; DIFFERENTIAL-DIAGNOSIS; MONOCLONAL-ANTIBODY; MEIGS SYNDROME; C-KIT AB The nature of the distinctive ovarian lesion often associated with sclerosing peritonitis, initially considered a variant of luteinized thecoma in the paper describing this phenomenon. remains uncertain as does its long-term prognosis. We describe the features of 27 cases. including immuno-histochemical analysis of 13 cases. Sclerosing peritonitis was documented in 25 cases. Patients ranged in age from 10 months to 85 cars. and typically presented with abdominal distension and pain with ascites and sometimes bowel obstruction. The ovarian lesions. clinically bilateral in 24 cases ranged from 2 to 31 cm and often had a striking cerebriform aspect. Microscopically. mitotically, active spindle cells with weakly lutenized cells, variable edema. and entrapped follicles were typical. The spindle cells were focally positive with calretinin in 2 cases, CD56 in 2 AE1/3 in 4. smooth Muscle actin in 12, and desmin in 8 cases. and negative with alpha-inhibin. epithelial membrane antigen. beta-catenin. CD34, and transforming growth factor-beta, with focal nuclear positivity for estrogen receptor in 5 and progesterone receptor in I I cases. Luteinized cells were positive with alpha-inhibin. calretinin, and/or CD56. The peritoneal lesions were strongly positive with AE1/3 and exhibited Focal weak or moderate positivity with estrogen receptor or progesterone receptor in 4 of 8 cases each. Follow-up in 20 cases (mean: 5.9y) disclosed no evidence of spread of the ovarian lesion, but 3 patients died of sclerosing peritonitis. The findings fail to allow definitive classification of the ovarian lesions, and we prefer at present to retain their Current designation as a subtype of luteinized the coma. but to allow for the possibility of a non-neoplastic nature. feel it reasonable to have the designation "thecomatosis" as it parenthetical alternative. We have documented for (lie first time that sclerosing peritonitis is not invariably associated with the distinctive ovarian pathology present in these cases. C1 [Staats, Paul N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs,Dept Pathol, Boston, MA 02114 USA. [McCluggage, W. Glenn] Royal Grp Hosp Trust, Dept Pathol, Belfast, Antrim, North Ireland. [Clement, Philip B.] Univ British Columbia, Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Staats, PN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs,Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM pstaats@partners.org NR 58 TC 18 Z9 26 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2008 VL 32 IS 9 BP 1273 EP 1290 DI 10.1097/PAS.0b013e3181666a5f PG 18 WC Pathology; Surgery SC Pathology; Surgery GA 347WL UT WOS:000259172000001 PM 18636018 ER PT J AU McCluggage, WG Young, RH AF McCluggage, W. Glenn Young, Robert H. TI Primary ovarian mucinous tumors with signet ring cells - Report of 3 cases with discussion of so-called primary Krukenberg tumor SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; mucinous tumor; signet ring cells; Krukenberg tumor ID MIXED-EPITHELIAL CARCINOMAS; CLINICOPATHOLOGICAL ANALYSIS; BORDERLINE TUMORS; IMMUNOHISTOCHEMISTRY; DISTINCTION; METASTASES; STOMACH; ORIGIN; TRACT AB The distinction between a primary ovarian mucinous carcinoma or even a borderline mucinous tumor and a metastatic mucinous carcinoma may be difficult. A constellation of clinical. gross pathologic and morphologic features is used in this distinction. One of the most important morphologic features suggesting a metastatic mucinous carcinoma in the ovary is the presence of signet ring cells; these are considered rare in primary ovarian mucinous tumors. In this Study, we report 3 primary ovarian mucinous tumors with a component of signet ring cells. The tumors arose in patients aged 27, 55, and 60, were unilateral, confined to the ovary and stage IA. They ranged from 9 to 27cm; 1 was grossly a multiloculated cystic lesion and 2 were cystic and solid. In one case, the neoplasm had the architecture of a mucinous adenofibroma but had frankly malignant cells lining glands and forming solid aggregates of cells. A second tumor also had the background of an adenofibroma. The third was mostly a mucinous cystadenoma. In one case, endometriosis was present in the same ovary: teratomatous elements were not identified in any case. Immunohistochemistry , performed in 2 cases, showed both to be diffusely positive with CK7 and CA 19.9, including the signet ring cells. CK20 was positive in both cases (I focal; I diffuse). Estrogen receptor and CA125 were diffusely positive and carcinoembryonic antigen and CDX2 focally positive in I case. Chromogranin and synaptophysin were negative. Investigations to exclude a gastrointestinal neoplasm in 2 cases were negative. Features favoring a primary rather than a metastatic neoplasm are unilateral tumor, low stage, background of adenofibroma or cystadenoma, associated endometriosis in I case and an absence of features which are characteristic of secondary mucinous carcinomas in the ovary, such as surface tumor deposits, a nodular growth pattern, and lymphovascular permeation. Immunohistochemistry is of limited value because of overlapping immunophenotype between a primary ovarian mucinous tumor and a metastasis front the stomach, pancreas, biliary tree, appendix, or colorectum, the most likely primary sites for a C1 [McCluggage, W. Glenn] Royal Grp Hosp Trust, Dept Pathol, Belfast BT12 6BL, Antrim, North Ireland. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02115 USA. [Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP McCluggage, WG (reprint author), Royal Grp Hosp Trust, Dept Pathol, Grosvenor Rd, Belfast BT12 6BL, Antrim, North Ireland. EM glenn.mccluggage@belfasttrust.hscni.net NR 34 TC 15 Z9 16 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 SEP PY 2008 VL 32 IS 9 BP 1373 EP 1379 DI 10.1097/PAS.0b013e31816b18c1 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 347WL UT WOS:000259172000013 PM 18670351 ER PT J AU Melo, MFV Leone, BJ AF Melo, Marcos F. Vidal Leone, Bruce J. TI Introduction of new monitors into clinical anesthesia SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID ESOPHAGEAL DOPPLER MONITOR; CATHETER C1 [Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cardiac Anesthesia Grp, Boston, MA 02114 USA. [Melo, Marcos F. Vidal] Harvard Univ, Sch Med, Boston, MA USA. [Leone, Bruce J.] Mayo Clin, Dept Anesthesiol, Jacksonville, FL 32224 USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cardiac Anesthesia Grp, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org NR 6 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 SEP PY 2008 VL 107 IS 3 BP 749 EP 750 DI 10.1213/ane.0b013e31817708c3 PG 2 WC Anesthesiology SC Anesthesiology GA 341GP UT WOS:000258702500006 PM 18713878 ER PT J AU Eger, EI Raines, DE Shafer, SL Hemmings, HC Sonner, JM AF Eger, Edmond I., II Raines, Douglas E. Shafer, Steven L. Hemmings, Hugh C., Jr. Sonner, James M. TI Is a new paradigm needed to explain how inhaled anesthetics produce immobility? SO ANESTHESIA AND ANALGESIA LA English DT Review ID MINIMUM ALVEOLAR CONCENTRATION; D-ASPARTATE RECEPTORS; GATED ION CHANNELS; OXIDE SYNTHASE INHIBITOR; DORSAL-HORN NEURONS; ACID TYPE-A; NICOTINIC ACETYLCHOLINE-RECEPTORS; SECONDARY ALCOHOL ENANTIOMERS; STRYCHNINE-SENSITIVE GLYCINE; PERSISTENT SODIUM CURRENT AB A paradox arises from present information concerning the mechanism(s) by which inhaled anesthetics produce immobility in the face of noxious stimulation. Several findings, such as additivity, suggest a common site at which inhaled anesthetics act to produce immobility. However, two decades of focused investigation have not identified a ligand- or voltage-gated channel that alone is sufficient to mediate immobility. Indeed, most putative targets provide minimal or no mediation. For example, opioid, 5-HT3, gamma-aminobutyric acid type A and glutamate receptors, and, potassium and calcium channels appear to be irrelevant or play only minor roles. Furthermore, no combination of actions on ligand- or voltage-gated channels seems sufficient. A few plausible targets (e.g., sodium channels) merit further study, but there remains the possibility that immobilization results from a nonspecific mechanism. C1 [Eger, Edmond I., II; Sonner, James M.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Raines, Douglas E.] Harvard Univ, Sch Med, Boston, MA USA. [Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Shafer, Steven L.] Columbia Univ, Dept Anesthesia, New York, NY USA. [Hemmings, Hugh C., Jr.] Weill Cornell Med Coll, Dept Anesthesiol, New York, NY USA. [Hemmings, Hugh C., Jr.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA. RP Eger, EI (reprint author), Univ Calif San Francisco, Dept Anesthesia, S-455, San Francisco, CA 94143 USA. EM egere@anesthesia.ucsf.edu FU NIH [1PO1GM47818] FX Supported by the NIH grant 1PO1GM47818 (UCSF). NR 231 TC 52 Z9 52 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2008 VL 107 IS 3 BP 832 EP 848 DI 10.1213/ane.0b013e318182aedb PG 17 WC Anesthesiology SC Anesthesiology GA 341GP UT WOS:000258702500020 PM 18713892 ER PT J AU Shnayderman, D Laster, MJ Eger, EI Oh, I Zhang, Y Jinks, SL Antognini, JF Raines, DE AF Shnayderman, Dimitry Laster, Michael J. Eger, Edniond I., II Oh, Irene Zhang, Yi Jinks, Steven L. Antognini, Joseph F. Raines, Douglas E. TI Increases in spinal cerebrospinal fluid potassium concentration do not increase isoflurane minimum alveolar concentration in rats SO ANESTHESIA AND ANALGESIA LA English DT Article ID ANESTHETIC CONCENTRATION; K+ CHANNEL; BRAIN; REQUIREMENTS; TEMPERATURE; HYPOTHERMIA; HALOTHANE; ACTIVATE; TREK-1; MAC AB BACKGROUND: Previous studies demonstrated that MAC for isoflurane directly correlates with the concentration of Na(+) in cerebrospinal fluid surrounding the spinal cord, the primary site for mediation of the immobility produced by inhaled anesthetics. If this correlation resulted from increased irritability of the cord, then infusion of increased concentrations of potassium (K(+)) might be predicted to act similarly. However, an absence of effect of K(+) might be interpreted to indicate that K(+) channels do not mediate the immobility produced by inhaled anesthetics whereas Na(+) channels remain as potential mediators. Accordingly, in the present study, we examined the effect of altering intrathecal concentrations of K(+) on MAC. METHODS: in rats prepared with chronic indwelling intrathecal catheters, we infused solutions deficient in K(+) and with an excess of K(+) into the lumbar space and measured MAC for isoflurane 24 h before, during, and 24 h after infusion. Rats similarly prepared were tested for the effect of altered osmolarity oil MAC (accomplished by infusion of mannitol) and for the penetration of Na(+) into the cord. RESULTS: MAC of isoflurane never significantly increased with increasing concentrations of K(+) infused intrathecally. At infused concentrations exceeding 12 times the normal concentration of KCl, i.e., 29 mEq/L, rats moved spontaneously at isoflurane concentrations just below, and sometimes at MAC, but the average MAC in these rats did not exceed their control MAC. At the largest infused concentration (58.1 mEq/L), MAC significantly decreased and did not Subsequently return to normal (i.e., such large concentrations produced injury). Infusions of lower concentrations of K(+) had no effect on MAC. Infusion of osmotically equivalent solutions of mannitol did not affect MAC. Na(+) infused intrathecally measurably penetrated the spinal cord. CONCLUSIONS: The results do not support a mediation or modulation of MAC by K(+) channels. C1 [Shnayderman, Dimitry; Laster, Michael J.; Eger, Edniond I., II; Oh, Irene; Zhang, Yi] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Jinks, Steven L.; Antognini, Joseph F.] Univ Calif Davis, Dept Anesthesiol & Pain Med, Davis, CA 95616 USA. [Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Eger, EI (reprint author), Univ Calif San Francisco, Dept Anesthesia, S-455, San Francisco, CA 94143 USA. EM egere@anesthesia.ucsf.edu FU NIH [1P01GM47818]; RO1 [GM 078167] FX Supported by NIH grant 1P01GM47818 and RO1 grant (GM 078167 to S.L.J.). NR 22 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2008 VL 107 IS 3 BP 879 EP 884 DI 10.1213/ane.0b013e3181815f2b PG 6 WC Anesthesiology SC Anesthesiology GA 341GP UT WOS:000258702500028 PM 18713900 ER PT J AU Sandberg, EH Sharma, R Wiklund, R Sandberg, WS AF Sandberg, Elisabeth H. Sharma, Ritu Wiklund, Richard Sandberg, Warren S. TI Clinicians consistently exceed a typical person's short-term memory during preoperative teaching SO ANESTHESIA AND ANALGESIA LA English DT Article ID PREANESTHETIC INFORMATION; PATIENT SATISFACTION; EMOTIONAL RESPONSES; ANESTHETIC VISIT; PRIMARY-CARE; COMMUNICATION; VIDEO; SURGERY; DOCTORS; SKILLS AB INTRODUCTION: Patient education is a critical part of preparation for surgery. Little research on provider-to-patient teaching has been conducted with systematic focus on the quantity of information provided to patients. This is important to assess because short-term memory capacity for information such as preoperative instruction is limited to roughly seven units of content. METHODS: We studied the information-giving practices of anesthesiologists and nurse practitioners during preoperative teaching by examining transcripts from 26 tape recorded preoperative evaluation appointments. We developed a novel coding system to measure: 1) quantity of information, 2) frequency of medical terminology, 3) number of patient questions, and 4) number of memory reinforcements used during the consultation. Results are reported as mean So. RESULTS: Anesthesiologists and nurse practitioners vastly exceeded patients' short-term memory capacity. Nurse practitioners gave significantly more information to patients than did physicians (112 +/- 37 vs 49 +/- 25 items per interview, P < 0.01). This higher level of information-giving was not influenced by the question-asking behaviors of the patients. Nurse practitioners and physicians used similar numbers of medical terms (4.0 +/- 2.4 vs 3.7 +/- 2.8 explained terms per interview), and memory-supporting reinforcements (2.3 +/- 3.0 vs 1.4 +/- 2.0 reinforcements per interview). DISCUSSION: Given the known limits of short-term memory, clinicians would be well advised to carefully consider their patterns of information-giving and their use of memory-reinforcing strategies for critical information. C1 [Sandberg, Elisabeth H.; Sharma, Ritu] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Wiklund, Richard; Sandberg, Warren S.] Harvard Univ, Sch Med, Dept Anesthesia, Cambridge, MA 02138 USA. [Wiklund, Richard; Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Sandberg, EH (reprint author), Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. EM elisabeth.sandberg@suffolk.edu OI Sandberg, Warren/0000-0002-9246-777X FU Department of Psychology, Suffolk University (Boston, MA); Massachusetts General Hospital Department of Anesthesia and Critical Care (Boston, MA) FX Supported by departmental funds of the Department of Psychology, Suffolk University (Boston, MA) and the Massachusetts General Hospital Department of Anesthesia and Critical Care (Boston, MA). NR 27 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2008 VL 107 IS 3 BP 972 EP 978 DI 10.1213/ane.0b013e31817eea85 PG 7 WC Anesthesiology SC Anesthesiology GA 341GP UT WOS:000258702500044 PM 18713916 ER PT J AU Monk, BJ Herzog, T Kaye, S Krasner, CN Vermorken, J Muggia, F Pujade-Lourraine, E Renshaw, FG Lebedinsky, C Poveda, A AF Monk, B. J. Herzog, T. Kaye, S. Krasner, C. N. Vermorken, J. Muggia, F. Pujade-Lourraine, E. Renshaw, F. G. Lebedinsky, C. Poveda, A. TI A RANDOMIZED PHASE III STUDY OF TRABECTEDIN WITH PEGYLATED LIPOSOMAL DOXORUBICIN (PLD) VERSUS PLD IN RELAPSED, RECURRENT OVARIAN CANCER (OC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Monk, B. J.] Univ Calif Irvine, Div Gynecol Oncol, Orange, CA 92668 USA. [Herzog, T.] Columbia Coll Phys & Surg, Dept Gynecol Oncol, New York, NY USA. [Kaye, S.] Royal Marsden Hosp, Dept Med, Surrey, England. [Krasner, C. N.] Massachusetts Gen Hosp, Gillette Ctr Womens Studies, Boston, MA 02114 USA. [Vermorken, J.] Univ Antwerp Hosp, Dept Oncol, Edegem, Belgium. [Muggia, F.] New York Univ Hosp, New York, NY USA. [Pujade-Lourraine, E.] Hop Hotel Dieu, F-75181 Paris, France. [Renshaw, F. G.] LLC, Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Lebedinsky, C.] Pharma Mar, Madrid, Spain. [Poveda, A.] Inst Valenciano Oncol, Valencia, Spain. NR 0 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 2 EP 2 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300941 ER PT J AU Cappuzzo, F Toschi, L AF Cappuzzo, F. Toschi, L. TI SIGNATURES OF METASTATIC BEHAVIOR IN LUNG ADENOCARCINOMA (PREDICTS WHICH TUMOR TYPES GO ON TO AFFECT THE BRAIN, ETC.) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Cappuzzo, F.] Ist Clin Humanitas IRCCS, Rozzano, Italy. [Toschi, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 43 EP 43 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300066 ER PT J AU Blackwell, KL Burstein, HJ Storniolo, AM Rugo, H Sledge, G Koehler, M Ellis, C Casey, M Baselga, J Shaughnessy, JO AF Blackwell, K. L. Burstein, H. J. Storniolo, A. M. Rugo, H. Sledge, G. Koehler, M. Ellis, C. Casey, M. Baselga, J. Shaughnessy, J. O. TI A RANDOMIZED STUDY OF THE EFFICACY AND SAFETY OF LAPATINIB IN COMBINATION WITH TRASTUZUMAB AND AS MONOTHERAPY AFTER PROGRESSION ON TRASTUZUMAB IN HEAVILY PRETREATED ERBB2+METASTATIC BREAST CANCER (MBC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Blackwell, K. L.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Burstein, H. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sledge, G.] Indiana Univ, Ctr Canc, Sch Med, Indianapolis, IN 46204 USA. [Rugo, H.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Koehler, M.; Ellis, C.; Casey, M.] GSK, Med Dev Ctr Oncol, Collegeville, MN USA. [Baselga, J.] Vall Hebron Univ Hosp, Dept Oncol, Barcelona, Spain. [Shaughnessy, J. O.] Baylor Sammons Canc Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 64 EP 64 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300137 ER PT J AU Burstein, HJ Wu, Y Blackwell, K Storniolo, AM Rugo, H Amonkar, M Ellis, C Sledge, G Baselga, J Shaughnessy, JO AF Burstein, H. J. Wu, Y. Blackwell, K. Storniolo, A. M. Rugo, H. Amonkar, M. Ellis, C. Sledge, G. Baselga, J. Shaughnessy, J. O. TI LAPATINIB PLUS TRASTUZUMAB VERSUS LAPATINIB MONOTHERAPY IN TRASTUZUMAB-REFRACTORY ERBB2+METASTATIC BREAST CANCER (MBC) PATIENTS (PTS): QUALITY OF LIFE (QOL) ASSESSMENT SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Burstein, H. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, Y.] RTI, Global Hlth Outcomes, Res Triangle Pk, NC USA. [Blackwell, K.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Storniolo, A. M.] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Rugo, H.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Amonkar, M.] GlaxoSmithKline Inc, Global Project Strategy, Collegeville, PA USA. [Ellis, C.] GSK, Med Dev Ctr Oncol, Collegeville, PA USA. [Sledge, G.] Indiana Univ, Sch Med, Ctr Canc, Indianapolis, IN USA. [Baselga, J.] Vall Hebron Univ Hosp, Dept Oncol, Barcelona, Spain. [Shaughnessy, J. O.] Baylor Sammons Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 64 EP 64 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300138 ER PT J AU Badwe, R Kuter, I Hegg, R Sapunar, F McCormack, P AF Badwe, R. Kuter, I. Hegg, R. Sapunar, F. McCormack, P. TI AN ANALYSIS OF THE PHARMACOKINETIC (PK) PROFILE OF FULVESTRANT 500 MG VS 250 MG: DATA FROM THE NEWEST STUDY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Badwe, R.] Tata Mem Hosp, Bombay 400012, Maharashtra, India. [Kuter, I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hegg, R.] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Hegg, R.] Perola Bygton Hosp, Sao Paulo, Brazil. [Sapunar, F.; McCormack, P.] AstraZeneca, Macclesfield, Cheshire, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 71 EP 71 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300161 ER PT J AU Dang, C Lin, N Lake, D Theodoulou, M Drullinsky, P Gorsky, M Chen, C Norton, L Winer, E Hudis, C AF Dang, C. Lin, N. Lake, D. Theodoulou, M. Drullinsky, P. Gorsky, M. Chen, C. Norton, L. Winer, E. Hudis, C. TI DOSE-DENSE (DD) DOXORUBICIN AND CYCLOPHOSPHAMIDE (AC) FOLLOWED BY WEEKLY PACLITAXEL (P) WITH TRASTUZUMAB (T) AND LAPATINIB (L) IN HER2 OVEREXPRESSED/AMPLIFIED BREAST CANCER (BC): FIRST SAFETY RESULTS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Dang, C.; Lake, D.; Theodoulou, M.; Drullinsky, P.; Gorsky, M.; Chen, C.; Norton, L.; Hudis, C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Winer, E.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 77 EP 77 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300181 ER PT J AU Giobbie-Hurder, AE Gelber, RD AF Giobbie-Hurder, A. E. Gelber, R. D. TI DESIGN AND EVOLUTION OF BIG 1-98: A RANDOMIZED, DOUBLE-BLIND, PHASE-III STUDY COMPARING LETROZOLE AND TAMOXIFEN AS ADJUVANT ENDOCRINE THERAPY FOR POSTMENOPAUSAL WOMEN WITH RECEPTOR-POSITIVE, EARLY BREAST CANCER - BIG 1-98 COLLABORATIVE AND INTERNATIONAL BREAST CANCER STUDY GROUPS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Giobbie-Hurder, A. E.; Gelber, R. D.] Dana Farber Canc Inst, Ibcsg Stat Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 80 EP 80 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300192 ER PT J AU Lynch, T Jahanzeb, M Kosty, M Robles, R Wozniak, A Teng, SL Wang, L Navarro, WH AF Lynch, T. Jahanzeb, M. Kosty, M. Robles, R. Wozniak, A. Teng, S. L. Wang, L. Navarro, W. H. TI CLINICAL OUTCOMES FOR NON-SMALL CELL LUNG CANCER (NSCLC) FROM THE ARIES STUDY: A BEVACIZUMAB (BV) TREATMENT OBSERVATIONAL COHORT STUDY (OCS) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Lynch, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jahanzeb, M.] Univ Tennessee, Inst Canc, Memphis, TN USA. [Kosty, M.] Scripps Clin, La Jolla, CA USA. [Robles, R.] Diablo Valley Oncol & Hematol, Oncol & Hematol, Walnut Creek, CA USA. [Wozniak, A.] Wayne State Univ, Internal Med Hudson Webber Canc Res Ctr At, Detroit, MI USA. [Teng, S. L.] Genentech Inc, Biostat Oncol, San Francisco, CA 94080 USA. [Wang, L.] Genentech Inc, Epidemiol, San Francisco, CA 94080 USA. [Navarro, W. H.] Genentech Inc, Biooncol, San Francisco, CA 94080 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 93 EP 93 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300239 ER PT J AU Gandhi, L Camidge, DR Khaira, D Bonomi, P De Oliveira, MR Gandara, D Shapiro, GI Xiong, H Krivoshik, A Rudin, CM AF Gandhi, L. Camidge, D. R. Khaira, D. Bonomi, P. De Oliveira, M. R. Gandara, D. Shapiro, G. I. Xiong, H. Krivoshik, A. Rudin, C. M. TI AN ONGOING PHASE 1 STUDY OF ABT-263 IN PATIENTS WITH RELAPSED SMALL CELL LUNG CANCER AND OTHER SOLID TUMORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Gandhi, L.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Camidge, D. R.] Univ Colorado Canc Ctr, Aurora, CO USA. [Khaira, D.] Dedicated Phase 1, Hematol Oncol, Phoenix, AZ USA. [Bonomi, P.] Dana Farber Canc Inst, Div Hematol Oncol & Stem Cell Transplant, Chicago, IL USA. [De Oliveira, M. R.] PLLC, NW Med Specialties, Hematol Oncol NW Pc, Tacoma, WA USA. [Gandara, D.] UC Davis Canc Ctr, Ucdhs Hematol & Oncol, Sacramento, CA USA. [Shapiro, G. I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xiong, H.] Abbott Labs, Clin Pharmacokinet & Pharmacodynam, Abbott Pk, IL 60064 USA. [Krivoshik, A.] Abbott Labs, Abbott Pk, IL 60064 USA. [Rudin, C. M.] Johns Hopkins Univ, Lung Canc Therapeut Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 116 EP 116 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300324 ER PT J AU Lassen, U Braly, P de Bono, JS Celano, P Dizon, D Glasspool, R Micha, J Penson, RT Finkler, N AF Lassen, U. Braly, P. de Bono, J. S. Celano, P. Dizon, D. Glasspool, R. Micha, J. Penson, R. T. Finkler, N. TI PHASE (PH) I/II STUDY OF THE HISTONE DEACETYLASE INHIBITOR BELINOSTAT (BEL) IN COMBINATION WITH CARBOPLATIN (CA) AND PACLITAXEL (P) IN ADVANCED SOLID TUMORS (PH I) AND RELAPSED OVARIAN CANCER (PH II) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Lassen, U.] Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark. [Braly, P.] Dept Oncol Hematol & Oncol Specialists, Metairie, LA USA. [de Bono, J. S.] Inst Canc Res, Sutton SM2 5PT, Surrey, England. [Celano, P.] Greater Baltimore Med Ctr, Dept Oncol, Baltimore, MD USA. [Dizon, D.] Brown Univ, Women & Infants Hosp, Dept Oncol, Providence, RI USA. [Glasspool, R.] Beatson W Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Micha, J.] Gynecol Oncol Assoc, Dept Oncol, Newport Beach, CA USA. [Penson, R. T.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. [Finkler, N.] Florida Hosp, Inst Canc, Dept Oncol, Orlando, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 154 EP 154 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300462 ER PT J AU Michaelson, MD Schwarzberg, A Ryan, D McDermott, D Shapiro, GI Tye, L Chen, I Selaru, P Wang, E Zhu, A AF Michaelson, M. D. Schwarzberg, A. Ryan, D. McDermott, D. Shapiro, G. I. Tye, L. Chen, I. Selaru, P. Wang, E. Zhu, A. TI A PHASE I DOSE-FINDING STUDY OF SUNITINIB (SU) IN COMBINATION WITH GEMCITABINE (G) IN PATIENTS (PTS) WITH ADVANCED SOLID TUMORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Michaelson, M. D.; Schwarzberg, A.; Ryan, D.; Zhu, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McDermott, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tye, L.; Chen, I.; Selaru, P.; Wang, E.] Pfizer Inc, Global Res & Dev, San Diego, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 156 EP 156 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300468 ER PT J AU Marshall, J Shapiro, GI Terlizzi, E Stopfer, P Amelsberg, A Gordon, M AF Marshall, J. Shapiro, G. I. Terlizzi, E. Stopfer, P. Amelsberg, A. Gordon, M. TI A PHASE I DOSE ESCALATION TRIAL OF BIBW 2992, AN IRREVERSIBLE EGFR/HER2 KINASE INHIBITOR, FOR 20 AND 13 DAYS IN COMBINATION WITH DOCETAXEL EVERY 21 DAYS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Marshall, J.] Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. [Shapiro, G. I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Terlizzi, E.; Amelsberg, A.] Boehringer Ingelheim Pharmaceut Inc, Clin Res, Ridgefield, CT 06877 USA. [Stopfer, P.] Boehringer Ingelheim Pharma GmbH & Co KG, Dept Drug Metab & Pharmacokinet, Biberach, Germany. [Gordon, M.] Premiere Oncol, Oncology, Scottsdale, AZ USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 158 EP 158 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300474 ER PT J AU Enzinger, P Fidias, P Regan, E Lehman, N Abrams, T Hezel, A Sequist, L Fuchs, C Ryan, D AF Enzinger, P. Fidias, P. Regan, E. Lehman, N. Abrams, T. Hezel, A. Sequist, L. Fuchs, C. Ryan, D. TI PHASE II TRIAL OF DOCETAXEL, CISPLATIN, IRINOTECAN, AND BEVACIZUMAB IN METASTATIC ESOPHAGOGASTRIC CANCER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Enzinger, P.; Fidias, P.; Regan, E.; Lehman, N.; Abrams, T.; Hezel, A.; Sequist, L.; Fuchs, C.; Ryan, D.] Dana Farber Partners Canc Care, Med Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 171 EP 172 PG 2 WC Oncology SC Oncology GA 359GB UT WOS:000259973300522 ER PT J AU Tolcher, A Appleman, L Mita, A Shapiro, GI Chihon, F Mazzu, A Sundaresan, PR AF Tolcher, A. Appleman, L. Mita, A. Shapiro, G. I. Chihon, F. Mazzu, A. Sundaresan, P. R. TI EFFECT OF SORAFENIB TREATMENT ON LEFT VENTRICULAR EJECTION FRACTION IN CANCER PATIENTS: AN OPEN-LABEL, PHASE I STUDY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Tolcher, A.] START, Clin Res, San Antonio, TX USA. [Mita, A.] Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78229 USA. [Appleman, L.] Univ Pittsburgh, Pittsburgh, PA USA. [Shapiro, G. I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 179 EP 179 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300551 ER PT J AU McDermott, D Choueiri, TK Clement, J Brick, AJ Kwabi, C Shah, K Banerjee, A Duh, MS Neary, MP Oh, WK AF McDermott, D. Choueiri, T. K. Clement, J. Brick, A. J. Kwabi, C. Shah, K. Banerjee, A. Duh, M. S. Neary, M. P. Oh, W. K. TI PATIENTS (PTS) WITH METASTATIC RENAL CELL CARCINOMA (MRCC) RECEIVING ANGIOGENESIS INHIBITOR (AIS) THERAPIES: TREATMENT EFFICACY AND SAFETY IN CLINICAL PRACTICE SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [McDermott, D.] Beth Israel Deaconess Med Ctr, Hmfp Hematol Oncol, Boston, MA 02215 USA. [Choueiri, T. K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Brick, A. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Banerjee, A.; Duh, M. S.] Anal Grp Inc, Boston, MA USA. [Neary, M. P.] GlaxoSmithKline Inc, Global Hlth Outcomes Oncol, Collegeville, NC USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 190 EP 191 PG 2 WC Oncology SC Oncology GA 359GB UT WOS:000259973300589 ER PT J AU Negrier, S Figlin, RA Hutson, TE Tomczak, P Michaelson, MD Bukowski, RM Huang, X Kim, ST Chen, I Motzer, RJ AF Negrier, S. Figlin, R. A. Hutson, T. E. Tomczak, P. Michaelson, M. D. Bukowski, R. M. Huang, X. Kim, S. T. Chen, I. Motzer, R. J. TI OVERALL SURVIVAL WITH SUNITINIB VERSUS INTERFERON (IFN)-ALFA AS FIRST-LINE TREATMENT OF METASTATIC RENAL CELL CARCINOMA (MRCC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Negrier, S.] Ctr Leon Berard, Cytokines & Canc Res Unit, F-69373 Lyon, France. [Figlin, R. A.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Hutson, T. E.] Baylor Sammons Texas Oncol PA, Dallas, TX USA. [Tomczak, P.] Klin Onkol Oddzial Chernioterapii, Poznan, Poland. [Michaelson, M. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bukowski, R. M.] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. [Huang, X.; Kim, S. T.; Chen, I.] Pfizer Inc, Global Res & Dev, La Jolla, CA USA. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 190 EP 190 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300587 ER PT J AU Choueiri, TK Brick, AJ McDermott, D Clement, J Kwabi, C Shah, K Chen, K Duh, MS Neary, MP Oh, WK AF Choueiri, T. K. Brick, A. J. McDermott, D. Clement, J. Kwabi, C. Shah, K. Chen, K. Duh, M. S. Neary, M. P. Oh, W. K. TI TREATMENT AND DOSING PATTERNS FOR ANGIOGENESIS INHIBITOR (AIS) THERAPIES IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA (MRCC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Choueiri, T. K.; Oh, W. K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Brick, A. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McDermott, D.] Beth Israel Deaconess Med Ctr, Hmfp Hematol Oncol, Boston, MA 02215 USA. [Chen, K.; Duh, M. S.] Anal Grp Inc, Boston, MA USA. [Neary, M. P.] GlaxoSmithKline Inc, Global Hlth Outcomes Oncol, Collegeville, MN USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 191 EP 192 PG 2 WC Oncology SC Oncology GA 359GB UT WOS:000259973300592 ER PT J AU Rathkopf, DE Wong, BY Ross, RW George, DJ Picus, J Atadja, P Yang, W Culver, KW Woo, MM Scher, HI AF Rathkopf, D. E. Wong, B. Y. Ross, R. W. George, D. J. Picus, J. Atadja, P. Yang, W. Culver, K. W. Woo, M. M. Scher, H. I. TI A PHASE I STUDY OF ORAL PANOBINOSTAT (LBH589) ALONE AND IN COMBINATION WITH DOCETAXEL (DOC) AND PREDNISONE IN CASTRATION-RESISTANT PROSTATE CANCER (CRPC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Rathkopf, D. E.] Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, New York, NY 10021 USA. [Wong, B. Y.] Nevada Canc Inst, Dept Hematol Malignancies, Las Vegas, NV USA. [Ross, R. W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [George, D. J.] Duke Univ, Med Ctr, Dept Med & Surg, Durham, NC 27706 USA. [Picus, J.] Washington Univ, Div Med Oncol, St Louis, MO USA. [Atadja, P.] Novartis Inst Biomed Res, Cambridge, MA USA. [Yang, W.; Culver, K. W.] Novartis Pharmaceut, Oncol Early Clin Dev, Florham Pk, NJ USA. [Woo, M. M.] Novartis Oncol, Clin Pharmacol, Florham Pk, NJ USA. [Scher, H. I.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 199 EP 200 PG 2 WC Oncology SC Oncology GA 359GB UT WOS:000259973300620 ER PT J AU Cullen, KJ Schumaker, L Nikitakis, N Sarlis, N Tan, M Goloubeva, O Haddad, R Posner, M AF Cullen, K. J. Schumaker, L. Nikitakis, N. Sarlis, N. Tan, M. Goloubeva, O. Haddad, R. Posner, M. TI BETA-TUBULIN-II (BETA-T-II) EXPRESSION STRONGLY PREDICTS OUTCOME IN PATIENTS (PTS) RECEIVING NEOADJUVANT CHEMOTHERAPY FOR LOCALLY ADVANCED SQUAMOUS CARCINOMA OF THE HEAD & NECK (LASCCHN). A COMPANION ANALYSIS OF THE TAX 324 TRIAL SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Cullen, K. J.; Schumaker, L.; Nikitakis, N.; Tan, M.; Goloubeva, O.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Sarlis, N.] Sanofi Aventis, Bridgewater, MA USA. [Haddad, R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Posner, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 217 EP 217 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300684 ER PT J AU Hitt, R Posner, MR Cucherat, M Paccagnella, A Nole, F Lefebvre, J Chan, ATC Tsukuda, M Vokes, EE Vermorken, JB AF Hitt, R. Posner, M. R. Cucherat, M. Paccagnella, A. Nole, F. Lefebvre, J. Chan, A. T. C. Tsukuda, M. Vokes, E. E. Vermorken, J. B. TI DOCETAXEL-BASED INDUCTION CHEMOTHERAPY (ICT) IN LOCALLY ADVANCED HEAD AND NECK CANCER (LAHNC): A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (RCTS) USING INDIRECT COMPARISONS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Hitt, R.] Hosp Univ 12 Octubre, Med Oncol Serv, Madrid, Spain. [Posner, M. R.] Dana Farber Canc Inst, Head & Neck Surg, Boston, MA 02115 USA. [Cucherat, M.] Univ Lyon, Fac Med Laennec, Lyon, France. [Paccagnella, A.] Osped Civile Venezia, Dept Med Oncol, Venice, Italy. [Nole, F.] Inst Europeo Oncol, Milan, Italy. [Lefebvre, J.] Ctr Oscar Lambret, Head & Neck Surg, Dept Otolaryngol, F-59020 Lille, France. [Chan, A. T. C.] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Tsukuda, M.] Yokohama City Univ, Sch Med, Dept Otorhinolaryngol, Yokohama, Kanagawa 232, Japan. [Tsukuda, M.] Yokohama City Univ, Sch Med, Head & Neck Surg, Yokohama, Kanagawa 232, Japan. [Vokes, E. E.] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Vermorken, J. B.] Univ Ziekenhuis, Dept Oncol, Edegem, Belgium. RI Cucherat, Michel/B-2343-2008 OI Cucherat, Michel/0000-0003-2150-5932 NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 219 EP 219 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300693 ER PT J AU Brown, J Roberts, A Seymour, JF Wierda, W O'Connor, O Czuczman, M Xiong, H Enschede, S Krivoshik, A Wilson, W AF Brown, J. Roberts, A. Seymour, J. F. Wierda, W. O'Connor, O. Czuczman, M. Xiong, H. Enschede, S. Krivoshik, A. Wilson, W. TI ONGOING PHASE 1 STUDIES OF ABT-263; PHARMACOKINETICS, SAFETY AND ANTI-TUMOR ACTIVITY IN PATIENTS WITH RELAPSED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Brown, J.] Harvard Univ, Dept Med, Boston, MA USA. [Brown, J.] Dana Farber Canc Inst, Lymphoma Program Dfci, Boston, MA 02115 USA. [Roberts, A.] Royal Melbourne Hosp, Dept Clin Haematol & Med Oncol, Parkville, Vic 3050, Australia. [Seymour, J. F.] Peter MacCallum Canc Inst, Dept Clin Haematol & Med Oncol, Melbourne, Australia. [Wierda, W.] MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA. [O'Connor, O.] Columbia Univ, Ctr Med, Irving Canc Res Ctr, New York, NY USA. [Czuczman, M.] Roswell Pk Canc Inst, Lymphoma Myeloma Serv, Buffalo, NY 14263 USA. [Xiong, H.; Enschede, S.; Krivoshik, A.] Abbott Labs, Abbott Pk, IL 60064 USA. [Wilson, W.] NCI, Lymphoma Therapeut Sect, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 229 EP 229 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300727 ER PT J AU Paz-Ares, L Haddad, R Krebs, AD Vasselli, J Robinson, B AF Paz-Ares, L. Haddad, R. Krebs, A. D. Vasselli, J. Robinson, B. TI A PHASE II STUDY OF VANDETANIB IN METASTATIC HEREDITARY MEDULLARY THYROID CANCER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Paz-Ares, L.] Doce Octubre Univ Hosp, Madrid, Spain. [Haddad, R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Krebs, A. D.] AstraZeneca, Em Oncol & Infect, Wilminton, DE USA. [Vasselli, J.] AstraZeneca, Clin Res Oncol, Wilmington, DE USA. [Robinson, B.] Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2006, Australia. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 247 EP 247 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300792 ER PT J AU Galanis, E Jaeckle, K Buckner, J Maurer, M Hardwick, J Puduvalli, V Lamborn, K Kuhn, J Prados, M Wen, P AF Galanis, E. Jaeckle, K. Buckner, J. Maurer, M. Hardwick, J. Puduvalli, V. Lamborn, K. Kuhn, J. Prados, M. Wen, P. TI VORINOSTAT IN GLIOBLASTOMA MULTIFORME (GBM): UPDATED RESULTS FROM PHASE I AND II TRIALS PROVIDE THE RATIONALE FOR FURTHER CLINICAL DEVELOPMENT SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Galanis, E.; Buckner, J.; Maurer, M.] Mayo Clin & Mayo Fdn, Div Med Oncol, Rochester, MN USA. [Galanis, E.; Buckner, J.; Maurer, M.] NCCTG, Rochester, MN USA. [Jaeckle, K.] Mayo Clin & Mayo Fdn, Dept Neurol, Jacksonville, FL USA. [Jaeckle, K.] NCCTG, Jacksonville, FL USA. [Hardwick, J.] Merck Res Labs, Upper Gwynedd, PA USA. [Wen, P.] NABTC, Ctr Neurooncol, Boston, MA USA. [Wen, P.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 249 EP 250 PG 2 WC Oncology SC Oncology GA 359GB UT WOS:000259973300803 ER PT J AU Demetri, GD Gajiwala, KS Diehl, W DiNitto, JP He, Y Lunney, EA Wells, PA Wu, JC AF Demetri, G. D. Gajiwala, K. S. Diehl, W. DiNitto, J. P. He, Y. Lunney, E. A. Wells, P. A. Wu, J. C. TI NOVEL MECHANISMS OF RESISTANCE TO IMATINIB (IM) OR SUNITINIB (SU) IN KIT MUTANTS FROM PATIENTS WITH GIST: STRUCTURAL BIOLOGY AND FUNCTIONAL ENZYMOLOGY STUDIES OF WILD-TYPE (WT) AND MUTATED PROTEINS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Demetri, G. D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Ctr Sarcoma & Bone Oncol, Boston, MA USA. [Gajiwala, K. S.; Diehl, W.; He, Y.; Lunney, E. A.; Wells, P. A.] Pfizer Inc, Global Res & Dev, La Jolla, CA USA. [DiNitto, J. P.; Wu, J. C.] Pfizer Inc, Res Technol Ctr, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 266 EP 266 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300863 ER PT J AU Schoffski, P Huang, X Casali, PG Garrett, CR Blackstein, ME Shah, MH Verweij, J Tassell, V Baum, CM Demetri, GD AF Schoeffski, P. Huang, X. Casali, P. G. Garrett, C. R. Blackstein, M. E. Shah, M. H. Verweij, J. Tassell, V. Baum, C. M. Demetri, G. D. TI PHASE III TRIAL OF SUNITINIB (SU) IN IMATINIB (IM)-RESISTANT/INTOLERANT GIST WITH NOVEL STATISTICAL ANALYSIS OF LONG-TERM SURVIVAL TO ACCOUNT FOR CROSSOVER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Schoeffski, P.] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Huang, X.; Tassell, V.; Baum, C. M.] Pfizer Inc, Global Res & Dev, La Jolla, CA USA. [Casali, P. G.] Ist Nazl Tumori, Adult Sarcoma Med Treatment Unit, I-20133 Milan, Italy. [Garrett, C. R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Blackstein, M. E.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Blackstein, M. E.] Univ Toronto, Toronto, ON, Canada. [Shah, M. H.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Verweij, J.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Demetri, G. D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Ctr Sarcoma & Bone Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 266 EP 266 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300862 ER PT J AU Blay, J George, S Casali, PG Le Cesne, A Ray-Coquard, I Harmon, CS Law, CNJ Tassell, V Baum, CM Demetri, GD AF Blay, J. George, S. Casali, P. G. Le Cesne, A. Ray-Coquard, I. Harmon, C. S. Law, C. N. J. Tassell, V. Baum, C. M. Demetri, G. D. TI EFFICACY, SAFETY, PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSIS OF SUNITINIB (SU) ADMINSTERED ON A CONTINUOUS DAILY DOSING (CDD) SCHEDULE IN PATIENTS WITH ADVANCED GIST SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Blay, J.; Ray-Coquard, I.] Ctr Leon Berard, F-69373 Lyon, France. [George, S.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Casali, P. G.] Ist Nazl Tumori, Adult Sarcoma Med Treatment Unit, I-20133 Milan, Italy. [Le Cesne, A.] Inst Gustave Roussy, Villejuif, France. [Harmon, C. S.; Law, C. N. J.; Tassell, V.; Baum, C. M.] Pfizer Inc, Global Res & Dev, La Jolla, CA USA. [Demetri, G. D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Ctr Sarcoma & Bone Oncol, Boston, MA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 267 EP 268 PG 2 WC Oncology SC Oncology GA 359GB UT WOS:000259973300868 ER PT J AU Reichardt, P Kang, Y Ruka, W Seddon, B Nieto, A Breazna, A Lechner, T Demetri, GD AF Reichardt, P. Kang, Y. Ruka, W. Seddon, B. Nieto, A. Breazna, A. Lechner, T. Demetri, G. D. TI SUNITINIB (SU) IN A WORLDWIDE TREATMENT-USE TRIAL OF PATIENTS WITH GIST: UPDATED EFFICACY AND SAFETY ANALYSIS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol C1 [Reichardt, P.] HELIOS Klinikum Bad Saarow, Bad Saarow Pieskow, Germany. [Kang, Y.] Asan Med Ctr, Dept Internal Med, Seoul, South Korea. [Ruka, W.] Maria Sklodowska Curie Mem Canc Ctr, Dept Soft Tissue Bone Sarcomas, Warsaw, Poland. [Seddon, B.] Univ Coll Hosp NHS Trust, Sarcoma Unit, London, England. [Nieto, A.; Breazna, A.; Lechner, T.] Pfizer Inc, New York, NY USA. [Demetri, G. D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Ctr Sarcoma & Bone Oncol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2008 VL 19 BP 267 EP 267 PG 1 WC Oncology SC Oncology GA 359GB UT WOS:000259973300866 ER PT J AU Yang, M Barner, JC Lawson, KA Rascati, KL Wilson, JP Crismon, ML Worchel, J Mascarenas, CA AF Yang, Min Barner, Jamie C. Lawson, Kenneth A. Rascati, Karen L. Wilson, James P. Crismon, M. Lynn Worchel, Jason Mascarenas, Cynthia A. TI Antipsychotic medication utilization trends among Texas veterans: 1997-2002 SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE antipsychotic; medication utilization; trends ID ATYPICAL ANTIPSYCHOTICS; CHRONIC-SCHIZOPHRENIA; PSYCHIATRIC-PATIENTS; UNITED-STATES; RISPERIDONE; DISORDER; OLANZAPINE; CLOZAPINE; AGENTS; DRUGS AB BACKGROUND: An antipsychotic utilization pattern has evolved substantially over the past 20 years or so due to the introduction of the second-generation antipsychotics (SGAs) and the increasing understanding of their adverse effect profile. OBJECTIVE: To understand antipsychotic utilization trends (including monotherapy, antipsychotic switching, and combination therapy) and to investigate factors associated with antipsychotic index medication selection (SGAs vs first-generation antipsychotics [FGAs]) among Texas veterans. METHODS: Data were taken from the Veterans Administration North Texas Health Care System (VANTHCS) and South Texas Veterans Health Care System (STVHCS) from January 1996 to December 2003. Adults with continuous enrollment (1 y before and after the index date) who had newly initiated antipsychotic therapy were included. Prescriptions were followed for up to 12 months. Descriptive analyses examined utilization trends; logistic regression evaluated factors associated with antipsychotic index medication selection. RESULTS: A total of 8096 patients were included in the study (VANTHCS n = 4477; STVHCS n = 3619), with the majority being male (93.6%) and white (62.6%) and nearly half aged 55 years or older (44.1%). Between 1997 and 2002, antipsychotic prescriptions changed from primarily FGAs (1997: 71.7%; 1999: 25.2%; 2002: 5.7%) to SGAs. Over the 6-year time frame, risperidone (31.0%) and olanzapine (30.7%) were most commonly prescribed. The overall combination therapy slightly increased over time (4.3%), switching to another antipsychotic remained stable (14.2%), and antipsychotic monotherapy remained dominant (81.5%). Hispanic and black patients were less likely than white patients to be initiated on SGAs. Patients who were older, had hypertension, and were in STVHCS were less likely to start on SGAs. Patients with dyslipidemia, bipolar disorder, and treatment in recent years were more likely to start on SGAs. CONCLUSIONS: SGAs have replaced FGAs as first-line medications for patients with mental disorders. Race, age, physical comorbidities (ie, dyslipidemia, hyperlension), and treatment initiation year were important factors in index medication selection. C1 [Yang, Min] QualityMetr Hlth Outcomes Solut, Outcomes Insight Consulting, Lincoln, RI 02865 USA. [Barner, Jamie C.; Lawson, Kenneth A.; Rascati, Karen L.; Wilson, James P.; Crismon, M. Lynn] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Worchel, Jason] Cent Texas Vet Hlth Care Syst, US Dept Vet Affairs, Temple, TX USA. [Mascarenas, Cynthia A.] S Texas Vet Hlth Care Syst, US Dept Vet Affairs, San Antonio, TX USA. RP Yang, M (reprint author), QualityMetr Hlth Outcomes Solut, Outcomes Insight Consulting, 640 George Washington Hwy,Ste 201, Lincoln, RI 02865 USA. EM myang@QualityMetric.com NR 55 TC 19 Z9 19 U1 2 U2 4 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 SEP PY 2008 VL 42 IS 9 BP 1229 EP 1238 DI 10.1345/aph.1L155 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 346WE UT WOS:000259099500007 PM 18682544 ER PT J AU Gilbert, TW Gilbert, S Madden, M Reynolds, SD Badylak, SF AF Gilbert, Thomas W. Gilbert, Sebastien Madden, Matthew Reynolds, Susan D. Badylak, Stephen F. TI Morphologic assessment of extracellular matrix scaffolds for patch tracheoplasty in a canine model SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 28-30, 2008 CL Ft Lauderdale, FL SP Soc Thorac Surg ID TRACHEAL BIOARTIFICIAL ORGAN; INTESTINAL SUBMUCOSA; RABBIT MODEL; TISSUE; RECONSTRUCTION; CELLS; EPITHELIUM; DETERGENT; STENOSIS; STENTS AB Background. The optimal management of benign tracheal stricture remains surgical resection. Resection is not always an option because of the challenges posed by anastomotic tension and a tenuous blood supply. Regenerative medicine approaches, such as extracellular matrix (ECM) scaffold technology, may alleviate some of the limitations to tracheal replacement. ECM scaffolds facilitate site-specific tissue remodeling when used to reconstruct a variety of soft-tissue structures. Methods. A 1-cm wide x 2-cm-long defect was created in the ventral trachea of 15 dogs and repaired with one of three acellular biologic scaffolds: urinary bladder matrix (UBM), UBM crosslinked with carbodiimide (UBMC), and decellularized tracheal matrix (DTM). The grafts were evaluated periodically using bronchoscopy and by macroscopic and microscopic morphologic examination at either 2 months or 6 months. Results. The UBM, UBMC, and DTM groups showed no evidence of stenosis or tracheomalacia. The UBM, UBMC, and DTM groups all showed deposition of organized collagenous tissue at the site of scaffold placement and an intact epithelial layer. Scattered areas of mucociliary differentiation were present at the edges of the graft site. There was no evidence cartilage observed within the remodeled tissue at 6 months. Conclusions. ECM scaffolds promote healing of significantly sized tracheal defects without stricture and with some, but not all, of the necessary structures required for tracheal reconstruction, including complete coverage with ciliated epithelium and dense organized collagenous tissue. C1 [Badylak, Stephen F.] Univ Pittsburgh, McGowan Inst Regenerat Med, Dept Surg, Heart Lung & Esophageal Inst,Med Ctr, Pittsburgh, PA 15219 USA. Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Natl Jewish Med & Res Ctr, Dept Pediat, Denver, CO USA. RP Badylak, SF (reprint author), Univ Pittsburgh, McGowan Inst Regenerat Med, Dept Surg, Heart Lung & Esophageal Inst,Med Ctr, 100 Technol Dr,Ste 200, Pittsburgh, PA 15219 USA. EM badylaks@upmc.edu OI Gilbert, Sebastien/0000-0003-4357-9553; Badylak, Stephen/0000-0003-3555-0689 NR 25 TC 49 Z9 52 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2008 VL 86 IS 3 BP 967 EP 974 DI 10.1016/j.athoracsur.2008.04.071 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 340AT UT WOS:000258619100038 PM 18721593 ER PT J AU Grochow, RM Raffetto, JD AF Grochow, Rebecca M. Raffetto, Joseph D. TI Chronic traumatic pseudoaneurysm of polytetrafluoroethylene axillofemoral bypass graft in a quadriplegic patient SO ANNALS OF VASCULAR SURGERY LA English DT Article ID ARTERY BYPASS; COMPLICATION; ANEURYSM; DISEASE AB A case of nonanastomotic pseudoaneurysm of a polytetrafluoroethylene (PTFE) axillofemoral bypass graft due to chronic abrasion and pressure of the graft by external sources is reported. A quadriplegic patient presented with a pulsatile mass beneath his seatbelt straps in the midleft chest region, consistent by computed tomography angiography and duplex ultrasound with a pseudoaneurysm of the PTFE graft, which had been placed 9 years previously. The patient underwent a successful endovascular repair of the pseudoaneurysm, and at 6- month follow- up the mass had resolved. To our knowledge this represents the. first case of a chronic nonanastomotic pseudoaneurysm of a PTFE axillofemoral bypass graft secondary to abrasion and pressure that was repaired via an endovascular approach. C1 [Raffetto, Joseph D.] VA Boston Healthcare Syst, Div Vasc Surg, W Roxbury, MA 02132 USA. [Grochow, Rebecca M.; Raffetto, Joseph D.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Raffetto, JD (reprint author), VA Boston Healthcare Syst, Div Vasc Surg, Surg 112,1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM joseph.raffetto@med.va.gov OI /0000-0002-4804-3128 NR 17 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD SEP-OCT PY 2008 VL 22 IS 5 BP 688 EP 691 DI 10.1016/j.avsg.2008.02.009 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 343FG UT WOS:000258837700015 PM 18375099 ER PT J AU Baffy, G AF Baffy, Gyorgy TI MITOCHONDRIA AND CANCER: PROSPECTS FOR NOVEL THERAPEUTIC TARGETS SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Baffy, Gyorgy] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Baffy, Gyorgy] VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2008 VL 28 IS 5C MA 39 BP 3204 EP 3205 PG 2 WC Oncology SC Oncology GA 367ME UT WOS:000260555300040 ER PT J AU Cascio, P Bianchi, G Oliva, L Cerruti, F Sitia, R Cenci, S AF Cascio, Paolo Bianchi, Giada Oliva, Laura Cerruti, Fulvia Sitia, Roberto Cenci, Simone TI IMBALANCE BETWEEN SYNTHETIC LOAD AND PROTEASOMAL CAPACITY SENSITIZES NORMAL AND MALIGNANT PLASMA CELLS TO PROTEASOME INHIBITORS SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Cascio, Paolo; Cerruti, Fulvia] Univ Turin, Dept Morphophysiol, Sch Vet Med, I-10095 Grugliasco, TO, Italy. [Bianchi, Giada] Ist Sci San Raffaele, Dept Biol & Technol, DiBiT, I-20132 Milan, Italy. [Oliva, Laura; Sitia, Roberto; Cenci, Simone] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2008 VL 28 IS 5C MA 94 BP 3231 EP 3232 PG 2 WC Oncology SC Oncology GA 367ME UT WOS:000260555300095 ER PT J AU Song, KS Yun, EJ Park, HD Kim, JS Heo, JY Jung, YJ Han, C Wu, T Kang, JX Park, JI Kweon, GR Yoon, WH Hwang, BD Lim, K AF Song, Kyoung-Sub Yun, Eun-Jin Park, Hae-Duck Kim, Jong-Seok Heo, Jun-Young Jung, Yeon-Joo Han, Chang Wu, Tong Kang, Jing X. Park, Jong-Il Kweon, Gi-Ryang Yoon, Wan-Hee Hwang, Byung-Doo Lim, Kyu TI TUMORIGENICITY AND ANGIOGENESIS OF PANCREATIC CANCER ARE INHIBITED IN FAT1 (omega-3 DESATURASE) TRANSGENIC MICE SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Hwang, Byung-Doo; Lim, Kyu] Chungnam Natl Univ, Canc Res Inst, Taejon, South Korea. [Park, Hae-Duck] Dr Pk Breast Clin, Taejon, South Korea. [Han, Chang; Wu, Tong] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. [Kang, Jing X.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2008 VL 28 IS 5C MA 406 BP 3380 EP 3380 PG 1 WC Oncology SC Oncology GA 367ME UT WOS:000260555300407 ER PT J AU Yun, EJ Song, KS Park, HD Kim, JS Heo, JY Jung, YJ Han, C Wu, T Kang, JX Park, JI Kweon, GR Yoon, WH Hwang, BD Lim, K AF Yun, Eun-Jin Song, Kyoung-Sub Park, Hae-Duck Kim, Jong-Seok Heo, Jun-Young Jung, Yeon-Joo Han, Chang Wu, Tong Kang, Jing X. Park, Jong-Il Kweon, Gi-Ryang Yoon, Wan-Hee Hwang, Byung-Doo Lim, Kyu TI OMEGA-3 POLYUNSATURATED FATTY ACIDS SUPPRESS CELL INVASION AND ANGIOGENESIS BY INHIBITION OF MMPs/COX-2/VEGF THROUGH NF-kappa B AND AP-1 SIGNAL IN BREAST CANCER SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Hwang, Byung-Doo; Lim, Kyu] Chungnam Natl Univ, Canc Res Inst, Taejon, South Korea. [Park, Hae-Duck] Dr Pk Breast Clin, Taejon, South Korea. [Han, Chang; Wu, Tong] Univ Pittsburgh, Dept Pathol, Sch Med, Pittsburgh, PA 15213 USA. [Kang, Jing X.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2008 VL 28 IS 5C MA 407 BP 3380 EP 3381 PG 2 WC Oncology SC Oncology GA 367ME UT WOS:000260555300408 ER PT J AU Nagai, Y Ishikawa, S Baba, Y Karashima, R Sato, N Imamura, Y Yukiharu, H Yoshida, N Toyama, E Hayashi, N Watanabe, M Baba, H AF Nagai, Youhei Ishikawa, Shinji Baba, Yoshihumi Karashima, Ryuichi Sato, Nobutaka Imamura, Yu Yukiharu, Hiyoshi Yoshida, Naoya Toyama, Eiichirou Hayashi, Naoko Watanabe, Masayuki Baba, Hideo TI CLINICAL SIGNIFICANCE OF WNT-INDUCED SECRETED PROTEIN-1 (WISP-1/CCN4) IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Nagai, Youhei; Karashima, Ryuichi; Sato, Nobutaka; Imamura, Yu; Yukiharu, Hiyoshi; Yoshida, Naoya; Toyama, Eiichirou; Hayashi, Naoko; Watanabe, Masayuki; Baba, Hideo] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto 8608556, Japan. [Ishikawa, Shinji] Kumamoto Reg Hosp, Dept Surg, Kumamoto 8600811, Japan. [Baba, Yoshihumi] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2008 VL 28 IS 5C MA 474 BP 3415 EP 3416 PG 2 WC Oncology SC Oncology GA 367ME UT WOS:000260555300475 ER PT J AU Sansom, CE Shepherd, A Brusic, V Motta, S Lollini, PL Lefranc, MP Moss, DS AF Sansom, C. E. Shepherd, A. Brusic, V. Motta, S. Lollini, P. L. Lefranc, M. -P Moss, D. S. TI MULTI-SCALE MODELLING OF THE IMMUNE SYSTEM: APPLICATIONS TO CANCER IMMUNOTHERAPY SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Sansom, C. E.; Shepherd, A.; Moss, D. S.] Birkbeck Coll, Sch Crystallog, London WC1E 7HX, England. [Brusic, V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Brusic, V.] Univ Queensland, LCAFS, Brisbane, Qld, Australia. [Motta, S.] Univ Catania, Dept Math & Informat, I-95124 Catania, Italy. [Lollini, P. L.] Univ Bologna, Dept Hematol & Oncol Sci, I-40126 Bologna, Italy. [Lefranc, M. -P] CNRS, Inst Genet Humaine, IMGT, Montpellier, France. RI Motta, Santo/I-5177-2012 NR 5 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2008 VL 28 IS 5C MA 582 BP 3471 EP 3471 PG 1 WC Oncology SC Oncology GA 367ME UT WOS:000260555300584 ER PT J AU Holodniy, M Penzak, SR Straight, TM Davey, RT Lee, KK Goetz, MB Raisch, DW Cunningham, F Lin, ET Olivo, N Deyton, LR AF Holodniy, Mark Penzak, Scott R. Straight, Timothy M. Davey, Richard T. Lee, Kelvin K. Goetz, Matthew Bidwell Raisch, Dennis W. Cunningham, Francesca Lin, Emil T. Olivo, Noemi Deyton, Lawrence R. TI Pharmacokinetics and tolerability of oseltamivir combined with probenecid SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INFLUENZA-A H5N1; NEURAMINIDASE; VIRUS; TRANSMISSION; INHIBITOR; ELIMINATION; VOLUNTEERS; PHOSPHATE; BINDING; H9N2 AB Oseltamivir is an inhibitor of influenza virus neuraminidase, which is approved for use for the treatment and prophylaxis of influenza A and B virus infections. In the event of an influenza pandemic, oseltamivir supplies may be limited; thus, alternative dosing strategies for oseltamivir prophylaxis should be explored. Healthy volunteers were randomized to a three-arm, open-label study and given 75 mg oral oseltamivir every 24 h (group 1), 75 mg oseltamivir every 48 h (q48h) combined with 500 mg probenecid four times a day (group 2), or 75 mg oseltamivir q48h combined with 500 mg probenecid twice a day (group 3) for 15 days. Pharmacokinetic data, obtained by noncompartmental methods, and safety data are reported. Forty-eight subjects completed the pharmacokinetic analysis. The study drugs were generally well tolerated, except for one case of reversible grade 4 thrombocytopenia in a subject in group 2. The calculated 90% confidence intervals (CIs) for the geometric mean ratios between groups 2 and 3 and group 1 were outside the bioequivalence criteria boundary (0.80 to 1.25) at 0.63 to 0.89 for group 2 versus group 1 and 0.57 to 0.90 for group 3 versus group 1. The steady-state apparent oral clearance of oseltamivir carboxylate was significantly less in groups 2 (7.4 liters/h; 90% CI, 6.08 to 8.71) and 3 (7.19 liters/h; 90% CI, 6.41 to 7.98) than in group 1 (9.75 liters/h; 90% CI, 6.91 to 12.60) (P < 0.05 for both comparisons by analysis of variance). The (arithmetic) mean concentration at 48 h for group 2 was not significantly different from the mean concentration at 24 h for group 1 (42 +/- 76 and 81 +/- 54 ng/ml, respectively; P = 0.194), but the mean concentration at 48 h for group 3 was significantly less than the mean concentration at 24 h for group 1 (23 +/- 26 and 81 +/- 54 ng/ml, respectively; P = 0.012). Alternate-day dosing of oseltamivir plus dosing with probenecid four times daily achieved trough oseltamivir carboxylate concentrations adequate for neuraminidase inhibition in vitro, and this combination should be studied further. C1 [Holodniy, Mark] VA Palo Alto Hlth Care Syst, Publ Hlth Res Ctr, Palo Alto, CA 94304 USA. [Holodniy, Mark; Deyton, Lawrence R.] US Dept Vet Affairs, Off Publ Hlth & Environm Hazards, Washington, DC USA. [Holodniy, Mark] Stanford Univ, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. [Penzak, Scott R.] NIH, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. [Straight, Timothy M.] Brooke Army Med Ctr, Dept Clin Invest, Ft Sam Houston, TX 78234 USA. [Davey, Richard T.] CRS LIR NIAID, NIH, Bethesda, MD USA. [Lee, Kelvin K.] VA Cooperat Studies Program, Palo Alto, CA USA. [Goetz, Matthew Bidwell] Greater Angeles Hlth Care Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Infect Dis Sect, Los Angeles, CA 90095 USA. [Raisch, Dennis W.] Clin Res Pharm Coordinating Ctr, VA Cooperat Studies Program, Albuquerque, NM USA. [Cunningham, Francesca] US Dept Vet Affairs, Pharm Benefits Management Grp, Hines, IL USA. [Lin, Emil T.] UCSF, Dept Biopharmaceut Sci, San Francisco, CA USA. [Deyton, Lawrence R.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. RP Holodniy, M (reprint author), VA Palo Alto Hlth Care Syst, Publ Hlth Res Ctr, 3801 Miranda Ave 132, Palo Alto, CA 94304 USA. EM Holodniy@stanford.edu OI Goetz, Matthew/0000-0003-4542-992X FU U.S. Department of Veterans Affairs Merit; U.S. Departments of Defense; Health and Human Services FX This work was supported by a U.S. Department of Veterans Affairs Merit review grant to Mark Holodniy and additional financial support from the U.S. Departments of Defense (T. M. Straight) and Health and Human Services (R. T. Davey and S. R. Penzak).; None of the authors have any significant conflict of interest related to this study.; We thank the study participants, Cooperative Studies Program staff (Nigel Gladhart, Lauren Uyeda, Sachiko Kutsuna) for data management, and the data safety monitoring committee members (Thomas C. Merigan, Rex Jamison, and Larry Mole). NR 37 TC 33 Z9 35 U1 2 U2 2 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 SEP PY 2008 VL 52 IS 9 BP 3013 EP 3021 DI 10.1128/AAC.00047-08 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 340TG UT WOS:000258667300003 PM 18559644 ER PT J AU Tegos, GP Masago, K Aziz, F Higginbotham, A Stermitz, FR Hamblin, MR AF Tegos, George P. Masago, Kayo Aziz, Fatima Higginbotham, Andrew Stermitz, Frank R. Hamblin, Michael R. TI Inhibitors of bacterial multidrug efflux pumps potentiate antimicrobial photoinactivation SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; GRAM-NEGATIVE BACTERIA; PHOTODYNAMIC THERAPY; PHOTOBACTERICIDAL ACTIVITY; PSEUDOMONAS-AERUGINOSA; PHENOTHIAZINIUM DYES; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; TRANSPORTER; NORA AB Antimicrobial photodynamic inactivation (APDI) combines a nontoxic photoactivatable dye or photosensitizer ( PS) with harmless visible light to generate singlet oxygen and reactive oxygen species that kill microbial cells. Cationic phenothiazinium dyes, such as toluidine blue O (TBO), are the only PS used clinically for APDI, and we recently reported that this class of PS are substrates of multidrug efflux pumps in both gram-positive and gram-negative bacteria. We now report that APDI can be significantly potentiated by combining the PS with an efflux pump inhibitor (EPI). Killing of Staphylococcus aureus mediated by TBO and red light is greatly increased by coincubation with known inhibitors of the major facilitator pump ( NorA): the diphenyl urea INF271, reserpine, 5'-methoxyhydnocarpin, and the polyacylated neohesperidoside, ADH7. The potentiation effect is greatest in the case of S. aureus mutants that overexpress NorA and least in NorA null cells. Addition of the EPI before TBO has a bigger effect than addition of the EPI after TBO. Cellular uptake of TBO is increased by EPI. EPI increased photodynamic inactivation killing mediated by other phenothiazinium dyes, such as methylene blue and dimethylmethylene blue, but not that mediated by nonphenothiazinium PS, such as Rose Bengal and benzoporphyrin derivative. Killing of Pseudomonas aeruginosa mediated by TBO and light was also potentiated by the resistance nodulation division pump (MexAB-OprM) inhibitor phenylalanine-arginine beta-naphthylamide but to a lesser extent than for S. aureus. These data suggest that EPI could be used in combination with phenothiazinium salts and light to enhance their antimicrobial effect against localized infections. C1 [Tegos, George P.; Masago, Kayo; Aziz, Fatima; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA USA. [Masago, Kayo] Univ Tokyo, Grad Sch Engn, Dept Mat Sci & Engn, Tokyo, Japan. [Aziz, Fatima] Aga Khan Med Sch, Karachi, Pakistan. [Higginbotham, Andrew] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 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 RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU National Institute of Allergy and Infectious Diseases [AI050875] FX This work was supported by the National Institute of Allergy and Infectious Diseases (grant AI050875 to M.R.H.).; We are grateful to Kim Lewis (Northeastern University, Boston, MA), Olga Lomovskaya (Mpex Pharmaceuticals, Inc., San Diego, CA), and David C. Hooper (Massachusetts General Hospital, Boston, MA) for gifts of bacterial strains. We are grateful to QLT Inc. (Vancouver, Canada) for the generous gift of BPD. We thank Tatiana N. Demidova-Rice for helpful suggestions and a critical reading of the manuscript. NR 39 TC 53 Z9 53 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2008 VL 52 IS 9 BP 3202 EP 3209 DI 10.1128/AAC.00006-08 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 340TG UT WOS:000258667300028 PM 18474586 ER PT J AU Clark, FL Sahay, A Bertenthal, D Maddock, L Lindquist, K Grekin, R Chren, MM AF Clark, F. Landon Sahay, Anju Bertenthal, Daniel Maddock, Leah Lindquist, Karla Grekin, Roy Chren, Mary-Margaret TI Variation in care for recurrent nonmelanoma skin cancer in a university-based practice and a veterans affairs clinic SO ARCHIVES OF DERMATOLOGY LA English DT Article ID BASAL-CELL CARCINOMA; MOHS MICROGRAPHIC SURGERY; FACE AB Objective: To learn if treatment of recurrent nonmelanoma skin cancer (NMSC) varied in different practice settings. Design: Prospective cohort study of consecutive patients with recurrent NMSC. Setting: A university-based dermatology practice and the dermatology clinic at the affiliated Veterans Affairs Medical Center (VAMC). Conventional therapies for NMSC were available at both sites. Patients: All 191 patients diagnosed as having recurrent NMSC in 1999 and 2000 were included in the study. Data were collected from medical record review and surveys mailed to patients. Main Outcome Measure: Performance of Mohs micrographic surgery (Mohs). Results: Patients at the VAMC were older, less educated, poorer, and had more comorbid illnesses, but their tumors were similar to those of patients at the university-based practice. Treatment choices differed at the 2 sites: the proportions of tumors treated in the VAMC and university sites were 60% and 14%, respectively, for excisional surgery; and 24% and 61%, respectively, for Mohs(P<.001). In multivariate analyses adjusting for patient, tumor, and physician features that may have affected treatment choice, tumors treated at the university-based site remained significantly more likely to be treated with Mohs (odds ratio, 8.68 [95% confidence interval, 3.66-20.55]; P<.001). Conclusions: Substantial variation existed in the treatment of recurrent NMSC in different practice settings. This variation was not explained by measured clinical characteristics of the patients or the tumors. C1 [Bertenthal, Daniel; Maddock, Leah; Lindquist, Karla; Chren, Mary-Margaret] San Francisco VA Med Ctr, San Francisco, CA USA. [Clark, F. Landon] Stanford Univ, Med Ctr, Dept Dermatol, Stanford, CA 94305 USA. [Sahay, Anju] Palo Alto Vet Affairs Hlth Care Syst, Res Serv, Palo Alto, CA USA. [Bertenthal, Daniel; Maddock, Leah; Lindquist, Karla; Chren, Mary-Margaret] Hlth Serv Res & Dev Ser, Res Enhancement Award Program, Dept Vet Affairs, San Francisco, CA USA. [Grekin, Roy; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. RP Chren, MM (reprint author), San Francisco VA Med Ctr, 151R,4150 Clement St, San Francisco, CA USA. EM chrenm@derm.ucsf.edu FU Health Services Research and Development Service of the Department of Veterans Affairs [97010-2, 04-043-3]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K02 AR 02203, K24-AR052667]; National Institutes of Health FX This work was supported by Investigator-Initiated Research (IIR) grants 97010-2 and 04-043-3 from the Health Services Research and Development Service of the Department of Veterans Affairs, and by an Independent Scientist Award (K02 AR 02203) and Midcareer Investigator Award (K24-AR052667) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. NR 11 TC 4 Z9 4 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD SEP PY 2008 VL 144 IS 9 BP 1148 EP 1152 DI 10.1001/archderm.144.9.1148 PG 5 WC Dermatology SC Dermatology GA 348RQ UT WOS:000259228000006 PM 18794460 ER PT J AU Hadlock, TA Sabini, P Quatela, V Cheney, ML AF Hadlock, Tessa A. Sabini, Paul Quatela, Vito Cheney, Mack L. TI Multistaged reconstructive efforts via medical missions - Keys to optimizing outcome SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Editorial Material ID SURGICAL RECONSTRUCTION; INTERNATIONAL HEALTH; THIRD-WORLD; EPIDEMIOLOGY; DEFORMITIES; 3RD-WORLD C1 [Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 13 TC 1 Z9 1 U1 0 U2 3 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 SEP-OCT PY 2008 VL 10 IS 5 BP 350 EP 352 DI 10.1001/archfaci.10.5.350 PG 3 WC Surgery SC Surgery GA 348RS UT WOS:000259228200011 PM 18794415 ER PT J AU Brickman, AM Honig, LS Scarmeas, N Tatarina, O Sanders, L Albert, MS Brandt, J Blacker, D Stern, Y AF Brickman, Adam M. Honig, Lawrence S. Scarmeas, Nikolaos Tatarina, Oksana Sanders, Linda Albert, Marilyn S. Brandt, Jason Blacker, Deborah Stern, Yaakov TI Measuring cerebral atrophy and white matter hyperintensity burden to predict the rate of cognitive decline in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID SIGNAL HYPERINTENSITIES; APOLIPOPROTEIN-E; BICAUDATE INDEX; BRAIN ATROPHY; MOTOR SIGNS; DEMENTIA; LESIONS; AD; MRI; SEVERITY AB Objective: To determine if baseline measurements of cerebral atrophy and severity of white matter hyperintensity (WMH) predict the rate of future cognitive decline in patients with Alzheimer disease (AD). Design: Data were drawn from the Predictors Study, a longitudinal study that enrolls patients with mild AD and reassesses them every 6 months with use of the Columbia modified Mini-Mental State (mMMS) examination (score range, 0-57). Magnetic resonance images were analyzed to determine the severity of WMH, using the Scheltens scale, and the degree of atrophy, using the bicaudate ratio. Generalized estimating equations were used to determine whether severity of baseline magnetic resonance image measurements and their interaction predicted the rate of mMMS score decline at subsequent visits. Setting: Three university-based AD centers in the United States. Participants: At baseline, 84 patients with AD from the Predictors Study received structural magnetic resonance imaging and were selected for analysis. They had a mean of 6 follow-up evaluations. Main Outcome Measure: The mMMS score. Results: Generalized estimating equation models demonstrated that the degree of baseline atrophy (beta = -0.316; P = .04), the severity of WMH (beta = -0.173; P = .03), and their interaction (beta = -6.061; P = .02) predicted the rate of decline in mMMS scores. Conclusions: Both degree of cerebral atrophy and severity of WMH are associated with the rapidity of cognitive decline in AD. Atrophy and WMH may have a synergistic effect on future decline in AD, such that patients with a high degree of both have a particularly precipitous cognitive course. These findings lend further support to the hypothesis that cerebrovascular pathological abnormalities contribute to the clinical syndrome of AD. C1 [Brickman, Adam M.; Honig, Lawrence S.; Scarmeas, Nikolaos; Tatarina, Oksana; Sanders, Linda; Stern, Yaakov] Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Brickman, Adam M.; Honig, Lawrence S.; Scarmeas, Nikolaos; Stern, Yaakov] Columbia Univ, Dept Neurol, Med Ctr, New York, NY 10032 USA. [Albert, Marilyn S.; Brandt, Jason] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Brandt, Jason] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. [Blacker, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Brickman, AM (reprint author), Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, 630 W 168th St,Campus Box 16, New York, NY 10032 USA. EM amb2139@columbia.edu OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [M01 RR000645, RR000645]; NIA NIH HHS [AG029949, K23 AG029949, K23 AG029949-01, R01 AG007370, R01 AG007370-18, Z01 AG007370] NR 56 TC 65 Z9 65 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2008 VL 65 IS 9 BP 1202 EP 1208 DI 10.1001/archneur.65.9.1202 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 345XJ UT WOS:000259030700010 PM 18779424 ER PT J AU Haroutunian, V Schnaider-Beeri, M Schmeidler, J Wysocki, M Purohit, DP Perl, DP Libow, LS Lesser, GT Maroukian, M Grossman, HT AF Haroutunian, Vahram Schnaider-Beeri, Michal Schmeidler, James Wysocki, Michael Purohit, Dushyant P. Perl, Daniel P. Libow, Leslie S. Lesser, Gerson T. Maroukian, Maria Grossman, Hillel T. TI Role of the neuropathology of Alzheimer disease in dementia in the oldest-old SO ARCHIVES OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; NEUROFIBRILLARY TANGLES; REGIONAL-DISTRIBUTION; STEREOLOGIC ANALYSIS; NEURITIC PLAQUES; ELDERLY SUBJECTS; CEREBRAL-CORTEX; RATING-SCALE; NONAGENARIANS; CENTENARIANS AB Background: Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in the brain, especially in the hippocampus, entorhinal cortex, and isocortex, are hallmark lesions of Alzheimer disease and dementia in the elderly. However, this association has not been extensively studied in the rapidly growing population of the very old. Objective: To assess the relationship between estimates of cognitive function and NP and NFT pathologic conditions in 317 autopsied persons aged 60 to 107 years. Design: We studied the relationship between severity of dementia and the density of these characteristic lesions of Alzheimer disease in young-old, middle-old, and oldest-old persons. The relationship of the severity of dementia as measured by the Clinical Dementia Rating scale to the density of NPs and NFTs was then assessed in each age group. Participants: Three hundred seventeen brains of persons aged 60 years and older were selected to have either no remarkable neuropathological lesions or only NP and NFT lesions. Brains with any other neuropathological conditions, either alone or in addition to Alzheimer disease findings, were excluded. The study cohort was then stratified into the youngest quartile (aged 60-80 years), middle 2 quartiles (aged 81-89 years), and oldest quartile (aged 90-107 years). Results: While the density of NPs and NFTs rose significantly by more than 10-fold as a function of the severity of dementia in the youngest-old group, significant increases in the densities of NPs and NFTs were absent in the brains of the oldest-old. This lack of difference in the densities of NPs and NFTs was due to reduced lesion densities in the brains of oldest-old persons with dementia rather than to increased density of these lesions in the brains of nondemented oldest-old persons. Conclusions: These findings suggest that the neuropathological features of dementia in the oldest-old are not the same as those of cognitively impaired younger-old persons and compel a vigorous search for neuropathological indices of dementia in this most rapidly growing segment of the elderly population. C1 [Haroutunian, Vahram; Schnaider-Beeri, Michal; Schmeidler, James; Wysocki, Michael; Maroukian, Maria; Grossman, Hillel T.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Purohit, Dushyant P.; Perl, Daniel P.] Mt Sinai Sch Med, Dept Pathol, New York, NY USA. [Libow, Leslie S.; Lesser, Gerson T.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Haroutunian, Vahram; Grossman, Hillel T.] Bronx VA Med Ctr, Dept Psychiat, Bronx, NY USA. [Haroutunian, Vahram; Libow, Leslie S.] Jewish Home & Hosp, New York, NY USA. RP Haroutunian, V (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu FU NCRR NIH HHS [M01 RR000071, M01 RR000071-36, M01RR00071]; NIA NIH HHS [AG02219, P01 AG002219, P01 AG002219-23] NR 44 TC 84 Z9 87 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2008 VL 65 IS 9 BP 1211 EP 1217 DI 10.1001/archneur.65.9.1211 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 345XJ UT WOS:000259030700011 PM 18779425 ER PT J AU Boulos, PR Rubin, PAD AF Boulos, Patrick Roland Rubin, Peter A. D. TI A lacrimal sac abscess incision and drainage technique SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ACUTE DACRYOCYSTITIS; ORBITAL CELLULITIS; MANAGEMENT; SECONDARY AB A comfortable, anatomically based lacrimal sac abscess incision and drainage technique is described. The records of 52 patients were reviewed. The procedure was relieving and well tolerated because of adequate infraorbital and anterior ethmoidal nerve blocks. To promote rapid resolution, both components of the abscess were drained: the distended lacrimal sac and its associated submuscular pocket. The contiguous cavities were packed and allowed to heal by secondary intention. Of 49 cases, 39 (79.6%) were done as outpatient procedures and 41 (83.7%) were performed under locoregional anesthesia. Edema completely resolved by a median of 7 days. A repeat drainage procedure within 1 month was required in only 4 of 48 cases (8.3%). Fistulas and ectropion were not found. Four of 16 patients (25.0%) who did not eventually receive a definitive procedure (dacryocystorhinostomy or dacryocystectomy) developed a recurrent lacrimal sac abscess after complete resolution of the primary episode. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Rubin, PAD (reprint author), Eye Plast Consultants, 44 Washington St, Brookline, MA 02445 USA. EM padrmd@aol.com NR 14 TC 7 Z9 7 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2008 VL 126 IS 9 BP 1297 EP 1300 DI 10.1001/archopht.126.9.1297 PG 4 WC Ophthalmology SC Ophthalmology GA 345XQ UT WOS:000259031500020 PM 18779495 ER PT J AU Moriarty, AT Schwartz, MR Eversole, G Means, M Clayton, A Souers, R Fatheree, L Tench, WD Henry, M Wilbur, DC AF Moriarty, Ann T. Schwartz, Mary R. Eversole, Galen Means, Marilee Clayton, Amy Souers, Rhona Fatheree, Lisa Tench, William D. Henry, Michael Wilbur, David C. TI Human papillomavirus testing and reporting rates - Practices of participants in the College of American Pathologists Interlaboratory Comparison Program in Gynecologic Cytology in 2006 SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ATYPICAL SQUAMOUS-CELLS; CURRENT LABORATORY PRACTICES; UNDETERMINED SIGNIFICANCE; CERVICOVAGINAL CYTOLOGY; SPECIMEN ADEQUACY; CERVICAL CYTOLOGY; QUALITY-ASSURANCE; WOMEN; HPV; TERMINOLOGY AB Context.-Oncogenic, high-risk human papillomavirus (HR-HPV) testing is used to evaluate women who are older than 20 years with atypical squamous cells of undetermined significance (ASC-US) and in conjunction with a screening Papanicolaou test in women older than 30 years. Objectives.-To evaluate the 2006 laboratory practice data from laboratories incorporating human papillomavirus (HPV) testing with the Papanicolaou test. Design.-To use the College of American Pathologists (CAP) Supplemental Questionnaire Survey for 2006 to determine laboratory practices of participants in the CAP Interlaboratory Comparison Program in Cervicovaginal Cytology. Results.-A total of 679 laboratories responded to the questionnaire. Most (73%) refer HPV testing to reference laboratories. Nine percent perform HPV testing in cytology. Forty-five percent offer low-risk HPV (LR-HPV) testing. The most common reflex is ASC-US, although HR-HPV is also offered with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), or any other Papanicolaou test result. Digene Hybrid Capture II is the most common method. Human papilloma virus median test volumes are 55 monthly. Frequency distributions of HPV test volumes are significantly different from those found in 2003. Laboratories performing in-house testing reported significantly higher monthly HPV volumes (P < .001). Median rates for HR-HPV positivity are 36.6% for ASC-US, 50.0% for atypical squamous cells, cannot exclude HSIL (ASC-H), and 4% for women 30 years of age and older in conjunction with a screening Papanicolaou test. Conclusions.-Reference HPV testing remains the most common pattern. The most common reflex indication is for ASC-US, but HPV testing is modified locally to include a variety of scenarios. LR-HPV testing is commonly offered despite its lack of clinical significance. These data form a baseline for ongoing monitoring of HPV testing practice trends. C1 [Moriarty, Ann T.] AmeriPath Indiana, Dept Pathol, Indianapolis, IN 46219 USA. [Moriarty, Ann T.; Schwartz, Mary R.; Eversole, Galen; Means, Marilee; Clayton, Amy; Tench, William D.; Henry, Michael; Wilbur, David C.] Coll Amer Pathologists, Cytopathol Resource Comm, Northfield, IL USA. [Souers, Rhona] Coll Amer Pathologists, Dept Biostat, Northfield, IL USA. [Fatheree, Lisa] Coll Amer Pathologists, Dept Cytol Surveys, Northfield, IL USA. [Schwartz, Mary R.] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. [Eversole, Galen] Quest Diagnost Inc, Denver, CO USA. [Means, Marilee] Univ Kansas, Med Ctr, Dept Cytopathol, Kansas City, KS USA. [Clayton, Amy; Henry, Michael] Mayo Clin, Dept Pathol, Rochester, MN USA. [Tench, William D.] Palomar Med Ctr, Dept Lab Med, Escondido, CA USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Moriarty, AT (reprint author), AmeriPath Indiana, Dept Pathol, 2560 N Shadeland Ave,Suite A, Indianapolis, IN 46219 USA. EM amoriarty@ameripath.com NR 20 TC 24 Z9 24 U1 0 U2 0 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 SEP PY 2008 VL 132 IS 8 BP 1290 EP 1294 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 335MC UT WOS:000258293700012 PM 18684028 ER PT J AU Nero, C Dighe, AS AF Nero, Christopher Dighe, Anand S. TI Analysis of pathology department Web sites and practical recommendations SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID APPLICANTS; INTERNET; SEARCH AB Context. - There are numerous customers for pathology departmental Web sites, including pathology department staff, clinical staff, residency applicants, job seekers, and other individuals outside the department seeking department information. Despite the increasing importance of departmental Web sites as a means of distributing information, no analysis has been done to date of the content and usage of pathology department Web sites. Objective. - In this study, we analyzed pathology department Web sites to examine the elements present on each site and to evaluate the use of search technology on these sites. Further, we examined the usage patterns of our own departmental Internet and intranet Web sites to better understand the users of pathology Web sites. Design. - We reviewed selected departmental pathology Web sites and analyzed their content and functionality. Our institution's departmental pathology Web sites were modified to enable detailed information to be stored regarding users and usage patterns, and that information was analyzed. Results. - We demonstrate considerable heterogeneity in departmental Web sites with many sites lacking basic content and search features. In addition, we demonstrate that increasing the traffic of a department's informational Web sites may result in reduced phone inquiries to the laboratory. We propose recommendations for pathology department Web sites to maximize promotion of a department's mission. Conclusions. - A departmental pathology Web site is an essential communication tool for all pathology departments, and attention to the users and content of the site can have operational impact. C1 [Nero, Christopher; Dighe, Anand S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Dighe, AS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Bigelow Bldg,Room 510,55 Fruit St, Boston, MA 02114 USA. EM asdighe@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2008 VL 132 IS 9 BP 1423 EP 1427 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 347DY UT WOS:000259122000011 PM 18788853 ER PT J AU Walsh, NE Brooks, P Hazes, JM Walsh, RM Dreinhoefer, K Woolf, AA Akesson, K Lidgren, L AF Walsh, Nicolas E. Brooks, Peter Hazes, J. Mieke Walsh, Rorey M. Dreinhoefer, Karsten Woolf, Anthony A. Akesson, Kristina Lidgren, Lars CA Bone TI Standards of care for acute and chronic musculoskeletal pain: The bone and joint decade (2000-2010) SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE musculoskeletal system; pain; rehabilitation; treatment outcome ID POPULATION; MANAGEMENT; SIGNS AB Musculoskeletal conditions often manifest with the onset of pain and the resulting physical limitations. Musculoskeletal pain is almost inevitable in in individual's lifetime. It is one of the most common reasons for self-medication and entry into the health care system. Musculoskeletal pain affects in 4 adults and is the Most commons Source of serious long-term pain and physical disability. The Monumental impact Of musculoskeletal conditions is now recognized by the United Nations, the World Health Organization, World Bank, and numerous governments throughout the World through Support of the Bone and Joint Decade 2000 to 2010 initiative. Individuals With musculoskeletal pain concerns are regularly ignored. their complaints often Misunderstood by health care providers, and accordingly they do not receive timely or effective treatment. The standards of care in this document are designed to provide generic guidelines for appropriate care of people with acute or chronic musculoskeletal pain, This document was developed over a 4-year period using Multiple international meetings and a Task Force of the Bone and Joint Decade for developing international standards for the care of acute and chronic musculoskeletal pain. The final document is a product of the World Health Organization Collaborating Centre for Evidence-Based Health Care ill Musculoskeletal Disorders. C1 [Walsh, Nicolas E.; Walsh, Rorey M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Rehabil Med, San Antonio, TX 78229 USA. [Walsh, Nicolas E.] S Texas Vet Adm Hlth Care Syst, Pain Med Serv, San Antonio, TX USA. [Brooks, Peter] Univ Queensland, Brisbane, Qld, Australia. [Hazes, J. Mieke] Erasmus Med Coll, Dept Rheumatol, Rotterdam, Netherlands. [Dreinhoefer, Karsten] Univ Ulm, Dept Orthoped, Ulm, Germany. [Woolf, Anthony A.] Royal Cornwall Hosp, Duke Cornwall Rheumatol Unit, Truro, England. [Akesson, Kristina] Malmo Univ Hosp, Dept Orthopaed Surg, Malmo, Sweden. [Lidgren, Lars] Univ Lund Hosp, Dept Orthoped, World Hlth Org Collaborat Ctr Evidenced Based Hea, Lund, Sweden. RP Walsh, NE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Rehabil Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM walshn@uthscsa.edu OI Dreinhoefer, Karsten/0000-0001-6021-2804 NR 36 TC 23 Z9 25 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2008 VL 89 IS 9 BP 1830 EP 1845 DI 10.1016/j.apmr.2008.04.009 PG 16 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 346GR UT WOS:000259057300029 PM 18760171 ER PT J AU Bilimoria, KY Bentrem, D Nelson, H Stryker, S Stewart, AK Soper, NJ Russell, TR Ko, CY AF Bilimoria, Karl Y. Bentrem, Davidj. Nelson, Heidi Stryker, Steven J. Stewart, Andrew K. Soper, Nathaniel J. Russell, Thomas R. Ko, Clifford Y. TI Use and outcomes of laparoscopic-assisted colectomy for cancer in the United States SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 16-17, 2008 CL San Diego, CA SP Pacific Coast Surg Assoc ID MRC CLASICC TRIAL; COST STUDY-GROUP; COLON-CANCER; COLORECTAL-CANCER; RANDOMIZED-TRIAL; PROCEDURE VOLUME; HOSPITAL VOLUME; RESECTION; SURGERY; IMPACT AB Background: Laparoscopic-assisted colectomy (LAC) has gained acceptance for the treatment of colon cancer. However, long-term outcomes of LAC have not been examined at the national level outside of experienced centers. Objective: To compare use and outcomes of LAC and open colectomy (OC). Design: Retrospective cohort study. Setting: National Cancer Data Base. Patients: Patients who underwent LAC (n = 11038) and OC (n = 23138 1) for nonmetastatic colon cancer (19982002). Main Outcome Measures: Regression methods were used to assess use and outcomes of LAC compared with OC. Results: Laparoscopic-assisted colectomy use increased from 3.8% in 1998 to 5.2% in 2002 (P < .001). Patients were significantly more likely to undergo LAC if they were younger than 75 years, had private insurance, lived in higher-income areas, had stage I cancer, had descending and/or sigmoid cancers, or were treated at National Cancer Institute-designated hospitals. Compared with those undergoing OC, patents undergoing LAC had 12 or more nodes examined less frequently (P < .001), similar perioperative mortality and recurrence rates, and higher 5-year survival rates (64.1% vs 58.5%, P < .001). After adjusting for patient, tumor, treatment, and hospital factors, 5-year survival was significantly better after LAC compared with OC for stage I and 11 but not for stage III cancer. Highest-volume centers had comparable short- and long-term LAC outcomes compared with lowest-volume hospitals, except highest-volume centers had significantly higher lymph node counts (median, 12 vs 8 nodes; P < .001). Conclusions: Laparoscopic-assisted colectomy and OC outcomes are generally comparable in the population. However, survival was better after an LAC than after an OC in select patients. C1 [Bilimoria, Karl Y.; Stewart, Andrew K.; Russell, Thomas R.; Ko, Clifford Y.] Amer Coll Surg, Canc Programs, Chicago, IL 60611 USA. [Bilimoria, Karl Y.; Bentrem, Davidj.; Stryker, Steven J.; Soper, Nathaniel J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL USA. [Nelson, Heidi] Mayo Clin, Dept Surg, Rochester, MN USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Canc Programs, 633 N St Clair St,25th Floor, Chicago, IL 60611 USA. EM kbilimoria@facs.org NR 35 TC 65 Z9 70 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 SEP PY 2008 VL 143 IS 9 BP 832 EP 839 DI 10.1001/archsurg.143.9.832 PG 8 WC Surgery SC Surgery GA 346SJ UT WOS:000259089200002 PM 18794419 ER PT J AU Suding, P Jensen, E Abramson, MA Itani, K Wilson, SE AF Suding, Paul Jensen, Erin Abramson, Murray A. Itani, Kamal Wilson, Samuel Eric TI Definitive risk factors for anastomotic leaks in elective open colorectal resection SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 16-17, 2008 CL San Diego, CA SP Pacific Coast Surg Assoc ID MECHANICAL BOWEL PREPARATION; CLINICALLY SIGNIFICANT; POLYETHYLENE-GLYCOL; MESORECTAL EXCISION; CURATIVE RESECTION; LEFT COLECTOMY; RECTAL-CANCER; SURGERY; INFECTION; SURVIVAL AB Hypothesis: Anastomotic leaks following elective colorectal resections increase morbidity, mortality, and the need for additional interventions. An accurate understanding of risk factors would potentially reduce anastomotic leaks and/or allow appropriate selection of patients for diverting stomas. Design: Prospective review of patient and operative characteristics that contribute to anastomotic leaks. Setting: Fifty-one sites within the United States (May 2002-March 2005). Patients: Six hundred seventy-two patients who participated in a trial comparing preoperative antimicrobials in elective open colorectal surgery. Main Outcome Measures: Anastomotic leaks were diagnosed using clinical findings and were confirmed with imaging. We examined 20 variables possibly affecting anastomotic healing in univariate and multivariate analyses. Results: There were 24 anastomotic leaks in 672 patients (3.6%) undergoing elective colorectal resection. There were 10 deaths (1.5%). A baseline albumin level of less than 3.5 g/dL (to convert to grams per liter, multiply by 10) (P = .04) and male sex (P = .03) were associated with anastomotic leaks in both univariate and multivariate analyses (adjusted odds ratios, 2.56 and 3.12, respectively). Increased duration of surgery (SD, 60 minutes; odds ratio, 1.53; 95% confidence interval, 1.06-2.22; P = .03) and steroid use at the time of surgery (odds ratio, 3.85; 95% confidence interval, 1.24-11.93; P = .02) were significant in univariate analysis. Surgical procedure with rectal resection; prophylaxis with ertapenem (VS cefotetan); or history of obesity, tobacco use, or diabetes was not associated with anastomotic leaks. Conclusions: Significant risk factors for anastomotic leaks include low preoperative serum albumin level, steroid use, male sex, and increased duration of surgery. Appreciation of risk factors provides a rational basis for temporary diversion. C1 [Suding, Paul; Wilson, Samuel Eric] Univ Calif Irvine, Orange, CA 92868 USA. [Jensen, Erin; Abramson, Murray A.] Merck & Co Inc, Whitehouse Stn, NJ USA. [Itani, Kamal] VA Boston Healthcare Syst, Boston, MA USA. [Itani, Kamal] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Wilson, SE (reprint author), Univ Calif Irvine, 333 City Blvd W,Ste 810, Orange, CA 92868 USA. EM sewilson@uci.edu NR 27 TC 44 Z9 45 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD SEP PY 2008 VL 143 IS 9 BP 907 EP 911 DI 10.1001/archsurg.143.9.907 PG 5 WC Surgery SC Surgery GA 346SJ UT WOS:000259089200024 PM 18794430 ER PT J AU Altshuler, LL Cohen, LS Vitonis, AF Faraone, SV Harlow, BL Suri, R Frieder, R Stowe, ZN AF Altshuler, Lori L. Cohen, Lee S. Vitonis, Allison F. Faraone, Stephen V. Harlow, Bernard L. Suri, Rita Frieder, Richard Stowe, Zachary N. TI The Pregnancy Depression Scale (PDS): a screening tool for depression in pregnancy SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Pregnancy; Depression; Screening; Rating scale ID POSTNATAL DEPRESSION; PERINATAL DEPRESSION; PSYCHOLOGICAL DISTRESS; POSTPARTUM DEPRESSION; PRENATAL ANXIETY; WOMEN; SYMPTOMS; MOOD; RISK; VALIDATION AB Depression in pregnancy can be underdiagnosed as a consequence of the symptoms being misattributed to "normal pregnancy." There are currently no validated clinician-rated scales that assess for depression specifically during pregnancy. We sought to develop a brief, convenient screening tool to identify depression in pregnant women in the community setting. Prospective mood data using the 28-item Hamilton Depression Rating Scale (HDRS) were collected monthly in 196 pregnant women with a history of a major depressive disorder. These data were analyzed to delineate those HDRS items associated (elevated) with normal pregnancy vs. those indicative of a pregnant woman meeting diagnostic criteria for a major depressive episode. Endorsement of symptoms on seven items of the HDRS were highly predictive of having a major depressive episode during pregnancy. We present a well-validated, brief scale to screen pregnant women for clinical depression. Whether this study will generalize to women who do not have a history of major depression remains to be studied. C1 [Altshuler, Lori L.; Suri, Rita] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Mood Disorders Res Program, Los Angeles, CA 90095 USA. [Cohen, Lee S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Perinatal & Reprod Psychiat Clin Re, Boston, MA USA. [Vitonis, Allison F.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Neurosci, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA. [Harlow, Bernard L.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Frieder, Richard] Univ Calif Los Angeles, Dept Obstet & Gynecol, Dept Family Med, Los Angeles, CA 90024 USA. [Stowe, Zachary N.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Womens Mental Hlth, Atlanta, GA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Mood Disorders Res Program, 300 UCLA Med Plaza,Suite 1544,POB 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 40 TC 10 Z9 10 U1 0 U2 4 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD SEP PY 2008 VL 11 IS 4 BP 277 EP 285 DI 10.1007/s00737-008-0020-y PG 9 WC Psychiatry SC Psychiatry GA 366RN UT WOS:000260501200005 PM 18581042 ER PT J AU Bartels, CM Bell, CL Shinki, K Bridges, AJ AF Bartels, Christie M. Bell, Carolyn L. Shinki, Kazuhiko Bridges, Alan J. TI Declines in rheumatoid arthritis and rheumatoid vasculitis among US veterans SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Bartels, Christie M.; Bell, Carolyn L.; Shinki, Kazuhiko] Univ Wisconsin, Madison, WI USA. [Bridges, Alan J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S MA 790 BP S460 EP S460 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244201053 ER PT J AU Buchanan, J Fleischmann, R Genovese, MC Kay, J Hsia, EC Doyle, MK Rahman, MU Han, C Parasuraman, S AF Buchanan, J. Fleischmann, R. Genovese, M. C. Kay, J. Hsia, E. C. Doyle, M. K. Rahman, M. U. Han, C. Parasuraman, S. TI Golimumab significantly improves self-reported productivity in patients with rheumatoid arthritis: Results from three phase III studies SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Buchanan, J.; Han, C.; Parasuraman, S.] JJPS LLC, Malvern, PA USA. [Fleischmann, R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genovese, M. C.] Stanford Univ, Palo Alto, CA 94304 USA. [Kay, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hsia, E. C.; Doyle, M. K.; Rahman, M. U.] Univ Penn, Sch Med, Centocor R&D Inc, Malvern, PA 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S548 EP S549 PG 2 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244201287 ER PT J AU Castelino, FV Goldberg, H Dellaripa, PF AF Castelino, Flavia V. Goldberg, Hilary Dellaripa, Paul F. TI The impact of rheumatologic evaluation on the management of patients with interstitial lung disease (ILD) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Castelino, Flavia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldberg, Hilary; Dellaripa, Paul F.] Brigham & Womens Hosp, Boston, MA 02115 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S401 EP S402 PG 2 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244200658 ER PT J AU Furst, DE Doyle, MK Kay, J Wasko, MC Moreland, L Keystone, E Kavanaugh, A Deodhar, A Murphy, F Han, J Buchanan, J Rahman, MU AF Furst, D. E. Doyle, M. K. Kay, J. Wasko, M. C. Moreland, L. Keystone, E. Kavanaugh, A. Deodhar, A. Murphy, F. Han, J. Buchanan, J. Rahman, M. U. TI Golimumab, a new human Anti-TNF-alpha monoclonal antibody administered subcutaneously every 4 weeks, improves anemia & well-being in patients with rheumatoid arthritis, psoriatic arthritis, or Ankylosing spondylitis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Furst, D. E.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Doyle, M. K.; Rahman, M. U.] Univ Penn, Philadelphia, PA 19104 USA. [Kay, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wasko, M. C.; Moreland, L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kavanaugh, A.] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Deodhar, A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Murphy, F.] Altoona Ctr Clin Res, Duncansville, PA USA. [Doyle, M. K.; Han, J.] Centocor R&D Inc, Malvern, PA USA. [Buchanan, J.] JJPS LLC, Malvern, PA 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S545 EP S545 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244201279 ER PT J AU Hajj-Ali, RA Singhal, AB Calabrese, LH AF Hajj-Ali, Rula A. Singhal, Aneesh B. Calabrese, Leonard H. TI Reversible cerebral vasoconstriction syndromes SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Hajj-Ali, Rula A.; Calabrese, Leonard H.] Cleveland Clin, Cleveland, OH 44106 USA. [Singhal, Aneesh B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S906 EP S906 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244202498 ER PT J AU Jeffries, M Hamadeh, F Aberle, T Glenn, S Kamen, DL Kelly, JA Reichlin, M Harley, JB Sawalha, AH AF Jeffries, Matlock Hamadeh, Fahed Aberle, Teresa Glenn, Stuart Kamen, Diane L. Kelly, Jennifer A. Reichlin, Morris Harley, John B. Sawalha, Amr H. TI Hemolytic anemia in a multi-ethnic cohort of lupus patients: A clinical and serological perspective SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Jeffries, Matlock; Reichlin, Morris] Univ Oklahoma, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Hamadeh, Fahed] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Kamen, Diane L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Harley, John B.; Sawalha, Amr H.] Univ Oklahoma, US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S337 EP S337 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244200481 ER PT J AU Kane, M Singh, SC Ghimire, S Kryder, JC AF Kane, Michael Singh, Surya C. Ghimire, Sanjay Kryder, J. Christian TI Genetic testing for rituximab responsiveness SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Kane, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kane, Michael] MIT, Boston, MA USA. [Singh, Surya C.; Ghimire, Sanjay; Kryder, J. Christian] D2Hawkeye Inc, Boston, MA USA. [Singh, Surya C.] Brigham & Womens Hosp, Boston, MA 02115 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S MA 791 BP S460 EP S461 PG 2 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244201054 ER PT J AU Kay, J Doyle, MK Smolen, J Buchanan, J Matteson, EL Hsia, EC Landewe, R Zhou, Y Parasuraman, S Rahman, MU AF Kay, J. Doyle, M. K. Smolen, J. Buchanan, J. Matteson, E. L. Hsia, E. C. Landewe, R. Zhou, Y. Parasuraman, S. Rahman, M. U. TI Golimumab significantly improves physical function & fatigue in RA patients previously treated with Anti-TNF alpha agents: Results from the GO-AFTER study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Kay, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Doyle, M. K.; Hsia, E. C.; Zhou, Y.; Rahman, M. U.] Centocor R&D Inc, Malvern, PA USA. [Doyle, M. K.; Hsia, E. C.; Rahman, M. U.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Smolen, J.] Med U Vienna, Hietzing Hosp, Vienna, Austria. [Buchanan, J.; Parasuraman, S.] JJPS LLC, Malvern, PA USA. [Matteson, E. L.] Mayo Clin, Rochester, MN USA. [Landewe, R.] U Hosp Maastricht, Maastricht, Netherlands. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S551 EP S551 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244201295 ER PT J AU Kiel, DP Hannan, MT Barton, BA Lang, TF Bouxsein, ML Brown, K Shane, E Magaziner, J Zimmerman, S Harris, T Rubin, CT AF Kiel, D. P. Hannan, M. T. Barton, B. A. Lang, T. F. Bouxsein, M. L. Brown, K. Shane, E. Magaziner, J. Zimmerman, S. Harris, T. Rubin, C. T. TI Non-pharmacologic low magnitude mechanical stimulation (LMMS) to improve bone mineral densitv (BMD): the "VIBES" trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Kiel, D. P.; Hannan, M. T.] Inst Aging Res, Boston, MA USA. [Barton, B. A.; Brown, K.] Maryland Med Res Inst, Baltimore, MD USA. [Lang, T. F.] UCSF, San Francisco, CA USA. [Bouxsein, M. L.] BIDMC, Ortho Biomech Lab, Boston, MA USA. [Shane, E.] Columbia Univ, Dept Med, New York, NY USA. [Magaziner, J.] Univ MD, Baltimore, MD USA. [Zimmerman, S.] UNC, Cecil G Sheps Ctr Hlth Serv Rsch, Chapel Hill, NC USA. [Harris, T.] NIA, Bethesda, MD 20892 USA. [Rubin, C. T.] SUNY Stony Brook, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S162 EP S162 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244200005 ER PT J AU Luk, AJ Moore, EE Levin, GP Zhou, XH Choi, HK Kestenbamn, BR AF Luk, Andrew J. Moore, Elya E. Levin, Gregory P. Zhou, Xiao-Hua Choi, Hyon K. Kestenbamn, Bryan R. TI Allopurinol treatment and mortality in hyperuricemic veterans SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Luk, Andrew J.; Zhou, Xiao-Hua] VA Puget Sound, Seattle, WA USA. [Moore, Elya E.; Levin, Gregory P.; Kestenbamn, Bryan R.] Univ Washington, Seattle, WA 98195 USA. [Choi, Hyon K.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S179 EP S179 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244200051 ER PT J AU Mikuls, TR Michaud, KD Thiele, GM O'Dell, JR Cannella, AC Reimold, AM Hooker, RS Caplan, L Johnson, DS Richards, JS Kerr, GS Cannon, GW AF Mikuls, Ted R. Michaud, Kaleb D. Thiele, Geoffrey M. O'Dell, James R. Cannella, Amy C. Reimold, Andreas M. Hooker, Roderick S. Caplan, Liron Johnson, Dannette S. Richards, John S. Kerr, Gail S. Cannon, Grant W. TI Autoantibody status in USveterans with rheumatoid arthritis (RA): Implications of discordance between anti-CCP antibody and rheumatoid factor SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Mikuls, Ted R.; Michaud, Kaleb D.; Thiele, Geoffrey M.; O'Dell, James R.; Cannella, Amy C.] Omaha VAMC, Omaha, NE USA. [Reimold, Andreas M.; Hooker, Roderick S.] Dallas VAMC, Dallas, TX USA. [Caplan, Liron] Denver VAMC, Aurora, CO USA. [Johnson, Dannette S.] Jackson VAMC, Jackson, MS USA. [Richards, John S.; Kerr, Gail S.] Washington DC VAMC, Washington, DC USA. [Cannon, Grant W.] Salt Lake City VAMC, Salt Lake City, UT 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S763 EP S763 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244202108 ER PT J AU Mikuls, TR Michaud, KD Thiele, GM O'Dell, JR Cannella, AC Reimold, AM Hooker, RS Caplan, L Johnson, DS Cannon, GW Kerr, GS Richards, JS AF Mikuls, Ted R. Michaud, Kaleb D. Thiele, Geoffirey M. O'Dell, James R. Cannella, Amy C. Reimold, Andreas M. Hooker, Roderick S. Caplan, Liron Johnson, Dannette S. Cannon, Grant W. Kerr, Gail S. Richards, John S. TI The association of cigarette smoking with disease expression in US veterans with rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Mikuls, Ted R.; Michaud, Kaleb D.; Thiele, Geoffirey M.; O'Dell, James R.; Cannella, Amy C.] Omaha VAMC, Omaha, NE USA. [Reimold, Andreas M.; Hooker, Roderick S.] Dallas VAMC, Dallas, TX USA. [Caplan, Liron] Denver VAMC, Denver, CO USA. [Johnson, Dannette S.] Jackson VAMC, Jackson, MS USA. [Cannon, Grant W.] Salt Lake City VAMC, Salt Lake City, UT USA. [Kerr, Gail S.; Richards, John S.] Washington DC VAMC, Washington, DC 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S273 EP S274 PG 2 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244200312 ER PT J AU Moghadam-Kia, S Chilek, K Gaines, E Costner, M Rose, M Okawa, J Werth, VP AF Moghadam-Kia, Siamak Chilek, Katherine Gaines, Elizabeth Costner, Melissa Rose, Mathew Okawa, Joyce Werth, Victoria P. TI Skin manifestations of lupus erythematosus: A cohort of 119 prospectively enrolled patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Moghadam-Kia, Siamak; Chilek, Katherine; Gaines, Elizabeth; Rose, Mathew; Okawa, Joyce] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Costner, Melissa] Univ Texas SW, Dallas, TX USA. [Werth, Victoria P.] Univ Penn, Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S810 EP S810 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244202236 ER PT J AU Niewold, TB Kelly, JA Kariuki, SN Thomas, K Walker, D Merrill, JT Alarcon-Riquelme, ME James, JA Vyse, TJ Kimberly, RP Edberg, JC Gaffney, PM Moser, KL Crow, MK Harley, JB AF Niewold, T. B. Kelly, J. A. Kariuki, S. N. Thomas, K. Walker, D. Merrill, J. T. Alarcon-Riquelme, M. E. James, J. A. Vyse, T. J. Kimberly, R. P. Edberg, J. C. Gaffney, P. M. Moser, K. L. Crow, M. K. Harley, J. B. TI Association of IRF5 with systemic lupus erythematosus is driven by particular patient subgroups defined by autoantibodies and serum interferon SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Niewold, T. B.; Kariuki, S. N.] Univ Chicago, Chicago, IL 60637 USA. [Merrill, J. T.; James, J. A.; Harley, J. B.] Univ Oklahoma, Oklahoma Med Res Fdn, Dept Med, Oklahoma City, OK USA. [Alarcon-Riquelme, M. E.] Uppsala Univ, Uppsala, Sweden. [Alarcon-Riquelme, M. E.] Oklahoma Med Res Fdn, Uppsala, Sweden. [Vyse, T. J.] Univ London Imperial Coll Sci Technol & Med, London, England. [Kimberly, R. P.; Edberg, J. C.] Univ Alabama, Birmingham, AL USA. [Crow, M. K.] Hosp Special Surg, Mary Kirkland Ctr Lupus Res, New York, NY 10021 USA. [Harley, J. B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RI Vyse, Tim/G-3887-2011 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S341 EP S341 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244200491 ER PT J AU Ogdie, AR Schumacher, HR Chen, L Dai, L Frank, P AF Ogdie, Alexis R. Schumacher, H. Ralph Chen, Lan Dai, L. Frank, Pessler TI Histopathologic features of synovial biopsies in arthritis associated with hepatitis C virus infection SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Ogdie, Alexis R.; Chen, Lan] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Schumacher, H. Ralph] Sun Yat Sen Univ, Affiliated Hosp 2, Guangzhou 510275, Guangdong, Peoples R China. [Frank, Pessler] Tech Univ Dresden, Klin & Poliklin Kinder & Jugendmed, Dresden, Germany. 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S700 EP S700 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244201688 ER PT J AU Pan, YJ Fei, YP Sawalha, AH AF Pan, Yujun Fei, Yiping Sawalha, Anir H. TI CD40L overexpression in human T cells results in autologous B cell activation and plasma cell differentiation in vitro in the absence of antigen presentation SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Fei, Yiping] Univ Oklahoma, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Sawalha, Anir H.] Univ Oklahoma, Oklahoma Med Res Fdn, US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Pan, Yujun] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S845 EP S845 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244202335 ER PT J AU Petri, M Naqibuddin, M Wallace, DJ Weisman, MH Holliday, SL Sampedro, MM Carson, KA Padilla, P Brey, RL AF Petri, Michelle Naqibuddin, Mohammad Wallace, Daniel J. Weisman, Michael H. Holliday, Stephen L. Sampedro, Margaret M. Carson, Kathryn A. Padilla, Patricia Brey, Robin L. TI Cognitive function over time in SLE: The brain CONECTIONS inception cohort SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Petri, Michelle; Naqibuddin, Mohammad; Sampedro, Margaret M.; Carson, Kathryn A.] Johns Hopkins Univ, Baltimore, MD USA. [Weisman, Michael H.] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. [Holliday, Stephen L.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Padilla, Patricia; Brey, Robin L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S635 EP S636 PG 2 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244201510 ER PT J AU Sawalha, AH Jeftries, M Webb, R Lu, Q Gorelik, G Ray, D Osban, J Knowlton, N Johnson, K Richardson, B AF Sawalha, Amr H. Jeftries, Matlock Webb, Ryan Lu, Qianjin Gorelik, Gabriela Ray, Donna Osban, Jeanette Knowlton, Nicholas Johnson, Kent Richardson, Bruce TI Defective T-cell ERK signaling induces interferon-regulated gene expression and overexpression of methylation sensitive genes similar to lupus patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Sawalha, Amr H.] Univ Oklahoma, Oklahoma Med Res Fdn, US Dept Vet Affairs, Oklahoma City, OK USA. [Lu, Qianjin] Cent S Univ, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. [Richardson, Bruce] Univ Michigan, US Dept Vet Affairs, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S318 EP S318 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244200426 ER PT J AU Sawalha, AH Webb, R Han, S Kelly, JA Kaufman, KM Kimberl, RP Alarcon-Riquelme, ME James, JA Vyse, TJ Gilkeson, GS Choi, CB Scofield, RH Bae, SC Nath, SK Harley, JB AF Sawalha, Amr H. Webb, Ryan Han, Shizhon Kelly, Jennifer A. Kaufman, Kenneth M. Kimberl, Robert P. Alarcon-Riquelme, Marta E. James, Judith A. Vyse, Timothy J. Gilkeson, Gary S. Choi, Chan-Burn Scofield, R. Hal Bae, Sang-Cheol Nath, Swapan K. Harley, John B. TI Genetic association of the X-chromosome gene MECP2 with systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Sawalha, Amr H.; Scofield, R. Hal; Harley, John B.] Univ Oklahoma, US Dept Vet Affairs, Med Ctr, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Kimberl, Robert P.] Univ Alabama, Birmingham, AL USA. [Alarcon-Riquelme, Marta E.] Uppsala Univ, Uppsala, Sweden. [Vyse, Timothy J.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Choi, Chan-Burn; Bae, Sang-Cheol] Hanyang Univ, Seoul 133791, South Korea. 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S219 EP S219 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244200163 ER PT J AU Seo, P Silva, F Hofftnan, GS Spiera, R Davis, JC McCune, WJ Clair, EWS Specks, U Stone, JH Merkel, VPA AF Seo, Phili Silva, Francisco Hofftnan, Gary S. Spiera, Robert Davis, John C. McCune, W. Joseph Clair, E. William St. Specks, Ulrich Stone, John H. Merkel, V. Peter A. TI Damage caused by Wegener's Granulomatosis: Data from a multicenter longitudinal cohort SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Seo, Phili] Johns Hopkins Univ, Baltimore, MD USA. [Silva, Francisco; Specks, Ulrich] Mayo Clin, Coll Med, Rochester, MN USA. [Hofftnan, Gary S.] Cleveland Clin, Cleveland, OH 44106 USA. [Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA. [Davis, John C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McCune, W. Joseph] Univ Michigan, Ann Arbor, MI 48109 USA. [Clair, E. William St.] Duke Univ, Durham, NC USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merkel, V. Peter A.] Boston Univ, Boston, MA 02215 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S852 EP S852 PG 1 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244202357 ER PT J AU Seo, P Silva, F Hoffman, GS Spiera, R Davis, JC McCune, WJ Clair, EWS Specks, U Stone, JHV Merkel, PA AF Seo, Philip Silva, Francisco Hoffman, Gary S. Spiera, Robert Davis, John C. McCune, W. Joseph Clair, E. William St. Specks, Ulrich Stone, John H., V Merkel, Peter A. TI Morbidity and mortality of Wegener's Granulomatosis: Data from a current multicenter longitudinal cohort SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA. [Silva, Francisco; Specks, Ulrich] Mayo Clin, Coll Med, Rochester, MN USA. [Hoffman, Gary S.] Cleveland Clin, Cleveland, OH 44106 USA. [Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA. [Davis, John C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McCune, W. Joseph] Univ Michigan, Ann Arbor, MI 48109 USA. [Clair, E. William St.] Duke Univ, Durham, NC USA. [Stone, John H., V] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merkel, Peter A.] Boston Univ, Boston, MA 02215 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S852 EP S853 PG 2 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244202359 ER PT J AU Smolen, J Kay, J Doyle, MK Landewe, R Matteson, EL Willenhaupt, J Gaylis, N Murphy, F Neal, J Zhou, Y Visvanathan, S Hsia, EC Rahman, MU AF Smolen, J. Kay, J. Doyle, M. K. Landewe, R. Matteson, E. L. Willenhaupt, J. Gaylis, N. Murphy, F. Neal, J. Zhou, Y. Visvanathan, S. Hsia, E. C. Rahman, M. U. TI Golimumab, a human Anti-TNF alpha monoclonal antibody, injected every 4 weeks: Efficacy & safety in RA patients previously treated with anti-TNFa agents (GO-A-FTER study) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Smolen, J.] Med U Vienna, Hietzing Hosp, Vienna, Austria. [Kay, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Doyle, M. K.; Hsia, E. C.; Rahman, M. U.] Univ Penn, Sch Med, Centocor R&D Inc, Malvern, PA USA. [Landewe, R.] U Hosp Maastricht, Maastricht, Netherlands. [Matteson, E. L.] Mayo Clin, Rochester, MN USA. [Willenhaupt, J.] Klin Eibek, Hamburg, Germany. [Murphy, F.] Altoona Ctr Clin Res, Duncansville, PA USA. [Neal, J.] Arth Ctr Lexington, Lexington, KY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2008 VL 58 IS 9 SU S BP S523 EP S524 PG 2 WC Rheumatology SC Rheumatology GA 348XU UT WOS:000259244201228 ER PT J AU Salters-Pedneault, K Suvak, M Roemer, L AF Salters-Pedneault, Kristalyn Suvak, Michael Roemer, Lizabeth TI An experimental investigation of the effect of worry on responses to a discrimination learning task SO BEHAVIOR THERAPY LA English DT Article ID GENERALIZED ANXIETY DISORDER; SCHEDULE-CONTROLLED BEHAVIOR; QUESTIONNAIRE; INDIVIDUALS; COMORBIDITY; PERFORMANCE; RELAXATION; THERAPY; SHIPLEY; BIAS AB The current study examined the impact of both the tendency to worry (trait worry) and the process of worry (state worry) on subsequent behavioral responding in a schedule discrimination learning task. High and low trait worriers were randomly assigned to a state worry or relaxation incubation condition and completed a test of executive functioning and a dual contingency learning task that utilized neutral discriminative cues over the course of 2 contingency phases. Although state and trait worry did not impact executive functioning, the state worry condition was associated with diminished sensitivity to learning task contingencies over the course of the first contingency learning trials in comparison to the relaxation condition. This relationship was unique to the state worry condition above and beyond shared variance with subjective anxiety level. Results suggest that state worry may lead to a decrement in selective behavioral responding to neutral discriminative cues in the environment. The findings suggest that the process of worry may lead to less adaptive responding to neutral cues and interfere with adaptive behaviors, which may thereby contribute to and maintain anxiety. C1 [Salters-Pedneault, Kristalyn; Roemer, Lizabeth] Univ Massachusetts, Boston, MA 02125 USA. [Suvak, Michael] Boston Univ, Boston, MA 02215 USA. [Suvak, Michael] VA Boston Healthcare Syst, Boston, MA USA. RP Salters-Pedneault, K (reprint author), VA Boston Healthcare Syst 116B 5, Natl Ctr PTSD, Behav Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. EM kristalyn.salters@va.gov OI Roemer, Lizabeth/0000-0002-2453-5435 FU NIMH NIH HHS [MH068962] NR 43 TC 8 Z9 10 U1 3 U2 7 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD SEP PY 2008 VL 39 IS 3 BP 251 EP 261 DI 10.1016/j.beth.2008.01.001 PG 11 WC Psychology, Clinical SC Psychology GA 351LJ UT WOS:000259425500005 PM 18721639 ER PT J AU Samuels, JF Bienvenu, OJ Pinto, A Murphy, DL Piacentini, J Rauch, SL Fyer, AJ Grados, MA Greenberg, BD Knowles, JA McCracken, JT Cullen, B Riddle, MA Rasmussen, SA Pauls, DL Liang, KY Hoehn-Saric, R Pulver, AE Nestadt, G AF Samuels, Jack F. Bienvenu, O. Joseph Pinto, Anthony Murphy, Dennis L. Piacentini, John Rauch, Scott L. Fyer, Abby J. Grados, Marco A. Greenberg, Benjamin D. Knowles, James A. McCracken, James T. Cullen, Bernadette Riddle, Mark A. Rasmussen, Steven A. Pauls, David L. Liang, Kung-Yee Hoehn-Saric, Rudolf Pulver, Ann E. Nestadt, Gerald TI Sex-specific clinical correlates of hoarding in obsessive-compulsive disorder SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE obsessive-compulsive disorder; hoarding; comorbidity; personality disorders; personality; sex differences ID OCD COLLABORATIVE GENETICS; FACTOR-ANALYZED SYMPTOM; PERSONALITY-DISORDER; COGNITIVE ASPECTS; SIBLING PAIRS; DIMENSIONS; FAMILY; RATIONALE; SEVERITY AB Little is known about whether the clinical correlates of hoarding behavior are different in men and women with obsessive-compulsive disorder (OCD). In the current study, we evaluated the association of hoarding with categories of obsessions and compulsions, psychiatric disorders, personality dimensions, and other clinical characteristics separately in 151 men and 358 women with OCD who were examined during the OCD Collaborative Genetics Study. We found that, among men but not women, hoarding was associated with aggressive, sexual, and religious obsessions and checking compulsions. In men, hoarding was associated with generalized anxiety disorder and tics whereas, among women, hoarding was associated with social phobia, post-traumatic stress disorder, body dysmorphic disorder, nail biting, and skin picking. In women but not men, hoarding was associated with schizotypal and dependent personality disorder dimensions, and with low conscientiousness. These findings indicate that specific clinical correlates of hoarding in OCD are different in men and women and may reflect sex-specific differences in the course, expression, and/or etiology of hoarding behavior in OCD. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Samuels, Jack F.; Bienvenu, O. Joseph; Grados, Marco A.; Cullen, Bernadette; Riddle, Mark A.; Hoehn-Saric, Rudolf; Pulver, Ann E.; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Pinto, Anthony; Greenberg, Benjamin D.; Rasmussen, Steven A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Piacentini, John; McCracken, James T.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rauch, Scott L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fyer, Abby J.] Columbia Univ, New York State Psychiat Inst, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Knowles, James A.] Univ So Calif, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Pauls, David L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Liang, Kung-Yee] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. RP Samuels, JF (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-81, Baltimore, MD 21287 USA. EM jacks@jhmi.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU NCRR NIH HHS [RR00052, M01 RR000052]; NIMH NIH HHS [K23 MH064543, K23-MH64543, R01 MH050214, R01 MH050214-09, R01 MH071507, R01 MH079487, R01 MH50214] NR 43 TC 13 Z9 14 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD SEP PY 2008 VL 46 IS 9 BP 1040 EP 1046 DI 10.1016/j.brat.2008.06.005 PG 7 WC Psychology, Clinical SC Psychology GA 357FZ UT WOS:000259833000008 PM 18692168 ER PT J AU Flessner, CA Woods, DW Franklin, ME Keuthen, NJ Piacentini, J AF Flessner, Christopher A. Woods, Douglas W. Franklin, Martin E. Keuthen, Nancy J. Piacentini, John CA TLC SAB TI Styles of pulling in youths with trichotillomania: Exploring differences in symptom severity, phenomenology, and comorbid psychiatric symptoms SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE focused; automatic; pulling styles; youths; trichotillomania ID TREATING TRICHOTILLOMANIA; PSYCHOMETRIC PROPERTIES; DEPRESSION INVENTORY; HABIT-REVERSAL; SCALE; CHILD; VALIDITY; THERAPY AB To date, no studies have examined possible phenomenological differences between the automatic and focused styles of pulling in youths with TTM. The aims of the current study were to examine differences in TTM severity, phenomenology, comorbid psychiatric symptoms, and functional impact across youths with varying degrees of these pulling styles. Youths between the ages of 10 and 17 years (and their parent) were recruited via an Internet-based survey. A total of 186 youths with chronic hair pulling was classified as "high-focused" or "low-focused" and either "high-automatic" or "low-automatic" based upon scores obtained on the Milwaukee Inventory for Styles of Trichotillomania-Child Version (MIST-C) using a median-split procedure. Results demonstrated significant differences between pulling styles. More specifically, "high-focused" pullers reported more severe TTM and greater symptoms of anxiety and depression than "low-focused" pullers, and "high-automatic" pullers reported greater symptoms of depression than "low-automatic" pullers. Subsequent analyses suggest that, in comparison to youths with low levels of both automatic and focused pulling, those experiencing high levels of focused Pulling but low levels of automatic pulling reported phenomenological differences and were more likely to engage in additional repetitive behaviors (i.e., skin picking, lip/cheek biting). Clinical and research implications, study limitations, and future areas of research are discussed. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Flessner, Christopher A.; Woods, Douglas W.] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53201 USA. [Franklin, Martin E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Keuthen, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Piacentini, John] Univ Calif Los Angeles, Los Angeles, CA USA. RP Flessner, CA (reprint author), Bradley Hasbro Res Clin, Coro W Bldg,2nd Floor,1 Hoppin St, Providence, RI 02915 USA. EM christopher_flessner@brown.edu RI Piacentini, John/C-4645-2011; Flessner, Christopher/K-1483-2015; OI Stein, Dan/0000-0001-7218-7810 NR 27 TC 18 Z9 18 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD SEP PY 2008 VL 46 IS 9 BP 1055 EP 1061 DI 10.1016/j.brat.2008.06.006 PG 7 WC Psychology, Clinical SC Psychology GA 357FZ UT WOS:000259833000010 PM 18675401 ER PT J AU Soiffer, RJ AF Soiffer, Robert J. TI Donor lymphocyte infusions for acute myeloid leukaemia SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE acute myeloid leukaemia; donor lymphocyte infusions; graft-vs-leukaemia effect ID BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; CYTOTOXIC T-LYMPHOCYTES; MINOR HISTOCOMPATIBILITY ANTIGENS; MHC CLASS-I; LEUKOCYTE INFUSIONS; RELAPSED LEUKEMIA; ADOPTIVE IMMUNOTHERAPY AB The success of donor lymphocyte infusion (DLI) in treating chronic myeloid leukaemia that had recurred after allogeneic haematopoietic stem cell transplantation provided direct evidence for the existence of an immunologically mediated graft-vs-leukaemia effect and led to the development of non-myeloablative transplantation. For patients with acute myeloid leukaemia (AML), DLI has been less effective, both as a result of its rapid growth kinetics and its decreased susceptibility to alloimmune-mediated effects. This chapter reviews the historical experience with DLI for AML, both as treatment for and prophylaxis of relapse. New approaches aimed at improving the efficacy of DLI are discussed, including administration of chemotherapy prior to DLI, use of immunomodulatory cytokines to bolster the cytotoxic effector response, priming of donor lymphocytes to recipient tumour antigens ex vivo, and infusions of alloreactive natural killer cells. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM rsoiffer@partners.org NR 75 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD SEP PY 2008 VL 21 IS 3 BP 455 EP 466 DI 10.1016/j.beha.2008.07.009 PG 12 WC Hematology SC Hematology GA 359CL UT WOS:000259963700007 PM 18790449 ER PT J AU Mao, CG Obeid, LM AF Mao, Cungui Obeid, Lina M. TI Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE apoptosis; bioactive lipid; cell adhesion; differentiation; growth arrest; proliferation ID HUMAN ACID CERAMIDASE; NECROSIS-FACTOR-ALPHA; PROTEIN-KINASE-C; NORMAL HUMAN KERATINOCYTES; STRESS-INDUCED APOPTOSIS; LOW-DENSITY-LIPOPROTEIN; RENAL MESANGIAL CELLS; FULL-LENGTH CDNA; NEUTRAL CERAMIDASE; FARBER-DISEASE AB Ceramidases catalyze hydrolysis of ceramides to generate sphingosine (SPH). which is phosphorylated to form sphingosine-1-phosphate (S1P). Ceramide, SPH, and S1P are bioactive lipids that mediate cell proliferation. differentiation, apoptosis, adhesion, and migration. Presently, 5 human ceramidases encoded by 5 distinct genes have been cloned: acid ceramidase (AC), neutral ceramidase (NC) alkaline ceramidase 1 (ACER1), alkaline ceramidase 2 (ACER2), and alkaline ceramidase 3 (ACER3). Each human ceramidase has a mouse counterpart. AC, NC, and ACERI-3 have maximal activities in acidic, neutral, and alkaline environments, respectively. ACERI-3 have similar protein sequences but 110 homology to AC and NC. AC and NC also have distinct protein sequences. The human AC (hAC was implicated in Farber disease, and hAC may be important for cell Survival. The mouse AC (mAC) is needed for early embryo Survival. NC is protective against inflammatory cytokines, and the mouse NC(mNC) is required for the catabolism of ceramides in the digestive tract. ACER 1 is critical in mediating cell differentiation by controlling the generation of SPH and S1P and that ACER2's role in cell proliferation and survival depends on its expression or the cell type in which it is found. Here, we discuss the role of each ceramidase in regulating cellular responses mediated by ceramides, SPH. and S1P. Published by Elsevier B.V C1 [Mao, Cungui; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Mao, Cungui; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.] Med Univ S Carolina, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. RP Mao, CG (reprint author), Med Univ S Carolina, Dept Med, Room 646,STB,114 Doughty St, Charleston, SC 29425 USA. EM maoc@musc.edu; obeidi@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIH [R01 CA104834 (CM)]; VA merit award (LMO) FX Studies oil the role of the acid and alkaline ceramidases in our laboratories are supported by the NIH grant R01 CA104834 (CM) and a VA merit award (LMO). NR 140 TC 150 Z9 156 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD SEP PY 2008 VL 1781 IS 9 BP 424 EP 434 DI 10.1016/j.bbalip.2008.06.002 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 355MC UT WOS:000259712000002 PM 18619555 ER PT J AU Berk, M Copolov, D Dean, O Lu, K Jeavons, S Schapkaitz, I Anderson-Hunt, M Judd, F Katz, F Katz, P Ording-Jespersen, S Little, J Conus, P Cuenod, M Do, KQ Bush, AI AF Berk, Michael Copolov, David Dean, Olivia Lu, Kristy Jeavons, Sue Schapkaitz, Ian Anderson-Hunt, Murray Judd, Fiona Katz, Fiona Katz, Paul Ording-Jespersen, Sean Little, John Conus, Philippe Cuenod, Michel Do, Kim Q. Bush, Ashley I. TI N-acetyl cysteine as a glutathione precursor for schizophrenia - A double-blind, randomized, placebo-controlled trial SO BIOLOGICAL PSYCHIATRY LA English DT Article DE adjunct therapy; clinical trials; glutathione; n-acetyl cysteine; schizophrenia ID INDUCED OXIDATIVE STRESS; ATYPICAL ANTIPSYCHOTICS; IN-VIVO; ACETYLCYSTEINE; BRAIN; ACID; IMPROVES; DEFICIT; RATS; PHARMACOKINETICS AB Background: Brain glutathione levels are decreased in schizophrenia, a disorder that often is chronic and refractory to treatment. N-acetyl cysteine (NAC) increases brain glutathione in rodents. This study was conducted to evaluate the safety and effectiveness of oral NAC (I g orally twice daily [b.i.d.]) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period. Methods: A randomized, multicenter, double-blind, placebo-control led study. The primary readout was change from baseline on the Positive and Negative Symptoms Scale (PANSS) and its components. Secondary readouts included the Clinical Global Impression (CGI) Severity and Improvement scales, as well as general functioning and extrapyramidal rating scales. Changes following a 4-week treatment discontinuation were evaluated. One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were randomized; 84 completed treatment. Results: Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [-5.97 (-10.44, -1.51), p = .0091, PANSS negative [mean difference -1.83 (95% confidence interval: -3.33, -.32), p = .0181, and PANSS general [-2.79 (-5.38, -.20), p = .035], CGI-Severity (CGI-S) [-.26 (-.44, -.08),p = .0041, and CGI-Improvement (CGI-I) [-.22 (-.41, -.03), p = .0251 scores. No significant change on the PANSS positive subscale was seen. N-acetyl cysteine treatment also was associated with an improvement in akathisia (p = .022). Effect sizes at end point were consistent with moderate benefits. Conclusions: These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia. C1 [Bush, Ashley I.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Berk, Michael; Copolov, David; Dean, Olivia; Bush, Ashley I.] Mental Hlth Res Inst, Parkville, Vic, Australia. [Berk, Michael; Lu, Kristy; Schapkaitz, Ian; Anderson-Hunt, Murray] Univ Melbourne, Dept Clin & Biomed Sci, Geelong, Vic, Australia. [Berk, Michael] Orygen Youth Hlth, Melbourne, Vic, Australia. [Copolov, David] Monash Univ, Clayton, Vic, Australia. [Dean, Olivia] Univ Melbourne, Dept Psychiat, Parkville, Vic 3052, Australia. [Katz, Fiona; Katz, Paul; Ording-Jespersen, Sean] Southwestern Hlth, Melbourne, Vic, Australia. [Little, John] Ballarat Hlth, Ballarat, Vic, Australia. [Bush, Ashley I.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Conus, Philippe; Cuenod, Michel; Do, Kim Q.] Univ Lausanne Hosp, Dept Psychiat, Lausanne, Switzerland. RP Bush, AI (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CNY 149,13th St, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007; Do, Kim/G-6694-2016; Berk, Michael/M-7891-2013 OI Bush, Ashley/0000-0001-8259-9069; Do, Kim/0000-0003-1968-1646; Berk, Michael/0000-0002-5554-6946 FU Stanley Medical Research Institue; Australian Research Council Federation; National Health and Medical Research Council of Australia; Lausanne-Switzerland Center; Stanley Medical Research Foundation FX This study was supported by a grant from the Stanley Medical Research Institue. AIB is supported by the Australian Research Council Federation Fellowship, The Woods Family Foundation. and the National Health and Medical Research Council of Australia supported OD. The Loterie Romande supported the Lausanne-Switzerland Center (grant to KQD).; Trial registration: Australian Clinical Trials Registry, Protocol 12605000363684, www.actr.org.au.; We thank Erihana Ryan, Warrick? Brewer, Patricia Deppen. Alexandra Solida, and Pierre Bovel for their assistance with this Project.; Dr Berk has received grant or research support from the Stanley Medical Research Foundation. The MBF Foundation. National Health and Medical Research Council of Australia. Beyond Blue. Geelong, Medical Research Foundation, Bristol Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis. Mayne Pharma, and Servier, is a consultant to Astra Zeneca. Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag. Lundbeck, and Pfizer, and has been a speaker for Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck? Organon, Pfizer. Sanofi Synthelabo. Solvay, and Wyeth. Dr. Bush is a shareholder and consultant for Prana Biotechnology Ltd and a shareholder of Cogstate Ltd. All other authors reported no biomedical financial interests or potential conflicts of interest. NR 43 TC 245 Z9 250 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2008 VL 64 IS 5 BP 361 EP 368 DI 10.1016/j.biopsych.2008.03-004 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 338XR UT WOS:000258543200002 PM 18436195 ER PT J AU Spencer, KM Salisbury, DF Shenton, ME McCarley, RW AF Spencer, Kevin M. Salisbury, Dean F. Shenton, Martha E. McCarley, Robert W. TI gamma-band auditory steady-state responses are impaired in first episode psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE auditory steady-state response; bipolar disorder; EEG; first episode psychosis; gamma oscillation; schizophrenia ID LEFT TEMPORAL-LOBE; BIPOLAR DISORDER; SCHIZOPHRENIA; SYNCHRONIZATION; STIMULATION; DYSFUNCTION; HANDEDNESS; CIRCUITRY; NEURONS; CORTEX AB Background: In chronic schizophrenia and chronic bipolar disorder, gamma band (30-100 Hz) auditory steady-state electroencephalogram responses (ASSRs) are reduced in power and phase locking, likely reflecting neural circuit dysfunction. Here we examined whether gamma ASSR deficits are also present at first hospitalization for psychosis. Methods: Subjects were 16 first episode schizophrenia patients (SZ), 16 first episode affective disorder patients (AFF) (13 with bipolar disorder), and 33 healthy control subjects (HC). Stimuli were 20-, 30-, and 40-Hz binaural click trains. The ASSR phase locking and evoked power were analyzed with the Morlet wavelet transform. Results: At 40-Hz stimulation, SZ and AFF had significantly reduced phase locking compared with HC. This deficit was more pronounced over the left hemisphere in SZ. Evoked power at 40 Hz was also reduced in the patients compared with HC. At 30-Hz stimulation phase locking and evoked power were reduced in both patient groups. The 20-Hz ASSR did not differ between groups, but phase locking and evoked power of the 40-Hz harmonic of the 20-Hz ASSR were reduced in both SZ and AFF. Phase locking of this 40-Hz harmonic was correlated with total positive symptoms in SZ. Conclusions: They ASSR deficit is present at first hospitalization for both schizophrenia and affective disorder but shows a left hemisphere bias in first hospitalized SZ. Some of the neural circuitry abnormalities underlying the gamma ASSR deficit might be common to psychoses in general, whereas others might be specific to particular disorders. C1 [Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. [Salisbury, Dean F.] McLean Hosp, Cognit Neurosci Lab, Dept Psychiat, Belmont, MA 02178 USA. [Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Spencer, KM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Psychiat 116A,940 Belmont St, Brockton, MA 02301 USA. EM kevin_spencer@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Spencer, Kevin/0000-0002-5500-7627 FU Department of Veterans Affairs Research Enhancement Award Program and Schizophrenia Center (RWM); National Institute of Mental Health [R01 40799, R01 58704, R03 07670-0]; National Alliance for Research in Schizophrenia and Depression FX This work was supported by a Department of Veterans Affairs Research Enhancement Award Program and Schizophrenia Center (RWM); National Institute of Mental Health Grants R01 40799 (RWM) R01 58704 (DFS), and R03 07670-0 (KMS), and a Young Invesgiator Award from the National Alliance for Research in Schizophrenia and Depression (KMS).; Drs. Spencer Salisbury, Shenton, and McCarley reported no biomedical financial interests or potential conflicts of interest. NR 40 TC 120 Z9 122 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2008 VL 64 IS 5 BP 369 EP 375 DI 10.1016/j.biopsych.2008.02.021 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 338XR UT WOS:000258543200003 PM 18400208 ER PT J AU Kuperberg, GR West, WC Lakshmanan, BM Goff, D AF Kuperberg, Gina R. West, W. Caroline Lakshmanan, Balaji M. Goff, Don TI Functional magnetic resonance imaging reveals neuroanatomical dissociations during semantic integration in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE context; DLPFC; fMRI; language; prefrontal cortex; schizophrenia; semantic; temporal cortex ID DORSOLATERAL PREFRONTAL CORTEX; EVENT-RELATED FMRI; WORKING-MEMORY CAPACITY; SURFACE-BASED ANALYSIS; LANGUAGE COMPREHENSION; SENTENCE COMPREHENSION; CORTICAL SURFACE; PROCESSING CONCRETE; COORDINATE SYSTEM; MAJOR DEPRESSION AB Background: Schizophrenia symptoms can be conceptualized in terms of a breakdown of a balance between 1) activating, retrieving, and matching stored representations to incoming information (semantic memory-based processing) and 2) fully integrating activated semantic representations with one another and with other types of representations to form a gestalt representation of meaning (semantic integration). Semantic memory-based processes are relatively more dependent on inferior frontal and temporal cortices, whereas particularly demanding integrative processes additionally recruit the dorsolateral prefrontal cortex (DLPFC) and sometimes parietal cortices. We used functional magnetic resonance imaging (fMRI) to determine whether the modulation of temporal/inferior frontal cortices and the DLPFC can be neuroanatomically dissociated in schizophrenia, as semantic integration demands increase. Integration demands were manipulated by varying the nature (concrete vs. abstract) and the congruity (incongruous vs. congruous) of words within sentences. Methods: Sixteen right-handed schizophrenia patients and 16 healthy volunteers, matched on age and parental socioeconomic status, underwent event-related fMRI scanning while they read sentences. Blood oxygen level dependent (BOLD) effects were contrasted to words within sentences that were 1) concrete versus abstract and 2) semantically incongruous versus congruous with their preceding contexts. Results: In both contrasts, large networks mediating the activation and retrieval of verbal and imagistic representations were normally modulated in patients. However, unlike control subjects, patients failed to recruit the DLPFC, medial frontal and parietal cortices to incongruous (relative to congruous) sentences, and failed to recruit the DLPFC to concrete (relative to abstract) sentences. Conclusions: As meaning is built from language, schizophrenia patients demonstrate a neuroanatomical dissociation in the modulation of temporal/inferior frontal cortices and the DLPFC. C1 [Kuperberg, Gina R.; Goff, Don] Massachusetts Gen Hosp East, Dept Psychiat, Charlestown, MA 02129 USA. [Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [West, W. Caroline] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kuperberg, GR (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM kuperber@nmr.mgh.harvard.edu FU National Institute of Mental Health [R01 MH071635]; Institute for Mental Illness and Neuroscience Discovery (MIND); National Alliance for Research on Schizophrenia And Depression (NARSAD); Massachusetts General Hospital FX This research was supported by the National Institute of Mental Health (R01 MH071635) and the Institute for Mental Illness and Neuroscience Discovery (MIND). Gina R. Kuperberg was also supported by a National Alliance for Research on Schizophrenia And Depression (NARSAD) (with the Sidney Baer Trust) and a Claflin Distinguished Scholars Award from Massachusetts General Hospital. We thank Jordana Cotton, Karin Blais, and Alexis Coty for their help with data acquisition; Christine Portal, Kaila Norman, and Daphne Holt for help with patient recruitment and assessement; Arim Choi for help with analysis; and Tatiana Sitnikova, Mante Nieuwland, and Tali Ditman for their helpful comments on the manuscript.; Dr. Goff has received honoraria or research support over the past year form Pfizer, Cephalon, Xenoport, Dainippon Sumitomo, Janssen Pharmaceuticals, Solvay/Wyeth, Eli Lilly, Bristol-MyerSquibb, Verusmed, Letters and Science, Primedia, SG Co-wen, Vista Research, Organon, Proteus, the National Institutes of Health, Narsad, Sidney Baer Foundation, Department of Energy (DOE), and Vanda Pharmaceuticals. All other authors reported no biomedical financial interests or potential conflicts of interest.; Supplementary material cited in this article is available online. NR 79 TC 30 Z9 32 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2008 VL 64 IS 5 BP 407 EP 418 DI 10.1016/j.biopsych.2008.03.018 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 338XR UT WOS:000258543200008 PM 18504037 ER PT J AU Puls, I Mohr, J Wrase, J Priller, J Behr, J Kitzrow, W Makris, N Breiter, HC Obermayer, K Heinz, A AF Puls, I. Mohr, J. Wrase, J. Priller, J. Behr, J. Kitzrow, W. Makris, N. Breiter, H. C. Obermayer, K. Heinz, A. TI Synergistic effects of the dopaminergic and glutamatergic system on hippocampal volume in alcohol-dependent patients SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE alcohol addiction; COMT; dopamine; mGluR3; glutamate; hippocampal volume; machine learning; P-SVM; variable selection ID CATECHOL-O-METHYLTRANSFERASE; FALSE DISCOVERY RATE; LONG-TERM-MEMORY; GENETIC-VARIATION; USE DISORDERS; HUMAN BRAIN; INDUCED REINSTATEMENT; RECEPTOR SUBTYPES; SUBSTANTIA-NIGRA; SEX-DIFFERENCES AB Several genes of the dopaminergic and glutamatergic neurotransmitter systems have been found to be associated with alcohol disease and related intermediate phenotypes. Here, we evaluated genetic variants of the catechol-O-methyltransferase (COMT) and the metabotropic glutamate receptor 3 (mGluR3) genes in alcohol-dependent patients and their association with volumetric measurements of brain structures. By combined analysis of imaging data and genotyping results, large numbers of variables are produced that overstrain conventional statistical methods based on tests for group differences. Limitations in assessment of epistatic effects and multiple testing problems are encountered. Therefore, we introduce a novel method for detecting associations between a set of genetic markers and phenotypical measurements based on machine learning techniques. Hippocampal volume was found to be associated with epistatic effects of the COMT-mGluR3 genes in alcohol-dependent patients but not in controls. These data are in line with prior studies supporting a role for dopamine-glutamate interaction in modulation of alcohol disease. (C) 2008 Elsevier B.V. All rights reserved. C1 [Puls, I.; Mohr, J.; Wrase, J.; Priller, J.; Behr, J.; Kitzrow, W.; Heinz, A.] Charite, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany. [Mohr, J.; Obermayer, K.] Bernstein Ctr Computat Neurosci, Berlin, Germany. [Makris, N.; Breiter, H. C.] Massachusetts Gen Hosp, Motivat & Emot Neurosci Collaborat, Boston, MA 02114 USA. [Makris, N.; Breiter, H. C.] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Makris, N.; Breiter, H. C.] Harvard Univ, Sch Med, Boston, MA USA. [Obermayer, K.] Berlin Inst Technol, Sch Elect Engn & Comp Sci, Berlin, Germany. RP Heinz, A (reprint author), Charite, Dept Psychiat & Psychotherapy, Charite Campus Mitte,Charitepl 1, D-10117 Berlin, Germany. EM andreas.heinz@charite.de FU NCRR NIH HHS [M01 RR001066]; NIDA NIH HHS [R01 DA014118, P20 DA026002] NR 90 TC 13 Z9 13 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 EI 1873-6246 J9 BIOL PSYCHOL JI Biol. Psychol. PD SEP PY 2008 VL 79 IS 1 BP 126 EP 136 DI 10.1016/j.biopsycho.2008.03.001 PG 11 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 341TU UT WOS:000258738800013 PM 18423838 ER PT J AU Ballen, KK King, RJ Chitphakdithai, P Bolan, CD Agura, E Hartzman, RJ Kernan, NA AF Ballen, Karen K. King, Roberta J. Chitphakdithai, Pintip Bolan, Charles D., Jr. Agura, Edward Hartzman, Robert J. Kernan, Nancy A. TI The National Marrow Donor Program 20 years of unrelated donor hematopoietic cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE National Marrow Donor Program; NMDP; unrelated donor; stem cell transplant; transplantation ID ANTILYMPHOCYTE GLOBULIN; APLASTIC-ANEMIA; CYCLOSPORINE; DISEASES; THERAPY AB In the 20 years since the National Marrow Donor Program (NMDP) facilitated the first unrelated donor transplant, the organization has grown to include almost 7 million donors, and has facilitated over 30,000 transplants on 6 continents. This remarkable accomplishment has been facilitated by the efforts of over 600 employees, and an extensive international network including 171 transplant centers, 73 donor centers, 24 cord blood banks, 97 bone marrow collection centers, 91 apheresis centers, 26 HLA typing laboratories, and 26 Cooperative Registries. In this article, we review the history of the NMDP, and cite the major trends in patient demographics, graft sources, and conditioning regimens over the last 20 years. (C) 2008 American Society for Blood and Marrow Transplantation. C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [King, Roberta J.; Chitphakdithai, Pintip] Natl Marrow Donor Program, Minneapolis, MN USA. [Bolan, Charles D., Jr.] NHLBI, Hematol Branch, NIH, Rockville, MD USA. [Agura, Edward] Baylor Univ, Med Ctr, Houston, TX 77030 USA. [Hartzman, Robert J.] USN, Med Res Ctr, CW Bill Young Dept, Def Marrow Donor Program, Rockville, MD USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Suite 118, Boston, MA 02114 USA. EM kballen@partners.org OI Kernan, Nancy/0000-0003-1417-1823 FU NMDP FX Financial Disclosure: Drs. King and Chitphakdithai are employees of the NMDP and have a financial relationship with the NMDP, in that capacity as employees. Drs. Ballen, Bolan, Agura, Hartzman, and Kernan have nothing to disclose. NR 16 TC 37 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2008 VL 14 IS 9 SU 3 BP 2 EP 7 DI 10.1016/j.bbmt.2008.05.017 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 352QU UT WOS:000259513100001 PM 18721774 ER PT J AU Karanes, C Nelson, GO Chitphakdithai, P Agura, E Ballen, KK Bolan, CD Porter, DL Uberti, JP King, RJ Confer, DL AF Karanes, Chatchada Nelson, Gene O. Chitphakdithai, Pintip Agura, Edward Ballen, Karen K. Bolan, Charles D. Porter, David L. Uberti, Joseph P. King, Roberta J. Confer, Dennis L. TI Twenty years of unrelated donor hematopoietic cell transplantation for adult recipients facilitated by the National Marrow Donor Program SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE National Marrow Donor Program; NMDP; adult; hematopoietic; stem cell; transplantation ID VERSUS-HOST-DISEASE; BONE-MARROW; CLASS-I; HLA AB For more than 20 years the National Marrow Donor Program has facilitated unrelated donor hematopoietic cell transplants for adult recipients. In this time period, the volunteer donor pool has expanded to nearly 12 million adult donors worldwide, improvements have occurred in the understanding and technology of HLA matching, there have been many changes in clinical practice and supportive care, and the more common graft source has shifted from bone marrow (BM) to peripheral blood stem cells (PBSCs). The percentage of older patients who are receiving unrelated donor transplants is increasing; currently over 1 in 10 adult transplant recipients is over the age of 60 years. Chronic myelogenous leukemia (CML) was previously the most common diagnosis for unrelated donor transplantation, but it now comprises less than 10% of transplants for adult recipients. Transplants for acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and myelodysplastic syndromes (MDS) all outnumber CML. Treatment-related mortality (TRM) has declined significantly over the years, particularly in association with myeloablative transplant preparative regimens. Correspondingly, survival within each disease category has improved. Particularly gratifying are the results in severe aplastic anemia (AA) where 2-year survival has doubled in just 10 years. (C) 2008 American Society for Blood and Marrow Transplantation. C1 [Nelson, Gene O.; Chitphakdithai, Pintip; King, Roberta J.; Confer, Dennis L.] Natl Marro Donor Program, Minneapolis, MN 55413 USA. [Karanes, Chatchada] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Agura, Edward] Baylor Univ, Med Ctr, Dallas, TX USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bolan, Charles D.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Porter, David L.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Uberti, Joseph P.] Karmanos Canc Inst, Detroit, MI USA. RP Confer, DL (reprint author), Natl Marro Donor Program, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55413 USA. EM dconfer@nmdp.org FU NMDP FX Financial Disclosure: Drs. Nelson, Chitphakdithal, King, and Confer are employees of the NMDP and have a financial relationship with the NMDP, in that capacity as employees. Drs. Karanes, Agura, Ballen, Bolan, Porter, and Uberti have nothing to disclose. NR 16 TC 61 Z9 71 U1 1 U2 4 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 SEP PY 2008 VL 14 IS 9 SU 3 BP 8 EP 15 DI 10.1016/j.bbmt.2008.06.006 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 352QU UT WOS:000259513100002 PM 18721775 ER PT J AU Bredeson, CN Zhang, MJ Agovi, MA Bacigalupo, A Bahlis, NJ Ballen, K Brown, C Chaudhry, MA Horowitz, MM Kurian, S Quinlan, D Muehlenbien, CE Russell, JA Savoie, L Rizzo, JD Stewart, DA AF Bredeson, Christopher N. Zhang, Mei-Jie Agovi, Manza-A. Bacigalupo, Andrea Bahlis, Nizar J. Ballen, Karen Brown, Christopher Chaudhry, M. Ahsan Horowitz, Mary M. Kurian, Seira Quinlan, Diana Muehlenbien, Catherine E. Russell, James A. Savoie, Lynn Rizzo, J. Douglas Stewart, Douglas A. TI Outcomes following HSCT using fludarabine, busulfan, and thymoglobulin: A matched comparison to allogeneic transplants conditioned with busulfan and cyclophosphamide SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE antithymocyte globulin; allogeneic transplantation; busulfan ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; DAILY INTRAVENOUS BUSULFAN; ACUTE MYELOID-LEUKEMIA; DAILY IV BUSULFAN; ANTITHYMOCYTE GLOBULIN; UNRELATED DONORS; MARROW-TRANSPLANTATION; TARGETED BUSULFAN; PAIR ANALYSIS AB We have reported a lower incidence of acute graft-versus-host disease (aGVHD) with a novel conditioning regimen using low-dose rabbit antithymocyte globulin (ATG; Thymoglobulin [TG]) with fludarabine and intravenous busulfan (FluBuTG). To assess further this single-center experience, we performed a retrospective matched-pair analysis comparing outcomes of adult patients transplanted using the FluBuTG conditioning regimen with matched controls from patients reported to tire CIBMTR receiving a first allogeneic hematopoietic stem cell transplant (HCT) after standard oral busulfan and cyclophosphamide (BuCy). One hundred twenty cases and 215 matched controls were available for comparison. Patients receiving FluBuTG has significantly less treatment related mortality (TRM; 12% versus 34%, P < .001) and grades II-IV aGVHD (15% versus 34%, P < .001) compared to BuCy patients. The risk of relapse was higher in the FluBuTG patients (42% versus 20%, P < .001). The risks of chronic GVHD (cGVHD) and disease free survival (DFS),A,ere similar in the cases and controls. These results suggest that the novel regimen FluBuTG decreases the risk of aGVHD and TRM after HILA-identical sibling HSCT, but is associated with an increased risk of relapse, resulting in similar DFS. Whether these conditioning regimens may be more suitable for specific patient populations based on relapse risk requires testing in prospective randomized trials. (C) 2008 American Society for Blood and Marrow Transplantation. C1 [Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Bahlis, Nizar J.; Brown, Christopher; Chaudhry, M. Ahsan; Quinlan, Diana; Russell, James A.; Savoie, Lynn; Stewart, Douglas A.] Alberta Blood & Marrow Transplant Program, Calgary, AB, Canada. [Bacigalupo, Andrea] San Martino Hosp, Genoa, Italy. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kurian, Seira] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Muehlenbien, Catherine E.] Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Rizzo, JD (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. EM rizzo@mcw.edu FU National Cancer Institute [U24-CA76518]; National Institute of Allergy and Infectious Diseases; National Heart, Lung and Blood Institute; Office of Naval Research; Health Resources and Services Administration (DHHS); American International Group, Inc.; American Society for Blood and Marrow Transplantation; Amgen, Inc. FX This work was supported by Public Health Service Grant U24-CA76518 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung and Blood Institute; Office of Naval Research; Health Resources and Services Administration (DHHS); and grants from AABB; Aetna; American International Group, Inc.; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin, Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; BioOne Corporation; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Bristol-Myers Squibb Company; Cangene Corporation; Celgene Corporation; CellGenix, GmbH; Cerus Corporation; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; EKR Therapeutics; Enzon Pharmaceuticals, Inc.; Gambro BCT, Inc.- Gamida Cell, Ltd.- Genzyme Corporation; Gift of Life Bone Marrow Foundation; GlaxoSmithKline, Inc.; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma, Kirin Brewery Co., Ltd.; Merck & Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; MultiPlan, Inc.-, National Marrow Donor Program, Nature Publishing Group; Oncology Nursing Society; Osiris Therapeutics, Inc.; Pall Life Sciences; PDL BioPharma, Inc; Pfizer Inc; Pharmion Corporation; Roche Laboratories; Schering Plough Corporation; Society for Healthcare Epidemiology of America; StemCyte, Inc.; StemSoft Software, Inc.; SuperGen, Inc., Sysmex; Teva Pharmaceutical Industries; The Marrow Foundation; THERAKOS, Inc., University of Colorado Cord Blood Bank, ViaCell, Inc.; Vidacare Corporation; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 32 TC 58 Z9 64 U1 0 U2 6 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 SEP PY 2008 VL 14 IS 9 BP 993 EP 1003 DI 10.1016/j.bbmt.2008.06.009 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 352QT UT WOS:000259513000005 PM 18721762 ER PT J AU Oral, E Beckos, CG Malhi, AS Muratoglu, OK AF Oral, Ebru Beckos, Christine Godleski Malhi, Arnaz S. Muratoglu, Orhun K. TI The effects of high dose irradiation on the cross-linking of vitamin E-blended ultrahigh molecular weight polyethylene SO BIOMATERIALS LA English DT Article DE antioxidant; arthroplasty; cross-linking; gamma irradiation; joint replacement; polyethylene ID ALPHA-TOCOPHEROL; WEAR-RESISTANCE; UHMWPE; RADIATION; OXIDATION AB Vitamin E-stabilized, highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) is a promising oxidation and wear resistant UHMWPE with improved mechanical strength in comparison with the first generation, irradiated and melted UHMWPE. One approach of incorporating vitamin E in UHMWPE is through blending of vitamin E in UHMWPE powder followed by consolidation and radiation cross-linking. However, radiation cross-linking efficiency of UHMWPE decreases in the presence of vitamin E. Therefore an optimum vitamin E concentration and radiation dose level need to be determined to achieve a cross-link density comparable to 100-kGy irradiated and melted UHMWPE, which has shown excellent wear properties in vivo. We investigated the cross-link density and mechanical properties of vitamin E-blended UHMWPEs as a function of vitamin E concentration in the blend and gamma irradiation doses up to 200 kGy. We found that 0.3 wt% vitamin E-blended UHMWPE could not be crosslinked above a cross-link density achieved at a radiation dose of 65 kGy for virgin UHMWPE and 1.0 wt% vitamin E-blended UHMWPE could not be cross-linked above a cross-link density achieved at a radiation dose of 25 kGy for virgin UHMWPE even when the these UHMWPEs were irradiated to a radiation dose of 200 kGy. In addition, higher plasticity at vitamin E concentrations at and above 0.3 wt% indicated that increased chain scissioning may be prevalent. Since the wear resistance of this irradiated UHMWPE would be expected to be low, vitamin E concentrations equal to or above 0.3 wt% are not recommended for subsequent irradiation to achieve a wear resistant cross-linked UHMWPE. The long-term oxidative stability of irradiated blends with low vitamin E concentrations has yet to be studied to determine an optimum between cross-link density and long-term oxidative stability. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM omuratoglu@partners.org FU NIAMS NIH HHS [R01 AR051142, R01 AR051142-02, AR051142, R01 AR051142-01, R01 AR051142-03] NR 15 TC 57 Z9 59 U1 1 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2008 VL 29 IS 26 BP 3557 EP 3560 DI 10.1016/j.biomaterials.2008.05.004 PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 336IH UT WOS:000258357000008 PM 18514813 ER PT J AU Uriel, S Huang, JJ Moya, ML Francis, ME Wang, R Chang, SY Cheng, MH Brey, EM AF Uriel, Shiri Huang, Jung-Ju Moya, Monica L. Francis, Megan E. Wang, Rui Chang, Shu-ying Cheng, Ming-Huei Brey, Eric M. TI The role of adipose protein derived hydrogels in adipogenesis SO BIOMATERIALS LA English DT Article DE preadipocytes; extracellular matrix; basement membrane; adipogenesis; angiogenesis; differentiation ID FIBROBLAST-GROWTH-FACTOR; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; TISSUE FORMATION; STEM-CELLS; IN-VIVO; LAMININ; DIFFERENTIATION; ANGIOGENESIS; LOCALIZATION AB Biomaterials that induce adipogenesis may ultimately serve as alternatives to traditional tissue reconstruction and regeneration techniques. In addition, these materials can provide environments for studying factors that regulate adipogenesis. The present study investigates the potential of adipose-derived matrices to induce adipogenesis in vitro and in vivo. Solutions containing basement membrane proteins and growth factors were extracted from subcutaneous adipose tissue. These extracts could be induced to form gels by either incubating the solutions at 37 degrees C or adjusting the pH to 4.0. The adipose extracts Promoted rapid preadipocyte aggregation and formation of lipid-loaded colonies in vitro. Differentiation on adipose-derived gels was greater than tissue culture dishes and the tumor-derived product Matrigel (TM) (p < 0.05). Significant adipose formation was observed when adipose-derived gels were implanted around a rat epigastric pedicle bundle. Adipose levels in these gels were significantly greater than Matrigel (TM) (p < 0.05). The duration of adipose formation depended on the mechanism for gelling the solutions, with acid gelled matrices having greater adipose levels at 6 weeks than temperature gelled matrices. These adipose-derived hydrogels promote rapid adipogenesis in vitro and in vivo. They may lead to new materials for adipose tissue engineering, and provide an environment for studying cell-matrix interactions in adipogenesis. Published by Elsevier Ltd. C1 [Cheng, Ming-Huei] Chang Gung Univ, Chang Gung Med Coll, Chang Gung Mem Hosp, Dept Plast & Reconstruct Surg,Div Reconstruct Mic, Tao Yuan 333, Kweishan, Taiwan. [Uriel, Shiri; Moya, Monica L.; Francis, Megan E.; Wang, Rui; Brey, Eric M.] IIT, Dept Biomed Engn, Pritzker Inst Biomed Sci & Engn, Chicago, IL 60616 USA. [Francis, Megan E.; Brey, Eric M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Res, Hines, IL 60141 USA. RP Cheng, MH (reprint author), Chang Gung Univ, Chang Gung Med Coll, Chang Gung Mem Hosp, Dept Plast & Reconstruct Surg,Div Reconstruct Mic, 5 Fu Hsing St, Tao Yuan 333, Kweishan, Taiwan. EM minghueicheng@gmail.com NR 36 TC 44 Z9 44 U1 0 U2 7 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 SEP PY 2008 VL 29 IS 27 BP 3712 EP 3719 DI 10.1016/j.biomaterials.2008.05.028 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 337MD UT WOS:000258439300011 PM 18571717 ER PT J AU Altshuler, L Bookheimer, S Townsend, J Proenza, MA Sabb, F Mintz, J Cohen, MS AF Altshuler, Lori Bookheimer, Susan Townsend, Jennifer Proenza, Manuel A. Sabb, Fred Mintz, Jim Cohen, Mark S. TI Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study SO BIPOLAR DISORDERS LA English DT Article DE amygdala; bipolar depression; bipolar disorder; functional magnetic resonance imaging; orbitofrontal cortex ID POSITRON-EMISSION-TOMOGRAPHY; ORBITAL PREFRONTAL CORTEX; SPATIAL WORKING-MEMORY; CEREBRAL-BLOOD-FLOW; GLUCOSE-METABOLISM; HUMAN AMYGDALA; FACIAL EXPRESSIONS; SYMPTOMATIC STATUS; INTERFERENCE TASK; MAJOR DEPRESSION AB Objective: To investigate neural activity in prefrontal cortex and amygdala during bipolar depression. Methods: Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second-level random effects analysis. Results: Random effects between-group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within-group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between-group difference, however, was not significant. Conclusions: Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood-dependent and disease-dependent functional brain abnormalities in bipolar disorder. C1 [Altshuler, Lori; Mintz, Jim] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, W Los Angeles Healthcare Ctr, Los Angeles, CA 90095 USA. [Altshuler, Lori; Bookheimer, Susan; Proenza, Manuel A.; Mintz, Jim; Cohen, Mark S.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Bookheimer, Susan; Townsend, Jennifer; Sabb, Fred; Cohen, Mark S.] Univ Calif Los Angeles, Sch Med, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA USA. RP Altshuler, L (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, W Los Angeles Healthcare Ctr, Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU Stanley Medical Research Institute; National Alliance for Research on Schizophrenia and Depression; National Institute of Mental Health [K24 MH01848]; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Robson Family; Northstar Fund; National Institute of Drug Abuse [DA13054]; National Center for Research Resources [RR12169, RR13642, RR08655] FX The authors gratefully acknowledge the Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, and the National Institute of Mental Health (K24 MH01848) for their financial support of this study. For generous support, the authors also wish to thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, the Ahmanson Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family, Northstar Fund, the National Institute of Drug Abuse grant DA13054 and the National Center for Research Resources grants RR12169, RR13642, and RR08655. NR 81 TC 79 Z9 80 U1 3 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2008 VL 10 IS 6 BP 708 EP 717 DI 10.1111/j.1399-5618.2008.00617.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 337XU UT WOS:000258469600007 PM 18837865 ER PT J AU Gilbert, GE AF Gilbert, Gary E. TI Where does von Willebrand factor go? SO BLOOD LA English DT Editorial Material C1 VA Boston Healthcare Syst, Boston, MA USA. RP Gilbert, GE (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2008 VL 112 IS 5 BP 1549 EP 1550 DI 10.1182/blood-2008-07-167742 PG 2 WC Hematology SC Hematology GA 344VU UT WOS:000258956200003 PM 18725568 ER PT J AU Farrar, JE Nater, M Caywood, E McDevitt, MA Kowalski, J Takemoto, CM Talbot, CC Meltzer, P Esposito, D Beggs, AH Schneider, HE Grabowska, A Ball, SE Niewiadomska, E Sieff, CA Vlachos, A Atsidaftos, E Ellis, SR Lipton, JM Gazda, HT Areci, RJ AF Farrar, Jason E. Nater, Michelle Caywood, Emi McDevitt, Michael A. Kowalski, Jeanne Takemoto, Clifford M. Talbot, C. Conover, Jr. Meltzer, Paul Esposito, Diane Beggs, Alan H. Schneider, Hal E. Grabowska, Agnieszka Ball, Sarah E. Niewiadomska, Edyta Sieff, Colin A. Vlachos, Adrianna Atsidaftos, Eva Ellis, Steven R. Lipton, Jeffrey M. Gazda, Hanna T. Areci, Robert J. TI Abnormalities of the large ribosomal subunit protein, Rp135a, in Diamond-Blackfan anemia SO BLOOD LA English DT Article ID SACCHAROMYCES-CEREVISIAE; RNA INTERFERENCE; GENE; RPS19; CELLS; IDENTIFICATION; EXPRESSION; MUTATIONS; STRESS; S19 AB Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, congenital abnormalities, and cancer predisposition. Small ribosomal subunit genes RPS19, RPS24, and RPS17 are mutated in approximately one-third of patients. We used a candidate gene strategy combining high-resolution genomic mapping and gene expression microarray in the analysis of 2 DBA patients with chromosome 3q deletions to identify RPL35A as a potential DBA gene. Sequence analysis of a cohort of DBA probands confirmed involvement RPL35A in DBA. shRNA inhibition shows that Rp135a is essential for maturation of 28S and 5.8S rRNAs, 60S subunit biogenesis, normal proliferation, and cell survival. Analysis of pre-rRNA processing in primary DBA lymphoblastoid cell lines demonstrated similar alterations of large ribosomal subunit rRNA in both RPL35A-mutated and some RPL35A wild-type patients, suggesting additional large ribosomal subunit gene defects are likely present in some cases of DBA. These data demonstrate that alterations of large ribosomal subunit proteins cause DBA and support the hypothesis that DBA is primarily the result of altered ribosomal function. The results also establish that haploinsufficiency of large ribosomal subunit proteins contributes to bone marrow failure and potentially cancer predisposition. C1 [Farrar, Jason E.; Nater, Michelle; Caywood, Emi; Areci, Robert J.] Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Dept Oncol,Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. [McDevitt, Michael A.] Johns Hopkins Univ, Sch Med, Div Hematol, Dept Med, Baltimore, MD USA. [Kowalski, Jeanne] Johns Hopkins Univ, Sch Med, Div Oncol Biostat, Dept Oncol,Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Takemoto, Clifford M.] Johns Hopkins Univ, Sch Med, Div Pediat Hematol, Dept Pediat, Baltimore, MD USA. [Talbot, C. Conover, Jr.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. [Meltzer, Paul] Natl Human Genome Res Inst, Canc Genet Branch, Natl Inst Hlth, Bethesda, MD USA. [Esposito, Diane] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Beggs, Alan H.; Schneider, Hal E.; Grabowska, Agnieszka; Gazda, Hanna T.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Beggs, Alan H.; Schneider, Hal E.; Grabowska, Agnieszka; Gazda, Hanna T.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Beggs, Alan H.; Sieff, Colin A.; Gazda, Hanna T.] Harvard Univ, Sch Med, Boston, MA USA. [Ball, Sarah E.] Univ London St Georges Hosp, Dept Cellular & Mol Med, London, England. [Niewiadomska, Edyta] Univ Med Sch, Dept Pediat Hematol Oncol, Warsaw, Poland. [Sieff, Colin A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sieff, Colin A.] Childrens Hosp, Div Pediat Hematol, Boston, MA 02115 USA. [Vlachos, Adrianna; Atsidaftos, Eva; Lipton, Jeffrey M.] Schneider Childrens Hosp, Div Hematol Oncol & Stem Cell Transplantat, New Hyde Pk, NY USA. Feinstein Inst Med Res, Manhasset, NY USA. [Ellis, Steven R.] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40292 USA. RP Farrar, JE (reprint author), Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Dept Oncol,Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. OI Farrar, Jason/0000-0003-2148-5839 FU Children's Cancer Foundation; Lyles Parachini Fund; Michael Corb Fund; Michael Garil Leukemia Survivors Program; Pediatric Cancer Foundation; Alex's Lemonade Stand Foundation; ASCO Foundatio; Diamond Blackfan Anemia Foundation; National Institutes of Health [HL079583, HL079571, M01RR0918535, CA120535]; Ruth L. Kirschstein National Research Service Award [CA60441] FX The authors thank the patients and families for their participation in this Study, Drs Gita Massey and Nancy Dunn for the identification of the second deletion patient, Dr Joseph Palumbo for caring for the first deletion patient, and Amanda Black for computational microarray assistance.; This work was supported in part by grants from the Children's Cancer Foundation (R.J.A.), the Lyles Parachini Fund (R.J.A.), the Michael Corb Fund (R.J.A.), file Michael Garil Leukemia Survivors Program (R.J.A.), the Pediatric Cancer Foundation (J.M.L.), Alex's Lemonade Stand Foundation (J.E.F.), ASCO Foundation (J.E.F), the Diamond Blackfan Anemia Foundation (H.T.G.) and National Institutes of Health (NIH) grants HL079583 (S.R.E.), HL079571 (J.M.L.), GCRC Grant M01RR0918535 (J.M.L., A.V., E.A.), and CA120535 (R.J.A.). I.E.F. also received NIH Support under Ruth L. Kirschstein National Research Service Award CA60441. NR 52 TC 120 Z9 123 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2008 VL 112 IS 5 BP 1582 EP 1592 DI 10.1182/blood-2008-02-140012 PG 11 WC Hematology SC Hematology GA 344VU UT WOS:000258956200011 PM 18535205 ER PT J AU Gerstner, ER Abrey, LE Schiff, D Ferreri, AJM Lister, A Montoto, S Tsang, R Thiel, E Graus, F Behringer, D Illerhaus, G Weaver, S Wen, P Voloschin, A Harris, NL Batchelor, TT AF Gerstner, Elizabeth R. Abrey, Lauren E. Schiff, David Ferreri, Andres J. M. Lister, Andrew Montoto, Silvia Tsang, Richard Thiel, Eckhard Graus, Francesc Behringer, Dirk Illerhaus, Gerald Weaver, Susan Wen, Patrick Voloschin, Alfredo Harris, Nancy Lee Batchelor, Tracy T. TI CNS Hodgkin lymphoma SO BLOOD LA English DT Article ID DISEASE; INVOLVEMENT AB Central nervous system (CNS) involvement by Hodgkin lymphoma (HL) is rare. As a result, there is limited guidance for clinicians on how to manage these patients. Detailed information was collected on 16 patients, the largest number to date, with meningeal or parenchymal CNS-HL confirmed by histopathology (15) or CSF (1). Eight patients presented with CNS-HL at diagnosis, 2 of whom had isolated CNS disease, while 8 patients developed CNS-HL at relapse. Patients received a range of treatments including surgery or radiation alone, radiation with chemotherapy, or chemotherapy alone. Median overall survival for all 16 patients was 60.9 months from first diagnosis of HL (systemic or CNS) and 43.8 months from diagnosis of CNS-HL. Although a majority of patients have died, long-term survival is possible in patients who achieve a complete response to treatment, particularly those who present with CNS involvement or involvement of the CNS is the sole site of relapsed disease. C1 [Gerstner, Elizabeth R.; Harris, Nancy Lee; Batchelor, Tracy T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Schiff, David] Univ Virginia, Charlottesville, VA USA. [Ferreri, Andres J. M.] Hosp San Raffaele, Inst Sci, I-20132 Milan, Italy. [Lister, Andrew; Montoto, Silvia] St Bartholomews Hosp, London, England. [Tsang, Richard] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Thiel, Eckhard] Charite Campus Benjamin Franklin, Berlin, Germany. [Graus, Francesc] Hosp Clin Barcelona, Barcelona, Spain. [Behringer, Dirk] Augusta Kranken Anstalt, Bochum, Germany. [Illerhaus, Gerald] Univ Hosp, Freiburg, Germany. [Weaver, Susan] Albany Med Ctr, Albany, NY 12208 USA. [Wen, Patrick] Dana Farber Canc Inst, Boston, MA USA. [Voloschin, Alfredo] Med Coll Georgia, Augusta, GA 30912 USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Ferreri, Andres Jose Maria/A-6662-2013 OI Ferreri, Andres Jose Maria/0000-0001-9606-6124 FU NCI NIH HHS [R13 CA124293] NR 11 TC 31 Z9 33 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2008 VL 112 IS 5 BP 1658 EP 1661 DI 10.1182/blood-2008-04-151563 PG 4 WC Hematology SC Hematology GA 344VU UT WOS:000258956200020 PM 18591379 ER PT J AU Peng, BW Ye, PQ Blazar, BR Freeman, GJ Rawlings, DJ Ochs, HD Miao, CH AF Peng, Baowei Ye, Peiqing Blazar, Bruce R. Freeman, Gordon J. Rawlings, David J. Ochs, Hans D. Miao, Carol H. TI Transient blockade of the inducible costimulator pathway generates long-term tolerance to factor VIII after nonviral gene transfer into hemophilia A mice SO BLOOD LA English DT Article ID REGULATORY T-CELLS; COAGULATION-FACTOR VIII; NAKED DNA TRANSFER; IN-VIVO; FACTOR-IX; B-CELLS; ALLOGRAFT-REJECTION; ADENOVIRAL VECTORS; TRANSGENE PRODUCT; IMMUNE-RESPONSE AB Formation of inhibitory antibodies is a common problem encountered in clinical treatment for hemophilia. Human factor VIII(hFVIII) plasmid genetherapy in hemophilia A mice also leads to strong humoral responses. We demonstrate that short-term therapy with an anti-ICOS monoclonal antibody to transiently block the inducible costimulator/inducible costimulator ligand (ICOS/ICOSL) signaling pathway led to sustained tolerance to hFVIII in hFVIII plasmid-treated hemophilia A mice and allowed persistent, high-level FVIII functional activity (100%-300% of normal). Anti-ICOS treatment resulted in depletion of ICOS(+)CD4(+) T cells and activation of CD25(+)Foxp3(+) Tregs in the peripheral blood, spleen, and lymph nodes. CD4(+) T cells from anti-ICOS-treated mice did not proliferate in response to hFVIII stimulation and produced high levels of regulatory cytokines, including interleukin-10 and transforming growth factor-P. Moreover, CD4(+)CD25(+) Tregs from tolerized mice adoptively transferred dominant tolerance in syngeneic hFVIII plasmid-treated hemophilia A mice and reduced the production of antibodies against FVIII. Anti-ICOS-treated mice tolerized to hFVIII generated normal primary and secondary antibody responses after immunization with the T-dependent antigen, bacteriophage Phi x 174, indicating maintenance of immune competency. Our data indicate that transient anti-ICOS monoclonal antibody treatment represents a novel single-agent immunomodulatory strategy to overcome the immune responses against transgene product after gene therapy. C1 [Peng, Baowei; Ye, Peiqing; Rawlings, David J.; Ochs, Hans D.; Miao, Carol H.] Seattle Childrens Hosp Res Inst, Dept Pediat, Seattle, WA USA. [Peng, Baowei; Ye, Peiqing; Rawlings, David J.; Ochs, Hans D.; Miao, Carol H.] Univ Washington, Seattle, WA 98195 USA. [Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [Blazar, Bruce R.] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Peng, BW (reprint author), Seattle Childrens Hosp Res Inst, Dept Pediat, Seattle, WA USA. FU National Hemophilia Foundation; NIH [R01 HL069049, HL82600, P01 A 156299] FX C.H.M. was supported by a Career Development Grant from the National Hemophilia Foundation and NIH grants R01 HL069049 and HL82600. G.J.F and B.R.B. were supported by NIH grant P01 A 156299. NR 72 TC 38 Z9 38 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2008 VL 112 IS 5 BP 1662 EP 1672 DI 10.1182/blood-2008-01-128413 PG 11 WC Hematology SC Hematology GA 344VU UT WOS:000258956200021 PM 18574023 ER PT J AU Cifuni, SM Wagner, DD Bergmeier, W AF Cifuni, Stephen M. Wagner, Denisa D. Bergmeier, Wolfgang TI CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alpha IIb beta 3 in platelets SO BLOOD LA English DT Article ID FIBRINOGEN RECEPTOR ACTIVATION; INTEGRIN ACTIVATION; THROMBIN RECEPTOR; P2Y(12) RECEPTOR; LAD-III; RAP1; GTPASE; SECRETION; ADHESION; MICE AB Second messenger-mediated inside-out activation of integrin (alpha IIb beta 3) is a key step in platelet aggregation. We recently showed strongly impaired but not absent (alpha IIb beta 3-mediated aggregation of CalDAG-GEFI-deficient platelets activated with various agonists. Here we further evaluated the roles of CalDAG-GEFI and protein kinase C (PKC) for alpha IIb beta 3 activation in platelets activated with a PAR4 receptor-specific agonist, GYPGKF (PAR4p). Compared with wild-type controls, platelets treated with the PKC inhibitor Ro31-8220 or CalDAG-GEFI-deficient platelets showed a marked defect in aggregation at low (< 1mM PAR4p) but not high PAR4p concentrations. Blocking of PKC function in CalDAG-GEFI-deficient platelets, however, strongly decreased aggregation at all PAR4p concentrations, demonstrating that CaIDAG-GEF1 and PKC represent separate, but synergizing, pathways important for alpha IIb beta 3 activation. PAR4p-induced aggregation in the absence of CalDAG-GEFI required cosignaling through the G(xi-coupled receptor for ADP, P2Y12. Independent roles for CalDAG-GEFI and PKC/G alpha i signaling were also observed for PAR4p-induced activation of the small GTPase Rap1, with CalDAG-GEFI mediating the rapid but reversible activation of this small GTPase. In summary, our study identifies CalDAG-GEFI and PKC as independent pathways leading to Rap1 and alpha IIb beta 3 activation in mouse platelets activated through the PAR4 receptor. C1 [Cifuni, Stephen M.; Wagner, Denisa D.; Bergmeier, Wolfgang] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Bergmeier, Wolfgang] Thomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19107 USA. [Bergmeier, Wolfgang] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA. RP Cifuni, SM (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. FU Scientist Development [0630044N]; American Heart Association; National Heart, Lung, and Blood Institute of the National Institutes of Health [R37 HL41002, P01 HL56949] FX The authors thank Crystal Piffath for her excellent technical support throughout the study, Janos Polgar for help with the serotonin release assay and helpful discussions, and Jill Crittenden and Ann Graybiel for providing the mice and for helpful discussions.; This work was supported by a Scientist Development Grant 0630044N from the American Heart Association (W.B.) and the National Heart, Lung, and Blood Institute of the National Institutes of Health (grants R37 HL41002 and P01 HL56949; D.D.W.) NR 47 TC 66 Z9 68 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2008 VL 112 IS 5 BP 1696 EP 1703 DI 10.1182/blood-2008-02-139733 PG 8 WC Hematology SC Hematology GA 344VU UT WOS:000258956200025 PM 18544684 ER PT J AU Rao, R Fiskus, W Yang, YH Lee, P Joshi, R Fernandez, P Mandawat, A Atadja, P Bradner, JE Bhalla, K AF Rao, Rekha Fiskus, Warren Yang, Yonghua Lee, Pearl Joshi, Rajeshree Fernandez, Pravina Mandawat, Aditya Atadja, Peter Bradner, James E. Bhalla, Kapil TI HDAC6 inhibition enhances 17-AAG-mediated abrogation of hsp90 chaperone function in human leukemia cells SO BLOOD LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; MULTIPLE-MYELOMA; HYDROXAMIC ACID; DOWN-REGULATION; CANCER CELLS; BCR-ABL; PROTEIN; ACETYLATION; HEAT-SHOCK-PROTEIN-90; CONFORMATION AB Histone deacetylase 6 (HDAC6) is a heat shock protein 90 (hsp90) deacetylase. Treatment with pan-HDAC inhibitors or depletion of HDAC6 by siRNA induces hyperacetylation and inhibits ATP binding and chaperone function of hsp90. Treatment with 17-allylamino-demothoxy geldanamycin (17-AAG) also inhibits ATP binding and chaperone function of hsp90, resulting in polyubiquitylation and proteasomal degradation of hsp90 client proteins. In this study, we determined the effect of hsp90 hyperacetylation on the anti-hsp90 and antileukemia activity of 17-AAG. Hyperacetylation of hsp90 increased its binding to 17-AAG, as well as enhanced 17-AAG-mediated attenuation of ATIP and the cochaperone p23 binding to hsp90. Notably, treatment with 17-AAG alone also reduced HDAC6 binding to hsp90 and induced hyperacetylation of hsp90. This promoted the proteasomal degradation of HDAC6. Cotreatment with 17-AAG and siRNA to HDAC6 induced more inhibition of hsp90 chaperone function and depletion of BCR-ABL and c-Raf than treatment with either agent alone. In addition, cotreatment with 17-AAG and tubacin augmented the loss of survival of K562 cells and viability of primary acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) samples. These findings demonstrate that HDAC6 is an hsp90 client protein and hyperacetylation of hsp90 augments the anti-hsp90 and anti-leukemia effects of 17-AAG. C1 [Rao, Rekha; Fiskus, Warren; Yang, Yonghua; Lee, Pearl; Joshi, Rajeshree; Fernandez, Pravina; Mandawat, Aditya; Bhalla, Kapil] Med Coll Georgia, Ctr Canc, Augusta, GA 30912 USA. [Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Atadja, Peter] Novartis Inst Biomed Res, Cambridge, MA USA. RP Bhalla, K (reprint author), Med Coll Georgia, Ctr Canc, 1120 15th St,CN2101A, Augusta, GA 30912 USA. EM kbhalla@mcg.edu RI Fernandez, Pravina/H-6279-2011 NR 44 TC 106 Z9 113 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2008 VL 112 IS 5 BP 1886 EP 1893 DI 10.1182/blood-2008-03-143644 PG 8 WC Hematology SC Hematology GA 344VU UT WOS:000258956200046 PM 18591380 ER PT J AU Rassenti, LZ Jain, S Keating, MJ Wierda, WG Grever, MR Byrd, JC Kay, NE Brown, JR Gribben, JG Neuberg, DS He, F Greaves, AW Rai, KR Kipps, TJ AF Rassenti, Laura Z. Jain, Sonia Keating, Michael J. Wierda, William G. Grever, Michael R. Byrd, John C. Kay, Neil E. Brown, Jennifer R. Gribben, John G. Neuberg, Donna S. He, Feng Greaves, Andrew W. Rai, Kanti R. Kipps, Thomas J. TI Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia SO BLOOD LA English DT Article ID B-CELL-RECEPTOR; TYROSINE KINASE ACTIVATION; VARIABLE-REGION MUTATIONS; V-H GENES; PROGNOSTIC-FACTOR; CLINICAL-SIGNIFICANCE; FLOW-CYTOMETRY; ZETA-CHAIN; EXPRESSION; DIAGNOSIS AB Leukemia-cell expression of ZAP-70, CD38, or unmutated immunoglobulin heavy chain variable region genes (U-IGHV) each is associated with aggressive disease in patients with chronic lymphocytic leukemia (CLL). To assess the relative strength of each marker, we defined thresholds for designating a case as positive for CD38 or ZAP-70 in a test cohort of 307 patients and used these data-defined criteria to stratify patients in an independent cohort of 705 patients. Multivariable analysis revealed that ZAP-70 was the strongest risk factor. Knowledge of the IGHV mutation status or CD38 did not improve our ability to predict the time to first treatment except for ZAP-70-negative cases, which could be segregated into 2 groups of intermediate-risk or low-risk disease based on whether they expressed unmutated or mutated IGHV. ZAP-70 maintained its high relative prognostic value for the subset of patients with early-stage, asymptomatic disease, including patients evaluated within 1 year of diagnosis. Although it is premature to recommend therapy based on these risk factors, patients with ZAP-70-positive CLL cells should be monitored closely for disease progression as they have a median time from diagnosis to requiring initial therapy by standard criteria of approximately 3 years. C1 [Rassenti, Laura Z.; Jain, Sonia; Keating, Michael J.; Wierda, William G.; Grever, Michael R.; Byrd, John C.; Kay, Neil E.; Brown, Jennifer R.; Gribben, John G.; Neuberg, Donna S.; He, Feng; Greaves, Andrew W.; Rai, Kanti R.; Kipps, Thomas J.] Chron Lymphocyt Leukemia Res Consortium, La Jolla, CA USA. [Rassenti, Laura Z.; Greaves, Andrew W.; Kipps, Thomas J.] Univ Calif San Diego, Dept Med, Div Hematol Oncol, San Diego, CA 92103 USA. [Rassenti, Laura Z.; Greaves, Andrew W.; Kipps, Thomas J.] Moores UCSD Canc Ctr, La Jolla, CA USA. [Jain, Sonia; He, Feng] Univ Calif San Diego, Div Biostat & Bioinformat, San Diego, CA 92103 USA. [Keating, Michael J.; Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Grever, Michael R.; Byrd, John C.] Ohio State Univ, James Canc Inst, Columbus, OH 43210 USA. [Kay, Neil E.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Brown, Jennifer R.; Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gribben, John G.] Barts & London Queen Marys Sch Med & Dent, London, England. [Rai, Kanti R.] Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. RP Kipps, TJ (reprint author), Moores Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM tkipps@ucsd.edu FU National Institutes of Health (Bethesda, MD) [PO1-CA81534]; Chronic Lymphocytic Leukemia Research Consortium; Leukemia & Lymphoma Society of America FX This work was supported by a grant (PO1-CA81534) from the National Institutes of Health (Bethesda, MD) to the Chronic Lymphocytic Leukemia Research Consortium. J.C.B. is a clinical scholar of the Leukemia & Lymphoma Society of America. NR 48 TC 168 Z9 175 U1 0 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2008 VL 112 IS 5 BP 1923 EP 1930 DI 10.1182/blood-2007-05-092882 PG 8 WC Hematology SC Hematology GA 344VU UT WOS:000258956200050 PM 18577710 ER PT J AU Tam, WF Gu, TL Chen, J Lee, BH Bullinger, L Frohling, S Wang, A Monti, S Golub, TR Gilliland, DG AF Tam, Winnie F. Gu, Ting-Lei Chen, Jing Lee, Benjamin H. Bullinger, Lars Froehling, Stefan Wang, Andrew Monti, Stefano Golub, Todd R. Gilliland, D. Gary TI Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; INTERNAL TANDEM DUPLICATION; LOOP-HELIX PROTEIN; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOMONOCYTIC LEUKEMIA; HUMAN CD34(+) CELLS; BETA-R FUSION; GENE-EXPRESSION; DNA-BINDING AB Oncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGF beta R, and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways. To identify the critical target genes required for transformation in hematopoietic cells, we used a comparative gene expression strategy in which selective small molecules were applied to 32Dcl3 cells that had been transformed to factor-independent growth by these respective oncogenic alleles. We identified inhibitor of DNA binding 1 (Id1), a gene involved in development, cell cycle, and tumorigenesis, as a common target of these oncogenic kinases. These findings were prospectively confirmed in cell lines and primary bone marrow cells engineered to express the respective tyrosine kinase alleles and were also confirmed in vivo in murine models of disease. Moreover, human AML cell lines Molm-14 and K562, which express the FLT3-ITD and BCR-ABL tyrosine kinases, respectively, showed high levels of Id1 expression. Antisense and siRNA based knockdown of Id1-inhibited growth of these cells associated with increased p27(Kip1) expression and increased sensitivity to Trail-induced apoptosis. These findings indicate that Id1 is an important target of constitutively activated tyrosine kinases and may be a therapeutic target for leukemias associated with oncogenic tyrosine kinases. C1 [Tam, Winnie F.; Gu, Ting-Lei; Lee, Benjamin H.; Froehling, Stefan; Gilliland, D. Gary] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Gu, Ting-Lei; Chen, Jing; Lee, Benjamin H.; Wang, Andrew; Golub, Todd R.; Gilliland, D. Gary] Harvard Univ, Sch Med, Boston, MA USA. [Tam, Winnie F.; Chen, Jing; Golub, Todd R.; Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Lee, Benjamin H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Bullinger, Lars] Univ Hosp, Dept Internal Med 3, Ulm, Germany. [Monti, Stefano] Harvard Ctr Genome Res, Cambridge, MA USA. [Monti, Stefano] MIT, Broad Inst, Cambridge, MA 02139 USA. [Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Div Hematol, Childrens Hosp Res Bldg,1 Blackfan Circle,5th Flo, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu RI Wang, Andrew /F-9719-2011; OI Monti, Stefano/0000-0002-9376-0660 FU Leukemia & Lymphoma Society; National Institutes of Health [CA66996, DK50654] FX We gratefully acknowledge valuable discussions with members of the Gilliland laboratory.; This work was supported in part by the Leukemia & Lymphoma Society (D.G.G.), and National Institutes of Health grants CA66996 and DK50654 (D.G.G.). D.G.G. is an investigator of the Howard Hughes Medical Institute. NR 73 TC 29 Z9 29 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2008 VL 112 IS 5 BP 1981 EP 1992 DI 10.1182/blood-2007-07-103010 PG 12 WC Hematology SC Hematology GA 344VU UT WOS:000258956200056 PM 18559972 ER PT J AU Haspot, F Fehr, T Gibbons, C Zhao, G Hogan, T Honjo, T Freeman, GJ Sykes, M AF Haspot, Fabienne Fehr, Thomas Gibbons, Carrie Zhao, Guiling Hogan, Timothy Honjo, Tasuku Freeman, Gordon J. Sykes, Megan TI Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MEDIATED ALLORESISTANCE; COSTIMULATORY BLOCKADE; ALLOGRAFT-REJECTION; MONOCLONAL-ANTIBODY; DENDRITIC CELLS; LYMPHOCYTES-T; IN-VIVO; ACTIVATION; EXPRESSION AB Although interaction between programmed death-1 (PID-11) and the ligand PD-L1 has been shown to mediate CD8 cell exhaustion in the setting of chronic infection or the absence of CD4 help, a role for this pathway in attenuating early alloreactive CD8 cell responses has not been identified. We demonstrate that the PD-1/PD-L1 pathway is needed to rapidly tolerize alloreactive CD8 cells in a model that requires Cl cells and culminates in CD8 cell deletion. This protocol involves allogeneic bone marrow transplantation (BMT) following conditioning with low-dose total body irradiation and anti-CD154 antibody. Tolerized donor-reactive T-cell receptor transgenic CD8 cells are shown to be in an abortive activation state prior to their deletion, showing early and prolonged expression of activation markers (compared with rejecting CD8 cells) while being functionally silenced by day 4 after transplantation. Although both tolerized and rejecting alloreactive Cl cells up-regulate PD-1, CD8 cell tolerance is dependent on the PD-1/PD-L1 pathway. In contrast, CD4 cells are tolerized independently of this pathway following BMT with anti-CD154. These studies demonstrate a dichotomy between the requirements for CD4 and CD8 tolerance and identify a role for PD-1 in the rapid tolerization of an alloreactive T-cell population via a deletional mechanism. C1 [Haspot, Fabienne; Fehr, Thomas; Gibbons, Carrie; Zhao, Guiling; Hogan, Timothy; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Honjo, Tasuku] Kyoto Univ Yoshida Konoe, Fac Med, Dept Med Chem, Kyoto, Japan. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E Bldg 149-5102,l3th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu RI Honjo, Tasuku/N-4470-2016 FU NHLBI NIH HHS [R01 HL049915, R01 HL49915]; NIAID NIH HHS [P01 AI056299, P01AI56299] NR 32 TC 41 Z9 43 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2008 VL 112 IS 5 BP 2149 EP 2155 DI 10.1182/blood-2007-12-127449 PG 7 WC Hematology SC Hematology GA 344VU UT WOS:000258956200077 PM 18577709 ER PT J AU Wiren, KM Sernirale, AA Zhang, XW Woo, A Tornmasini, SM Price, C Schaffler, MB Jepsen, KJ AF Wiren, Kristine M. Sernirale, Anthony A. Zhang, Xiao-Wei Woo, Adrian Tornmasini, Steven M. Price, Christopher Schaffler, Mitchell B. Jepsen, Karl J. TI Targeting of androgen receptor in bone reveals a lack of androgen anabolic action and inhibition of osteogenesis - A model for compartment-specific androgen action in the skeleton SO BONE LA English DT Article DE androgen receptor; osteocyte; bone histomorphometry; biomechanics; dual energy X-ray absorptiometry ID MINERAL DENSITY; ELDERLY-MEN; MALE-MICE; DIFFERENTIATED OSTEOBLASTS; OSTEOSARCOMA CELLS; GENDER DIFFERENCES; TESTOSTERONE GEL; PROSTATE-CANCER; SEX-DIFFERENCES; I COLLAGEN AB Androgens are anabolic hormones that affect many tissues, including bone. However, an anabolic effect of androgen treatment oil bone in eugonadal subjects has not been observed and clinical trials have been disappointing. The androgen receptor(AR) mediates biological responses to androgens. In bone tissue, both AR and the estrogen receptor (ER) are expressed. Since androgens can be converted into estrogen, the specific role of the AR in maintenance of skeletal homoeostasis remains controversial. The goal of this study was to use skeletally targeted overexpression of AR in differentiated osteoblasts as a means of elucidating the specific role(s) for AR transactivation in the mature bone compartment. Transgenic mice overexpressing AR under the control of the 2.3-kb alpha 1(1)-collagen promoter fragment showed no difference in body composition, testosterone, or 17 beta-estradiol levels. However, transgenic males have reduced serum osteocalcin, CTx and TRAPC5b levels, and a bone phenotype was observed. In cortical bone, high-resolution micro-computed tomography revealed no difference in periosteal perimeter but a significant reduction in cortical bone area due loan enlarged marrow cavity. Endocortical bone formation rate was also significantly inhibited. Biomechanical analyses showed decreased whole bone strength and quality, with significant reductions in all parameters tested. Trabecular morphology was altered, with increased bone volume comprised of more trabeculae that were closer together but not thicker. Expression of genes involved in bone formation and bone resorption was significantly reduced. The consequences of androgen action are compartment-specific; anabolic effects are exhibited exclusively at periosteal Surfaces, but in mature osteoblasts androgens inhibited osteogenesis with detrimental effects oil matrix quality, bone fragility and whole bone strength. Thus, the present data demonstrate that enhanced androgen signaling targeted to bone results in low bone turnover and inhibition of bone formation by differentiated osteoblasts. These results indicate that direct androgen action in mature osteoblasts is not anabolic, and raise concerns regarding anabolic steroid abuse in the developing skeleton or high-close treatment in eugonadal adults. Published by Elsevier Inc. C1 [Wiren, Kristine M.; Sernirale, Anthony A.; Zhang, Xiao-Wei] Portland VA Med Ctr, Bone & Mineral Res Unit, Portland, OR 97239 USA. [Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Wiren, Kristine M.; Sernirale, Anthony A.; Zhang, Xiao-Wei] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Woo, Adrian; Tornmasini, Steven M.; Price, Christopher; Schaffler, Mitchell B.; Jepsen, Karl J.] Mt Sinai Sch Med, Dept Orthopaed, New York, NY USA. RP Wiren, KM (reprint author), Portland VA Med Ctr, Bone & Mineral Res Unit, P3-R&D39,3710 SW Vet Hosp Rd, Portland, OR 97239 USA. EM wirenk@ohsu.edu OI Wiren, Kristine/0000-0002-6159-4450 FU United States Army Research Acquisition Activity [W81XWH-05-1-0086 (KMW)]; National Institute of Diabetes, Digestive and Kidney Disease [R01 DK067541 (KMW)] FX The authors would like to thank Dr. David Rowe (University of Connecticut Health Center) for providing the plasmids containing the rat col alpha 1 promoter sequences, Dr. Shutsung Liao (University of Chicago) for the rat AR cDNA, Dr. Robert Klein (Oregon Health and Science University) for the use of equipment for DXA analysis, Drs. Russell Turner and Urszula Iwaniec (Oregon State University) for the careful reading of the manuscript, and Joel Hashimoto for the excellent technical assistance. This material is based upon work Supported by grants from the United States Army Research Acquisition Activity Award No. W81XWH-05-1-0086 (KMW) and the National Institute of Diabetes, Digestive and Kidney Disease R01 DK067541 (KMW). The information contained in this publication does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. All work was performed in facilities provided by the Department of Veterans Affairs. NR 69 TC 36 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD SEP PY 2008 VL 43 IS 3 BP 440 EP 451 DI 10.1016/j.bone.2008.04.026 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344UW UT WOS:000258953800005 PM 18595795 ER PT J AU Ting, DT Spitzer, TR Chaudhary, A Muzikansky, A Colby, C Power, K McAfee, S Ballen, K Attar, E Saidman, SL Preffer, F Sykes, M Dey, BR AF Ting, D. T. Spitzer, T. R. Chaudhary, A. Muzikansky, A. Colby, C. Power, K. McAfee, S. Ballen, K. Attar, E. Saidman, S. L. Preffer, F. Sykes, M. Dey, B. R. TI Clinical outcomes of late rather than early full-donor chimerism in patients with advanced lymphomas receiving nonmyeloablative allogeneic hematopoietic SCT SO BONE MARROW TRANSPLANTATION LA English DT Article DE chimerism; lymphoma; DLI; hematopoietic SCT ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; NON-HODGKINS-LYMPHOMA; HEMATOLOGIC MALIGNANCIES; MYELOABLATIVE THERAPY; DELAYED INFUSION; MIXED CHIMERISM; T-CELLS; LEUKEMIA AB Allogeneic hematopoietic SCT (HSCT) can ideally provide long-term remission in advanced lymphoma patients by capturing a graft-vs-tumor (GVT) effect. On the basis of a murine model, we attempted to optimize a GVT effect through nonmyeloablative therapy and HLA-matched related donor HSCT with intentional induction of mixed chimerism followed by prophylactic donor lymphocyte infusion. A total of 26 advanced lymphoma patients were separated into an early and late full-donor chimerism (FDC) group using a median of 45 days post-HSCT as the de. ning point for FDC. Upon generating these groups, analysis by Student's t-test demonstrated that they were statistically distinct in time to develop FDC (P<0.01). There was a trend toward improved CR rates in the late group relative to the early group (62 vs 31%; P = 0.12). A trend toward improved progression-free survival at 5 years was also observed in the late compared to the early group by Kaplan-Meier analysis (38 vs 8%; P = 0.081). However, this did not correlate to a significant overall survival benefit. In conclusion, these data support the observation from our mouse models that the most potent GVT effect occurs in mixed chimeras with late chimerism conversion. C1 [Spitzer, T. R.; Chaudhary, A.; Colby, C.; McAfee, S.; Ballen, K.; Attar, E.; Dey, B. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplantat Program, Boston, MA 02114 USA. [Ting, D. T.; Spitzer, T. R.; McAfee, S.; Ballen, K.; Attar, E.; Dey, B. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Muzikansky, A.; Preffer, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02114 USA. [Power, K.; Saidman, S. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Sykes, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Dey, BR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplantat Program, MGH E00-1-118,Zero Emerson Pl, Boston, MA 02114 USA. EM BDey@partners.org OI Ting, David/0000-0002-3261-2322 NR 36 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 2008 VL 42 IS 5 BP 329 EP 335 DI 10.1038/bmt.2008.167 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 346II UT WOS:000259061600004 PM 18587439 ER PT J AU Thakkar, KN Polli, FE Joseph, RM Tuch, DS Hadjikhani, N Barton, JJS Manoach, DS AF Thakkar, Katharine N. Polli, Frida E. Joseph, Robert M. Tuch, David S. Hadjikhani, Nouchine Barton, Jason J. S. Manoach, Dara S. TI Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD) SO BRAIN LA English DT Review DE autism; anterior cingulate cortex; response monitoring; functional MRI; diffusion tensor imaging ID OBSESSIVE-COMPULSIVE DISORDER; EVENT-RELATED FMRI; HIGH-FUNCTIONING AUTISM; EMOTIONAL PROCESSING DISORDER; ERROR-RELATED NEGATIVITY; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; ANTISACCADE TASK; ANTI-SACCADES; PRO-SACCADES AB Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing factors to autistic disorders. We investigated whether ACC structure and function during response monitoring were associated with repetitive behaviour in ASD. We compared ACC activation to correct and erroneous antisaccades using rapid presentation event-related functional MRI in 14 control and ten ASD participants. Because response monitoring is the product of coordinated activity in ACC networks, we also examined the microstructural integrity of the white matter (WM) underlying this brain region using diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) in 12 control and 12 adult ASD participants. ACC activation and FA were examined in relation to Autism Diagnostic Interview-Revised ratings of restricted and repetitive behaviour. Relative to controls, ASD participants: (i) made more antisaccade errors and responded more quickly on correct trials; (ii) showed reduced discrimination between error and correct responses in rostral ACC (rACC), which was primarily due to (iii) abnormally increased activation on correct trials and (iv) showed reduced FA in WM underlying ACC. Finally, in ASD (v) increased activation on correct trials and reduced FA in rACC WM were related to higher ratings of repetitive behaviour. These findings demonstrate functional and structural abnormalities of the ACC in ASD that may contribute to repetitive behaviour. rACC activity following errors is thought to reflect affective appraisal of the error. Thus, the hyperactive rACC response to correct trials can be interpreted as a misleading affective signal that something is awry, which may trigger repetitive attempts at correction. Another possible consequence of reduced affective discrimination between error and correct responses is that it might interfere with the reinforcement of responses that optimize outcomes. Furthermore, dysconnection of the ACC, as suggested by reduced FA, to regions involved in behavioural control might impair on-line modulations of response speed to optimize performance (i.e. speed-accuracy trade-off) and increase error likelihood. These findings suggest that in ASD, structural and functional abnormalities of the ACC compromise response monitoring and thereby contribute to behaviour that is rigid and repetitive rather than flexible and responsive to contingencies. Illuminating the mechanisms and clinical significance of abnormal response monitoring in ASD represents a fruitful avenue for further research. C1 [Thakkar, Katharine N.; Polli, Frida E.; Manoach, Dara S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02215 USA. [Polli, Frida E.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Joseph, Robert M.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Tuch, David S.; Hadjikhani, Nouchine] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Tuch, David S.; Hadjikhani, Nouchine; Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Barton, Jason J. S.] Univ British Columbia, Dept Neurol, Vancouver, BC V5Z 1M9, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada. RP Manoach, DS (reprint author), 149 13th St,Room 2608, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008; Barton, Jason/A-6362-2012 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU National Institute for Mental Health [R01 MH67720]; Mental Illness Neuroscience Discovery (MIND) Institute [DOE DE-FG02-99ER62764]; National Center for Research Resources [P41RR14075]; National Institute for Mental Health NRSA [MH72120] FX The authors wish to thank Mark Vangel for statistical consultation, Robert Levy, Kim Ono, Christopher Sherman and Jeremy Young for help with manuscript preparation, and Matt Cain and Jay Edelman for technical assistance. Some of these data were presented at the annual meeting of the Society for Neuroscience in Washington, DC, in November, 2005. This study was supported by National Institute for Mental Health [R01 MH67720 (D. S. M.); MH72120 (F. E. P.)]; Mental Illness Neuroscience Discovery (MIND) Institute (DOE DE-FG02-99ER62764): The National Center for Research Resources (P41RR14075). Funding to pay the Open Access publication charges for this article was provided by the National Institute for Mental Health NRSA MH72120. NR 116 TC 159 Z9 161 U1 18 U2 40 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2008 VL 131 BP 2464 EP 2478 DI 10.1093/brain/awn099 PN 9 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 343OA UT WOS:000258862200021 PM 18550622 ER PT J AU Rusby, JE Kirstein, LJ Brachtel, EF Michaelson, JS Koerner, FC Smith, BL AF Rusby, Jennifer E. Kirstein, Laurie J. Brachtel, Elena F. Michaelson, James S. Koerner, Frederick C. Smith, Barbara L. TI Nipple-sparing mastectomy: Lessons from ex vivo procedures SO BREAST JOURNAL LA English DT Article DE ex vivo; nipple-sparing mastectomy; surgical technique ID AREOLA COMPLEX INVOLVEMENT; BREAST-CANCER PATIENTS; SUBCUTANEOUS MASTECTOMY; RECONSTRUCTION; RISK AB Moderate size series have reported successful nipple-sparing mastectomy using a variety of surgical techniques. This study aimed to understand which aspects of these techniques are safe, necessary, and successful. Eight skin-sacrificing mastectomy specimens were used as ex vivo models of nipple-sparing mastectomy. After inking the resection margins of the specimen, the skin ellipse was elevated in the subcutaneous plane using a scalpel. The retroareolar breast tissue was taken as a margin specimen. The nipple was inverted and the nipple core removed. The hollowed-out nipple remnant (which would have remained with the patient in a true nipple-sparing mastectomy) was submitted for confirmatory histopathologic analysis. Precise identification of the duct margin directly beneath the nipple proved difficult once the duct bundle had been divided. Successful retroareolar margin identification was achieved by grasping the duct bundle with atraumatic forceps as soon as it became exposed. A cut made below and above the forceps resulted in a full cross-section of the duct bundle. Nipple core tissue was difficult to excise in one piece and cannot be oriented, thus complete evaluation of the specimen required examination of multiple levels. Histologic artifacts caused by freezing may be present in frozen sections of nipple core and retroareolar margin specimens; the impact of such changes must be considered when developing institutional protocols for this procedure. Evaluation of the hollowed-out nipple revealed that the inverted nipple must be substantially thinned to remove all ducts. Modification of technique resulted in more complete excision of duct tissue. This series of ex vivo procedures provides information that can be used to modify surgical and pathologic techniques for nipple-sparing mastectomy. When performing nipple-sparing mastectomy for breast cancer, these measures may be advisable as complements to careful patient selection. C1 [Rusby, Jennifer E.; Kirstein, Laurie J.; Michaelson, James S.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Brachtel, Elena F.; Koerner, Frederick C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA. EM blsmith1@partners.org NR 20 TC 21 Z9 22 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X EI 1524-4741 J9 BREAST J JI Breast J. PD SEP-OCT PY 2008 VL 14 IS 5 BP 464 EP 470 DI 10.1111/j.1524-4741.2008.00623.x PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 345EL UT WOS:000258978800009 PM 18821932 ER PT J AU Eikermann, M Zaremba, S Malhotra, A Jordan, AS Rosow, C Chamberlin, NL AF Eikermann, M. Zaremba, S. Malhotra, A. Jordan, A. S. Rosow, C. Chamberlin, N. L. TI Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE airway, muscles; airway, obstruction; airway, patency; airway, pharynx; airway, reflexes; airway, tongue; neuromuscular block, antagonism : neuromuscular block neurotransmission effects; neuromuscular block, pharmacology; neuromuscular block, recovery; ventilation, airway muscles; ventilation, pattern ID INDUCED NEUROMUSCULAR BLOCKADE; RESIDUAL PARALYSIS; RHESUS-MONKEY; ROCURONIUM; ANTAGONISM; VECURONIUM; REVERSAL; ATRACURIUM; ACETYLCHOLINE; GENIOGLOSSUS AB Background. Cholinesterase inhibitor-based reversal agents, given in the absence of neuromuscular block, evoke a partial upper airway obstruction by decreasing skeletal upper airway muscle function. Sugammadex reverses neuromuscular block by encapsulating rocuronium. However, its effects on upper airway integrity and breathing are unknown. Methods. Fifty-one adult male rats were anaesthetized with isoflurane, tracheostomized, and a femoral artery and vein were cannulated. First, we compared the efficacy of sugammadex 15 mg kg(-1) and neostigmine 0.06 mg kg(-1) to reverse respiratory effects of rocuronium-induced partial paralysis [train-of-four ratio (T4/T1)=0.5]. Subsequently, we compared the safety of sugammadex and neostigmine given after recovery of the T4/T1 to 1, by measuring phasic genioglossus activity and breathing. Results. During partial paralysis (T4/T1=0.5), time to recovery of minute volume to baseline values was 10.9 (2), 75.8 (18), and 153 (54) s with sugammadex, neostigmine, and placebo, respectively ( sugammadex was significantly faster than neostigmine and placebo, P<0.05). Recovery of T4/T1 was also faster for sugammadex than neostigmine and placebo. Neostigmine administration after complete recovery of T4/T1 decreased upper airway dilator muscle activity to 64 (30)% of baseline and decreased tidal volume (P<0.05 for both variables), whereas sugammadex had no effect on either variable. Conclusions. In contrast to neostigmine, which significantly impairs upper airway dilator muscle activity when given after recovery from neuromuscular block, a reversal dose of sugammadex given under the same conditions does not affect genioglossus muscle activity and normal breathing. Human studies will be required to evaluate the clinical relevance of our findings. C1 [Eikermann, M.; Zaremba, S.; Malhotra, A.; Jordan, A. S.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Eikermann, M.; Zaremba, S.; Malhotra, A.; Jordan, A. S.; Chamberlin, N. L.] Harvard Univ, Sch Med, Boston, MA USA. [Eikermann, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care Med, Boston, MA 02114 USA. [Eikermann, M.; Rosow, C.] Univ Duisburg Essen, Klin Anasthesiol & Intens Med, Essen, Germany. [Chamberlin, N. L.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Eikermann, M (reprint author), Brigham & Womens Hosp, Div Sleep Med, 75 Francis St, Boston, MA 02115 USA. EM meikermann@partners.org OI Jordan, Amy/0000-0001-8561-9766 FU Organon International Inc., a part of Schering-Plough Corporation FX This work was supported by a grant from Organon International Inc., a part of Schering-Plough Corporation. Organon did not participate in generation of the protocol, data analysis and interpretation, or writing. NR 31 TC 39 Z9 43 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD SEP PY 2008 VL 101 IS 3 BP 344 EP 349 DI 10.1093/bja/aen176 PG 6 WC Anesthesiology SC Anesthesiology GA 346TX UT WOS:000259093300009 PM 18559352 ER PT J AU Moreau, AS Jia, X Patterson, CJ Roccaro, AM Xu, L Sacco, A O'Connor, K Soumerai, J Ngo, HT Hatjiharissi, E Hunter, ZR Ciccarelli, B Manning, R Ghobrial, IM Leleu, X Treon, SP AF Moreau, Anne-Sophie Jia, Xiaoying Patterson, Christopher J. Roccaro, Aldo M. Xu, Lian Sacco, Antonio O'Connor, Kelly Soumerai, Jacob Ngo, Hai T. Hatjiharissi, Evdoxia Hunter, Zachary R. Ciccarelli, Bryan Manning, Robert Ghobrial, Irene M. Leleu, Xavier Treon, Steven P. TI The HMG-CoA inhibitor, simvastatin, triggers in vitro anti-tumour effect and decreases IgM secretion in Waldenstrom macroglobulinaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Waldenstrom macroglobulinemia; simvastatin; HMG-CoA reductase inhibitor ID MULTIPLE-MYELOMA CELLS; NF-KAPPA-B; INTERNATIONAL WORKSHOP; THERAPEUTIC TARGET; INDUCED APOPTOSIS; CANCER; LOVASTATIN; RECOMMENDATIONS; CERIVASTATIN; COMBINATION AB Waldenstrom macroglobulinaemia (WM) is an incurable lymphoplasmacytic lymphoma with secretion of serum monoclonal immunoglobulin M (IgM). We previously showed that patients receiving cholesterol-lowering statins, had the lowest IgM value in a large cohort of patients with WM. Simvastatin, a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, induced inhibition of proliferation, cytotoxic effect and apoptosis in IgM secreting cell lines as well as in primary CD19(+) WM cells. Interestingly, those effects were reversed by addition of mevalonate and geranylgeranylpyrophosphate, demonstrating that simvastatin inhibited cell growth, survival and IgM secretion on BCWM.1 WM cells by inhibition of geranylgeranylated proteins. Furthermore, simvastatin overcame tumour cell growth induced by co-culture of WM cells with bone-marrow stromal cells. Simvastatin also decreased IgM secretion by BCWM.1 cells at an early time-point that had not affected cell survival. Simvastatin-induced cytotoxicity was preceded by a decrease in Akt (protein kinase B, PKB) and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathways at 18 h. In addition, simvastatin induced an increase in stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) MAPK followed by caspase-8, -9, -3 and poly(ADP-ribose) polymerase (PARP) cleavages at 18 h, leading to apoptosis. Furthermore, simvastatin enhanced the cytotoxicity induced by bortezomib, fludarabine and dexamethasone. Our studies therefore support our earlier observation of statin-mediated anti-WM activity and provide the framework for future clinical trials testing simvastatin in WM. C1 [Moreau, Anne-Sophie; Jia, Xiaoying; Patterson, Christopher J.; Roccaro, Aldo M.; Xu, Lian; Sacco, Antonio; O'Connor, Kelly; Soumerai, Jacob; Ngo, Hai T.; Hatjiharissi, Evdoxia; Hunter, Zachary R.; Ciccarelli, Bryan; Manning, Robert; Ghobrial, Irene M.; Leleu, Xavier; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Moreau, Anne-Sophie; Leleu, Xavier] INSERM, U837, F-59045 Lille, France. [Moreau, Anne-Sophie; Leleu, Xavier] Ctr Hosp Reg & Univ Lille, Serv Malad Sang, F-59037 Lille, France. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013; Sacco, Antonio/K-4681-2016; OI Hunter, Zachary/0000-0002-1689-1691; Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128 NR 33 TC 13 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2008 VL 142 IS 5 BP 775 EP 785 DI 10.1111/j.1365-2141.2008.07257.x PG 11 WC Hematology SC Hematology GA 333KV UT WOS:000258152300009 PM 18537966 ER PT J AU Wu, L Bonanno, G DuHamel, K Redd, WH Rini, C Austin, J Nereo, N Ostroff, J Parsons, S Martini, R Williams, S Mee, L Sexson, S Manne, S AF Wu, Lisa Bonanno, George DuHamel, Katherine Redd, William H. Rini, Christine Austin, Jane Nereo, Nancy Ostroff, Jamie Parsons, Susan Martini, Richard Williams, Sharon Mee, Laura Sexson, Sandra Manne, Sharon TI Pre-bereavement meaning and post-bereavement distress in mothers of children who underwent haematopoietic stem cell transplantation SO BRITISH JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; DEPRESSIVE SYMPTOMS; PSYCHOLOGICAL DISTRESS; SOCIAL SUPPORT; LIFE EVENTS; ADJUSTMENT; ANXIETY; FAMILY; CANCER; PREDICTORS AB Objectives. The purpose of this study was to explore the association of meaning-making with psychological adjustment to bereavement among mothers of children who had undergone haematopoietic stem cell transplantation (HSCT). Design. A prospective research design was used. Regression analyses were conducted to determine the relations between pre-bereavement variables (distress, searching for meaning, and finding meaning) and distress post-bereavement. Methods. Thirty-five mothers of children who had undergone HSCT were interviewed at the time of their child's HSCT and 3 months post-bereavement. Results. Mothers who reported searching for meaning at HSCT reported greater post-bereavement distress, and mothers who reported finding meaning at HSCT reported less post-bereavement distress. Distress at HSCT and the number of days between the time of death and the post-bereavement time point were also found to be significant predictors of post-bereavement distress. Conclusions. This study provides partial support for the role of meaning in adjustment to loss. C1 [Wu, Lisa; Redd, William H.; Rini, Christine; Austin, Jane] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Bonanno, George] Columbia Univ Teachers Coll, Dept Counseling & Clin Psychol, New York, NY 10027 USA. [DuHamel, Katherine; Ostroff, Jamie] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10065 USA. [Nereo, Nancy] Hosp Special Surg, Dept Rehabil, New York, NY 10021 USA. [Parsons, Susan] Tufts Univ, Sch Med, Tufts New England Med Ctr, Medford, MA 02155 USA. [Parsons, Susan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Martini, Richard] Northwestern Univ, Med Ctr, Childrens Mem Hosp, Evanston, IL 60208 USA. [Williams, Sharon] Stanford Univ, Med Ctr, Packard Childrens Hosp, Stanford, CA 94305 USA. [Mee, Laura; Sexson, Sandra] Emory Univ, Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Manne, Sharon] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Wu, L (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1425 Madison Ave,Box 1130, New York, NY 10029 USA. EM lisa.wu@mssm.edu OI DuHamel, Katherine/0000-0002-4519-6057; Ostroff, Jamie/0000-0003-2671-5680 FU NIMH NIH HHS [MH 57738] NR 56 TC 16 Z9 17 U1 2 U2 4 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 1359-107X J9 BRIT J HEALTH PSYCH JI Br. J. Health Psychol. PD SEP PY 2008 VL 13 BP 419 EP 433 DI 10.1348/135910707X204236 PN 3 PG 15 WC Psychology, Clinical SC Psychology GA 333XL UT WOS:000258186800004 PM 17535504 ER PT J AU Nelson, KR Edwards, D AF Nelson, Kerrie R. Edwards, Don TI On population-based measures of agreement for binary classifications SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE Agreement; Cohen's kappa; crossed random effects; generalized linear mixed model; model-based kappa; prevalence; reliability; Scott's pi ID LINEAR MIXED MODELS; INTERRATER AGREEMENT; ESTIMATING EQUATIONS; KAPPA-COEFFICIENT; CATEGORICAL-DATA; VARIABILITY; ASSOCIATION; REPRODUCIBILITY; PATHOLOGISTS; RADIOLOGISTS AB The authors describe a model-based kappa statistic for binary classifications which is interpretable in the same manner as Scott's pi and Cohen's kappa, yet does not suffer from the same flaws. They compare this statistic with the data-driven and population-based forms of Scott's pi in a population-based setting where many raters and subjects are involved, and inference regarding the underlying diagnostic procedure is of interest. The authors show that Cohen's kappa and Scott's pi seriously underestimate agreement between experts classifying subjects for a rare disease; in contrast, the new statistic is robust to changes in prevalence. The performance of the three statistics is illustrated with simulations and prostate cancer data. C1 [Nelson, Kerrie R.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Edwards, Don] Univ S Carolina, Dept Stat, Columbia, SC 29208 USA. RP Nelson, KR (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St,Suite 560, Boston, MA 02114 USA. EM kpnelson@partners.org; edwards@stat.sc.edu FU United States Institutes of Health FX The authors are grateful for the support provided by a grant from the United States Institutes of Health. We thank Dr Allsbrook for kindly providing LIS With the prostate cancer data set. We are grateful for helpful advice and suggestions from Charles McCulloch, Patrick Graham and Robert Best. NR 49 TC 2 Z9 2 U1 1 U2 7 PU CANADIAN JOURNAL STATISTICS PI OTTAWA PA 675 DENBURY AVENUE, OTTAWA, ON K2A 2P2, CANADA SN 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD SEP PY 2008 VL 36 IS 3 BP 411 EP 426 PG 16 WC Statistics & Probability SC Mathematics GA 360VT UT WOS:000260087000006 ER PT J AU Rowe, BH Cydulka, RK Tsai, CL Clark, S Sinclair, D Camargo, CA AF Rowe, Brian H. Cydulka, Rita K. Tsai, Chu-Lin Clark, Sunday Sinclair, Douglas Camargo, Carlos A., Jr. TI Comparison of Canadian versus United States emergency department visits for chronic obstructive pulmonary disease exacerbation SO CANADIAN RESPIRATORY JOURNAL LA English DT Article DE Canada-USA; chronic obstructive pulmonary disease; emergency department; exacerbation ID MANAGEMENT; METAANALYSIS; PROGRAMS AB INTRODUCTION: Despite the frequency of emergency department (ED) visits for chronic obstructive pulmonary disease (COPD) exacerbation, little is known about practice variation in EDs. OBJECTIVES: To examine the differences between Canadian and United States (US) COPD patients, and the ED management they receive. METHODS: A prospective multicentre cohort study was conducted involving 29 EDs in the US and Canada. Using a standard protocol, consecutive ED patients with COPD exacerbations were interviewed, their charts reviewed and a two-week telephone follow-up completed. Comparisons between Canadian and US patients, as well as their treatment and and outcomes, were made. Predictors of antibiotic use were determined by multivariate logistic regression. RESULTS: Of 584 patients who had physician-diagnosed COPD, 397 (68%) were enrolled. Of these, 63 patients (16%) were from Canada. Canadians were older (73 years versus 69 years; P=0.002), more often white (97% versus 65%; P<0.001) less educated (P=0.003) and more commonly Insured (P<0.001) than the US patients. US patients more commonly used the ED for their usual COPD medications (17% versus 3%; P=0.005). Although Canadian patients had fewer pack-years of smoking (45 pack-years Versus 53 pack-years; P=0.001), Current COPD medications and comorbidities were similar. At ED presentation, Canadian patients were more often hypoxic and symptomatic. ED treatment with inhaled beta-agonists (approximately 90%) and systemic corticosteroids (approximately 65%) were similar; Canadians received more antibiotics (46% versus 25%; P<0.001) and other treatments (29% versus 11%; P=0.002). Admission rates were similar in both countries (approximately 65%), although Canadian patients remained in the ED longer than the US patients (10 h versus 5 1), respectively; P<0.001). CONCLUSIONS: Overall, patients with acute COPD in Canada and the US appear to have similar history, ED treatment and outcomes; however, Canadian patients are older and receive more aggressive treatment in the ED. In both countries, the prolonged length of stay and high admission rate contribute to the ED over-crowding crisis facing EDs. C1 [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB T6G 2B7, Canada. [Cydulka, Rita K.] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. [Tsai, Chu-Lin; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tsai, Chu-Lin; Clark, Sunday; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Emergency Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sinclair, Douglas] Dalhousie Univ, Dept Emergency Med, Halifax, NS, Canada. [Sinclair, Douglas] Dalhousie Univ, Dept Pediat, Halifax, NS, Canada. RP Rowe, BH (reprint author), Univ Alberta, Dept Emergency Med, 1G1-43 Walter C Mackenzie Ctr, 8440-112 St, Edmonton, AB T6G 2B7, Canada. EM brian.rowe@ualberta.ca OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Government of Canada; Institute for United States Policy Studies (IUSPS) FX Dr Rowe's research is supported by the Government of Canada through the 21st Century Research Chairs Program. The study was partially funded by a grant from the Institute for United States Policy Studies (IUSPS) at the University of Alberta. NR 24 TC 11 Z9 11 U1 1 U2 2 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 1198-2241 J9 CAN RESPIR J JI Can. Respir. J. PD SEP PY 2008 VL 15 IS 6 BP 295 EP 301 PG 7 WC Respiratory System SC Respiratory System GA 355ZD UT WOS:000259747600004 PM 18818783 ER PT J AU Hezel, AF Bardeesy, N AF Hezel, Aram F. Bardeesy, Nabeel TI Prognostic markers in pancreatic ductal adenocarcinomas SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE mTOR; HIF-1 alpha; everolimus; cyclophosphamide; metronomic chemotherapy; gastric cancer ID CANCER; PIM C1 [Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, Boston, MA 02114 USA. RP Bardeesy, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, 185 Cambridge St,CPZN4216, Boston, MA 02114 USA. EM Bardeesy.Nabeel@mgh.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP PY 2008 VL 7 IS 9 BP 1361 EP 1362 PG 2 WC Oncology SC Oncology GA 350EX UT WOS:000259336500008 ER PT J AU McDermott, DF Atkins, MB AF McDermott, David F. Atkins, Michael B. TI Immunotherapy of metastatic renal cell carcinoma SO CANCER JOURNAL LA English DT Article DE immunotherapy; renal cancer; interleukin-2; interferon-alpha; carbonic anhydrase IX ID DOSE RECOMBINANT INTERLEUKIN-2; PHASE-II TRIAL; ESTABLISHED PULMONARY METASTASES; RANDOMIZED CONTROLLED-TRIAL; AUTOLOGOUS DENDRITIC CELLS; CARBONIC-ANHYDRASE-IX; INTERFERON-ALPHA; SUBCUTANEOUS INTERLEUKIN-2; SPONTANEOUS REGRESSION; SOLID TUMORS AB In 1992, high-dose bolus interleukin (IL)-2 was granted Food and Drug Administration approval based on its ability to produce durable complete responses in a small number of patients with metastatic renal cell carcinoma (RCC). However, the substantial toxicity and limited efficacy that is associated with IL-2 has narrowed its application to highly selected patients treated at specialized centers. In recent years, the relative merits of low- and high-dose cytokine regimens have been clarified by the results of 4 randomized trials. Taken together, these studies suggest that highdose IV bolus IL-2 is Superior in terms of response rate and possibly response quality to regimens that involve either low-dose IL-2 and interferon-alpha, intermediate- or low-dose IL-2 alone, or low-close interferon-a alone. More significantly, investigations associated with these trials suggest that the potential exists for identifying predictors of response (or resistance) and limiting IL-2 therapy to those most likely to benefit. The Cytokine Working Group has launched the high-dose IL-2 "select" trial to determine, in a prospective fashion, if the predictive model proposed by Atkins et al. can identify a group of patients with advanced RCC who are significantly more likely to respond to high dose IL-2-based therapy ("good" risk) than a historical, unselected patient population. For patients unlikely to benefit from IL-2, are unable to receive it or who progress after IL-2, the emergence of molecularly targeted therapies offers hope for improved clinical outcome. As the list of effective therapies for metastatic RCC grows, improvements in patient selection and more "targeted" approaches will be required to optimize the benefits of cytokine therapy in metastatic RCC. C1 [McDermott, David F.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Dana Farber Harvard Canc Ctr, Renal Canc Program, Boston, MA USA. RP McDermott, DF (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, 375 Longwood Ave,MS-428, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu FU DF/HCC Renal Cancer SPORE [P50 CA101942-01] FX This work was supported, in part, by the DF/HCC Renal Cancer SPORE: P50 CA101942-01. NR 61 TC 18 Z9 18 U1 0 U2 0 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 SEP-OCT PY 2008 VL 14 IS 5 BP 320 EP 324 PG 5 WC Oncology SC Oncology GA 358KR UT WOS:000259916200007 PM 18836337 ER PT J AU Ahn, A Frishman, WH Gutwein, A Passeri, J Nelson, M AF Ahn, Anna Frishman, William H. Gutwein, Andrew Passeri, Jonathan Nelson, Michael TI Therapeutic Angiogenesis A New Treatment Approach for Ischemic Heart Disease - Part II SO CARDIOLOGY IN REVIEW LA English DT Review DE angiogenesis; angiogenic growth factors; vascular endothelial growth factor; fibroblast growth factor; myocardial ischemia; gene therapy ID FIBROBLAST-GROWTH-FACTOR; CHRONIC MYOCARDIAL-ISCHEMIA; CORONARY-ARTERY-DISEASE; ENHANCES COLLATERAL PERFUSION; MARROW MONONUCLEAR-CELLS; MEDIATED GENE-TRANSFER; NO-OPTION PATIENTS; INTRAMYOCARDIAL INJECTION; DOUBLE-BLIND; PORCINE MODEL AB Angiogenesis is the biologic process of forming new blood vessels and is being investigated as an innovative therapeutic approach to help manage ischemic heart disease and peripheral vascular disease. Research studies have identified various angiogenic growth factors and progenitor cells that can enhance new blood vessel formation. This is Part II of an article that began publication in the July/August issue of Cardiology in Review. Preclinical investigations in animal models have explored the potential use of growth factors with and without progenitor cells to treat myocardial ischemia. The results of clinical trials with growth factor infusions and gene therapy techniques to enhance growth factor production have shown some promise, but therapeutic angiogenesis remains at an early stage of development. C1 [Frishman, William H.; Gutwein, Andrew] New York Med Coll, Dept Med, Westchester Cty Med Ctr, Valhalla, NY 10595 USA. [Ahn, Anna] Long Isl Jewish Med Ctr, Albert Einstein Coll Med, Dept Med, New Hyde Pk, NY 11042 USA. [Passeri, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Nelson, Michael] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Hosp, Boston, MA 02215 USA. RP Frishman, WH (reprint author), New York Med Coll, Dept Med, Westchester Cty Med Ctr, Munger 263, Valhalla, NY 10595 USA. EM William_Frishman@nymc.edu NR 90 TC 22 Z9 30 U1 0 U2 1 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 SEP-OCT PY 2008 VL 16 IS 5 BP 219 EP 229 DI 10.1097/CRD.0b013e3181620e50 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 382XT UT WOS:000261639400001 PM 18708823 ER PT J AU Rehman, SU Januzzi, JL AF Rehman, Shafiq U. Januzzi, James L., Jr. TI Natriuretic Peptide Testing in Clinical Medicine SO CARDIOLOGY IN REVIEW LA English DT Review DE natriuretic peptides; heart failure; ischemia ID CHRONIC HEART-FAILURE; ACUTE CORONARY SYNDROMES; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT PRIDE; ACUTE PULMONARY-EMBOLISM; N-TERMINAL PROBNP; RISK STRATIFICATION; GENE-EXPRESSION; DIASTOLIC DYSFUNCTION AB Since the discovery of atrial natriuretic factor in 1981 by de Bold et al, there has been tremendous progress in our understanding of natriuretic peptides (NPs). Recently, testing for brain-type NP (BNP) and its amino terminal cleavage equivalent (NT-proBNP) has been rapidly adopted in clinical medicine for numerous indications, including the diagnosis and exclusion of heart failure (HF). In this regard, logical application of BNP or NT-proBNP testing may not only reduce healthcare costs but also potentially reduce adverse clinical outcomes. With respect to this fact, the potential importance of the concentration of the NPs for prognosis and the response of BNP or NT-proBNP to therapeutic intervention in terms of clinical events has been demonstrated. On the basis of these observations it is reasonable to expect that concentrations of these peptides might be useful for the management of patients with HF, acting as a gauge of therapeutic accuracy and/or stability of disease. Besides HF, the prognostic utility of NPs has been explored in other settings, particularly in ischemic heart disease and those conditions that lead to right ventricular dysfunction. C1 [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Div Cardiol, Boston, MA USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, 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 Researc FX Supported by the Dennis and Marilyn Barry Fellowship in Cardiology (to S.U.R.) and Balson Fund for Cardiovascular Research (to J.L.J.). NR 124 TC 18 Z9 19 U1 0 U2 1 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 SEP-OCT PY 2008 VL 16 IS 5 BP 240 EP 249 DI 10.1097/CRD.0b013e3181815333 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 382XT UT WOS:000261639400003 PM 18708825 ER PT J AU Aqel, RA Hage, FG AF Aqel, Raed A. Hage, Fadi G. TI Time is muscle; But should it be D2B or D2T? SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; ANGIOPLASTY C1 [Aqel, Raed A.; Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Aqel, Raed A.; Hage, Fadi G.] Univ Alabama, Div Cardiovasc Dis, Dept Internal Med, Birmingham, AL 35294 USA. RP Aqel, RA (reprint author), BDB 383,1530 3rd Ave S, Birmingham, AL 35294 USA. EM raed.aqel@med.va.gov OI Hage, Fadi/0000-0002-1397-4942 NR 8 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP 1 PY 2008 VL 72 IS 3 BP 424 EP 425 DI 10.1002/ccd.21613 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 344CI UT WOS:000258902800024 PM 18727124 ER PT J AU Borsook, D Moulton, EA Tully, S Schmahmann, JD Becerra, L AF Borsook, D. Moulton, E. A. Tully, S. Schmahmann, J. D. Becerra, L. TI Human cerebellar responses to brush and heat stimuli in healthy and neuropathic pain subjects SO CEREBELLUM LA English DT Review DE trigemino-cerebellar pathways; chronic pain; allodynia; cerebellar muclei; pain; fMRI; BOLD ID POSITRON-EMISSION-TOMOGRAPHY; COGNITIVE-AFFECTIVE SYNDROME; NOXIOUS THERMAL-STIMULATION; STEM SUBNUCLEUS INTERPOLARIS; TRIGEMINAL PRIMARY AFFERENTS; CERVICAL DORSAL HORNS; HUMAN BRAIN; TRIGEMINOCEREBELLAR PROJECTION; CEREBRAL ACTIVATION; SOMATOTOPIC ORGANIZATION AB Though human pain imaging studies almost always demonstrate activation in the cerebellum, the role of the cerebellum in pain function is not well understood. Here we present results from two studies on the effects of noxious thermal heat and brush applied to the right side of the face in a group of healthy subjects (Group I) and a group of patients with neuropathic pain (Group II) who are more sensitive to both thermal and mechanical stimuli. Statistically significant activations and volumes of activations were defined in the cerebellum. Activated cerebellar structures were identified by colocalization of fMRI activation with the 'MRI Atlas of the Human Cerebellum'. Functional data (obtained using a 3T magnet) were defined in terms of maximum voxels and volume of activation in the cerebellum. Volume maps were then mapped onto two millimeter serial slices taken through the cerebellum in order to identify activation within regions defined by the activation volume. The data indicate that different regions of the cerebellum are involved in acute and chronic pain processing. Heat produces greater contralateral activation compared with brush, while brush resulted in more ipsilateral/bilateral cerebellar activation. Further, innocuous brush stimuli in healthy subjects produced decreased cerebellar activation in lobules concerned with somatosensory processing. The data also suggest a dichotomy of innocuous stimuli/sensorimotor cerebellum activation versus noxious experience/cognitive/limbic cerebellum activation. These results lead us to propose that the cerebellum may modulate the emotional and cognitive experience that distinguishes the perception of pain from the appreciation of innocuous sensory stimulation. C1 [Borsook, D.; Moulton, E. A.; Tully, S.; Becerra, L.] Harvard Univ, Sch Med, McLean Hosp,Brain Imaging Ctr, PAIN Grp, Belmont, MA 02178 USA. [Schmahmann, J. D.] Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Cerebellar Res Grp, Boston, MA 02114 USA. RP Borsook, D (reprint author), Harvard Univ, Sch Med, McLean Hosp,Brain Imaging Ctr, PAIN Grp, 115 Mill St, Belmont, MA 02178 USA. EM dborsook@mclean.harvard.edu FU NINDS [NS 042721] FX This work was supported by a grant from NINDS (NS 042721). NR 137 TC 34 Z9 34 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1473-4222 J9 CEREBELLUM JI Cerebellum PD SEP PY 2008 VL 7 IS 3 BP 252 EP 272 DI 10.1007/s12311-008-0011-6 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 359OI UT WOS:000259996900004 PM 18418691 ER PT J AU Whitney, ER Kemper, TL Bauman, ML Rosene, DL Blatt, GJ AF Whitney, Elizabeth R. Kemper, Thomas L. Bauman, Margaret L. Rosene, Douglas L. Blatt, Gene J. TI Cerebellar Purkinje Cells are Reduced in a Subpopulation of Autistic Brains: A Stereological Experiment Using Calbindin-D28k SO CEREBELLUM LA English DT Article DE Purkinje cells; Autism; Calbindin-D28k ID COGNITIVE-AFFECTIVE SYNDROME; RHESUS-MONKEY; BASIS PONTIS; CEREBROCEREBELLAR SYSTEM; MENTAL-RETARDATION; PREFRONTAL CORTEX; PHENYTOIN THERAPY; COUNTING METHODS; PROJECTIONS; DEGENERATION AB Although a decreased number of cerebellar Purkinje cells (PCs) in the autistic brain has been widely reported with a variety of qualitative and quantitative methods, the more accurate method of cell counting with modern stereology has not yet been employed. An additional possible problem with prior reports is the use of Nissl staining to identify the PCs, as this can miss cells due to staining irregularities. In the present study, PCs were immunostained for calbindin-D28k (CB), as this has been shown to be a more reliable marker for PCs than the Nissl stain, with more than 99% of the PCs immunopositive (Whitney, Kemper, Rosene, Bauman, Blatt, J Neurosci Methods 168:42-47, 2008). Using stereology and CB immunostaining, the density of PCs was determined in serial sections from a consistently defined area of the cerebellar hemisphere in four control and six autistic brains, with the density of PCs then correlated with the clinical severity of autism. Overall, there was no significant difference in the density of PCs between the autistic and control groups. However, three of six autistic brains had PC numbers that fell within the control range, whereas the remaining three autistic brains revealed a reduction compared with the control brains. These data demonstrate that a reduction in cerebellar PCs was not a consistent feature of these autistic brains and that it occurred without discernible correlation between their density and the clinical features or severity of autism. C1 [Whitney, Elizabeth R.; Kemper, Thomas L.; Bauman, Margaret L.; Rosene, Douglas L.; Blatt, Gene J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Bauman, Margaret L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Whitney, ER (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, L-1004,715 Albany St, Boston, MA 02118 USA. EM ewhitney@bu.edu RI Rosene, Douglas/G-1973-2015; OI Rosene, Douglas/0000-0001-8719-1441 FU NICHD NIH HHS [HD39459] NR 43 TC 98 Z9 99 U1 5 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1473-4222 J9 CEREBELLUM JI Cerebellum PD SEP PY 2008 VL 7 IS 3 BP 406 EP 416 DI 10.1007/s12311-008-0043-y PG 11 WC Neurosciences SC Neurosciences & Neurology GA 359OI UT WOS:000259996900018 PM 18587625 ER PT J AU Liu, S Heitz, RP Sampson, AR Zhang, W Bradberry, CW AF Liu, S. Heitz, R. P. Sampson, A. R. Zhang, W. Bradberry, C. W. TI Evidence of temporal cortical dysfunction in rhesus monkeys following chronic cocaine self-administration SO CEREBRAL CORTEX LA English DT Article DE addiction; cognition; prefrontal; primate; psychostimulant ID PREFRONTAL CORTEX; DECISION-MAKING; WORKING-MEMORY; EXTRACELLULAR DOPAMINE; LESIONS; PERFORMANCE; DEPENDENCE; DEFICITS; ABUSERS; SENSITIZATION AB Cocaine abusers show impaired performance on cognitive tasks that engage prefrontal cortex. These deficits may contribute to impaired control and relapse in abusers. Understanding the neuronal substrates that lead to these deficits requires animal models that are relevant to the human condition. However, to date, models have mostly focused on behaviors mediated by subcortical systems. Here we evaluated the impact of long-term self-administration of cocaine in the rhesus monkey on cognitive performance. Tests included stimulus discrimination (SD)/reversal and delayed alternation tasks. The chronic cocaine animals showed marked deficits in ability to organize their behavior for maximal reward. This was demonstrated by an increased time needed to acquire SDs. Deficits were also indicated by an increased time to initially learn the delayed alternation task, and to adapt strategies for bypassing a reliance on working memory to respond accurately. Working memory per se (delay dependent performance) was not affected by chronic self-administration. This pattern of cognitive deficits suggests dysfunction that extends beyond localized prefrontal cortical areas. In particular, it appears that temporal cortical function is also compromised. This agrees with other recent clinical and preclinical findings, and suggests further study into addiction related dysfunction across more widespread cortical networks is warranted. C1 [Liu, S.; Bradberry, C. W.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA. [Heitz, R. P.] Vanderbilt Univ, Ctr Integrat & Cognit Neurosci, Nashville, TN 37203 USA. [Sampson, A. R.; Zhang, W.] Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15261 USA. [Bradberry, C. W.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15261 USA. [Bradberry, C. W.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. RP Bradberry, CW (reprint author), Univ Pittsburgh, Dept Psychiat, Rm 4078,3501 5th Ave, Pittsburgh, PA 15261 USA. EM bradberrycw@upmc.edu RI bradberry, charles/M-2082-2015 OI bradberry, charles/0000-0003-2630-4144 FU National Institutes of Health [DA 10331, MH 78789]; Veteran's Administration Biomedical Laboratory Research and Development Service FX National Institutes of Health (DA 10331, MH 78789); and the Veteran's Administration Biomedical Laboratory Research and Development Service. NR 52 TC 14 Z9 14 U1 1 U2 2 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 SEP PY 2008 VL 18 IS 9 BP 2109 EP 2116 DI 10.1093/cercor/bhm236 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 347MD UT WOS:000259144800014 PM 18096561 ER PT J AU Wang, AZ Bagalkot, V Vasilliou, CC Gu, F Alexis, F Zhang, L Shaikh, M Yuet, K Cima, MJ Langer, R Kantoff, PW Bander, NH Jon, SY Farokhzad, OC AF Wang, Andrew Z. Bagalkot, Vaishali Vasilliou, Christophoros C. Gu, Frank Alexis, Frank Zhang, Liangfang Shaikh, Mariam Yuet, Kai Cima, Michael J. Langer, Robert Kantoff, Philip W. Bander, Neil H. Jon, Sangyong Farokhzad, Omid C. TI Superparamagnetic iron oxide nanoparticle-aptamer bioconjugates for combined prostate cancer imaging and therapy SO CHEMMEDCHEM LA English DT Article DE doxorubicin; nanoparticles; superparamagnetic; TCL-SPION ID LYMPH-NODE METASTASES; HER2-POSITIVE BREAST-CANCER; DRUG-DELIVERY; MEMBRANE ANTIGEN; MAGNETIC NANOPARTICLES; ADJUVANT CHEMOTHERAPY; CHOP CHEMOTHERAPY; CONTRAST AGENTS; LOW-GRADE; IN-VIVO C1 [Wang, Andrew Z.; Alexis, Frank; Farokhzad, Omid C.] Brigham & Womens Hosp, Dept Anesthesia, Lab Nanomed & Biomat, Boston, MA 02115 USA. [Wang, Andrew Z.; Alexis, Frank; Kantoff, Philip W.; Farokhzad, Omid C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bagalkot, Vaishali; Jon, Sangyong] Gwangju Inst Sci & Technol, Dept Life Sci, Res Ctr Biomol Nanotechnol, Kwangju 500712, South Korea. [Vasilliou, Christophoros C.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Wang, Andrew Z.; Gu, Frank; Alexis, Frank; Zhang, Liangfang; Shaikh, Mariam; Yuet, Kai; Langer, Robert] MIT, Div Hlth Sci & Technol, Dept Chem Engn, Cambridge, MA 02139 USA. [Cima, Michael J.] MIT, David H Koch Inst Integrat Canc Res, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Bander, Neil H.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY 10021 USA. RP Wang, AZ (reprint author), Brigham & Womens Hosp, Dept Anesthesia, Lab Nanomed & Biomat, 75 Francis St, Boston, MA 02115 USA. EM syjon@gist.ac.kr; ofarokhzad@parrtners.org RI Jon, Sangyong/C-3725-2012; Gu, Frank/C-5187-2008; Wang, Andrew /F-9719-2011; Gu, Frank/G-8381-2011; bagalkot, vaishali/D-5603-2015; OI Gu, Frank/0000-0001-8749-9075; bagalkot, vaishali/0000-0002-6135-6698; Yuet, Kai/0000-0002-1381-8923; Wang, Andrew/0000-0002-9781-4494 FU National Institutes of Health(USA) [CA119349, EB003647]; David H. Koch-Prostate Cancer Foundation Award in Nanotherapeutics; National R&D Program for Cancer Control, Ministry of Health and Welfare(Republic of Korea) [0720210] FX We thank Drs. Ralph Weissleder and Lee Josephson for helpful discussions throughout this study. This work was supported by the National Institutes of Health(USA) grants CA119349 (R.L., O.C.F), EB003647 (O.C.F), David H. Koch-Prostate Cancer Foundation Award in Nanotherapeutics (R.L., P.W.K, N.H.B, O.C.F), and by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare(Republic of Korea) 0720210 (S.J.). NR 38 TC 162 Z9 167 U1 9 U2 86 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD SEP PY 2008 VL 3 IS 9 BP 1311 EP 1315 DI 10.1002/cmdc.200800091 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 354HA UT WOS:000259628300002 PM 18613203 ER PT J AU Camargo, CA Barr, RG Chen, R Speizer, FE AF Camargo, Cartos A., Jr. Barr, R. Graham Chen, Rong Speizer, Frank E. TI Prospective study of inhaled corticosteroid use, cardiovascular mortality, and all-cause mortality in asthmatic women SO CHEST LA English DT Article DE all-cause mortality; asthma; cardiovascular mortality; inhaled corticorsteroids ID OBSTRUCTIVE PULMONARY-DISEASE; C-REACTIVE PROTEIN; BODY-MASS INDEX; ONSET ASTHMA; RISK; INFLAMMATION; THERAPY; FLUTICASONE; NURSES; COHORT AB Background: Therapy, with inhaled corticosteroids (ICSs) decreases the risk of asthma exacerbations. Recent studies have suggested that ICS therapy also may decrease the risk of cardiovascular disease, and perhaps of all-cause mortality. We examined this hypothesis in a large well-characterized cohort of asthmatic women. Methods: In 1976, the Nurses' Health Study enrolled 121,700 registered nurses, who were 30 to 55 years of age. Participants were asked about "physician-diagnosed asthma" on biennial questionnaires. In 1998, asthmatic participants were sent a supplementary questionnaire on asthma diagnosis and management, including ICS use. Mortality was assessed through 2003, without knowledge of the 1998 (baseline) ICS status. The odds ratios (ORs) for death were adjusted for age, asthma severity, smoking, heart disease, cancer, stroke, aspirin, and statin use. Results: Among 2,671 eligible women (ie, those who responded to the 1998 supplement [85%], met criteria for persistent asthma, and had not received a prior diagnosis of COPD), 54% reported ICS use. Over the next 5 years, 87 women (3.3%) died (cardiovascular deaths, 22; cancer deaths,31; other, 34 [including 4 from asthma]). Compared to asthmatic women who did not use ICSs, those receiving therapy,.,with ICSs had lower all-cause mortality (OR, 0.58; 95% confidence interval [CI], 0.36 to 0.92). ICS users were at significantly tower risk of cardiovascular death (OR, 0.35; 95% CI, 0.13 to 0.93), but not of death from cancer (OR, 0.66; 95% CI, 0.32 to 1.38) or other causes (OR, 0.62; 95% CI, 0.30 to 1.27). Conclusions: ICS use was associated with significantly lower cardiovascular and all-cause mortality in women with asthma. These observational data suggest that ICSs may, indeed have antiinflammatory benefits beyond the airway, which is a possibility that merits further study. C1 [Camargo, Cartos A., Jr.; Chen, Rong; Speizer, Frank E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. [Barr, R. Graham] Columbia Univ, Med Ctr, New York, NY USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU National Institutes of Health [HL-63841, AI-52338, CA-87969]; GlaxoSmithKline FX Funding for this research was provided by grants HL-63841, AI-52338, and CA-87969 from the National Institutes of Health (Bethesda, MD); and an investigator-initiated grant to Dr. Camargo from GlaxoSmithKline (Research Triangle Park, NC). Dr. Camargo has received financial support from diverse groups of sponsors for participation in conferences, consulting, and research. Recent industry sponsors with all interest in asthma were AstraZeneca, Dey, Genentech, GlaxoSinithKline, Merck, Novartis, Respironics, and Schering-Plough. Dr. Barr, Ms. Chen, and Dr. Speizer have reported to the ACCP that no significant conflicts of interest exist with any, companies/organizations whose products or services may be discussed in this article. NR 25 TC 9 Z9 10 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2008 VL 134 IS 3 BP 546 EP 551 DI 10.1378/chest.07-3126 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 349OP UT WOS:000259290500015 PM 18641096 ER PT J AU Tolin, DF Diefenbach, GJ Flessner, CA Franklin, ME Keuthen, NJ Moore, P Piacentini, J Stein, DJ Woods, DW AF Tolin, David F. Diefenbach, Gretchen J. Flessner, Christopher A. Franklin, Martin E. Keuthen, Nancy J. Moore, Phoebe Piacentini, John Stein, Dan J. Woods, Douglas W. CA Trichotillomania Learning Ctr Sci TI The Trichotillomania Scale for Children: Development and validation SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE hair-pulling; questionnaire; impulse control disorders; child disorders ID MGH HAIRPULLING SCALE; CLINICAL CHARACTERISTICS; PSYCHOMETRIC EVALUATION; INTERNET; PHENOMENOLOGY; ADOLESCENTS; RELIABILITY; DISORDERS; VALIDITY; QUESTIONNAIRES AB Trichotillomania (TTM) is a chronic impulse control disorder characterized by repetitive hair-pulling resulting in alopecia. Although this condition is frequently observed in children and adolescents, research on pediatric TTM has been hampered by the absence of validated measures. The aim of the present study was to develop and test a new self-report measure of pediatric TTM, the Trichotillomania Scale for Children (TSC), a measure that can be completed by children and/or their parents. One hundred thirteen children meeting self-report criteria for TTM, and 132 parents, provided data over the internet. An additional 41 child-parent dyads from an outpatient clinic also provided data. Replicated principal components analysis, with elimination of poorly-loading items, yielded two components, which we labeled Severity (five items) and Distress/Impairment (seven items). The TSC total score and subscales showed adequate internal consistency and test-retest reliability. Parent-child agreement was good in the internet sample, but more modest in the clinic sample. Children's TSC scores correlated significantly with other measures of TTM severity, although some exceptions were noted. Parents' TSC scores correlated significantly with other measures of parent-rated TTM severity in the internet sample, but showed more attenuated relationships with child- and interviewer-rated TTM severity in the clinic sample. The present results suggest that the TSC may be a useful measure of TTM for child and adolescent samples, although additional clarification of convergent validity is needed. C1 [Tolin, David F.; Diefenbach, Gretchen J.] Anxiety Disorders Ctr, Inst Living, Hartford, CT 06106 USA. [Tolin, David F.] Yale Univ, Sch Med, New Haven, CT USA. [Flessner, Christopher A.; Woods, Douglas W.] Univ Wisconsin, Milwaukee, WI 53201 USA. [Franklin, Martin E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Keuthen, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Moore, Phoebe] Duke Univ, Med Ctr, Durham, NC USA. [Piacentini, John] Univ Calif Los Angeles, Los Angeles, CA USA. [Stein, Dan J.] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Stein, Dan J.] Mt Sinai Sch Med, New York, NY USA. RP Tolin, DF (reprint author), Anxiety Disorders Ctr, Inst Living, 200 Retreat Ave, Hartford, CT 06106 USA. EM dtolin@harthosp.org RI Piacentini, John/C-4645-2011; Citations, TLC SAB/C-4006-2011; Flessner, Christopher/K-1483-2015; Stein, Dan/A-1752-2008 OI Stein, Dan/0000-0001-7218-7810 FU NIMH NIH HHS [R21MH061457] NR 43 TC 35 Z9 37 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-398X J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD SEP PY 2008 VL 39 IS 3 BP 331 EP 349 DI 10.1007/s10578-007-0092-3 PG 19 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 312WD UT WOS:000256702200010 PM 18183484 ER PT J AU Weintraub, WS Boden, WE Zhang, ZG Kolm, P Zhang, ZF Spertus, JA Hartigan, P Veledar, E Jurkovitz, C Bowen, J Maron, DJ O'Rourke, R Dada, M Teo, KK Goeree, R Barnett, PG AF Weintraub, William S. Boden, William E. Zhang, Zugui Kolm, Paul Zhang, Zefeng Spertus, John A. Hartigan, Pamela Veledar, Emir Jurkovitz, Claudine Bowen, Jim Maron, David J. O'Rourke, Robert Dada, Marcin Teo, Koon K. Goeree, Ron Barnett, Paul G. CA Cooperative Studies Program 424 CO TI Cost-Effectiveness of Percutaneous Coronary Intervention in Optimally Treated Stable Coronary Patients SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE coronary disease; angina; epidemiology; cost-benefit analysis; stents AB Background-The COURAGE ( Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluations) trial compared the effect of percutaneous coronary intervention (PCI) plus optimal medical therapy with optimal medical therapy alone on cardiovascular events in 2287 patients with stable coronary disease. After 4.6 years, there was no difference in the primary end point of death or myocardial infarction, although PCI improved quality of life. The present study evaluated the relative cost and cost-effectiveness of PCI in the COURAGE trial. Methods and Results-Resource use was assessed by diagnosis-related group for hospitalizations and by current procedural terminology code for outpatient visits and tests and then converted to costs by use of 2004 Medicare payments. Medication costs were assessed with the Red Book average wholesale price. Life expectancy beyond the trial was estimated from Framingham survival data. Utilities were assessed by the standard gamble method. The incremental cost-effectiveness ratio was expressed as cost per life-year and cost per quality- adjusted life-year gained. The added cost of PCI was approximately $10 000, without significant gain in life-years or quality-adjusted life-years. The incremental cost-effectiveness ratio varied from just over $168 000 to just under $300 000 per life-year or quality- adjusted life-year gained with PCI. A large minority of the distributions found that medical therapy alone offered better outcome at lower cost. The costs per patient for a significant improvement in angina frequency, physical limitation, and quality of life were $154 580, $112 876, and $124 233, respectively. Conclusions-The COURAGE trial did not find the addition of PCI to optimal medical therapy to be a cost-effective initial management strategy for symptomatic, chronic coronary artery disease. (Circ Cardiovasc Qual Outcomes. 2008; 1: 12-20.) C1 [Weintraub, William S.] Christiana Care Hlth Syst, Cardiol Sect, Newark, DE 19718 USA. [Boden, William E.] Western New York Vet Affairs Healthcare Network, Buffalo, NY USA. [Boden, William E.] Kaleida Hlth Syst, Buffalo, NY USA. [Zhang, Zefeng] Emory Univ, Atlanta, GA 30322 USA. [Spertus, John A.] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. [Hartigan, Pamela] VA Connecticut Healthcare Syst, Coordinating Ctr, Cooperat Studies Program, West Haven, CT USA. [Maron, David J.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [O'Rourke, Robert] San Antonio Vet Affairs Med Ctr, San Antonio, TX USA. [Dada, Marcin] Hartford Hosp, Hartford, CT 06115 USA. [Teo, Koon K.; Goeree, Ron] McMaster Univ, Hamilton, ON, Canada. [Barnett, Paul G.] Vet Affairs Hlth Econ Resource Ctr, Palo Alto, CA USA. RP Weintraub, WS (reprint author), Christiana Care Hlth Syst, Cardiol Sect, 4755 Ogletown Stanton Rd, Newark, DE 19718 USA. EM wweintraub@christianacare.org RI Veledar, Emir/K-2808-2012 OI Veledar, Emir/0000-0002-3831-5433 FU Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; Canadian Institutes for Health Research; Merck Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Fujisawa; Kos Pharmaceuticals; Data Scope; AstraZeneca; Key Pharmaceutical Co, Ltd; Sanofi-Aventis, Inc; First Horizon; Nycomed Amersham; Department of Veterans Affairs FX This study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development, in collaboration with the Canadian Institutes for Health Research; unrestricted research grants were obtained from Merck & Co, Pfizer Pharmaceuticals, Bristol-Myers Squibb Medical Imaging, Fujisawa, Kos Pharmaceuticals, Data Scope, AstraZeneca, Key Pharmaceutical Co, Ltd, Sanofi-Aventis, Inc, First Horizon, and Nycomed Amersham. All industrial funding in support of the trial was directed through the Department of Veterans Affairs. NR 29 TC 58 Z9 58 U1 0 U2 1 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 SEP PY 2008 VL 1 IS 1 BP 12 EP U33 DI 10.1161/CIRCOUTCOMES.108.798462 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V11AK UT WOS:000207504300005 PM 20031783 ER PT J AU Keenan, PS Normand, SLT Lin, ZQ Drye, EE Bhat, KR Ross, JS Schuur, JD Stauffer, BD Bernheim, SM Epstein, AJ Wang, YF Herrin, J Chen, J Federer, JJ Mattera, JA Wang, Y Krumholz, HM AF Keenan, Patricia S. Normand, Sharon-Lise T. Lin, Zhenqiu Drye, Elizabeth E. Bhat, Kanchana R. Ross, Joseph S. Schuur, Jeremiah D. Stauffer, Brett D. Bernheim, Susannah M. Epstein, Andrew J. Wang, Yongfei Herrin, Jeph Chen, Jersey Federer, Jessica J. Mattera, Jennifer A. Wang, Yun Krumholz, Harlan M. TI An Administrative Claims Measure Suitable for Profiling Hospital Performance on the Basis of 30-Day All-Cause Readmission Rates Among Patients With Heart Failure SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE health policy; heart failure; quality of health care AB Background-Readmission soon after hospital discharge is an expensive and often preventable event for patients with heart failure. We present a model approved by the National Quality Forum for the purpose of public reporting of hospital-level readmission rates by the Centers for Medicare & Medicaid Services. Methods and Results-We developed a hierarchical logistic regression model to calculate hospital risk-standardized 30-day all-cause readmission rates for patients hospitalized with heart failure. The model was derived with the use of Medicare claims data for a 2004 cohort and validated with the use of claims and medical record data. The unadjusted readmission rate was 23.6%. The final model included 37 variables, had discrimination ranging from 15% observed 30-day readmission rate in the lowest predictive decile to 37% in the upper decile, and had a c statistic of 0.60. The 25th and 75th percentiles of the risk-standardized readmission rates across 4669 hospitals were 23.1% and 24.0%, with 5th and 95th percentiles of 22.2% and 25.1%, respectively. The odds of all-cause readmission for a hospital 1 standard deviation above average was 1.30 times that of a hospital 1 standard deviation below average. State-level adjusted readmission rates developed with the use of the claims model are similar to rates produced for the same cohort with the use of a medical record model (correlation, 0.97; median difference, 0.06 percentage points). Conclusions-This claims-based model of hospital risk-standardized readmission rates for heart failure patients produces estimates that may serve as surrogates for those derived from a medical record model. ( Circ Cardiovasc Qual Outcomes. 2008;1:29-37.) C1 [Keenan, Patricia S.; Epstein, Andrew J.; Krumholz, Harlan M.] Yale Univ, Sch Med, Sch Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06520 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lin, Zhenqiu; Drye, Elizabeth E.; Bhat, Kanchana R.; Mattera, Jennifer A.; Wang, Yun; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 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. [Ross, Joseph S.] HSR&D Targeted Res Enhancement Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Schuur, Jeremiah D.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Schuur, Jeremiah D.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Stauffer, Brett D.] Baylor Univ, Med Hosp Syst, Dallas, TX USA. [Bernheim, Susannah M.] Yale New Haven Hlth Syst, Performance Management, New Haven, CT USA. [Wang, Yongfei; Herrin, Jeph; Chen, Jersey; Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. [Federer, Jessica J.] Bayer Healthcare Pharmaceut, Wayne, NJ USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Internal Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Sch Publ Hlth, Sect Hlth Policy & Adm, Room I-456 SHM,333 Cedar St,POB 208088, New Haven, CT 06520 USA. EM harlan.krumholz@yale.edu FU Department of Veterans Affairs; CMS; US Department of Health and Human Services; [HHSM-500-2005-CO001C] FX The authors thank Dima Turkmani, Maureen O'Brien, and Debra Chromik at the Colorado Foundation for Medical Care; Geoffrey Schreiner from the Center for Outcomes Research and Evaluation, Yale-New Haven Hospital; Angela Merrill and Eric Schone from Mathematica Policy Research; and Lein Han and Michael Rapp at CMS for their contributions to this work. CMS reviewed and approved the use of its data for this work and approved submission of the manuscript.; Drs Stauffer and Schuur were funded by the Department of Veterans Affairs during the time the work was conducted. The analyses on which this publication is based were performed under contract No. HHSM-500-2005-CO001C, entitled "Utilization and Quality Control Quality Improvement Organization for the State (Commonwealth) of Colorado," funded by the CMS, an agency of the US Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. The authors assume full responsibility for the accuracy and completeness of the ideas presented. NR 29 TC 226 Z9 227 U1 3 U2 13 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 SEP PY 2008 VL 1 IS 1 BP 29 EP U56 DI 10.1161/CIRCOUTCOMES.108.802686 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V11AK UT WOS:000207504300007 PM 20031785 ER PT J AU Mahoney, EM Wang, KJ Cohen, DJ Hirsch, AT Alberts, MJ Eagle, K Mosse, F Jackson, JD Steg, PG Bhatt, DL AF Mahoney, Elizabeth M. Wang, Kaijun Cohen, David J. Hirsch, Alan T. Alberts, Mark J. Eagle, Kim Mosse, Frederique Jackson, Joseph D. Steg, P. Gabriel Bhatt, Deepak L. CA REACH Registry Investigators TI One-Year Costs in Patients With a History of or at Risk for Atherothrombosis in the United States SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE costs; coronary disease; cerebrovascular disorders; peripheral vascular disease; thrombosis AB Background-Atherothrombosis is the underlying cause of cardiovascular, cerebrovascular, and peripheral arterial disease and is the leading cause of death in the industrialized world. The objectives of the present study are ( 1) to examine the annual costs associated with vascular events and interventions that require hospitalization, as well as long-term medication use for the management of associated risk factors, in a US population of outpatients with multiple atherothrombotic risk factors or a history of symptomatic disease and ( 2) to compare costs across patient subgroups defined according to specific arterial bed(s) affected and the number of affected arterial beds. Methods and Results-The international REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled outpatients >= 45 years of age who had established coronary artery, cerebrovascular, or peripheral artery disease or >= 3 atherothrombotic risk factors. Data on risk factors, associated medications, and vascular hospitalizations and interventions were collected. Of the total 68 236-patient REACH cohort, 25 763 were enrolled from US sites. Complete 1-year data were available for 23 974 (93%) of the US patients. Annualized medication costs ranged from $2401 to $3481. Mean annual hospitalization costs per patient were $1344, $2864, $4824, and $8155 for patients with 0 (n = 6145), 1 (n = 14 353), 2 (n = 3106), and 3 (n = 370) affected arterial beds at baseline (P<0.0001 for trend). Among patients with 1 affected arterial bed, mean hospitalization costs were $2999, $2010, and $3911 for patients with coronary artery disease (n = 11 063), cerebrovascular disease (n = 2613), and peripheral arterial disease (n = 677), respectively. Annualized medication costs ranged from $2401 to $3481. Conclusions-These results reveal the high economic burden of atherothrombosis-related clinical events and procedures and the especially high economic burden associated with polyvascular disease. (Circ Cardiovasc Qual Outcomes. 2008; 1: 38-45.) C1 [Mahoney, Elizabeth M.; Wang, Kaijun; Cohen, David J.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Hirsch, Alan T.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Alberts, Mark J.] Northwestern Univ, Sch Med, Chicago, IL USA. [Eagle, Kim] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Mosse, Frederique] Sanofi Aventis, Paris, France. [Jackson, Joseph D.] Bristol Myers Squibb Co, Princeton, NJ USA. [Steg, P. Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris 18, France. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Mahoney, EM (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM emahoney1@saint-lukes.org FU Sanofi-Aventis; Bristol-Myers Squibb FX This study was supported by a grant from Sanofi-Aventis and Bristol-Myers Squibb. NR 22 TC 73 Z9 73 U1 0 U2 2 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 SEP PY 2008 VL 1 IS 1 BP 38 EP U68 DI 10.1161/CIRCOUTCOMES.108.775247 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V11AK UT WOS:000207504300008 PM 20031786 ER PT J AU Chen, SM Cheng, DS Williams, BJ Sherrill, TP Han, W Chont, M Saint-Jean, L Christman, JW Sadikot, RT Yull, FE Blackwell, TS AF Chen, S. M. Cheng, D. -S. Williams, B. J. Sherrill, T. P. Han, W. Chont, M. Saint-Jean, L. Christman, J. W. Sadikot, R. T. Yull, F. E. Blackwell, T. S. TI The nuclear factor kappa-B pathway in airway epithelium regulates neutrophil recruitment and host defence following Pseudomonas aeruginosa infection SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE chemokines; immune regulation; infections; lung immunology; transgenics ID VENTILATOR-ASSOCIATED PNEUMONIA; MACROPHAGE INFLAMMATORY PROTEIN-2; MYELOID DIFFERENTIATION FACTOR-88; INNATE IMMUNE-RESPONSE; ALVEOLAR MACROPHAGES; LUNG INFLAMMATION; RESPIRATORY EPITHELIUM; CELLS; EXPRESSION; ACTIVATION AB Pseudomonas aeruginosa pneumonia usually results from a deficit of the innate immune system. To investigate whether inflammatory signalling by airway epithelial cells provides a pivotal line of defence against P. aeruginosa infection, we utilized two separate lines of inducible transgenic mice that express a constitutive activator of the nuclear factor kappa-B (NF-kappa B) pathway (IKTA) or a dominant inhibitor of NF-kappa B (DNTA) in airway epithelial cells. Compared with control mice, IKTA mice showed an enhanced host response to P. aeruginosa infection with greater neutrophil influx into the lungs, increased expression of Glu-Leu-Arg-positive (ELR+) CXC chemokines macrophage inflammatory protein-2 and keratinocyte chemoattractant (KC), superior bacterial clearance and improved survival at 24 h after infection. Neutrophil depletion abrogated the improvement in host defence identified in IKTA mice. In contrast, DNTA mice showed impaired responses to P. aeruginosa infection with higher bacterial colony counts in the lungs, decreased neutrophilic lung inflammation and lower levels of KC in lung lavage fluid. DNTA mice given recombinant KC at the time of P. aeruginosa infection demonstrated improved neutrophil recruitment to the lungs and enhanced bacterial clearance. Our data indicate that the NF-kappa B pathway in airway epithelial cells plays an essential role in defence against P. aeruginosa through generation of CXC chemokines and recruitment of neutrophils. C1 [Blackwell, T. S.] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. [Chont, M.; Saint-Jean, L.; Yull, F. E.; Blackwell, T. S.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA. [Chen, S. M.; Cheng, D. -S.; Williams, B. J.; Sherrill, T. P.; Han, W.; Blackwell, T. S.] Vanderbilt Univ, Sch Med, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37232 USA. [Christman, J. W.; Sadikot, R. T.; Blackwell, T. S.] Univ Illinois, US Dept Vet Affairs, Chicago, IL USA. [Christman, J. W.; Sadikot, R. T.] Univ Illinois, Sect Pulm Crit Care & Sleep Med, Chicago, IL USA. RP Blackwell, TS (reprint author), Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Dept Cell & Dev Biol, T-1218 Med Ctr N,1161 21st Ave S, Nashville, TN 37232 USA. EM timothy.blackwell@vanderbilt.edu FU NHLBI NIH HHS [HL61419, HL66196, R01 HL061419, T32 HL007123, P01 HL066196, HL07123] NR 38 TC 18 Z9 18 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD SEP PY 2008 VL 153 IS 3 BP 420 EP 428 DI 10.1111/j.1365-2249.2008.03707.x PG 9 WC Immunology SC Immunology GA 336PD UT WOS:000258376200014 PM 18647324 ER PT J AU Kleer, CG Bloushtain-Qimron, N Chen, YH Carrasco, D Hu, M Yao, J Kraeft, SK Collins, LC Sabel, MS Argani, P Gelman, R Schnitt, SJ Krop, IE Polyak, K AF Kleer, Celina G. Bloushtain-Qimron, Noga Chen, Yu-Hui Carrasco, Daniel Hu, Min Yao, Jun Kraeft, Stine-Kathrein Collins, Laura C. Sabel, Michael S. Argani, Pedram Gelman, Rebecca Schnitt, Stuart J. Krop, Ian E. Polyak, Kornelia TI Epithelial and stromal cathepsin K and CXCL14 expression in breast tumor progression SO CLINICAL CANCER RESEARCH LA English DT Article ID CARCINOMA IN-SITU; CYSTEINE CATHEPSINS; MULTISTAGE TUMORIGENESIS; CHEMOKINE CXCL14; DENDRITIC CELLS; CANCER; GROWTH; TISSUE; ROLES; VIVO AB Purpose: To evaluate the expression of cathepsin K (CTSK) and CXCL14 in stroma land epithelial cells in human breast tumor progression. Experimental Design: We did immunohistochemical analyses of CTSK and CXCL14 expression in normal breast tissue, biopsy sites, benign lesions, ductal carcinoma in situ, and invasive breast tumors of different stages. Expression patterns were related to histopathologic characteristics of the tumors and clinical outcome. The effect of CTSK+ breast stromal fibroblasts on CTSK- breast cancer cells was assessed in coculture. Results: Epithelial expression of CTSK was rarely detected in any of the tissue samples analyzed, whereas CXCL14-positive epithelial cells were found in all tissue types. The expression of CXCL14 was not associated with any tumor or patient characteristics analyzed. Stromal CTSK expression was significantly higher in invasive compared with in situ carcinomas, and in one of the two data sets analyzed, it correlated with higher tumor stage. Among all samples examined, the highest stromal CTSK levels were detected in biopsy sites. Neither epithelial nor stromal expression of CTSK was significantly associated with recurrence-free or overall survival. Coculture of CTSK+ fibroblasts enhanced the invasion of CTSK- breast tumor epithelial cells and this was blocked by CTSK inhibitors. Conclusions: CTSK may function as a paracrine factor in breast tumorigenesis. CTSK+ fibroblasts may play a role in tumor progression by promoting the invasiveness of tumor epithelial cells. The possibility that CTSK inhibitors may have a clinical role in decreasing the risk of tumor progression merits further investigation. C1 [Bloushtain-Qimron, Noga; Carrasco, Daniel; Hu, Min; Yao, Jun; Krop, Ian E.; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kleer, Celina G.; Sabel, Michael S.] Univ Michigan, Ctr Canc, Dept Pathol, Ann Arbor, MI 48109 USA. [Kleer, Celina G.; Sabel, Michael S.] Univ Michigan, Ctr Canc, Dept Surg, Ann Arbor, MI 48109 USA. [Chen, Yu-Hui; Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hu, Min; Yao, Jun; Kraeft, Stine-Kathrein; Collins, Laura C.; Gelman, Rebecca; Schnitt, Stuart J.; Krop, Ian E.; Polyak, Kornelia] Harvard Univ, Sch Med, Boston, MA USA. [Gelman, Rebecca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kraeft, Stine-Kathrein; Collins, Laura C.; Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Argani, Pedram] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Bloushtain-Qimron, Noga] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St D740C, Boston, MA 02115 USA. EM Kornelia-Polyak@dfci.harvard.edu RI Sabel, Michael/A-7521-2009 FU National Cancer Institute SPORE in Breast Cancer [CA89393]; Dana-Farber/Harvard Cancer Center [CA006516]; Department of Defense [W81XWH-04-1-0452, BCO30054]; National Cancer Institute [CA116235, CA107469, CA090876]; American Cancer Society [RSG-05-154-01-MGO]; Susan G. Komen Foundation FX National Cancer Institute SPORE in Breast Cancer grant CA89393 and Dana-Farber/Harvard Cancer Center grant CA006516 (S.J. Schnitt, R. Gelman, Y-H. Chen, and K. Polyak); Department of Defense grant W81XWH-04-1-0452, National Cancer Institute grant CA116235, and American Cancer Society grant RSG-05-154-01-MGO (K. Polyak); Susan G. Komen Foundation fellowship (M. Hu), Department of Defense grant BCO30054 (P. Argani); and National Cancer Institute grants CA107469 and CA090876 (C.G. Kleer). NR 32 TC 47 Z9 49 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 SEP 1 PY 2008 VL 14 IS 17 BP 5357 EP 5367 DI 10.1158/1078-0432.CCR-08-0732 PG 11 WC Oncology SC Oncology GA 347UG UT WOS:000259166000008 PM 18765527 ER PT J AU de Bazelaire, C Alsop, DC George, D Pedrosa, I Wang, YY Michaelson, MD Rofsky, NM AF de Bazelaire, Cedric Alsop, David C. George, Daniel Pedrosa, Ivan Wang, Yongyu Michaelson, M. Dror Rofsky, Neil M. TI Magnetic resonance imaging - Measured blood flow change after antiangiogenic therapy with PTK787/ZK 222584 correlates with clinical outcome in metastatic renal cell carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; ADVANCED CANCER; PHASE-I; ANGIOGENESIS; TUMOR; INHIBITOR; COMBINATION; MECHANISMS; EXPRESSION AB Purpose: To measure changes in tumor blood flow following treatment with PTK787/ZK 222584, a pan -vascular enclothelial growth factor receptor tyrosine kinase inhibitor, and their association with clinical response in patients with metastatic renal cell carcinoma. Experimental Design: In 10 patients with metastatic renal cell carcinoma treated with PTK787/ ZK 222584, tumor blood flow was evaluated by arterial spin labeling (ASL) magnetic resonance imaging before and 1 month on treatment. Changes in blood flow after 1 month of treatment were compared with bidimensional tumor response at 4 months of treatment using the Mann-Whitney test. Results: Changes in blood flow at 1 month and changes in tumor size measured at 4 months or at time of disease progression were significantly correlated (P = 0.01). Patients with progressive disease within 4 months on treatment (n = 4) had a nonsignificant increase in tumor blood flow at 1 month (+25 33%; P = 0.43), whereas patients with stable disease or partial response at 4 months (n = 6) had a significant decrease in tumor blood flow at 1 month (-42 +/- 22%; P = 0.02). Conclusion: These results suggest that decreasing tumor blood flow with PTK787/ZK 222584 therapy, as shown as soon as 1 month on therapy by ASL, may predict for a favorable clinical outcome. These data are consistent with a hypothetical functional role for tumor ischemia in the mechanism of response to anti -vascular enclothelial growth factor therapy. ASL blood flow magnetic resonance imaging shows promise as an early predictor of clinical response to antiangiogenic therapies. C1 [Alsop, David C.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Michaelson, M. Dror] Massachusetts Gen Hosp, Boston, MA 02114 USA. [George, Daniel] Dana Farber Canc Inst, Boston, MA 02115 USA. [Alsop, David C.; Pedrosa, Ivan; Rofsky, Neil M.] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Yongyu] Novartis Oncol, E Hanover, NJ USA. RP Alsop, DC (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, Ansin 226,330 Brookline Ave, Boston, MA 02215 USA. EM dalsop@bidmc.harvard.edu RI Alsop, David/J-5764-2013; OI Alsop, David/0000-0002-8206-1995; Michaelson, Dror/0000-0001-9249-6338 FU NCI NIH HHS [R21 CA121570] NR 32 TC 72 Z9 72 U1 1 U2 8 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 SEP 1 PY 2008 VL 14 IS 17 BP 5548 EP 5554 DI 10.1158/1078-0432.CCR-08-0417 PG 7 WC Oncology SC Oncology GA 347UG UT WOS:000259166000028 PM 18765547 ER PT J AU Jiang, Z Chu, PG Woda, BA Liu, Q Balaji, KC Rock, KL Wu, CL AF Jiang, Zhong Chu, Peigou G. Woda, Bruce A. Liu, Qin Balaji, K. C. Rock, Kenneth L. Wu, Chin-Lee TI Combination of quantitative IMP3 and tumor stage: A new system to predict metastasis for patients with localized renal cell carcinomas SO CLINICAL CANCER RESEARCH LA English DT Article ID RNA-BINDING PROTEIN; PROGNOSTIC FACTORS; INTERFERON-ALPHA; CANCER; NEPHRECTOMY; THERAPY; SUNITINIB; SURVIVAL; MARKER; DOMAIN AB Purpose: To create an easily applicable system based on a combination of the quantitative level of IMP3 (an oncofetal protein) and tumor stage to more accurately predict postoperative metastasis of localized renal cell carcinoma. Experimental Design: Three hundred sixty nine patients with localized renal cell carcinoma (without metastasis during nephrectomy) were investigated by the use of survival analysis. The expression of IMP3 was evaluated by immunohistochemistry and quantitated with a computerized image analyzer. Based on combining quantitative IMP3 results with tumor staging (QITS system), patients were divided into four distinct risk groups for the development of metastasis. Results: The four groups of patients in the QITS system showed significant differences in their metastasis-free (P < 0.0001) and overall survivals (P < 0.0001). Almost all patients of group IV with localized renal cell carcinomas developed metastasis and died after nephrectomy. The 5- and 10-year metastasis-free survival rates for the QITS groups were as follows: for group 1, 97% and 91%; 11, 62% and 55%; 111, 46% and 19%; and IV, 17% and 4%, respectively. The 5- and 10-year overall survival rates for the QITS groups were as follows: for group 1, 89% and 72%; 11, 58% and 41%; 111, 38% and 17%; and IV, 14% and 4%, respectively. Conclusions: The QITS is a simple and accurate system for the prediction of tumor metastasis. This system not only provides important prognostic information but also can be used at initial diagnosis of localized renal cell carcinoma to identify high-risk patients who may benefit from early systematic therapy. C1 [Jiang, Zhong; Woda, Bruce A.; Rock, Kenneth L.] Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA USA. [Liu, Qin] Univ Massachusetts, Med Ctr, Dept Med, Div Prevent & Behav Med,Biostat Res Grp, Worcester, MA USA. [Balaji, K. C.] Univ Massachusetts, Med Ctr, Dept Surg, Div Urol, Worcester, MA USA. [Chu, Peigou G.] City Hope Natl Med Ctr, Div Pathol, Los Angeles, CA USA. [Wu, Chin-Lee] Harvard Med Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Jiang, Z (reprint author), Dept Pathol Three Biotech, 1 Innovat Dr, Worcester, MA 01605 USA. EM jiangz@ummhc.org NR 31 TC 51 Z9 59 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 SEP 1 PY 2008 VL 14 IS 17 BP 5579 EP 5584 DI 10.1158/1078-0432.CCR-08-0504 PG 6 WC Oncology SC Oncology GA 347UG UT WOS:000259166000032 PM 18765551 ER PT J AU Haining, WN Davies, J Kanzler, H Drury, L Brenn, T Evans, J Angelosanto, J Rivoli, S Russell, K George, S Sims, P Neuberg, D Li, XC Kutok, J Morgan, J Wen, P Demetri, G Coffman, RL Nadler, LM AF Haining, W. Nicholas Davies, Jeffrey Kanzler, Holger Drury, Linda Brenn, Thomas Evans, John Angelosanto, Jill Rivoli, Steven Russell, Kate George, Suzanne Sims, Paul Neuberg, Donna Li, Xiaochun Kutok, Jeffrey Morgan, Jeffrey Wen, Patrick Demetri, George Coffman, Robert L. Nadler, Lee M. TI CpG oligodeoxynucleotides alter lymphocyte and dendritic cell trafficking in humans SO CLINICAL CANCER RESEARCH LA English DT Article ID CD8(+) T-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; ANTITUMOR IMMUNITY; GENE-EXPRESSION; INNATE IMMUNITY; OVARIAN-CANCER; CUTTING EDGE; PHASE-II; RESPONSES AB Purpose: CpG oligodeoxynucleotides (CpG-ODN) are being investigated as cancer vaccine adjuvants because they mature plasmacytoid dendritic cells (PDC) into potent antigen-presenting cells. CpG-ODN also induce PDC to secrete chemokines that alter lymphocyte migration. Whether CpG-ODN TLR signals enhance antigen-specific immunity and/or trafficking in humans is unknown. Experimental Design: We conducted a phase I study of CpG-ODN (1018 ISS) given as a vaccine adjuvant with granulocyte-macrophage colony-stimulating factor (GM-CSF) to induce T-cell immunity to a peptide vaccine from the tumor-associated antigen hTERT. Results: The adjuvant effect was limited; only 1 of 16 patients showed a high-frequency hTERT-specific tetramer CD8(+) T-cell response. However, CpG-ODN induced marked, transient peripheral blood lymphopenia. Biopsies showed dense lymphocytic infiltration at the vaccine site clustered around activated PDC. In vitro, CpG-ODN-treated PDC induced T-cell migration, showing that CpG-ODN stimulation of human PDC was sufficient to chemoattract T cells. Conclusions: Our results show that (a) CpG-ODN with GM-CSF may not be an effective adjuvant strategy for hTERT peptide vaccines but (b) GM-CSF/CpG-ODN causesa PDC-mediated chemokine response that recruits T-cell migration to the peripheral tissues. These findings suggest a novel therapeutic role for targeted injections of CpG-ODN to direct lymphocyte migration to specific sites such as the tumorbed. C1 [Davies, Jeffrey; Drury, Linda; Evans, John; Angelosanto, Jill; Rivoli, Steven; Russell, Kate; George, Suzanne; Morgan, Jeffrey; Wen, Patrick; Demetri, George; Nadler, Lee M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Haining, W. Nicholas] Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. [Haining, W. Nicholas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Neuberg, Donna; Li, Xiaochun] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kutok, Jeffrey] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kanzler, Holger; Sims, Paul; Coffman, Robert L.] Dynavax Technol Corp, Berkeley, CA USA. RP Nadler, LM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM lee_nadler@dfci.harvard.edu NR 50 TC 38 Z9 39 U1 0 U2 1 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 SEP 1 PY 2008 VL 14 IS 17 BP 5626 EP 5634 DI 10.1158/1078-0432.CCR-08-0526 PG 9 WC Oncology SC Oncology GA 347UG UT WOS:000259166000038 PM 18765557 ER PT J AU Bonaca, MP Morrow, DA AF Bonaca, Marc P. Morrow, David A. TI Defining a role for novel biomarkers in acute coronary syndromes SO CLINICAL CHEMISTRY LA English DT Review ID C-REACTIVE PROTEIN; CARDIAC TROPONIN-I; ELEVATION MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; STATIN THERAPY; CLINICAL-APPLICATION; RANDOMIZED-TRIAL; UNSTABLE ANGINA; ARTERY-DISEASE; HEART-DISEASE AB BACKGROUND: Biomarkers play a pivotal role in the diagnosis and treatment of patients with cardiovascular disease. Active investigation has brought forward an increasingly large number of novel candidate markers; however, few of these markers have yet to be incorporated into routine clinical use. CONTENT: This review discusses biomarkers currently used in the setting of acute coronary syndromes. In this context, we assess the contemporary unmet needs for novel biomarkers in acute ischemic heart disease and the related challenges faced in developing new biomarkers to the point of integration into clinical practice. In particular, we address the impact of the availability of increasingly sensitive biomarkers of myocardial necrosis on the potential roles for novel biomarkers of inflammation, thrombosis, and ischemia. SUMMARY: Although active investigation has produced a growing list of candidate novel biomarkers for the care of patients with cardiovascular disease, it has become increasingly challenging to find appreciable incremental clinical benefit for their addition to existing markers, in particular newer, more analytically sensitive cardiac troponin assays. A major challenge for researchers and clinicians will be to demonstrate whether candidate novel markers are useful in improving diagnosis and guiding clinical treatment. (C) 2008 American Association for Clinical Chemistry. C1 [Bonaca, Marc P.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 40 TC 16 Z9 18 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2008 VL 54 IS 9 BP 1424 EP 1431 DI 10.1373/clinchem.2008.105387 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 344CC UT WOS:000258902000005 PM 18641043 ER PT J AU Strate, LL Ayanian, JZ Kotler, G Syngal, S AF Strate, Lisa L. Ayanian, John Z. Kotler, Gregory Syngal, Sapna TI Risk factors for mortality in lower intestinal bleeding SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID LOWER-GASTROINTESTINAL HEMORRHAGE; HOSPITAL VOLUME; UNITED-STATES; SINGLE-CENTER; COLONOSCOPY; MANAGEMENT; PREDICTION; VALIDATION; EXPERIENCE; SURGERY AB Background & Aims: Previous studies of lower intestinal bleeding (LIB) have limited power to study mortality. We sought to identify characteristics associated with in-hospital mortality in a large cohort of patients with LIB. Methods: We used the 2002 Healthcare Cost and Utilization Project Nationwide Inpatient Sample to study a cross-sectional cohort of 227,022 hospitalized patients with discharge diagnoses indicating LIB. Predictors of mortality were identified by using multiple logistic regression. Results: In 2002, an estimated 8737 patients with LIB (3.9%) died while hospitalized. Independent predictors of in-hospital mortality were age (age >70 vs <50 years; odds ratio [OR], 4.91; 95% confidence interval [CI], 2.45-9.87), intestinal ischemia (OR, 3.47; 95% CI, 2.57-4.68), comorbid illness (>= 2 vs 0 comorbidities, OR, 3.00; 95% CI, 2.25-3.98), bleeding while hospitalized for a separate process (OR, 2.35; 95% CI, 1.81-3.04), coagulation defects (OR, 2.34; 95% CI, 1.50-3.65), hypovolemia (OR, 2.22; 95% CI, 1.69-2.90), transfusion of packed red blood cells (OR, 1.60; 95% CI, 1.23-2.08), and male gender (OR, 1.52; 95% CI, 1.21-1.92). Colorectal polyps (OR, 0.26; 95% CI, 0.15-0.45), and hemorrhoids (OR, 0.42; 95% CI, 0.28-0.64) were associated with a lower risk of mortality, as was diagnostic testing for LIB when added to the multivariate model (OR, 0.37; 95% CI, 0.28-0.48). Hospital characteristics were not significantly related to mortality. Predictors of mortality were similar in an analysis restricted to patients with diverticular bleeding. Conclusions: The all-cause in-hospital mortality rate in LIB was low (3.9%). Advanced age, intestinal ischemia, and comorbid illness were the strongest predictors of mortality. C1 [Strate, Lisa L.] Univ Washington, Harborview Med Ctr, Sch Med, Div Gastroenterol, Seattle, WA 98104 USA. [Ayanian, John Z.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Ayanian, John Z.] Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Kotler, Gregory] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. RP Strate, LL (reprint author), Univ Washington, Harborview Med Ctr, Sch Med, Div Gastroenterol, 325 9th Ave,Box 359773, Seattle, WA 98104 USA. EM lstrate@u.washington.edu FU Agency for Healthcare Research and Quality [K08 HS14062]; American Society for Gastrointestinal Endscopy; National Cancer Institute [K24 CA113433] FX This study was funded by grants from the Agency for Healthcare Research and Quality (K08 HS14062, L.L.S.), the American Society for Gastrointestinal Endscopy (L.L.S.), and the National Cancer Institute (K24 CA113433, S.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHRQ, ASGE, or NCI. NR 20 TC 52 Z9 53 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2008 VL 6 IS 9 BP 1004 EP 1010 DI 10.1016/j.cgh.2008.03.021 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 349GM UT WOS:000259269300013 PM 18558513 ER PT J AU Segal, BH Herbrecht, R Stevens, DA Ostrosky-Zeichner, L Sobel, J Viscoli, C Walsh, TJ Maertens, J Patterson, TF Perfect, JR Dupont, B Wingard, JR Calandra, T Kauffman, CA Graybill, JR Baden, LR Pappas, PG Bennett, JE Kontoyiannis, DP Cordonnier, C Viviani, MA Bille, J Almyroudis, NG Wheat, LJ Graninger, W Bow, EJ Holland, SM Kullberg, BJ Dismukes, WE De Pauw, BE AF Segal, Brahm H. Herbrecht, Raoul Stevens, David A. Ostrosky-Zeichner, Luis Sobel, Jack Viscoli, Claudio Walsh, Thomas J. Maertens, Johan Patterson, Thomas F. Perfect, John R. Dupont, Bertrand Wingard, John R. Calandra, Thierry Kauffman, Carol A. Graybill, John R. Baden, Lindsey R. Pappas, Peter G. Bennett, John E. Kontoyiannis, Dimitrios P. Cordonnier, Catherine Viviani, Maria Anna Bille, Jacques Almyroudis, Nikolaos G. Wheat, L. Joseph Graninger, Wolfgang Bow, Eric J. Holland, Steven M. Kullberg, Bart-Jan Dismukes, William E. De Pauw, Ben E. TI Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses study group and European Organization for Research and Treatment of Cancer consensus criteria SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID RECONSTITUTION INFLAMMATORY SYNDROME; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CELL TRANSPLANT RECIPIENTS; BETA-D-GLUCAN; AMPHOTERICIN-B; PULMONARY ASPERGILLOSIS; BACTERIAL-MENINGITIS; ANTIFUNGAL THERAPY; DISSEMINATED HISTOPLASMOSIS; CRYPTOCOCCAL MENINGITIS AB Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge. C1 [Segal, Brahm H.; Almyroudis, Nikolaos G.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Perfect, John R.] Duke Univ, Med Ctr, Durham, NC USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, San Antonio, TX USA. [Ostrosky-Zeichner, Luis] Univ Texas Hlth Sci Ctr Houston, San Antonio, TX USA. [Patterson, Thomas F.; Graybill, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Sobel, Jack] Wayne State Univ, Sch Med, Detroit, MI USA. [Wingard, John R.] Univ Florida, Coll Med, Gainesville, FL USA. [Stevens, David A.] Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. [Herbrecht, Raoul] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Pappas, Peter G.; Dismukes, William E.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Bennett, John E.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Wheat, L. Joseph] MiraVista Diagnost MiraBella Technol, Indianapolis, IN USA. [Baden, Lindsey R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Div Infect Dis, Cambridge, MA 02138 USA. [Bow, Eric J.] Univ Manitoba, Winnipeg, MB, Canada. [De Pauw, Ben E.] Univ Med Ctr St Raboud, Nijmegen, Netherlands. [Kullberg, Bart-Jan] Univ Nijmegen, Med Ctr, Dept Med, Nijmegen, Netherlands. [Kullberg, Bart-Jan] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Bille, Jacques] Univ Lausanne Hosp, Inst Microbiol, Lausanne, Switzerland. [Calandra, Thierry] CHU Vaudois, Dept Med, Infect Dis Serv, CH-1011 Lausanne, Switzerland. [Calandra, Thierry] Univ Lausanne, Lausanne, Switzerland. [Herbrecht, Raoul] Hosp Hautepierre, Dept Hematol & Oncol, Strasbourg, France. [Dupont, Bertrand] Hop Necker Enfants Malad, Paris, France. [Cordonnier, Catherine] Hop Henri Mondor, APHP, F-94010 Creteil, France. [Cordonnier, Catherine] Univ Paris 12, Creteil, France. [Graninger, Wolfgang] Med Univ Vienna, Vienna, Austria. [Graninger, Wolfgang] Univ Hosp Vienna, Div Infect Dis, Vienna, Austria. [Viviani, Maria Anna] Univ Milan, Dept Publ Hlth Microbiol & Virol, Sect Publ Hlth, Milan, Italy. [Viscoli, Claudio] Univ Genoa, Genoa, Italy. [Viscoli, Claudio] San Martino Univ Hosp, Div Infect Dis, Genoa, Italy. [Maertens, Johan] Univ Hosp Gasthuisberg, Dept Hematol, Acute Leukemia & Hematopoiet Stem Cell Transplant, B-3000 Louvain, Belgium. RP Segal, BH (reprint author), Roswell Pk Canc Inst, Dept Med, Elm & Carlton Sts, Buffalo, NY 14263 USA. EM brahm.segal@roswellpark.org RI Herbrecht, Raoul/D-3471-2013; Kullberg, Bart Jan/C-8520-2013; Calandra, Thierry/D-9017-2015; OI Calandra, Thierry/0000-0003-3051-1285; Herbrecht, Raoul/0000-0002-9381-4876 FU Intramural NIH HHS [Z01 AI000654-16] NR 78 TC 172 Z9 185 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2008 VL 47 IS 5 BP 674 EP 683 DI 10.1086/590566 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 333VN UT WOS:000258181000013 PM 18637757 ER PT J AU Bassett, IV Farel, C Szmuilowicz, ED Walensky, RP AF Bassett, Ingrid V. Farel, Claire Szmuilowicz, Emily D. Walensky, Rochelle P. TI AIDS Drug Assistance Programs in the era of routine HIV testing SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; HEPATITIS-C; HEALTH-CARE; INFECTION; DISEASE; OUTPATIENT; COSTS AB AIDS [Acquired Immunodeficiency Syndrome] Drug Assistance Programs, operating within the larger Ryan White Program, are state-based, discretionary programs that provide a drug "safety net" for low-income and uninsured individuals infected with human immunodeficiency virus (HIV). Although the AIDS Drug Assistance Programs and the primary care system that provides care for patients with HIV infection are already financially stressed, the Centers for Disease Control and Prevention recently issued guidelines recommending universal HIV testing to help identify the estimated 300,000 individuals in the United States who are unaware that they are infected with HIV. As the number of people living with HIV/AIDS who are coinfected with hepatitis C virus has grown and the cost and complexity of care have increased, the sustainability of the current HIV care system requires a reevaluation in light of the new testing guidelines. We examine the current state of the AIDS Drug Assistance Programs, discuss the implications of the Centers for Disease Control and Prevention guidelines for the already overstretched Ryan White Program, and consider a federally supported national program to ensure high-quality, efficient HIV care for low-income HIV-infected Americans. C1 [Bassett, Ingrid V.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bassett, Ingrid V.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Farel, Claire] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Szmuilowicz, Emily D.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. RP Bassett, IV (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM ibassett@partners.org FU NIAID NIH HHS [K23 AI068458-03, K23 AI068458, K23AI068458]; NIMH NIH HHS [R01 MH073445, R01 MH065869] NR 45 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2008 VL 47 IS 5 BP 695 EP 701 DI 10.1086/590936 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 333VN UT WOS:000258181000017 PM 18643759 ER PT J AU Weisbord, SD Mor, MK Resnick, AL Hartwig, KC Palevsky, PM Fine, MJ AF Weisbord, Steven D. Mor, Maria K. Resnick, Abby L. Hartwig, Kathryn C. Palevsky, Paul M. Fine, Michael J. TI Incidence and outcomes of contrast-induced AKI following computed tomography SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HIGH-RISK PATIENTS; RANDOMIZED CONTROLLED-TRIAL; INDUCED NEPHROPATHY; RENAL-FUNCTION; CORONARY-ANGIOGRAPHY; CARDIAC ANGIOGRAPHY; N-ACETYLCYSTEINE; MEDIA; PREVENTION; IODIXANOL AB Background and objectives: Most studies of contrast-induced acute kidney injury (CIAKI) have focused on patients undergoing angiographic procedures. The incidence and outcomes of CIAKI in patients undergoing nonemergent, contrast-enhanced computed tomography in the inpatient and outpatient setting were assessed. Design, setting, participants, & measurements: Patients with estimated glomerular filtration rates (GFRs) <60 ml/min per 1.73 m(2) undergoing nonemergent computed tomography with intravenous iodinated radiocontrast at an academic VA Medical Center were prospectively identified. Serum creatinine was assessed 48 to 96 h postprocedure to quantify the incidence of CIAKI, and the need for postprocedure dialysis, hospital admission, and 30-d mortality was tracked to examine the associations of CIAKI with these medical outcomes. Results: A total of 421 patients with a median estimated GFR of 53 ml/min per 1.73 m(2) were enrolled. Overall, 6.5% of patients developed an increase in serum creatinine >= 25%, and 3.5% demonstrated a rise in serum creatinine >= 0.5 mg/dl. Although only 6% of outpatients received preprocedure and postprocedure intravenous fluid, <1% of outpatients with estimated GFRs >45 ml/min per 1.73 m(2) manifested an increase in serum creatinine >= 0.5 mg/dl. None of the study participants required postprocedure dialysis. Forty-six patients (10.9%) were hospitalized and 10 (2.4%) died by 30-d follow-up; however, CIAKI was not associated with these outcomes. Conclusions: Clinically significant CIAKI following nonemergent computed tomography is uncommon among outpatients with mild baseline kidney disease. These findings have important implications for providers ordering and performing computed tomography and for future clinical trials of CIAKI. C1 [Weisbord, Steven D.; Mor, Maria K.; Resnick, Abby L.; Hartwig, Kathryn C.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Hartwig, Kathryn C.; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Mailstop 111F-U,7E Room 120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu FU VA Health Services Research and Development Career Development Award [RCD 03176]; VA Stars and Stripes Competitive Pilot Project; National Institute of Allergy and Infectious Diseases [K24 AI001769] FX This work was supported by a VA Health Services Research and Development Career Development Award of Dr. Weisbord (RCD 03176) and a VA Stars and Stripes Competitive Pilot Project Fund Award. Dr. Fine was supported in part by a mid-career development award (K24 AI001769) from the National Institute of Allergy and Infectious Diseases. NR 30 TC 101 Z9 104 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2008 VL 3 IS 5 BP 1274 EP 1281 DI 10.2215/CJN.01260308 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 342AR UT WOS:000258757500012 PM 18463172 ER PT J AU Winthrop, KL Nyendak, M Calvet, H Oh, P Lo, M Swarbrick, G Johnson, C Lewinsohn, DA Lewinsohn, DM Mazurek, GH AF Winthrop, Kevin L. Nyendak, Melissa Calvet, Helene Oh, Peter Lo, Melanie Swarbrick, Gwendolyn Johnson, Carol Lewinsohn, Deborah A. Lewinsohn, David M. Mazurek, Gerald H. TI Interferon-gamma release assays for diagnosing Mycobacterium tuberculosis infection in renal dialysis patients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SKIN-TEST; HEMODIALYSIS-PATIENTS; HIGH PREVALENCE; VACCINATION; ANERGY; CELLS AB Background and objectives: End-stage renal disease (ESRD) patients are at high risk for tuberculosis (TB). IFN-gamma release assays that assess immune responses to specific TB antigens offer potential advantages over tuberculin skin testing (TST) in screening such patients for Mycobacterium tuberculosis infection. This study sought to determine whether IFN-gamma release assay results are more closely associated with recent TB exposure than TST results. Design, setting, participants, and measures: Prospective cohort investigation of patients at a hemodialysis center with a smear-positive case of TB. Patients without a history of TB underwent initial and repeat testing with TST, and with the IFN-gamma assays QuantiFERON-TB Gold(R) (QFT-G) and ELISPOT test. Outcome measures included the prevalence of positive test results, identification of factors associated with positive results, and test result discordance. Results: A total of 100 (47% foreign born; median age, 55 yr, age range, 18 to 83 yr) of 124 eligible patients were enrolled. Twenty-six persons had positive TST results, 21 had positive QFT-G results, and 27 had positive ELISPOT results. Patients with TB case contact were likely to have a positive QFT-G result (P = 0.02) and ELISPOT results (P = 0.04), whereas TB case contact was not associated with positive TST results (P = 0.7). Positive TST results were associated with foreign birth (P = 0.04) and having had a TST in the previous year (P = 0.04). Conclusions: Positive IFN-gamma assay results were more closely associated with recent TB exposure than were positive TST results. QFT-G and ELISPOT might offer a better method for detecting TB infection in ESRD patients. C1 [Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. [Winthrop, Kevin L.; Mazurek, Gerald H.] Ctr Dis Control & Prevent, Div TB Eliminat, Natl Ctr HIV STD & TB Prevent, Atlanta, GA USA. [Johnson, Carol; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR USA. [Calvet, Helene] Long Beach Dept Hlth & Human Serv, Long Beach, CA USA. [Winthrop, Kevin L.; Oh, Peter; Lo, Melanie] Calif Dept Hlth Serv, Div Communicable Dis Control, Richmond, CA USA. RP Winthrop, KL (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM Winthrop@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 NR 22 TC 46 Z9 47 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2008 VL 3 IS 5 BP 1357 EP 1363 DI 10.2215/CJN.01010208 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 342AR UT WOS:000258757500023 PM 18550653 ER PT J AU Kramer, H Palmas, W Kestenbaum, B Cushman, M Allison, M Astor, B Shlipak, M AF Kramer, Holly Palmas, Walter Kestenbaum, Bryan Cushman, Mary Allison, Matt Astor, Brad Shlipak, Michael TI Chronic kidney disease prevalence estimates among racial/ethnic groups: The Multi-Ethnic Study of Atherosclerosis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SERUM CYSTATIN-C; GLOMERULAR-FILTRATION-RATE; CHINESE PATIENTS; RENAL-FUNCTION; CREATININE; MARKER; EQUATION AB Background and objectives: Muscle mass is not a major determinant of serum cystatin C levels, and its use to estimate GFR may lead to more congruent estimates of chronic kidney disease (CKD) across gender and racial/ethnic groups. Design, setting, participants, & measurements: The Multi-Ethnic Study of Atherosclerosis is a population-based study of 6814 men and women who are aged 45 to 85 yr and do not have clinical cardiovascular disease. Estimated CKD prevalence, defined as an estimated GFR <60 ml/min per 1.73 m(2) body surface area, was compared using three different GFR prediction equations: The abbreviated Modification of Diet in Renal Disease (MDRD) equation and two equations based on serum cystatin C. Results: Among women, CKD prevalence estimates across the four racial/ethnic groups using the MDRD- or the cystatin C-based GFR equations, which include gender and race coefficients, varied by approximately two-fold (P < 0.0001) but were more congruent with use of a serum cystatin C-based equation without the use of coefficients (P = 0.3). CKD prevalence estimates did not differ significantly across racial/ethnic groups among men with the MDRD (P = 0.07) or cystatin C formula without coefficients (P = 0.05) but did differ significantly with the cystatin C formula, which incorporates gender and race coefficients (P = 0.006). Conclusions: CKD prevalence estimates vary across racial/ethnic groups, and the degree of variability depends on the method used to estimate GFR, especially among women. Further research is needed to determine the accuracy and precision of GFR prediction equations in racially diverse populations. C1 [Kramer, Holly] Loyola Univ, Med Ctr, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA. [Kramer, Holly] Loyola Univ, Med Ctr, Div Nephrol, Maywood, IL 60153 USA. [Palmas, Walter] Columbia Univ, Dept Med, Div Gen Med, Mailman Sch Publ Hlth,Med Ctr, New York, NY USA. [Kestenbaum, Bryan] Univ Washington, Harborview Med Ctr, Div Nephrol, Seattle, WA 98104 USA. [Cushman, Mary] Univ Vermont, Dept Med, Colchester, VT USA. [Allison, Matt] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Astor, Brad] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Shlipak, Michael] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Shlipak, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kramer, H (reprint author), Loyola Med Ctr, Dept Epidemiol & Prevent Med, 2160 1st Ave, Maywood, IL 60153 USA. EM hkramer@lumc.edu OI Allison, Matthew/0000-0003-0777-8272 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95166]; American Heart Association Established Investigator Award [R01 DK066488-01] FX This research was supported by contracts N01-HC-95159 through N01-HC-95166 from the National Heart, Lung, and Blood Institute. M.S. is supported by R01 DK066488-01 and the American Heart Association Established Investigator Award. NR 22 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2008 VL 3 IS 5 BP 1391 EP 1397 DI 10.2215/CJN.04160907 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 342AR UT WOS:000258757500028 PM 18550650 ER PT J AU Heher, EC Thier, SO Rennke, H Humphreys, BD AF Heher, Eliot C. Thier, Samuel O. Rennke, Helmut Humphreys, Benjamin D. TI Adverse renal and metabolic effects associated with oral sodium phosphate bowel preparation SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID ELECTROLYTE LAVAGE SOLUTION; PHOSPHORUS-INDUCED NEPHROCALCINOSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYETHYLENE-GLYCOL; SEVERE HYPERPHOSPHATEMIA; HYPOPHOSPHATEMIC RICKETS; FATAL HYPERPHOSPHATEMIA; EXTRASKELETAL CALCIFICATION; EXTREME HYPERPHOSPHATEMIA; HYPOCALCEMIC TETANY AB Colorectal cancer can be prevented by the removal of adenomatous polyps during screening colonoscopy, but adequate bowel preparation is required. Oral sodium phosphate (OSP), an effective bowel purgative, is available over the counter and requires a substantially lower volume than polyethylene glycol-based preparative agents. Accumulating reports implicate OSP in electrolyte disturbances as well as acute kidney injury (AKI) in a syndrome termed phosphate nephropathy (a form of nephrocalcinosis). Despite published case reports and case series, the actual incidence, risk factors, and natural history of phosphate nephropathy remain largely undefined. Several recent observational studies have provided new information on these important issues while supporting a link between OSP and acute phosphate nephropathy as well as the development of chronic kidney disease in elderly patients, many of whom had a normal serum creatinine at the time of OSP ingestion. This review summarizes current knowledge about the renal complications of OSP, risk factors for its development, and the pathophysiology of acute and chronic kidney damage in nephrocalcinosis. C1 [Heher, Eliot C.; Thier, Samuel O.] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Thier, Samuel O.] Harvard Univ, Sch Med, Dept Med & Healthcare Policy, Boston, MA USA. [Humphreys, Benjamin D.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Heher, EC (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, GRB 1003,55 Fruit St, Boston, MA 02114 USA. EM eheher@partners.org NR 97 TC 36 Z9 38 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2008 VL 3 IS 5 BP 1494 EP 1503 DI 10.2215/CJN.02040408 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 342AR UT WOS:000258757500041 PM 18596115 ER PT J AU Nanda, A Dias-Santagata, DC Stubbs, H O'Hara, CJ Zaner, KS Lynch, TJ Willers, H AF Nanda, Akash Dias-Santagata, Dora C. Stubbs, Hannah O'Hara, Carl J. Zaner, Ken S. Lynch, Thomas J. Willers, Henning TI Unusual tumor response and toxicity from radiation and concurrent erlotinib for non-small-cell lung cancer SO CLINICAL LUNG CANCER LA English DT Article DE epidermal growth factor receptor; molecular targeted radiation therapy; S768I; tyrosine kinase inhibitor ID GEFITINIB; RADIOTHERAPY; INHIBITORS; MUTATIONS; THERAPY; TRIAL AB We report a case of a never-smoker female with non-small-cell lung cancer (NSCLC) who experienced a striking tumor response to combined low-dose radiation and the epidermal growth factor receptor inhibitor erlotinib, even though erlotinib alone was not effective in preventing tumor progression. Furthermore, the patient developed symptomatic pneumonitis, which is unusual for the small volume of lung that was exposed to a significant dose of radiation. This case demonstrates that combination therapy with radiation and erlotinib has the potential to significantly benefit a subset of patients with NSCLC in addition to those approximately 10% who have tumors which respond to erlotinib alone. It also highlights the potential risks of molecular targeted radiation therapy. C1 [Nanda, Akash; Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Nanda, Akash] Boston Med Ctr, Harvard Radiat Oncol Program, Boston, MA USA. [Nanda, Akash; Willers, Henning] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. [Dias-Santagata, Dora C.; Stubbs, Hannah] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [O'Hara, Carl J.] Boston Med Ctr, Dept Pathol, Boston, MA USA. [Zaner, Ken S.] Boston Med Ctr, Dept Med, Boston, MA USA. [Lynch, Thomas J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Willers, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM hwillers@partners.org NR 14 TC 17 Z9 19 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD SEP PY 2008 VL 9 IS 5 BP 285 EP 287 DI 10.3816/CLC.2008.n.044 PG 3 WC Oncology SC Oncology GA 353XU UT WOS:000259603300007 PM 18824451 ER PT J AU Swartz, BE McDonald, CR Patel, A Torgersen, D AF Swartz, Barbara E. McDonald, Carrie R. Patel, Ashok Torgersen, Denise TI The Effects of Guanfacine on Working Memory Performance in Patients With Localization-Related Epilepsy and Healthy Controls SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE alpha(2) agonists; guanfacine; working memory; frontal lobe epilepsy ID DEFICIT HYPERACTIVITY DISORDER; DORSOLATERAL PREFRONTAL CORTEX; CORTICAL COGNITIVE FUNCTION; FRONTAL-LOBE EPILEPSY; TO-SAMPLE PERFORMANCE; AGED RHESUS-MONKEYS; ALPHA-2-ADRENERGIC AGONIST; ALPHA(2)-ADRENERGIC ANTAGONIST; KORSAKOFFS PSYCHOSIS; SELECTIVE ATTENTION AB Objectives: Previous research has demonstrated that alpha(2) agonists improve working memory performances in healthy individuals and in primates with prefrontal lesions. We conducted this study to determine whether the a2 agonist, guanfacine, could improve working memory performances in patients with frontal lobe epilepsy (FLE) and/or in those with focal epilepsy outside the frontal lobes (ie, temporal lobe epilepsy [TLE]). Methods: Fourteen patients with FLE, 13 patients with TLE, and 10 healthy controls completed immediate and delayed match-to-sample tasks before and after ingestion of 2 to 3 mg of guanfacine. Results: All 3 groups showed an increase in accuracy on the delayed match-to-sample task, but not the immediate match-to-sample task, following administration of guanfacine. Inspection of the group means revealed somewhat greater benefits for the control and FLE groups relative to the TLE group. Increased accuracy was not associated with slower performances in any group, suggesting that the cognitive benefits of guanfacine did not occur at the expense of increased sedation. Conclusions: These data suggest that guanfacine improves working memory in patients with FLE and may be a viable treatment for attenuating such deficits in this patient population. C1 [Swartz, Barbara E.] Hoag Mem Hosp, Epilepsy Ctr, Newport Beach, CA USA. [Torgersen, Denise] VA Greater Angeles Hlth Care Syst, Div Res, Los Angeles, CA USA. [McDonald, Carrie R.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Patel, Ashok] Univ S Carolina, Dept Neurosci, Columbia, SC 29208 USA. RP Swartz, BE (reprint author), 351 Hosp Rd St 420, Newport Beach, CA 92663 USA. EM epidoc@cox.net NR 52 TC 14 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD SEP-OCT PY 2008 VL 31 IS 5 BP 251 EP 260 DI 10.1097/WNF.0B013E3181633461 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 360VX UT WOS:000260087400001 PM 18836342 ER PT J AU Magnee, MJCM de Gelder, B van Engeland, H Kemner, C AF Magnee, Maurice J. C. M. de Gelder, Beatrice van Engeland, Herman Kemner, Chantal TI A typical processing of fearful face-voice pairs in Pervasive Developmental Disorder: An ERP study SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE autism; facial expression; multisensory processing; voice prosody; EEG ID TIME-COURSE; EMOTION RECOGNITION; BRAIN RESPONSES; VISUAL-CORTEX; AUTISM; PERCEPTION; EXPRESSIONS; BINDING; HUMANS; INFORMATION AB Objective: An important premise for successful social-affective communication is rapid perception of visual and auditory emotional cues, as well as their multisensory integration (MSI). We investigated to what extent a deficit in recognition of emotions in individuals with Pervasive Developmental Disorder (PDD) may have its roots in abnormal MSI of emotional cues provided by the sight of a facial expression and an emotional tone of voice. Methods: In twelve high-functioning, adult PDD individuals and thirteen age- and IQ-matched controls, (1) the processing of fearful faces was compared with that of happy faces; (2) MSI was assessed by characterizing the interaction effects of crossmodal presentation, using EEG. Results: Increased PI and N170 amplitudes were seen in response to fearful faces compared with happy faces in both groups. However, PDD individuals differed from healthy controls in NISI of fearful information from visual and auditory cues. Conclusions: Both groups show a similar pattern as concerns the early components of visual emotion processing, but there are anomalies in processing of fearful face-voice combinations in the PDD group. Significance: Because of the importance of rapid MSI for social competence, MSI anomalies in PDD may be linked to the observed deficits in their emotional behavior. (c) 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Magnee, Maurice J. C. M.; van Engeland, Herman; Kemner, Chantal] Univ Med Ctr Utrecht, Dept Child & Adolescent Psychiat, Rudolf Magnus Inst Neurosci, NL-3584 CX Utrecht, Netherlands. [Magnee, Maurice J. C. M.; de Gelder, Beatrice] Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands. [Kemner, Chantal] Maastricht Univ, Fac Psychol, Sect Biol Dev Psychol, NL-6200 MD Maastricht, Netherlands. [de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [de Gelder, Beatrice] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Magnee, MJCM (reprint author), Univ Med Ctr Utrecht, Dept Child & Adolescent Psychiat, Rudolf Magnus Inst Neurosci, B01-201,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM M.J.C.M.Magnec@umcutrecht.nl FU Netherlands Organization for Scientific Research (NWO) [402-01-094] FX The work described was supported by an Innovational Research Incentives Grant (VIDI-scheme, 402-01-094) of the Netherlands Organization for Scientific Research (NWO) to Chantal Kemner. NR 34 TC 12 Z9 16 U1 1 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD SEP PY 2008 VL 119 IS 9 BP 2004 EP 2010 DI 10.1016/j.clinph.2008.05.005 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 342QS UT WOS:000258799200011 ER PT J AU Goudreau, KA Smolenski, M AF Goudreau, Kelly A. Smolenski, Mary TI Credentialing and certification - Issues for clinical nurse specialists SO CLINICAL NURSE SPECIALIST LA English DT Article DE advanced practice registered nurses; advanced practice regulation certification; credentialing AB This article will provide a brief overview of the concepts of credentialing and certification and will identify some of the issues around certification and credentialing for clinical nurse specialists (CNSs). The article will also describe some of the misconceptions about certification and licensure that cause problems to CNSs, identify the current questions on the debated regulation of CNSs, and outline some of the proactive steps that can be taken to stay ahead of the current wave of change anticipated with the suggested changes in the forthcoming regulation of CNSs. Information provided is pertinent for new graduates and seasoned CNSs and provides an opportunity for both to gain a better understanding of certification and credentialing. C1 [Goudreau, Kelly A.] Portland VA Med Ctr, Portland, OR 97239 USA. [Smolenski, Mary] Amer Nurses Credentialing Ctr, Silver Spring, MD USA. RP Goudreau, KA (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM kagoudreau@hotmail.com NR 9 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD SEP-OCT PY 2008 VL 22 IS 5 BP 240 EP 244 DI 10.1097/01.NUR.0000325369.61668.7c PG 5 WC Nursing SC Nursing GA 345CX UT WOS:000258974700017 PM 18753882 ER PT J AU Head, JG Storfer-Isser, A O'Connor, KG Hoagwood, KE Kelleher, KJ Heneghan, AM Park, ER Chaudron, LH Stein, REK Horwitz, SM AF Head, Julia G. Storfer-Isser, Amy O'Connor, Karen G. Hoagwood, Kimberly E. Kelleher, Kelly J. Heneghan, Amy M. Park, Elyse R. Chaudron, Linda H. Stein, Ruth E. K. Horwitz, Sarah McCue TI Does education influence pediatricians' perceptions of physician-specific barriers for maternal depression? SO CLINICAL PEDIATRICS LA English DT Article DE maternal depression; barriers-education ID RESPONSE RATES; PERCEIVED RESPONSIBILITIES; FINAL REPORT; IDENTIFICATION; MANAGEMENT; ATTITUDES; CHILDREN; RESIDENTS; WORKGROUP; SYMPTOMS AB Pediatric residency reforms have increased emphasis on psychosocial issues, but we do not know whether this has changed pediatricians' perceptions of barriers to addressing maternal depression. A survey of 1600 members of the American Academy of Pediatrics investigated whether training in adult mental health issues and perceived harriers to addressing maternal depression differed for current pediatric residents, pediatricians in practice <5 years, and those in practice >= 5 years. Training did not differ for respondents who were currently in training, in practice <5 years, or in practice >= 5 years. Those in practice >= 5 years reported more barriers to addressing maternal depression compared With Current residents. Current residents With training in adult mental techniques reported fewer barriers to the care of maternal depression. However, in spite of residency reforms, 81% of current residents reported no training in adult mental health issues. C1 [Horwitz, Sarah McCue] Stanford Univ, Dept Pediat, Ctr Hlth Policy, Sch Med, Stanford, CA 94305 USA. [Horwitz, Sarah McCue] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Head, Julia G.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Storfer-Isser, Amy] Case Western Reserve Univ, Sch Med, Ctr Clin Invest, Cleveland, OH 44106 USA. [O'Connor, Karen G.] Amer Acad Pediat, Dept Res, Elk Grove Village, IL USA. [Hoagwood, Kimberly E.] Columbia Univ, Dept Psychiat, New York, NY USA. [Kelleher, Kelly J.] Ohio State Univ, Dept Pediat, Coll Med & Publ Hlth, Columbus, OH 43210 USA. [Heneghan, Amy M.] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chaudron, Linda H.] Univ Rochester, Dept Psychiat, New York, NY USA. [Chaudron, Linda H.] Univ Rochester, Dept Pediat, New York, NY USA. [Chaudron, Linda H.] Univ Rochester, Dept Obstet & Gynecol, New York, NY USA. [Stein, Ruth E. K.] Childrens Hosp, Dept Pediat, Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA. RP Horwitz, SM (reprint author), Stanford Univ, Dept Pediat, Ctr Hlth Policy, Sch Med, 117 Encina Commons, Stanford, CA 94305 USA. EM sarah.horwitz@stanford.edu RI Kelleher, Kelly/E-3361-2011 NR 32 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD SEP PY 2008 VL 47 IS 7 BP 670 EP 678 DI 10.1177/0009922808315213 PG 9 WC Pediatrics SC Pediatrics GA 334XU UT WOS:000258255900006 PM 18441316 ER PT J AU Schelleman, H Chen, J Chen, Z Christie, J Newcomb, CW Brensinger, CM Price, M Whitehead, AS Kealey, C Thorn, CF Samaha, FF Kimmel, SE AF Schelleman, H. Chen, J. Chen, Z. Christie, J. Newcomb, C. W. Brensinger, C. M. Price, M. Whitehead, A. S. Kealey, C. Thorn, C. F. Samaha, F. F. Kimmel, S. E. TI Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GAMMA-GLUTAMYL-CARBOXYLASE; FACTOR-VII; LINKAGE-DISEQUILIBRIUM; ORAL ANTICOAGULATION; CLINICAL-PRACTICE; CYP2C9 GENOTYPE; GENE VARIANTS; VKORC1 GENE; FACTOR-II; POLYMORPHISMS AB The objective of this study was to determine whether warfarin dosing algorithms developed for Caucasians and African Americans on the basis of clinical, environmental, and genetic factors will perform better than an empirical starting dose of 5 mg/day. From April 2002 through December 2005, 259 subjects (Caucasians and African Americans) who started using warfarin were prospectively followed until they reached maintenance dose. The Caucasian algorithm included 11 variables (R-2 = 0.43). This model (which predicted 51% of the doses to within 1 mg of the observed dose) performed better than 5 mg/day (which predicted 29% of the doses to within 5 +/- 1 mg). The African-American algorithm included 10 variables (R-2 = 0.28). This model predicted 37% of the doses to within 1 mg of the observed dose, representing a small improvement compared with 5 mg/day (which predicted 34% of the doses to within 1 mg of 5 mg/day). These results were similar to the results we obtained from testing other published algorithms. The dosing algorithms explained < 45% of the observed variability in Caucasians, and the algorithms performed only marginally better for African Americans when compared with giving 5 mg empirically. C1 [Schelleman, H.; Chen, J.; Chen, Z.; Christie, J.; Newcomb, C. W.; Brensinger, C. M.; Price, M.; Kimmel, S. E.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Whitehead, A. S.; Kealey, C.; Thorn, C. F.] Univ Penn, Sch Med, Dept Pharmacol, Ctr Pharmacogenet, Philadelphia, PA 19104 USA. [Samaha, F. F.] Univ Penn, Sch Med, Dept Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Schelleman, H (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. EM hschelle@mail.med.upenn.edu FU National Institutes of Health (NIH) [R01HL066176, P20RR020741, K24HL070936] FX This study was funded by National Institutes of Health (NIH) grant R01HL066176. S.E.K. was supported by NIH grants P20RR020741 and K24HL070936, and A.S.W. was supported by NIH grant P20RR020741. The funding agencies had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. We thank Joseph A. Gascho and Francis Herrmann at Penn State Milton S. Hershey Medical Center; Mitchell Laskin at Hospital of the University of Pennsylvania; and Mabel Chin at the Philadelphia Veterans Affairs Medical Center for their dedication to our fieldwork. S. E. K. and H. S. had full access to all data in the study, and they take responsibility for the integrity of the data and the accuracy of the data analysis. The factor 2 and factor 7 data will be deposited in PharmGKB (http://www.pharmgkb.org). NR 36 TC 80 Z9 83 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2008 VL 84 IS 3 BP 332 EP 339 DI 10.1038/clpt.2008.101 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 339MW UT WOS:000258582700012 PM 18596683 ER PT J AU Pessler, F Chen, LX Dai, L Gomez-Vaquero, C Diaz-Torne, C Paessler, ME Scanzello, C Cakir, N Einhorn, E Schumacher, HR AF Pessler, F. Chen, L. X. Dai, L. Gomez-Vaquero, C. Diaz-Torne, C. Paessler, M. E. Scanzello, C. Cakir, N. Einhorn, E. Schumacher, H. R. TI A histomorphometric analysis of synovial biopsies from individuals with Gulf War Veterans' Illness and joint pain compared to normal and osteoarthritis synovium SO CLINICAL RHEUMATOLOGY LA English DT Article DE arthralgia; chronic fatigue syndrome; fibromyalgia; Gulf War Veterans' Illnesses; synovium ID HISTOPATHOLOGICAL GRADING SYSTEM; ANGIOGENESIS; SCORE AB We compared histologic, immunohistochemical, and vascular findings in synovial biopsies from individuals with Gulf War Veterans Illness and joint pain (GWVI) to findings in normal and osteoarthritis (OA) synovium. The following parameters were assessed in synovial biopsies from ten individuals with GWVI: lining thickness, histologic synovitis score, and vascular density in hematoxylin & eosin-stained sections; and CD68+ lining surface cells and CD15+, CD3+, CD8+, CD20+, CD38+, CD68+, and Ki-67+ subintimal cells and von Willebrand Factor+ vessels immunohistochemically. Comparisons were made to synovial specimens from healthy volunteers (n = 10) and patients with OA or RA (n = 25 each). Histologic appearance and quantitative assessments were nearly identical in the GWVI and normal specimens. Vascular density was between 25% (H & E stains; p = 0.003) and 31% (vWF immunostains; p = 0.02) lower in GWVI and normal specimens than in OA. CD68+ macrophages were the most common inflammatory cells in GWVI (45.3 +/- Ce10.1 SEM cells/mm(2)) and normal synovium (45.6 +/- Ce7.4) followed by CD3+ T cells (GWVI, 15.1 +/- Ce6.3; normal, 27.1 +/- Ce9.2), whereas there were practically no CD20+, CD38+, and CD15+ cells. All parameters except lining thickness and CD15 and CD20 expression were significantly higher in OA. Five (20%) OA specimens contained significant fractions of humoral immune cells in mononuclear infiltrates, although the overall differences in the relative composition of the OA mononuclear infiltrates did not reach statistical significance compared to GWVI and normal synovium. In summary, the GWVI and normal synovia were indistinguishable from each other and contained similar low-grade inflammatory cell populations consisting almost entirely of macrophages and T cells. C1 [Pessler, F.] Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA. [Dai, L.] Sun Yat sen Univ, Affiliated Hosp 2, Dept Rheumatol, Guangzhou, Peoples R China. [Chen, L. X.; Diaz-Torne, C.; Cakir, N.; Schumacher, H. R.] Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Chen, L. X.; Schumacher, H. R.] Philadelphia VA Med Ctr, Div Rheumatol, Philadelphia, PA USA. [Gomez-Vaquero, C.] Hosp Univ Belvitge, Dept Rheumatol, Barcelona, Spain. [Diaz-Torne, C.] Hosp Santa Creu & Sant Pau, Rheumatol Unit, Barcelona, Spain. [Paessler, M. E.] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Scanzello, C.] Hosp Special Surg, Dept Rheumatol, New York, NY 10021 USA. [Einhorn, E.] Philadelphia VA Med Ctr, Dept Pathol, Philadelphia, PA USA. RP Pessler, F (reprint author), Tech Univ Dresden, Klin & Poliklin Kinder & Jugendmed, Dresden, Germany. EM frank.pessler@uniklinikum-dresden.de OI Cesar, Diaz-Torne/0000-0001-6275-7699 FU NCI NIH HHS [T32-CA 09140]; NIAMS NIH HHS [T32-AR 007442] NR 19 TC 18 Z9 19 U1 0 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0770-3198 J9 CLIN RHEUMATOL JI Clin. Rheumatol. PD SEP PY 2008 VL 27 IS 9 BP 1127 EP 1134 DI 10.1007/s10067-008-0878-0 PG 8 WC Rheumatology SC Rheumatology GA 330DH UT WOS:000257919200008 PM 18414968 ER PT J AU Wylie, BJ Mirza, FG AF Wylie, Blair J. Mirza, Fadi G. TI Cesarean Delivery in the Developing World SO CLINICS IN PERINATOLOGY LA English DT Article DE Cesarean delivery; International maternal health; Health care access ID DEVELOPING-COUNTRIES; OBSTETRIC SERVICES; LATIN-AMERICA; SECTION; RATES; MORTALITY; AVAILABILITY; ANESTHESIA AB Two trends are apparent regarding cesarean delivery in the developing world. In the least developed countries, access to the procedure remains limited at levels much less than 5% of all births. This limited access is linked with increases in maternal and neonatal mortality. Safety concerns are equally valid when more than half of women in certain socioeconomic strata are having surgical delivery, as is evident in the more advanced developing economies of Latin America and China. The optimal minimum and maximum cesarean delivery rates continue to be a matter of debate and may never be resolved; however, these two extremes of cesarean delivery use evident in the developing world deserve critical examination. C1 [Wylie, Blair J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Div Maternal Fetal Med, Boston, MA 02115 USA. [Wylie, Blair J.] Boston Univ, Sch Publ Hlth, Ctr Int Hlth & Dev, Boston, MA USA. [Mirza, Fadi G.] Columbia Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, New York, NY 10032 USA. RP Wylie, BJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Div Maternal Fetal Med, 55 Fruit St, Boston, MA 02115 USA. EM bwylie@partners.org NR 31 TC 18 Z9 21 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD SEP PY 2008 VL 35 IS 3 BP 571 EP + DI 10.1016/j.clp.2008.06.002 PG 13 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 362UU UT WOS:000260223400010 PM 18952023 ER PT J AU Spencer, TJ AF Spencer, Thomas J. TI Neurobiology and genetics of ADHD in adults SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; BRAIN; ABNORMALITIES; BEHAVIOR C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Spencer, Thomas J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. FU Cephalon; Eli Lilly; GlaxoSmithKline; Janssen; National Institute of Mental Health; Novartis; Ortho-McNeil; Pfize; Shire FX Disclosures: Dr. Spencer is a speaker for Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Ortho-McNeil, and Shire; is on the advisory boards of Cephalon, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Ortho-McNeil, Pfizer, and Shire; and receives research support from Cephalon, Eli Lilly, GlaxoSmithKline, Janssen, National Institute of Mental Health, Novartis, Ortho-McNeil, Pfizer, and Shire. NR 12 TC 5 Z9 5 U1 2 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 SEP PY 2008 VL 13 IS 9 SU 13 BP 5 EP 7 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 353JL UT WOS:000259562500002 PM 18849903 ER PT J AU Chen, Z Cao, JT Cao, Y Zhang, Y Gu, FJ Zhu, GX Hong, Z Wang, B Cichocki, A AF Chen, Zhe Cao, Jianting Cao, Yang Zhang, Yue Gu, Fanji Zhu, Guoxian Hong, Zhen Wang, Bin Cichocki, Andrzej TI An empirical EEG analysis in brain death diagnosis for adults SO COGNITIVE NEURODYNAMICS LA English DT Article DE Brain death; Quantitative EEG; Independent component analysis; Approximate entropy; Detrended fluctuation analysis; Pattern classification ID INDEPENDENT COMPONENT ANALYSIS; TIME-SERIES; COMPLEXITY; CRITERIA; SIGNALS AB Electroencephalogram (EEG) is often used in the confirmatory test for brain death diagnosis in clinical practice. Because EEG recording and monitoring is relatively safe for the patients in deep coma, it is believed to be valuable for either reducing the risk of brain death diagnosis (while comparing other tests such as the apnea) or preventing mistaken diagnosis. The objective of this paper is to study several statistical methods for quantitative EEG analysis in order to help bedside or ambulatory monitoring or diagnosis. We apply signal processing and quantitative statistical analysis for the EEG recordings of 32 adult patients. For EEG signal processing, independent component analysis (ICA) was applied to separate the independent source components, followed by Fourier and time-frequency analysis. For quantitative EEG analysis, we apply several statistical complexity measures to the EEG signals and evaluate the differences between two groups of patients: the subjects in deep coma, and the subjects who were categorized as brain death. We report statistically significant differences of quantitative statistics with real-life EEG recordings in such a clinical study, and we also present interpretation and discussions on the preliminary experimental results. C1 [Chen, Zhe; Cao, Jianting; Cichocki, Andrzej] RIKEN Brain Sci Inst, Lab Adv Brain Signal Proc, Wako, Saitama 3510198, Japan. [Chen, Zhe] Harvard Univ, Sch Med, Neurosci Stat Res Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cao, Jianting] Saitama Inst Technol, Dept Human Robot, Fukaya, Saitama 3690293, Japan. [Cao, Yang; Gu, Fanji] Fudan Univ, Inst Brain Sci, Brain Sci Res Ctr, Shanghai 200433, Peoples R China. [Zhang, Yue; Zhu, Guoxian; Hong, Zhen] Fudan Univ, Huashan Hosp, Shanghai 200433, Peoples R China. [Wang, Bin] Fudan Univ, Dept Elect Engn, Shanghai 200433, Peoples R China. RP Chen, Z (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM zhechen@neurostat.mgh.harvard.edu RI Cichocki, Andrzej/A-1545-2015; OI Cichocki, Andrzej/0000-0002-8364-7226; Chen, Zhe/0000-0002-6483-6056 FU Japan Society for the Promotion Science (JSPS); National Natural Science Foundation of China (NSFC) in the Japan-China Research FX This work was supported in part by the Japan Society for the Promotion Science (JSPS) and the National Natural Science Foundation of China (NSFC) in the Japan-China Research Cooperative Program. We thank two anonymous reviewers for many valuable comments. NR 36 TC 23 Z9 23 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1871-4080 J9 COGN NEURODYNAMICS JI Cogn. Neurodynamics PD SEP PY 2008 VL 2 IS 3 BP 257 EP 271 DI 10.1007/s11571-008-9047-z PG 15 WC Neurosciences SC Neurosciences & Neurology GA 450PJ UT WOS:000266413000007 PM 19003489 ER PT J AU Muskavitch, MAT Barteneva, N Gubbels, MJ AF Muskavitch, Marc A. T. Barteneva, Natasha Gubbels, Marc-Jan TI Chemogenomics and parasitology: Small molecules and cell-based assays to study infectious processes SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Review DE protozoa; parasite; Trypanosoma; Plasmodium; Toxoplasma; small molecule; high throughput screen; HTS; cell-based ID LINKED-IMMUNOSORBENT-ASSAY; TOXOPLASMA-GONDII REVEALS; HUMAN MALARIA PARASITE; SEMIAUTOMATED MICRODILUTION TECHNIQUE; DEHYDROGENASE IMMUNODETECTION ASSAY; ANTIMALARIAL-DRUG DEVELOPMENT; VARIANT SURFACE GLYCOPROTEIN; TRYPANOSOMA-BRUCEI-BRUCEI; IN-VITRO ASSAY; PLASMODIUM-FALCIPARUM AB Infectious diseases caused by protozoan parasites - malaria, sleeping sickness, leishmaniasis, Chagas' disease, toxoplasmosis - remain chronic problems for humanity. We lack vaccines and have limited drug options effective against protozoa. Research into anti-protozoan drugs has accelerated with improved in vitro cultivation methods, enhanced genetic accessibility, completed genome sequences for key protozoa, and increased prominence of protozoan diseases on the agendas of well-resourced public figures and foundations. Concurrent advances in high-throughput screening (HTS) technologies and availability of diverse small molecule libraries offer the promise of accelerated discovery of new drug targets and new drugs that will reduce disease burdens imposed on humanity by parasitic protozoa. We provide a status report on HTS technologies in hand and cell-based assays under development for biological investigations and drug discovery directed toward the three best-characterized parasitic protozoa: Trypanosoma brucei, Plasmodium falciparum, and Toxoplasma gondii. We emphasize cell growth assays and new insights into parasite cell biology speeding development of better cell-based assays, useful in primary screens for anti-protozoan drug leads and secondary screens to decipher mechanisms of action of leads identified in growth assays. Small molecules that interfere with specific aspects of protozoan biology, identified in such screens, will be valuable tools for dissecting parasite cell biology and developing anti-protozoan drugs. We discuss potential impacts on drug development of new consortia among academic, corporate, and public partners committed to discovery of new, effective anti-protozoan drugs. C1 [Muskavitch, Marc A. T.; Gubbels, Marc-Jan] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Gubbels, MJ (reprint author), Boston Coll, Dept Biol, 355 Higgins Hall,140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM gubbelsj@bc.edu FU DeLuca Professorship; American Heart Association Scientist Development Grant; Ludcke Foundation; NIH Shared Instrumentation grant [1S10 RR023459-01] FX We apologize to those colleagues whose work we were unable to include in this review due to space constraints. We thank Leann Tilley for permission to reproduce images from her published work, and we appreciate the assistance of Brian Hall, Richard DeMarco and Dr. Tad George of Amnis, Inc. with ImageStream technology implementation. Preparation of this review was made possible by support from the DeLuca Professorship to M. A. T. M., an American Heart Association Scientist Development Grant as well as a Smith Family New Investigator Award (through the Ludcke Foundation) to M.J.G., and NIH Shared Instrumentation grant 1S10 RR023459-01 to N.B. NR 228 TC 15 Z9 17 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1386-2073 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PD SEP PY 2008 VL 11 IS 8 BP 624 EP 646 DI 10.2174/138620708785739989 PG 23 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 351SN UT WOS:000259446300007 PM 18795882 ER PT J AU Schmahmann, JD Pandya, DN AF Schmahmann, Jeremy D. Pandya, Deepak N. TI Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems SO CORTEX LA English DT Review DE cognition; anatomy; connections; fiber tracts; distributed neural systems ID COGNITIVE-AFFECTIVE SYNDROME; ARTERY TERRITORY INFARCTION; POSTERIOR PARIETAL CORTEX; MEDIAL PULVINAR NUCLEUS; PSYCHIC SELF-ACTIVATION; RHESUS-MONKEY; PARKINSONS-DISEASE; PREFRONTAL CORTEX; FRONTAL-LOBE; CORTICOTHALAMIC CONNECTIONS AB Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion. First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas, commissural fibers to contralateral cerebral regions, striatal fibers to basal ganglia, and projection subcortical bundles to thalamus, brainstem and/or pontocerebellar system. We note that cortical areas can be defined by their patterns of subcortical and cortical connections. Second, we consider motor, cognitive and neuropsychiatric disorders in patients with lesions restricted to basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic deficits resulting from cortical lesions, with qualitative differences between the manifestations of lesions in functionally related areas of cortical and subcortical nodes. We consider these findings on the basis of anatomical observations from tract tracing studies in monkey, viewing them as disconnection syndromes reflecting loss of the contribution of subcortical nodes to the distributed neural circuits. We introduce a new theoretical framework for the distributed neural circuits, based on general, and specific, principles of anatomical organization, and on the architecture of the nodes that comprise these systems. We propose that neural architecture determines function, i.e., each architectonically distinct cortical and subcortical area contributes a unique transform, or computation, to information processing; anatomically precise and segregated connections between nodes define behavior; and association fiber tracts that link cerebral cortical areas with each other enable the cross-modal integration required for evolved complex behaviors. This model enables the formulation and testing of future hypotheses in investigations using evolving magnetic resonance imaging techniques in humans, and in clinical studies in patients with cortical and subcortical lesions. (C) 2008 Published by Elsevier Masson Srl. C1 [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Ataxia Unit, Boston, MA 02114 USA. [Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pandya, Deepak N.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Ataxia Unit, Suite 340,Charles River Plaza S,SS Fruit St, Boston, MA 02114 USA. EM jschmahmann@partners.org FU Birmingham Foundation; [RO1 MH067980] FX Supported in part by RO1 MH067980, and the Birmingham Foundation. The assistance of Jason MacMore BA is greatly appreciated. NR 258 TC 115 Z9 116 U1 3 U2 22 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD SEP PY 2008 VL 44 IS 8 BP 1037 EP 1066 DI 10.1016/j.cortex.2008.04.004 PG 30 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 353HT UT WOS:000259557600013 PM 18614161 ER PT J AU Zhou, HJ Yang, K Lynch, SV Dotson, RH Glidden, DV Singh, G Webb, WR Elicker, BM Garcia, O Brown, R Sawa, Y Misset, B Wiener-Kronish, JP AF Zhou, Hangjing Yang, Katherine Lynch, Susan V. Dotson, Rachel H. Glidden, David V. Singh, Gaurav Webb, W. Richard Elicker, Brett M. Garcia, Oscar Brown, Ronald Sawa, Yoriko Misset, Benoit Wiener-Kronish, Jeanine P. TI Increased mortality of ventilated patients with endotracheal Pseudomonas aeruginosa without clinical signs of infection SO CRITICAL CARE MEDICINE LA English DT Article DE Pseudomonas aeruginosa; ventilator-associated pneumonia; endotracheal aspirate; surveillance culture; cytotoxin secretion ID III PROTEIN SECRETION; RANDOMIZED-TRIAL; SEPTIC SHOCK; PNEUMONIA; DIAGNOSIS; MANAGEMENT; LUNG; IDENTIFICATION; VALIDATION AB Objective: To investigate the frequency and outcomes of ventilated patients with newly acquired large burdens of Pseudomonas aeruginosa and to test the hypothesis that large quantities of bacteria are associated with adverse patient outcomes. Design: A prospective, single-center, observational, cohort study. Setting: Medical-surgical intensive care units in a tertiary care university hospital. Patients. All adult patients requiring >= 48 hrs of mechanical ventilation and identified as having newly acquired P. aeruginosa in their lower respiratory tracts between October 2002 and April 2006. Interventions: None. Measurements and Main Results. Daily surveillance cultures of endotracheal aspirates were performed on patients intubated :48 hrs; 69 patients with newly acquired P. aeruginosa were enrolled. Daily P. aeruginosa, quantification of endotracheal aspirates was performed; clinical signs of infection were noted. Of 45 patients with high P. aeruginosa burdens (>= 1,000,000 colony-forming units/mL in endotracheal aspirates; >= 10,000 colony-forming units/mL in bronchoalveolar-lavage), 17 (37.8%) patients did not meet clinical criteria for ventilator-associated pneumonia and had a statistically significant higher risk of death (adjusted hazard ratio, 37.53; 95% confidence interval, 3.79-371.96; p = 0.002) when compared with the patients who had P. aeruginosa ventilator-associated pneumonia. When excluding the ten patients who had ventilator-associated pneumonia attributed to bacteria other than P. aeruginosa or attributed to multiple bacteria including P. aeruginosa, the risk of death remained statistically significant (adjusted hazard ratio, 23.98; 95% confidence interval: 2.49-230.53; p = 0.006). Furthermore, more patients with high P. aeruginosa burdens secreted the type III secretion facilitator protein, Peril (p = 0.01). Conclusions: A group of patents with large burdens of P. aeruginosa who did not meet clinical criteria for ventilator-associated pneumonia had an increased risk of death when compared with patients who had high P. aeruginosa burdens and met ventilator-associated pneumonia criteria. Patients with high P. aeruginosa burden seemed to possess more virulent strains. C1 [Yang, Katherine] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. [Dotson, Rachel H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Glidden, David V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Webb, W. Richard; Elicker, Brett M.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Paris 05, Fac Med, Paris, France. [Misset, Benoit] St Joseph Hosp, Dept Med Surg Intens Care, Paris, France. [Wiener-Kronish, Jeanine P.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Zhou, Hangjing; Lynch, Susan V.; Sawa, Yoriko] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Singh, Gaurav; Garcia, Oscar; Brown, Ronald; Wiener-Kronish, Jeanine P.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. RP Zhou, HJ (reprint author), Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. EM jwiener-kronish@partners.org RI Lynch, Susan/B-6272-2009 FU NIH [HL74005, HL 69809, KL2 RR024130] FX Supported, in part, by NIH HL74005, HL 69809 and KL2 RR024130. NR 25 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2008 VL 36 IS 9 BP 2495 EP 2503 DI 10.1097/CCM.0b013e318183f3f8 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 345TV UT WOS:000259020800001 ER PT J AU Currier, PF Gong, MN Zhai, R Pothier, LJ Boyce, PD Xu, LL Yu, CL Thompson, BT Christiani, DC AF Currier, Paul F. Gong, Michelle N. Zhai, Rihong Pothier, Lucille J. Boyce, Paul D. Xu, Lilian Yu, Chu-Ling Thompson, B. Taylor Christiani, David C. TI Surfactant protein-B polymorphisms and mortality in the acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; surfactant; pulmonary; surfactant protein SFTP-B; SFTP-B+1580; genetic polymorphism ID ACUTE LUNG INJURY; ALZHEIMERS-DISEASE; GENE POLYMORPHISMS; FAILURE; SUSCEPTIBILITY; ONSET; ARDS; AGE; DEFINITIONS; DEFICIENCY AB Objective: To determine whether polymorphisms of the surfactant protein B gene may be associated with increased mortality in patients with the acute respiratory distress syndrome. Design: A prospective cohort study. Setting. Four adult intensive care units at a tertiary academic medical center. Patients. Two hundred fourteen white patients who had met criteria for acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: Patients were genotyped for a variable nuclear tandem repeat polymorphism in intron 4 of the surfactant protein B gene and the surfactant protein B gene + 1580 polymorphism. For the variable nuclear tandem repeat surfactant protein B gene polymorphism, patients were found to have either a homozygous wild-type genotype or a variant genotype consisting of either a heterozygous insertion or deletion polymorphism. Logistic regression was performed to analyze the relationship of the polymorphisms to mortality in patients with acute respiratory distress syndrome. In multivariate analysis, the presence of variable nuclear tandem repeat surfactant protein B gene polymorphism was associated with a 3.51 greater odds of death at 60 days in patients with acute respiratory distress syndrome as compared to those patients with the wild-type genotype (95% confidence interval 1.39-8.88, p = 0.008). There was no association found between the + 1580 variant and outcome (p = 0.15). Conclusions: In this study, the variable nuclear tandem repeat surfactant protein B gene polymorphism in intron 4 is associated with an increased 60 day mortality in acute respiratory distress syndrome after adjusting for age, severity of illness, and other potential confounders. Additional studies in other populations are needed to confirm this finding. C1 [Currier, Paul F.; Boyce, Paul D.; Thompson, B. Taylor; Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. [Currier, Paul F.; Zhai, Rihong; Pothier, Lucille J.; Boyce, Paul D.; Xu, Lilian; Yu, Chu-Ling; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Gong, Michelle N.] Mt Sinai Sch Med, Dept Med, Div Pulm & Crit Care Med, New York, NY USA. RP Christiani, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU NIH [R01 HL060710, T32 HL007874]; NHLBI [K23 HL 67197] FX Supported, in part, by NIH grant R01 HL060710 (to DCQ, NIH training grant T32 HL007874 (to PFC), and K23 HL 67197 from NHLBI (to MNG) NR 41 TC 12 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2008 VL 36 IS 9 BP 2511 EP 2516 DI 10.1097/CCM.0b013e318183f608 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 345TV UT WOS:000259020800003 PM 18679120 ER PT J AU Zeber, JE Copeland, LA Hosek, BJ Karnad, AB Lawrence, VA Sanchez-Reilly, SE AF Zeber, John E. Copeland, Laurel A. Hosek, Brandon J. Karnad, Arland B. Lawrence, Valerie A. Sanchez-Reilly, Sandra E. TI Cancer rates, medical comorbidities, and treatment modalities in the oldest patients SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE neoplasms; aged, 80 and over; radiation oncology; medical oncology; epidemiology; veterans ID GERIATRIC-ONCOLOGY; BREAST-CANCER; DEMENTIA; CHEMOTHERAPY; VETERANS; UNDERTREATMENT; POPULATION; PREVALENCE; MORTALITY; SERVICES AB Cancer disproportionately afflicts older patients, with 56% of incident diagnoses and 71% of deaths occurring in this population. Yet little is known about the "oldest of the old", oncology patients underrepresented in clinical trials. We examined elderly veterans diagnosed with lung, colorectal, prostate or head-neck cancer in 2005 (n = 194,797), analyses comparing treatment receipt by age group, 70-84 versus 85-115. Treatment was more common among younger elders, including surgery (1.3% versus 0.6%), chemotherapy (2.1% versus 0.8%) and radiation (1.7% versus 0.7%). Differences were sharper for certain cancers, e.g., chemotherapy for lung (9.0% versus 2.9%), or colorectal surgery (5.8% versus 3.4%). Cancer prevalence is high among elders yet treatment rates appear extremely low, despite evidence of well-tolerated treatment. Toxicity concerns and comorbidities may inhibit pursuit of definitive treatment. As we reconcile definitions of 'elderly' with appropriate treatment options, compassionate care requires identifying geriatric oncology guidelines that improve survival and quality of life. Published by Elsevier Ireland Ltd. C1 [Zeber, John E.; Copeland, Laurel A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Karnad, Arland B.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Div Med Oncol, San Antonio, TX USA. [Karnad, Arland B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Oncol, San Antonio, TX 78229 USA. [Sanchez-Reilly, Sandra E.] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. [Sanchez-Reilly, Sandra E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr, San Antonio, TX 78229 USA. [Zeber, John E.; Copeland, Laurel A.; Hosek, Brandon J.; Lawrence, Valerie A.] S Texas Vet Hlth Care Syst Verdict, HSR&D, Dept Vet Affairs, San Antonio, TX USA. RP Zeber, JE (reprint author), S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd,Verdict 11C6, San Antonio, TX 78229 USA. EM zeber@uthscsa.edu OI Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs, including the VERDICT Research Program at the South Texas Veterans Health Care System, San Antonio, Texas; HRSA's Geriatric Academic Career Award; VISN; VA Health Services Research and Development Career Development Award [MRP-05-145] FX This research was supported by the Department of Veterans Affairs, including the VERDICT Research Program at the South Texas Veterans Health Care System, San Antonio, Texas. Dr. Sanchez-Reilly is supported in part by a grant from HRSA's Geriatric Academic Career Award and a VISN Grant from the Department of Veteran Affairs. Dr. Copeland is funded by VA Health Services Research and Development Career Development Award #MRP-05-145. We wish to sincerely thank Mary Jo Pugh, Ph.D., for her contributions to this study and insightful comments on this manuscript. 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 33 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD SEP PY 2008 VL 67 IS 3 BP 237 EP 242 DI 10.1016/j.critrevonc.2008.02.002 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 351LE UT WOS:000259425000006 PM 18356072 ER PT J AU Goldfine, AB AF Goldfine, Allison B. TI Modulating LDL cholesterol and glucose in patients with type 2 diabetes mellitus: targeting the bile acid pathway SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE bile acid sequestrant; colesevelam HCl; farnesoid X receptor; glycemic control; lowdensity lipoprotein cholesterol; type 2 diabetes mellitus ID CORONARY-HEART-DISEASE; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; PRIOR MYOCARDIAL-INFARCTION; FARNESOID-X-RECEPTOR; COLESEVELAM HYDROCHLORIDE; RISK-FACTORS; GLYCEMIC CONTROL; MICROVASCULAR COMPLICATIONS; CARDIOVASCULAR EVENTS AB Purpose of review Individuals with type 2 diabetes mellitus (T2DM) have a number of potentially modifiable risk factors, including dyslipidemia, hypertension, and hyperglycemia, that contribute to coronary artery disease risk. Elevated low-density lipoprotein cholesterol (LDL-C) is a major contributor to coronary artery disease, and clinical trials have demonstrated significant macrovascular benefits associated with lowering LDL-C in individuals with T2DM, even in those with only a modest LDL-C elevation. Intensive glycemic control has been shown to reduce microvascular complications associated with T2DM. Therefore, it is important to treat both dyslipidemia and hyperglycemia to reduce complications. In this paper, the effect of elevated LDL-C and glucose concentrations on T2DM outcomes is reviewed. Recent findings Lipid and glucose homeostasis are linked in part through bile acid pathways. Recent clinical trials demonstrate that bile acid sequestrants, which significantly reduce LDL-C, can also significantly reduce glucose levels in patients with T2DM. These findings supported recent Food and Drug Administration approval of the bile acid sequestrant colesevelam HCl for reducing glycemia in patients with T2DM. Summary A multitargeted therapeutic approach using a bile acid sequestrant to improve both cholesterol and glucose management in patients with T2DM may be clinically beneficial. C1 Joslin Diabet Ctr, Clin Res Sect, Boston, MA 02115 USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Clin Res Sect, 1 Joslin Pl, Boston, MA 02115 USA. EM Allison.Goldfine@joslin.harvard.edu NR 73 TC 27 Z9 28 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD SEP PY 2008 VL 23 IS 5 BP 502 EP 511 DI 10.1097/HCO.0b013e32830c6c37 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 339WQ UT WOS:000258608400011 PM 18670263 ER PT J AU Devin, JK Young, PP AF Devin, Jessica K. Young, Pampee P. TI The effects of growth hormone and insulin-like growth factor-1 on the aging cardiovascular system and its progenitor cells SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Review DE aging; cardiovascular; endothelial progenitor cell; growth hormone; growth hormone secretagogue; nitric oxide ID ACUTE MYOCARDIAL-INFARCTION; FACTOR-BINDING PROTEIN-3; CORONARY-ARTERY DISEASE; ISCHEMIC-HEART-DISEASE; MESENCHYMAL STEM-CELLS; SEVERE GH DEFICIENCY; SMOOTH-MUSCLE-CELLS; RISK-FACTORS; NITRIC-OXIDE; THERAPEUTIC NEOVASCULARIZATION AB Aging is a major risk factor for the development of cardiovascular disease. Aging is also associated with a decline in the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) axis. This axis impacts endothelial and vascular smooth muscle cell biology, as well as cardiac function. The number of endothelial progenitor cells (EPCs) also decreases with age and is emerging as a surrogate measurement of vascular senescence. Studies suggest that EPCs impact vascular health by modulating vascular repair and function. Current evidence demonstrates that EPC number and function is restored with a GH-mediated increase in serum IGF-1. Modulation of the GH and IGF-1 system may therefore provide a useful therapy in the prevention of age-associated changes in the cardiovascular system and in future regenerative cell-based therapies. C1 [Young, Pampee P.] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. [Devin, Jessica K.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. [Young, Pampee P.] US Dept Vet Affairs, Nashville, TN 37203 USA. RP Young, PP (reprint author), Vanderbilt Univ, Sch Med, Dept Pathol, C-3321A Med Ctr N,1161 21st Ave S, Nashville, TN 37232 USA. EM Pampee.Young@Vanderbilt.edu NR 91 TC 14 Z9 14 U1 0 U2 3 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1472-4472 EI 2040-3429 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD SEP PY 2008 VL 9 IS 9 BP 983 EP 992 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 341EE UT WOS:000258696200006 PM 18729005 ER PT J AU Brown, D Hasler, U Nunes, P Bouley, R Lu, HAJ AF Brown, Dennis Hasler, Udo Nunes, Paula Bouley, Richard Lu, Hua A. J. TI Phosphorylation events and the modulation of aquaporin 2 cell surface expression SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE aquaporin 2 water channel; endocytosis; exocytosis; vasopressin ID RENAL EPITHELIAL-CELLS; COLLECTING DUCT CELLS; WATER CHANNEL; PRINCIPAL CELLS; CASEIN KINASE; RAT-KIDNEY; VASOPRESSIN TREATMENT; MEMBRANE INSERTION; IN-VIVO; TRAFFICKING AB Purpose of review This review highlights the role of phosphorylation in the trafficking and targeting of aquaporin 2. Current knowledge will be put into the context of modulating the cell surface expression of aquaporin 2 by vasopressin in renal epithelial cells, which is critical for regulation of urinary concentration and control of fluid and electrolyte homeostasis. Recent findings In addition to previously identified phosphorylation sites on aquaporin 2, new data have revealed three other serine residues in the C-terminus whose phosphorylation is altered by vasopressin. Several steps in aquaporin 2 recycling, including exocytosis and endocytosis, are coordinated by phosphorylation and dephosphorylation to regulate cell surface accumulation. Aquaporin 2 phosphorylation on serine 256 regulates aquaporin 2 association with proteins that are involved in trafficking, including hsc/hsp70 and myelin and lymphocyte-associated protein. Summary Aquaporin 2 trafficking is regulated by phosphorylation of serine 256 and other amino acid residues in its cytoplasmic domain. These events increase or decrease interaction of aquaporin 2 with key regulatory proteins to determine the cellular distribution and fate of aquaporin 2, both after vasopressin addition and under baseline conditions. Better understanding of these mechanisms may provide new therapeutic avenues for patients with X-linked nephrogenic diabetes insipidus, as well as providing basic cell biological information relevant to membrane trafficking processes in general. C1 [Brown, Dennis; Hasler, Udo; Nunes, Paula; Bouley, Richard; Lu, Hua A. J.] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, MGH Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis; Hasler, Udo; Nunes, Paula; Bouley, Richard; Lu, Hua A. J.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis; Hasler, Udo; Nunes, Paula; Bouley, Richard; Lu, Hua A. J.] Harvard Univ, Sch Med, Boston, MA USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, MGH Ctr Syst Biol, Room 8202,185 Cambridge St, Boston, MA 02114 USA. EM Dennis.Brown@mgh.harvard.edu RI Nunes-Hasler, Paula/N-4337-2015 OI Nunes-Hasler, Paula/0000-0002-4598-685X FU NIH [DK38452, DK075940-01]; National Kidney Foundation; MGH; NSERC; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Center for the Study of Inflammatory Bowel Disease [DK43341] FX This work was supported by NIH grant DK38452. R. Bouley received a Young Investigator Award from the National Kidney Foundation. U. Hasler is supported by a Swiss FSBMB Fellowship and an ECOR Fellowship from MGH. H. A. J. Lu is supported by an NIH KO8 grant DK075940-01, and a Doctoral Level Postgraduate Scholarship from NSERC supports P. Nunes. The Microscopy Core facility of the MGH Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the Center for the Study of Inflammatory Bowel Disease (DK43341). NR 62 TC 41 Z9 44 U1 1 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 SEP PY 2008 VL 17 IS 5 BP 491 EP 498 DI 10.1097/MNH.0b013e3283094eb1 PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 348XJ UT WOS:000259243100008 PM 18695390 ER PT J AU Beekman, JM Verhagen, LP Geijsen, N Coffer, PJ AF Beekman, Jeffrey M. Verhagen, Liesbeth P. Geijsen, Niels Coffer, Paul J. TI Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Beekman, Jeffrey M.; Verhagen, Liesbeth P.; Coffer, Paul J.] Univ Med Ctr Utrecht, Dept Immunol, Mol Immunol Lab, NL-3584 EA Utrecht, Netherlands. [Beekman, Jeffrey M.; Coffer, Paul J.] Univ Med Ctr Utrecht, Dept Pediat Immunol, NL-3584 EA Utrecht, Netherlands. [Geijsen, Niels] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. RI Beekman, Jeffrey/I-7781-2014 OI Beekman, Jeffrey/0000-0003-4886-3756 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 291 EP 291 DI 10.1016/j.cyto.2008.07.283 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900253 ER PT J AU Beard, S Pott, GB Morris, K Palmer, B Shapiro, L AF Beard, Scott Pott, Gregory B. Morris, Kristin Palmer, Brent Shapiro, Leland TI Alpha-1-antitrypsin is an inhibitor of intracellular pro-inflammatory cytokine production in monocytes and T-cells SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Beard, Scott; Pott, Gregory B.; Morris, Kristin; Shapiro, Leland] Denver Vet Affairs Med Ctr, Denver, CO USA. [Beard, Scott; Pott, Gregory B.; Morris, Kristin; Palmer, Brent; Shapiro, Leland] Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 310 EP 310 DI 10.1016/j.cyto.2008.07.365 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900331 ER PT J AU Pott, GB Chan, ED Dinarello, CA Shapiro, L AF Pott, Gregory B. Chan, Edward D. Dinarello, Charles A. Shapiro, Leland TI Alpha-1-antitrypsin is an endogenous and specific inhibitor of pro-inflammatory cytokine production in whole blood SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Pott, Gregory B.; Chan, Edward D.; Shapiro, Leland] Denver Vet Affairs Med Ctr, Denver, CO USA. [Pott, Gregory B.; Chan, Edward D.; Shapiro, Leland] Natl Jewish Med & Res Ctr, Denver, CO USA. [Chan, Edward D.; Dinarello, Charles A.] Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 310 EP 310 DI 10.1016/j.cyto.2008.07.364 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900330 ER PT J AU Munoz-Fontela, C Macip, S Martinez-Sobrido, L Elkholi, R Brown, L Ashour, J Garcia-Sastre, A Lee, SW Aaronson, SA AF Munoz-Fontela, Cesar Macip, Salvador Martinez-Sobrido, Luis Elkholi, Rana Brown, Lauren Ashour, Joseph Garcia-Sastre, Adolfo Lee, Sam W. Aaronson, Stuart A. TI p53 Transcriptionally activates IRF9 to enhance antiviral immunity SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Munoz-Fontela, Cesar; Elkholi, Rana; Aaronson, Stuart A.] Mt Sinai Sch Med, Div Infect Dis, Dept Oncol Sci, New York, NY USA. [Martinez-Sobrido, Luis; Ashour, Joseph; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Div Infect Dis, Dept Microbiol, New York, NY USA. [Martinez-Sobrido, Luis; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Div Infect Dis, Emerging Pathogens Inst, New York, NY USA. [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Div Infect Dis, Dept Med, New York, NY USA. [Brown, Lauren; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA USA. [Brown, Lauren; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Macip, Salvador] Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England. RI Macip, Salvador/K-5985-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 312 EP 313 DI 10.1016/j.cyto.2008.07.375 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900340 ER PT J AU Delhase, M Yagi, T Kobayashi, KS Nakanishi, M AF Delhase, Mireille Yagi, Takashi Kobayashi, Koichi S. Nakanishi, Makoto TI Role of the protein kinase TBK1 in TNF alpha-induced apoptosis SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Delhase, Mireille; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Immunol & AIDS, Boston, MA 02115 USA. [Yagi, Takashi; Kobayashi, Koichi S.; Nakanishi, Makoto] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Delhase, Mireille; Yagi, Takashi; Nakanishi, Makoto] Nagoya City Univ, Sch Med, Dept Biochem & Cell Biol, Aichi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 326 EP 326 DI 10.1016/j.cyto.2008.07.433 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900396 ER PT J AU Batut, J Schmierer, B Cao, J Raftery, LA Hill, CS Howell, M AF Batut, Julie Schmierer, Bernhard Cao, Jing Raftery, Laurel A. Hill, Caroline S. Howell, Michael TI Two highly related regulatory subunits of PP2A exert opposite effects on TGF-beta/Activin/Nodal signalling SO DEVELOPMENT LA English DT Article DE PP2A regulatory B subunits; TGF-beta/Activin/Nodal signalling; Xenopus; Drosophila ID PROTEIN PHOSPHATASE 2A; DROSOPHILA-MELANOGASTER; GASTRULATION MOVEMENTS; AXON GUIDANCE; X-CHROMOSOME; SMAD; RECEPTOR; GROWTH; IDENTIFICATION; PATHWAY AB We identify B alpha (PPP2R2A) and B delta (PPP2R2D), two highly related members of the B family of regulatory subunits of the protein phosphatase PP2A, as important modulators of TGF-beta/Activin/Nodal signalling that affect the pathway in opposite ways. Knockdown of B alpha in Xenopus embryos or mammalian tissue culture cells suppresses TGF-beta/Activin/Nodal-dependent responses, whereas knockdown of B delta enhances these responses. Moreover, in Drosophila, overexpression of Smad2 rescues a severe wing phenotype caused by overexpression of the single Drosophila PP2A B subunit Twins. We show that, in vertebrates, B alpha enhances TGF-beta/Activin/Nodal signalling by stabilising the basal levels of type I receptor, whereas B delta negatively modulates these pathways by restricting receptor activity. Thus, these highly related members of the same subfamily of PP2A regulatory subunits differentially regulate TGF-beta/Activin/Nodal signalling to elicit opposing biological outcomes. C1 [Batut, Julie; Schmierer, Bernhard; Hill, Caroline S.; Howell, Michael] Canc Res UK London Res Inst, Lab Dev Signalling, London WC2A 3PX, England. [Cao, Jing; Raftery, Laurel A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Cao, Jing; Raftery, Laurel A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Hill, CS (reprint author), Canc Res UK London Res Inst, Lab Dev Signalling, 44 Lincoln Inn Fields, London WC2A 3PX, England. EM caroline.hill@cancer.org.uk; michael.howell@cancer.org.uk RI Raftery, Laurel/H-1406-2012; Schmierer, Bernhard/C-1416-2009 OI Raftery, Laurel/0000-0003-4797-4163; Schmierer, Bernhard/0000-0002-9082-7022 FU Cancer Research UK; NIGMS NIH HHS [GM60501, R01 GM060501, R01 GM060501-08] NR 53 TC 40 Z9 42 U1 2 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP 1 PY 2008 VL 135 IS 17 BP 2927 EP 2937 DI 10.1242/dev.020842 PG 11 WC Developmental Biology SC Developmental Biology GA 336WL UT WOS:000258395500011 PM 18697906 ER PT J AU Macdonald, HZ Beeghly, M Grant-Knight, W Augustyn, M Woods, RW Cabral, H Rose-Jacobs, R Saxe, GN Frank, DA AF Macdonald, Helen Z. Beeghly, Marjorie Grant-Knight, Wanda Augustyn, Marilyn Woods, Ryan W. Cabral, Howard Rose-Jacobs, Ruth Saxe, Gleen N. Frank, Deborah A. TI Longitudinal association between infant disorganized attachment and childhood posttraumatic stress symptoms (vol 20, pg 493, 2008) SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Correction C1 [Macdonald, Helen Z.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Macdonald, Helen Z.; Augustyn, Marilyn; Cabral, Howard; Rose-Jacobs, Ruth; Frank, Deborah A.] Boston Univ, Boston, MA 02215 USA. [Beeghly, Marjorie] Wayne State Univ, Detroit, MI 48202 USA. [Beeghly, Marjorie; Saxe, Gleen N.] Childrens Hosp Boston, Boston, MA USA. [Grant-Knight, Wanda; Saxe, Gleen N.] Harvard Univ, Cambridge, MA 02138 USA. [Grant-Knight, Wanda] Rehabil Inst Chicago, Chicago, IL USA. [Woods, Ryan W.] Univ Wisconsin, Madison, WI 53706 USA. RP Macdonald, HZ (reprint author), VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, 1550 S Huntington Ave,116B-4, Boston, MA 02130 USA. NR 1 TC 3 Z9 3 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 2008 VL 20 IS 4 BP 1351 EP 1351 DI 10.1017/S0954579408000643 PG 1 WC Psychology, Developmental SC Psychology GA 373SU UT WOS:000260993800017 ER PT J AU De Gasperi, R Sosa, MAG Wen, PH Li, JJ Perez, GM Curran, T Elder, GA AF De Gasperi, Rita Sosa, Miguel A. Gama Wen, Paul H. Li, Jingjun Perez, Gissel M. Curran, Tom Elder, Gregory A. TI Cortical development in the presenilin-1 null mutant mouse fails after splitting of the preplate and is not due to a failure of reelin-dependent signaling SO DEVELOPMENTAL DYNAMICS LA English DT Article DE presenilin-1; reelin; gamma-secretase; cortical lamination ID CENTRAL-NERVOUS-SYSTEM; CAJAL-RETZIUS CELLS; NEURAL PROGENITOR CELLS; APOE RECEPTOR 2; INTRACELLULAR DOMAIN; WILD-TYPE; NEOCORTICAL DEVELOPMENT; LIPOPROTEIN RECEPTORS; EXTRACELLULAR-MATRIX; DEVELOPING BRAIN AB Cortical development is disrupted in presenilin-1 null mutant, (Psen1-/-) mice. Prior studies have commented on similarities between Psen1-/- and reeler mice. Reelin induces phosphorylation of Dab1 and activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Psen1 is known to modulate PI3K/Akt signaling and both known reelin receptors (apoER2 and VLDLR) are substrates for Psen1 associated gamma-secretase activity. The purpose of this study was to determine whether reelin signaling is disrupted in Psen1-/- mice. We show that, while Dab1 is hypophosphorylated late in cortical development in Psen1-/- mice, it is normally phosphorylated at earlier ages and reelin signaling is intact in Psen1-/- primary neuronal cultures. gamma-secretase activity was also not required for reelin-induced phosphorylation of Dab1. Unlike reeler mice the preplate splits in Psen1-/- brain. Thus cortical development in Psen1-/- mice fails only after splitting of the preplate and is not due to an intrinsic failure of reelin signaling. C1 [De Gasperi, Rita; Sosa, Miguel A. Gama; Wen, Paul H.; Perez, Gissel M.; Elder, Gregory A.] Res & Dev James J Peters Dept Vet Affairs Med Ctr, Bronx, NY USA. [De Gasperi, Rita; Sosa, Miguel A. Gama; Wen, Paul H.; Li, Jingjun; Perez, Gissel M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Curran, Tom; Elder, Gregory A.] Childrens Hosp Philadelphia, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Rehabil Med Serv, Bronx, NY USA. RP Elder, GA (reprint author), James J Peters VA Med Ctr, Res & Dev 3F22, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM gregory.elder@mssm.edu RI Curran, Tom/C-1164-2008; Curran, Tom/D-7515-2011 OI Curran, Tom/0000-0003-1444-7551; FU National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) FX R.D.G. received a Young Investigator Award from the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD). NR 58 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 2008 VL 237 IS 9 BP 2405 EP 2414 DI 10.1002/dvdy.21661 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 349OI UT WOS:000259289800012 PM 18729224 ER PT J AU Bujoreanu, IS Willis, WG AF Bujoreanu, I. Simona Willis, W. Grant TI Developmental and neuropsychological perspectives on the Wisconsin Card Sorting Test in children SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; COLOR; CHILDHOOD; NORMS AB The purpose of this study was to advance our understanding of the Wisconsin Card Sorting Test (WCST) as a measure of a set-shifting component of neuropsychological executive function among children by investigating the level of difficulty posed by the order of administering number (vs. shape and color) as a sorting criterion in the test. A total of 196 participants at three different ages groups (6, 11-12, and 18-19 yrs.)were administered the standard or a modified version of the WCST. Results revealed several age-related trends: (a) increases in the number of categories completed, (b) increases in test efficiency, and (c) differences in task difficulty as a function of the order in which the number sorting criterion was administered in the test. Implications of these finding are discussed in terms of the construct validity of the WCST for young children. C1 [Bujoreanu, I. Simona] Dana Farber Canc Inst, Boston, MA 02115 USA. [Willis, W. Grant] Univ Rhode Isl, Kingston, RI 02881 USA. RP Bujoreanu, IS (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM simona_bujoreanu@dfci.harvard.edu NR 33 TC 8 Z9 8 U1 2 U2 10 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PD SEP-OCT PY 2008 VL 33 IS 5 BP 584 EP 600 DI 10.1080/87565640902254364 PG 17 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 354YW UT WOS:000259676800002 PM 18788012 ER PT J AU DeAngelis, AM Heinrich, G Dai, T Bowman, TA Patel, PR Lee, SJ Hong, EG Jung, DY Assmann, A Kulkarni, RN Kim, JK Najjar, SM AF DeAngelis, Anthony M. Heinrich, Garrett Dai, Tong Bowman, Thomas A. Patel, Payal R. Lee, Sang Jun Hong, Eun-Gyoung Jung, Dae Young Assmann, Anke Kulkarni, Rohit N. Kim, Jason K. Najjar, Sonia M. TI Carcinoembryonic antigen-related cell adhesion molecule 1 - A link between insulin and lipid metabolism SO DIABETES LA English DT Article ID FATTY-ACID SYNTHASE; LA-CP RAT; BETA-CELL; ENDOGENOUS SUBSTRATE; TYROSINE KINASE; MICE; RECEPTOR; EXPRESSION; LIVER; CEACAM1 AB OBJECTIVE-Liver-specific inactivation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) by a dominant-negative transgene (L-SACC1 mice) impaired insulin clearance, caused insulin resistance, and increased hepatic lipogenesis. To discern whether this phenotype reflects a physiological function of CEACAM1 rather than the effect of the dominant-negative transgene, we characterized the metabolic phenotype of mice with null mutation of the Ceacam1 gene (Cc1(-/-)). RESEARCH DESIGN AND METHODS-Mice were originally generated on a mixed C57BL/6x129sv genetic background and then backcrossed 12 times onto the C57BL/6 background. More than 70 male mice of each of the Cc1(-/-) and wild-type Cc1(+/+) groups were subjected to metabolic analyses, including insulin tolerance, hyperinsulinemic-euglycemic clamp studies, insulin secretion in response to glucose, and determination of fasting serum insulin, C-peptide, triglyceride, and free fatty acid levels. RESULTS-Like L-SACC1, Cc1(-/-) mice exhibited impairment of insulin clearance and hyperinsulinemia, which caused insulin resistance beginning at 2 months of age, when the mutation was maintained on a mixed C57BL/6x129sv background, but not until 5-6 months of age on a homogeneous inbred C57BL/6 genetic background. Hyperinsulinemic-euglycemic clamp studies revealed that the inbred Cc1(-/-) mice developed insulin resistance primarily in liver. Despite substantial expression of CEACAM1 in pancreatic P-cells, insulin secretion in response to glucose in vivo and in isolated islets was normal in Cc1(-/-) mice (inbred and outbred strains). CONCLUSIONS-In tact insulin secretion in response to glucose and impairment of insulin clearance in L-SACC1 and Cc1(-/-) mice suggest that the principal role of CEACAM1 in insulin action is to mediate insulin clearance in liver. C1 [DeAngelis, Anthony M.; Heinrich, Garrett; Dai, Tong; Bowman, Thomas A.; Patel, Payal R.; Lee, Sang Jun; Najjar, Sonia M.] Univ Toledo, Ctr Diabet & Endocrine Res, Coll Med, Toledo, OH 43606 USA. [DeAngelis, Anthony M.; Heinrich, Garrett; Dai, Tong; Bowman, Thomas A.; Patel, Payal R.; Lee, Sang Jun; Najjar, Sonia M.] Univ Toledo, Dept Physiol & Pharmacol, Coll Med, Toledo, OH 43606 USA. [Hong, Eun-Gyoung; Jung, Dae Young; Kim, Jason K.] Penn State Univ, Dept Cellular & Mol Physiol, Coll Med, Hershey, PA USA. [Assmann, Anke; Kulkarni, Rohit N.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Najjar, SM (reprint author), Univ Toledo, Ctr Diabet & Endocrine Res, Coll Med, 2801 W Bancroft St, Toledo, OH 43606 USA. EM sonia.najjar@utoledo.edu RI Bowman, Thomas/I-4649-2013 OI Bowman, Thomas/0000-0002-9591-7561 FU National Institutes of Health [DK-67536, DK-54254]; American Diabetes Association and the Pennsylvania State Department of Health; American Diabetes Association; U.S. Department of Agriculture [USDA 38903-02315] FX R.N.K. has received National Institutes of Health Grant DK-67536. J.K.K. has received grants from the American Diabetes Association and the Pennsylvania State Department of Health. S.M.N. has received National Institutes of Health Grant DK-54254, a grant from the American Diabetes Association, and U.S. Department of Agriculture Grant USDA 38903-02315.; We thank Dr. N. Beauchemin (McGill University, Montreal, Canada) for providing the mice. We also thank Drs. Jill Schroeder-Gloeckler and Qusai Y. Al-Share and Mats Fernstrom for technical assistance and scientific discussions. NR 36 TC 35 Z9 35 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2008 VL 57 IS 9 BP 2296 EP 2303 DI 10.2337/db08-0379 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QP UT WOS:000258869000006 PM 18544705 ER PT J AU Butty, V Campbell, C Mathis, D Benoist, C AF Butty, Vincent Campbell, Christopher Mathis, Diane Benoist, Christophe CA DPT-1 Study Grp TI Impact of diabetes susceptibility loci on progression from pre-diabetes to diabetes in at-risk individuals of the diabetes prevention trial-type 1 (DPT-1) SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; PROPHYLACTIC INSULIN THERAPY; HLA CLASS-II; GENETIC SUSCEPTIBILITY; DQ HAPLOTYPES; NOD MICE; CENTRAL TOLERANCE; CELL FUNCTION; TYPE-1; POPULATION AB OBJECTIVE-The unfolding of type 1 diabetes involves a number of steps: defective immunological tolerance, priming of anti-islet autoimmunity, and destruction of insulin-producing P-cells. A number of genetic loci contribute to susceptibility to type 1 diabetes, but it is unclear which stages of the disease are influenced by the different loci. Here, we analyzed the frequency of type 1 diabetes-risk alleles among individuals from the Diabetes Prevention Trial-Type 1 (DPT-1) clinical trial, which tested a preventive effect of insulin in at-risk relatives of diabetic individuals, all of which presented with autoimmune manifestations but only one-third of which eventually progressed to diabetes. RESEARCH DESIGN AND METHODS-in this study, 708 individuals randomized into DPT-1 were genotyped for 37 single nucleotide polymorphisms in diabetes Susceptibility loci. RESULTS-Susceptibility alleles at loci expected to influence immunoregulation (PTPA122, CTLA4, and IL2RA) did not differ between progressors and nonprogressors but were elevated in both groups relative to general population frequencies, as was the INS promoter variant. In contrast, HLA DQB1*0302 and DQB1*0301 differed significantly in progressors versus nonprogressors (DQB*0302, 42.6 vs. 34.7%, P = 0.0047; DQB*0301, 8.6 vs. 14.3%, P = 0.0026). Multivariate analysis of the factors contributing to progression demonstrated that. initial titers of anti-insulin autoantibodies (IAAs) could account for some (P = 0.0016) but not all of this effect on progression (P = 0.00038 for the independent effect. of the number of DQB*0302 alleles). The INS-23 genotype was most strongly associated with anti-IAAs (median IAA levels in TT individuals, 60 nU/ml; AT, 121; and AA, 192; P = 0.000037) mid only suggestively to the outcome of oral insulin administration. CONCLUSIONS-With the exception of HLA, most susceptibility loci tested condition the risk of autoimmunity rather than the risk of failed immunoregulation that results in islet destruction. Future clinical trials might consider genotyping INS-23 in addition to HLA alleles as disease/treatment response modifier. C1 [Butty, Vincent; Campbell, Christopher; Mathis, Diane; Benoist, Christophe; DPT-1 Study Grp] Harvard Univ, Brigham & Womens Hosp, Sect Immunol & Immunogenet, Joslin Diabet Ctr,Dept Med,Med Sch, Boston, MA 02115 USA. RP Campbell, C (reprint author), Harvard Univ, Brigham & Womens Hosp, Sect Immunol & Immunogenet, Joslin Diabet Ctr,Dept Med,Med Sch, Boston, MA 02115 USA. EM cbdm@joslin.harvard.edu FU National Institutes of Health [AI-056299]; William T. Young Chairs in Diabetes Research; Joslin Diabetes and Endocrinology Research Center; NIDDK; National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development; American Diabetes Association; Juvenile Diabetes Research Foundation FX This work has been supported by National Institutes of Health Grant P01-AI-056299, the William T. Young Chairs in Diabetes Research, and the Joslin Diabetes and Endocrinology Research Center funded cores. The DPT-1 was supported through cooperative agreements by the NIDDK, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Human Development, the American Diabetes Association, and the Juvenile Diabetes Research Foundation.; We thank Drs. C. Greenbaum and the DPT-1 Publications Committee for inspiring discussions, the NIDDK Central DNA Repository for making samples available, W. Besse for help with genotyping, and all of the DPT-1 participants. NR 50 TC 21 Z9 22 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2008 VL 57 IS 9 BP 2348 EP 2359 DI 10.2337/db07-1736 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QP UT WOS:000258869000012 PM 18556337 ER PT J AU Moore, AF Jablonski, KA McAteer, JB Saxena, R Pollin, TI Franks, PW Hanson, RL Shuldiner, AR Knowler, WC Altshuler, D Florez, JC AF Moore, Allan F. Jablonski, Kathleen A. McAteer, Jarred B. Saxena, Richa Pollin, Toni I. Franks, Paul W. Hanson, Robert L. Shuldiner, Alan R. Knowler, William C. Altshuler, David Florez, Jose C. CA Diabetes Prevent Program Res Grp TI Extension of type 2 diabetes genome-wide association scan results in the Diabetes Prevention Program SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; VARIANTS; SUSCEPTIBILITY; LOCI; POLYMORPHISMS; SECRETION; CDKAL1; GENES AB OBJECTIVE-Genome-wide association scans (GWASs) have identified novel diabetes-associated genes. We evaluated how these variants impact diabetes incidence, quantitative glycemic traits, and response to preventive interventions in 3,548 Subjects at high risk of type 2 diabetes enrolled in the Diabetes Prevention Program (DPP), which examined the effects of lifestyle intervention, metformin, and troglitazone versus placebo. RESEARCH DESIGN AND METHODS-We genotyped selected single nucleotide polymorphisms (SNPs) in or near diabetes-associated loci, including EXT2, CDKAL1, CDKN2A/B, IGF2BP2, HHEX, LOC387761, and SLC30A8 in DPP participants and performed Cox regression analyses using genotype, intervention, and their interactions as predictors of diabetes incidence. We evaluated their effect on insulin resistance and secretion at 1 year. RESULTS-None of the selected SNPs were associated with increased diabetes incidence in this population. After adjustments for ethnicity, baseline insulin secretion was lower in subjects with the risk genotype at HHEX rs1111875 (P = 0.01); there were no significant differences in baseline insulin sensitivity. Both at baseline and at 1 year, subjects with the risk genotype at, LOC387761 had paradoxically increased insulin secretion; adjustment for self-reported effinicity abolished these differences. In ethnicity-adjusted analyses, we noted a nominal differential improvement in P-cell function for carriers of the protective genotype at CDKN2A/B after 1 year of troglitazone treatment (P = 0.01) and possibly lifestyle modification (P = 0.05). CONCLUSIONS-We were unable to replicate the GWAS findings regarding diabetes risk in the DPP. We did observe genotype associations with differences in baseline insulin secretion at the HHEX locus and a possible pharmacogenetic interaction at CDKNA2/B. C1 [Moore, Allan F.; McAteer, Jarred B.; Saxena, Richa; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Boston, MA 02114 USA. [Moore, Allan F.; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Diabet, Dept Med, Boston, MA 02114 USA. [Moore, Allan F.; Altshuler, David; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Moore, Allan F.; McAteer, Jarred B.; Saxena, Richa; Altshuler, David; Florez, Jose C.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Moore, Allan F.; McAteer, Jarred B.; Saxena, Richa; Altshuler, David; Florez, Jose C.] MIT, Cambridge, MA 02139 USA. [Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Pollin, Toni I.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Franks, Paul W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Div Med, S-90185 Umea, Sweden. [Hanson, Robert L.; Knowler, William C.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Boston, MA 02114 USA. EM dppmail@biostat.bsc.gwuj.edu RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009; Hanson, Robert/O-3238-2015; Uwaifo, Gabriel/M-2361-2016 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Hanson, Robert/0000-0002-4252-7068; Uwaifo, Gabriel/0000-0002-6962-9304 FU National Institutes of Health [R01-DK-072041]; Doris Duke Charitable Foundation Distinguished Scientist Clinical Award; NIH Research Career Award [K23-DK-65978-04]; The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; McKesson BioServices; Matthews Media Group; Henry M. Jackson Foundation FX K.A.J. has received National Institutes of Health (NIH) Grant R01-DK-072041. T.I.P. has received NIH Grant R01-DK-072041. A.R.S. has received NIH Grant R01-DK-072041. D.A. has received NIH Grant R01-DK-072041 and a Doris Duke Charitable Foundation Distinguished Scientist Clinical Award. J.C.F. has received NIH Grant R01-DK-072041 and NIH Research Career Award K23-DK-65978-04. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH provided funding to the clinical centers and the coordinating center for the design and conduct of the study, collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported in part by the intramural research program of the NIDDK. LifeScan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck, Nike Sports Marketing, Slim Fast Foods, and Quaker Oats donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices, Matthews Media Group, and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating center. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of centers, investigators, and staff can be found in the online appendix. We gratefully acknowledge the commitment and dedication of all participants in the DPP, without whom this work would not have been possible. NR 26 TC 60 Z9 61 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2008 VL 57 IS 9 BP 2503 EP 2510 DI 10.2337/db08-0284 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QP UT WOS:000258869000029 PM 18544707 ER PT J AU Rogus, JJ Poznik, GD Pezzolesi, MG Smiles, AM Dunn, J Walker, W Wanic, K Moczulski, D Canani, L Araki, S Makita, Y Warram, JH Krolewski, AS AF Rogus, John J. Poznik, G. David Pezzolesi, Marcus G. Smiles, Adam M. Dunn, Jonathon Walker, William Wanic, Krzysztof Moczulski, Dariusz Canani, Luis Araki, Shinichi Makita, Yuichiro Warram, James H. Krolewski, Andrzej S. TI High-density single nucleotide polymorphism genome-wide linkage scan for susceptibility genes for diabetic nephropathy in type 1 diabetes - Discordant sibpair approach SO DIABETES LA English DT Article ID SIB-PAIR ANALYSIS; CHROMOSOME 3Q; DISEQUILIBRIUM; COMPLICATIONS; DURATION; DISEASE; MARKERS; TRAITS; LOCUS AB OBJECTIVE-Epidemiological and family studies have demonstrated that, susceptibility genes play an important role in the etiology of diabetic nephropathy, defined as persistent proteinuria or end-stage renal disease (ESRD) in type 1 diabetes. RESEARCH DESIGN AND METHODS-To efficiently search for genomic regions harboring diabetic nephropathy genes, we conducted a scan using 5,382 informative single nucleotide polymorphisms on 100 sibpairs concordant for type 1 diabetes but discordant for diabetic nephropathy. In addition to being powerful for detecting linkage to diabetic nephropathy, this design allows linkage analysis on type 1 diabetes via traditional affected sibpair (ASP) analysis. In weighing the evidence for linkage, we considered maximum logarithm of odds score (maximum likelihood score [MLS]) values and corresponding allelic sharing patterns, calculated and viewed graphically using the software package SPLAT. RESULTS-Our primary finding for diabetic nephropathy, broadly defined, is oil chromosome 19q (MLS 3.1), and a secondary peak exists on chromosome 2q (MLS 2.1). Stratification of discordant sibpairs based on whether disease had progressed to ESRD suggested four tertiary peaks on chromosome 1q (ESRD only), chromosome 20p (proteinuria only), and chromosome 3q (two loci 58 cm apart, one for ESRD only and another for proteinuria only). Additionally, analysis of 130 ASPs for type 1 diabetes confirmed the linkage to the HLA region oil chromosome 6p (MLS = 9.2) and IDDM15 on chromosome 6q (MLS = 3.1). CONCLUSIONS-This study identified several novel loci as candidates for diabetic nephropathy, none of which appear to be the sole genetic determinant of diabetic nephropathy in type I diabetes. In addition, this study confirms two previously reported type 1 diabetes loci. C1 [Rogus, John J.; Poznik, G. David; Pezzolesi, Marcus G.; Smiles, Adam M.; Dunn, Jonathon; Walker, William; Wanic, Krzysztof; Moczulski, Dariusz; Canani, Luis; Araki, Shinichi; Makita, Yuichiro; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Rogus, John J.; Pezzolesi, Marcus G.; Wanic, Krzysztof; Moczulski, Dariusz; Canani, Luis; Araki, Shinichi; Makita, Yuichiro; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Moczulski, Dariusz] Med Univ Lodz, Dept Internal Med Nephrol & Dialysis, Lodz, Poland. [Canani, Luis] Univ Fed Rio Grande do Sul, Dept Endocrinol, Porto Alegre, RS, Brazil. [Araki, Shinichi] Shiga Univ Med Sci, Dept Internal Med, Otsu, Shiga 52021, Japan. [Makita, Yuichiro] Juntendo Univ, Sch Med, Div Nephrol, Dept Internal Med, Tokyo 113, Japan. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andriej.krolewski@joslin.harvard.edu RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 FU National Institutes of Health [DK 053534, DK 077532]; Juvenile Diabetes Research Federation Fellowship [3-2005-908] FX This research has been supported by National Institutes of Health Grants DK 053534 and DK 077532. K.W. has been supported by Juvenile Diabetes Research Federation Fellowship no. 3-2005-908.; All supplemental tables and figures can be obtained online at http://wwwjoslinresearch.org/LabSites/Krolewski/tldn.dsp/. NR 31 TC 30 Z9 31 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2008 VL 57 IS 9 BP 2519 EP 2526 DI 10.2337/db07-1086 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QP UT WOS:000258869000031 PM 18559660 ER PT J AU Wanic, K Placha, G Dunn, J Smiles, A Warram, JH Krolewski, AS AF Wanic, Krzysztof Placha, Grzegorz Dunn, Jonathon Smiles, Adam Warram, James H. Krolewski, Andrzej S. TI Exclusion of polymorphisms in carnosinase genes (CNDP1 and CNDP2) as a cause of diabetic nephropathy in type 1 diabetes - Results of large case-control and follow-up studies SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; COMPLICATION; REPLICATION; DURATION; MAPS AB OBJECTIVES-Recently, an association was found between diabetic nephropathy and the D18S880 microsatellite, located in the carnosinase gene (CNDP1) on chromosome 18q. Alleles of this microsatellite encode for a variable number of leucine residues (from four to seven) in the leader peptide of the carnosinase precursor. The frequency of subjects homozygous for the five leucines was higher in control subjects than in case subjects in studies focusing on type 2 diabetic patients. To test whether this finding can be extended to type I diabetic patients, we carried out a comprehensive study on association between diabetic nephropathy and the D18S880 microsatellite and 21 additional SNPs that tagged the genomic region containing CNDP1 and CNDP2. RESEARCH DESIGN AND METHODS-Overall, 1,269 Caucasian patients with type 1 diabetes were included in the study, including 613 patients with normoalbuminuria and a long duration of diabetes, 445 patients with persistent proteinuria, and 211 patients with end-stage renal disease (ESRD). All patients were genotyped for selected polymorphisms, the associations with diabetic nephropathy were tested by a chi(2) test, and odds ratios were calculated. RESULTS-We did not find any significant association between diabetic nephropathy and any examined genetic markers. The negative findings of the case-control study were supported further by negative findings obtained from the 6-year follow-up study of 445 patients with persistent proteinuria, during which 135 patients developed ESRD. CONCLUSIONS-Our large, comprehensive study did not find an association between the D18S880 microsatellite or any other polymorphisms in the CNDP2-CNDP1 genomic region and susceptibility for diabetic nephropathy in type 1 diabetes. C1 [Wanic, Krzysztof; Placha, Grzegorz; Dunn, Jonathon; Smiles, Adam; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Wanic, Krzysztof; Placha, Grzegorz; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Placha, Grzegorz] Warsaw Med Univ, Dept Hypertens, Warsaw, Poland. RP Krolewski, AS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. EM andrzej.krolewski@joslin.harvard.edu FU National Institutes of Health; Juvenile Diabetes Research Foundation [JDRF 3-2005-908, JDRF 3-2004-631]; [DK41526]; [DK77532] FX This research was supported by National Institutes of Health grants DK41526 and DK77532. K.W. and G.P. were supported by Juvenile Diabetes Research Foundation fellowships (JDRF 3-2005-908 and JDRF 3-2004-631). NR 23 TC 26 Z9 26 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2008 VL 57 IS 9 BP 2547 EP 2551 DI 10.2337/db07-1303 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 343QP UT WOS:000258869000035 PM 18753673 ER PT J AU Gonzalez, JS Safren, SA Delahanty, LM Cagliero, E Wexler, DJ Meigs, JB Grant, RW AF Gonzalez, J. S. Safren, S. A. Delahanty, L. M. Cagliero, E. Wexler, D. J. Meigs, J. B. Grant, R. W. TI Symptoms of depression prospectively predict poorer self-care in patients with Type 2 diabetes SO DIABETIC MEDICINE LA English DT Article DE adherence; compliance; depression; diabetes; self-care ID CO-MORBID DEPRESSION; COMORBID DEPRESSION; ADHERENCE; METAANALYSIS; PREVALENCE; ADULTS; ASSOCIATION; IMPACT AB Aims To examine prospectively the association of depression symptoms with subsequent self-care and medication adherence patients with Type 2 diabetes mellitus. Methods Two hundred and eight primary care patients with Type 2 diabetes completed the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) and the Summary of Diabetes Self-Care Activities (SDSCA) at baseline and at follow-up, an average of 9 months later. They also self-reported medication adherence at baseline and at a follow-up. Results Baseline HANDS scores ranged from 0 to 27, with a mean score of 5.15 +/- 4.99. In separate linear regression models that adjusted for baseline self-care, patients with higher levels of depressive symptoms at baseline reported significantly lower adherence to general diet recommendations and specific recommendations for consumption of fruits and vegetables and spacing of carbohydrates; less exercise; and poorer foot care at follow-up (beta ranging from -0.12 to -0.23; P < 0.05). Similarly, each one-point increase in baseline HANDS score was associated with a 1.08-fold increase in the odds of non-adherence to prescribed medication at follow-up (95% confidence interval 1.001, 1.158, P = 0.047). Increases in depression scores over rime also predicted poorer adherence to aspects of diet and exercise. Conclusions Depressive symptoms predict subsequent non-adherence to important aspects of self-care in patients with Type 2 diabetes, even after controlling for baseline self-care. Although the relationship between symptoms of depression and poorer diabetes self-care is consistent, it is not large, and interventions may need to address depression and self-care skills simultaneously in order to maximize effects on diabetes outcomes. C1 [Gonzalez, J. S.; Safren, S. A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Delahanty, L. M.; Cagliero, E.; Wexler, D. J.] Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. [Meigs, J. B.; Grant, R. W.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, JS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jsgonzalez@partners.org OI Grant, Richard/0000-0002-6164-8025 FU Pfizer; Aventis and the Massachusetts General Hospital Clinical Research Program; National Institute of Mental Health [1R01 MH078571-01]; American Diabetes Association Career Development Award [NIDDK K24 DK080140]; Career Development Award, NIDDK [K23 DK067452]; National Institute of Diabetes & Digestive Kidney Diseases FX This study was supported by a grant from Pfizer, with additional Support from Aventis and the Massachusetts General Hospital Clinical Research Program. J.S.G. and S.A.S. efforts were supported by a grant from the National Institute of Mental Health (1R01 MH078571-01). J.B.M. was supported by American Diabetes Association Career Development Award and by NIDDK K24 DK080140. J.B.M. currently has research grants from GlaxoSmithKline and Sanofi-Aventis, and Consults for GlaxoSmithKline, Sanofi-Aventis, Interleukin Genetics, Kalypsis, and Outcomes Science. R.W.G. is supported by a Career Development Award (NIDDK K23 DK067452) from the National Institute of Diabetes & Digestive Kidney Diseases. NR 26 TC 65 Z9 70 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD SEP PY 2008 VL 25 IS 9 BP 1102 EP 1107 DI 10.1111/j.1464-5491.2008.02535.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 353BW UT WOS:000259542100016 PM 19183315 ER PT J AU Adaikalakoteswari, A Perkins, B Krolewski, AS Rabbani, N Thornalley, PJ AF Adaikalakoteswari, A. Perkins, B. Krolewski, A. S. Rabbani, N. Thornalley, P. J. TI Thiamine status and risk of early renal function decline in type 1 diabetic patients SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Adaikalakoteswari, A.; Rabbani, N.; Thornalley, P. J.] Univ Warwick, Clin Sci Res Inst, Coventry CV4 7AL, W Midlands, England. [Perkins, B.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5S 1A1, Canada. [Krolewski, A. S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 220 BP S98 EP S98 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200220 ER PT J AU Bottcher, Y Schleinitz, D Unbehauen, H Kloting, N Ruschke, K Enigk, B Tonjes, A Wolf, S Tseng, YH Scholz, GH Bluher, M Stumvoll, M Kovacs, P AF Boettcher, Y. Schleinitz, D. Unbehauen, H. Kloeting, N. Ruschke, K. Enigk, B. Toenjes, A. Wolf, S. Tseng, Y. -H. Scholz, G. H. Blueher, M. Stumvoll, M. Kovacs, P. TI Expression of the bone morphogenetic protein receptor LA gene (BMPR1A) in adipose tissue and BMPR1A genetic variation are associated with human obesity SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Boettcher, Y.; Unbehauen, H.; Kloeting, N.; Ruschke, K.; Toenjes, A.; Wolf, S.; Blueher, M.; Stumvoll, M.] Univ Leipzig, Dept Med 3, Leipzig, Germany. [Schleinitz, D.; Enigk, B.; Kovacs, P.] Univ Leipzig, Interdisciplinary Ctr Clin Res IZKF, Leipzig, Germany. [Tseng, Y. -H.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Scholz, G. H.] St Elisabeth Hosp Leipzig, Dept Med, Leipzig, Germany. RI Ruschke, Karen/E-6320-2014 OI Ruschke, Karen/0000-0001-5285-9675 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 396 BP S166 EP S166 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200396 ER PT J AU Borg, R Kuenen, JC Carstensen, B Nerup, J Zheng, H Schoenfeld, D Heine, RJ Nathan, DM AF Borg, R. Kuenen, J. C. Carstensen, B. Nerup, J. Zheng, H. Schoenfeld, D. Heine, R. J. Nathan, D. M. TI Which blood glucose samples of the day predicts HbA(1c). Results from the ADAG (HbA(1c) Derived Average Glucose) study SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Borg, R.; Carstensen, B.; Nerup, J.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Kuenen, J. C.; Heine, R. J.] VU Med Ctr, Dept Endocrinol, Amsterdam, Netherlands. [Zheng, H.; Schoenfeld, D.; Nathan, D. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 1055 BP S429 EP S429 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660201345 ER PT J AU De Cosmo, S Minenna, A Zhang, YY Thompson, R Miscio, G Vedovato, M Rauseo, A Saller, A Mastroianno, S Pellegrini, F Trevisan, R Fioretto, P Doria, A Trischitta, V AF De Cosmo, S. Minenna, A. Zhang, Y. -Y. Thompson, R. Miscio, G. Vedovato, M. Rauseo, A. Saller, A. Mastroianno, S. Pellegrini, F. Trevisan, R. Fioretto, P. Doria, A. Trischitta, V. TI The Q121 variant of ENPPI (PC-1) gene is associated with chronic kidney disease among patients with type 2 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract C1 [De Cosmo, S.; Minenna, A.; Miscio, G.; Rauseo, A.; Mastroianno, S.; Trischitta, V.] IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, FG, Italy. [Zhang, Y. -Y.; Thompson, R.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Vedovato, M.] Univ Padua, Chair Metab Dis, I-35100 Padua, Italy. [Saller, A.] Univ Padua, Dept Med & Surg Sci, I-35100 Padua, Italy. [Pellegrini, F.] Consorzio Mario Negri Sud, Dept Clin Pharmacol & Epidemiol, Santa Maria Imbaro, Italy. [Trevisan, R.] Osped Riuniti Bergamo, Diabet Unit, Bergamo, Italy. [Trischitta, V.] Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RI De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016 OI De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 1166 BP S473 EP S473 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660201455 ER PT J AU Di Paola, R Marucci, A Miscio, G Padovano, L Boorryasrisawat, V Florez, JC Doria, A Trischitta, V AF Di Paola, R. Marucci, A. Miscio, G. Padovano, L. Boorryasrisawat, V. Florez, J. C. Doria, A. Trischitta, V. TI The role of HSP70 on in vitro ENPP1 expression and insulin receptor activation and in vivo insulin resistance-related traits SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Di Paola, R.; Marucci, A.; Miscio, G.; Padovano, L.; Boorryasrisawat, V.; Trischitta, V.] Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Florez, J. C.; Doria, A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, J. C.] Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Doria, A.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Trischitta, V.] Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RI Di Paola, Rosa/G-7813-2011; Trischitta, Vincenzo/K-1487-2016 OI Di Paola, Rosa/0000-0001-5837-9111; Trischitta, Vincenzo/0000-0003-1174-127X NR 0 TC 0 Z9 0 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 SEP PY 2008 VL 51 SU 1 MA 689 BP S277 EP S277 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200688 ER PT J AU Doupis, J Lyons, TE Dinh, T Veves, A AF Doupis, J. Lyons, T. E. Dinh, T. Veves, A. TI Microvascular reactivity in painful and painless peripheral diabetic neuropathy SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Doupis, J.; Lyons, T. E.; Dinh, T.; Veves, A.] Joslin Beth Israel Deaconess Med Ctr, Foot Ctr & Microcirculat Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 1156 BP S469 EP S470 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660201445 ER PT J AU Florez, JC Stolerman, ES Moore, AF Manning, AK McAteer, JB Dupuis, J Fox, CS Cupples, LA Jablonski, KA Arakaki, RF Goldstein, BJ Kahn, SE Kitabchi, AE Knowler, WC Meigs, JB AF Florez, J. C. Stolerman, E. S. Moore, A. F. Manning, A. K. McAteer, J. B. Dupuis, J. Fox, C. S. Cupples, L. A. Jablonski, K. A. Arakaki, R. F. Goldstein, B. J. Kahn, S. E. Kitabchi, A. E. Knowler, W. C. Meigs, J. B. TI ENPPI as an insulin resistance gene SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Florez, J. C.; Stolerman, E. S.; Moore, A. F.; McAteer, J. B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, J. C.; Stolerman, E. S.; Moore, A. F.; McAteer, J. B.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Florez, J. C.; Stolerman, E. S.; Moore, A. F.; McAteer, J. B.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Manning, A. K.; Dupuis, J.; Fox, C. S.; Cupples, L. A.; Meigs, J. B.] Framingham Heart Dis Epidemiol Study, Glycem Grp, Framingham, MA USA. [Jablonski, K. A.; Arakaki, R. F.; Goldstein, B. J.; Kahn, S. E.; Kitabchi, A. E.; Knowler, W. C.] Diabet Prevent Program, Res Grp, Rockville, MD USA. [Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 326 BP S137 EP S138 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200326 ER PT J AU Gonzalez, JS Vileikyte, L Peyrot, M Rubin, RR Ulbrecht, J Cavanagh, PR Boulton, AJ AF Gonzalez, J. S. Vileikyte, L. Peyrot, M. Rubin, R. R. Ulbrecht, J. Cavanagh, P. R. Boulton, A. J. TI Physical and psychological determinants of adherence to foot care in patients at high risk for foot ulceration SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Gonzalez, J. S.] Harvard Univ, Sch Med, Boston, MA USA. [Gonzalez, J. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vileikyte, L.; Boulton, A. J.] Univ Manchester, Manchester Diabet Ctr, Manchester M13 9PL, Lancs, England. [Peyrot, M.] Loyola Coll, Baltimore, MD 21210 USA. [Peyrot, M.; Rubin, R. R.] Johns Hopkins Univ, Baltimore, MD USA. [Ulbrecht, J.] Penn State Univ, State Coll, PA USA. [Cavanagh, P. R.] Cleveland Clin, Diabet Foot Clin, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 1274 BP S513 EP S514 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660201563 ER PT J AU Jacobson, AM Bolo, N Musen, G Simonson, D Weinger, K Raji, A Renshaw, P AF Jacobson, A. M. Bolo, N. Musen, G. Simonson, D. Weinger, K. Raji, A. Renshaw, P. TI BOLD brain activation in response to a cognitive challenge during hypoglycaemia among TIDM subjects SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Jacobson, A. M.; Musen, G.; Weinger, K.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bolo, N.; Renshaw, P.] McLean Hosp, Belmont, MA 02178 USA. [Simonson, D.; Raji, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 228 BP S101 EP S101 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200228 ER PT J AU Kahn, SE Herman, WH Holman, RR Haffner, SM Zinman, B Aftring, RP Kravitz, BG Paul, G Jones, NP Lachin, JM Viberti, GF AF Kahn, S. E. Herman, W. H. Holman, R. R. Haffner, S. M. Zinman, B. Aftring, R. P. Kravitz, B. G. Paul, G. Jones, N. P. Lachin, J. M. Viberti, G. F. CA Adopt Study Grp TI Changes in bone metabolism biomarkers in the ADOPT study SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Herman, W. H.] Univ Michigan, Ann Arbor, MI 48109 USA. [Holman, R. R.] Churchill Hosp, OCDEM, Diabet Trial Unit, Oxford OX3 7LJ, England. [Haffner, S. M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Zinman, B.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Paul, G.] GlaxoSmithKline Inc, Biomed Data Serv, King Of Prussia, PA USA. [Aftring, R. P.; Kravitz, B. G.] GlaxoSmithKline Inc, Metabol Med Dev Ctr, King Of Prussia, PA USA. [Jones, N. P.] GlaxoSmithKline Inc, Harlow, Essex, England. [Lachin, J. M.] George Washington Univ, Rockville, MD USA. [Viberti, G. F.] Kings Coll London, Sch Med, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 24 BP S16 EP S16 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200024 ER PT J AU Montori-Grau, M Minor, R Lerin, C Allard, J Garcia-Martinez, C de Cabo, R Gomez-Foix, AM AF Montori-Grau, M. Minor, R. Lerin, C. Allard, J. Garcia-Martinez, C. de Cabo, R. Gomez-Foix, A. M. TI Effects of aging and calorie restriction on rat skeletal muscle glycogen synthase and glycogen phosphorylase SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Montori-Grau, M.; Garcia-Martinez, C.; Gomez-Foix, A. M.] Univ Barcelona, E-08007 Barcelona, Spain. [Lerin, C.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Minor, R.; Allard, J.; de Cabo, R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 646 BP S261 EP S261 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200645 ER PT J AU Nathan, DM Zinman, B Cleary, PA Backlund, JYC Miller, R Orchard, T AF Nathan, D. M. Zinman, B. Cleary, P. A. Backlund, J. -Y. C. Miller, R. Orchard, T. TI Modern-day clinical course of type 1 diabetes mellitus. The DCCT/EDIC experience 1983-2008 SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Nathan, D. M.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Zinman, B.] Mt Sinai Hosp, Ctr Diabet, Toronto, ON M5G 1X5, Canada. [Cleary, P. A.; Backlund, J. -Y. C.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Miller, R.; Orchard, T.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 106 BP S50 EP S50 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200106 ER PT J AU Pratley, R Reusch, J Fleck, P Wilson, C Mekki, Q AF Pratley, R. Reusch, J. Fleck, P. Wilson, C. Mekki, Q. TI Alogliptin added to pioglitazone therapy improves glycaemic control in patients with type 2 diabetes without increasing weight gain or hypoglycaemia SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Pratley, R.] Univ Vermont, Burlington, VT 05405 USA. [Reusch, J.] Univ Colorado, Denver, CO 80202 USA. [Reusch, J.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Reusch, J.] Denver VAMC, Denver, CO USA. [Fleck, P.; Wilson, C.; Mekki, Q.] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 860 BP S343 EP S343 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660201150 ER PT J AU Russ, J Weingarten, G Takeda, J Kahn, C Wertheimer, E AF Russ, J. Weingarten, G. Takeda, J. Kahn, C. Wertheimer, E. TI Impaired insulin signalling is associated with decreased transformation potential of the skin SO DIABETOLOGIA LA English DT Meeting Abstract C1 [Russ, J.; Weingarten, G.; Wertheimer, E.] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Takeda, J.] Osaka Univ, Sch Med, Osaka, Japan. [Kahn, C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2008 VL 51 SU 1 MA 690 BP S277 EP S278 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QN UT WOS:000258660200689 ER PT J AU El-Serag, H AF El-Serag, Hashem TI The association between obesity and GERD: A review of the epidemiological evidence SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE gastroesophageal reflux disease; obesity; body mass index; epidemiology ID GASTROESOPHAGEAL-REFLUX DISEASE; BODY-MASS INDEX; BARRETTS-ESOPHAGUS; RISK-FACTORS; GASTRIC CARDIA; ABDOMINAL OBESITY; UNITED-STATES; EROSIVE ESOPHAGITIS; HIATAL-HERNIA; US CHILDREN AB The current epidemics of obesity and gastroesophageal reflux disease (GERD)-related disorders have generated much interest in studying the association between them. Results of multiple studies indicate that obesity satisfies several criteria for a causal association with GERD and some of its complications, including a generally consistent association with GERD symptoms, erosive esophagitis, and esophageal adenocarcinoma. An increase in GERD symptoms has been shown to occur in individuals who gain weight but continue to have a body mass index (BMI) in the normal range, contributing to the epidemiological evidence for a possible dose-response relationship between BMI and increasing GERD. Data are less clear on the relationship between Barrett's esophagus (BE) and obesity. However, when considered separately, abdominal obesity seems to explain a considerable part of the association with GERD, including BE. Overall, epidemiological data show that maintaining a normal BMI may reduce the likelihood of developing GERD and its potential complications. C1 [El-Serag, Hashem] Houston Vet Affairs Med Ctr 152, Houston, TX 77030 USA. [El-Serag, Hashem] Vet Affairs Med Ctr, Houston Dept, Gastroenterol Sect, Houston, TX 77030 USA. [El-Serag, Hashem] Vet Affairs Med Ctr, Houston Dept, Sect Hlth Serv Res, Houston, TX 77030 USA. [El-Serag, Hashem] Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, H (reprint author), Houston Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU TAP Pharmaceuticals; AstraZeneca; Eisai; Novartis FX Dr. El-Serag has served as a consultant for TAP Pharmaceuticals, AstraZeneca, Eisai, and Novartis. NR 51 TC 88 Z9 90 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2008 VL 53 IS 9 BP 2307 EP 2312 DI 10.1007/s10620-008-0413-9 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 339UC UT WOS:000258601800004 PM 18651221 ER PT J AU Ito, K Yamaoka, Y Yoffe, B Graham, DY AF Ito, Kyoko Yamaoka, Yoshio Yoffe, Boris Graham, David Y. TI Disturbance of apoptosis and DNA synthesis by Helicobacter pylori infection of hepatocytes SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Helicobacter; apoptosis; cell proliferations; hepatocytes; internalizations ID GASTRIC EPITHELIAL-CELLS; HEPATOCELLULAR-CARCINOMA; IN-VITRO; PROLIFERATION; LIVER; HEPATITIS; PATHOGENESIS; ADHERENCE; SURVIVAL; CIRRHOSIS AB We evaluated the effects of infection of hepatocytes with the well-characterized Helicobacter species, H. pylori. Cell number doubled during each 24 h period in mock cultures or following infection with H. pylori 401C (CagA-, VacA-, BabA-, OipA-) (P < 0.05). In contrast, infection with the more virulent H. pylori NCTC11637 (CagA+, VacA+, BabA+, OipA+) resulted in cell arrest (P < 0.05). Furthermore, NCTC11637 activated caspase-3 and increased DNA fragmentation 6.1 +/- 1.2 fold (P < 0.01) and the number of apoptotic bodies 9.4 +/- 3.5 fold (P < 0.01) compared to controls. The effect was greater than with the less virulent strain 401C (3.8 +/- 0.6 fold and 3.9 +/- 1.7, respectively, P < 0.05). Strain NCTC11637 at low concentrations increased cellular DNA synthesis 139 +/- 6% (P < 0.05) but decreased it to 16 +/- 7% (P < 0.01) at high concentrations. In contrast, strain 401C increased DNA synthesis 155 +/- 14% of controls (P < 0.05) at high concentrations. The presence of intracellular NCTC11637 within hepatocytes increased DNA fragmentation 3.0 +/- 0.4 fold (P < 0.01) greater than in controls. H. pylori infection resulted in strain-species-dependent effects on hepatocytes, and virulent strain caused cell arrest and apoptosis of infected hepatocytes. C1 [Ito, Kyoko; Yamaoka, Yoshio; Yoffe, Boris; Graham, David Y.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, GI Sect, Dept Med, Houston, TX 77030 USA. [Ito, Kyoko] Jikei Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Tokyo, Japan. RP Graham, DY (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, GI Sect, Dept Med, 2002 Holcombe Blvd 3A-320, Houston, TX 77030 USA. EM dgraham@bcm.edu FU Office of Research and Development Medical Research Service Department of Veterans Affairs; Texas Gulf Coast Digestive Diseases Center [DK56338]; NIH [DK 62813]; American College of Gastroenterology FX We are grateful to Dr. Andre Dubois and Dr. Cristina Semino- Mora for insightful discussions as assistance. We also thank Mr. Giovanni Suarez for performing the quantitative apoptosis ELISA assays and Dr. Reyes for his excellent advice. This material is based upon work supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs and by Public Health Service grant DK56338 which funds the Texas Gulf Coast Digestive Diseases Center. Dr. Yoshio Yamaoka is supported in part by NIH grant DK 62813. Dr. Kyoko Ito was supported in part by an International GI Training Grant from the American College of Gastroenterology. NR 38 TC 9 Z9 10 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 SEP PY 2008 VL 53 IS 9 BP 2532 EP 2540 DI 10.1007/s10620-007-0163-0 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 339UC UT WOS:000258601800033 PM 18253829 ER PT J AU Oviedo, NJ Pearson, BJ Levin, M Alvarado, AS AF Oviedo, Nestor J. Pearson, Bret J. Levin, Michael Alvarado, Alejandro Sanchez TI Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling SO DISEASE MODELS & MECHANISMS LA English DT Article ID TUMOR-SUPPRESSOR; GERMLINE MUTATIONS; SCHMIDTEA-MEDITERRANEA; CAENORHABDITIS-ELEGANS; PTEN/MMAC1 GENE; COWDEN DISEASE; MODEL SYSTEM; BASAL LAMINA; CANCER; PATHWAY AB We have identified two genes, Smed-PTEN-1 and Smed-PTEN-2, capable of regulating stern cell function in the planarian Schmidtea mediterranea. Both genes encode proteins homologous to the mammalian tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Inactivation of Smed-PTEN-1 and -2 by RNA interference (RNAi) in planarians disrupts regeneration, and leads to abnormal outgrowths in both cut and uncut animals followed soon after by death (lysis). The resulting phenotype is characterized by hyperproliferation of neoblasts (planarian stem cells), tissue disorganization and a significant accumulation of postmitotic cells with impaired differentiation capacity. Further analyses revealed that rapamycin selectively prevented such accumulation without affecting the normal neoblast proliferation associated with physiological turnover and regeneration. In animals in which PTEN function is abrogated, we also detected a significant increase in the number of cells expressing the planarian Akt gene homolog (Smed-Akt). However, functional abrogation of Smed-Akt in Smed-PTEN RNAi-treated animals does not prevent cell overproliferation and lethality, indicating that functional abrogation of Smed-PTEN is sufficient to induce abnormal outgrowths. Altogether, our data reveal roles for PTEN in the regulation of planarian stem cells that are strikingly conserved to mammalian models. In addition, our results implicate this protein in the control of stem cell maintenance during the regeneration of complex structures in planarians. C1 [Oviedo, Nestor J.; Levin, Michael] Harvard Univ, Sch Dent Med, Forsyth Inst, Ctr Regenerat & Dev Biol, Boston, MA 02115 USA. [Oviedo, Nestor J.; Levin, Michael] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Pearson, Bret J.; Alvarado, Alejandro Sanchez] Univ Utah, Howard Hughes Med Inst, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. RP Oviedo, NJ (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Ctr Regenerat & Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM noviedo@drmichaellevin.org; sanchez@neuro.utah.edu OI Pearson, Bret/0000-0002-3473-901X FU NIH [F32 GM078774, R21 HD055850]; NSF [0347295]; NHTSA [DTNH22-06-G-00001]; NIH-NIGMS [RO-1 GM57260]; Damon Runyon Fellow [1888-05]; Howard Hughes Medical Institute Investigator; National Center for Research Resources, NIH [C06RR11244] FX We thank P. Newmark, K. Agata and R. Romero for reagents; J. LaVecchio, B. Girijesh and the Harvard Stern Cell Institute Flow Cytometry Cores for FACS analysis; P. Reddien for sharing protocols, reagents and valuable suggestions; S. Morrison for rapamycin advice; J. Dobeck for histological assistance; R. Kent for assistance with data analysis; J. Jenkin, K. Gallant, D. Qiu and J. Morokuma for lab assistance; and C.B. Chien and C. Rodesh for advice with imaging. N.J.O. is an NIH fellow supported under Ruth L. Kirschstein National Research Service Award (F32 GM078774). N.J.O. also thanks the Oviedo-Pfister family for encouragement. This work was supported by NSF grant IBN#0347295, NHTSA grant DTNH22-06-G-00001, and NIH grant R21 HD055850 to M.L. and NIH-NIGMS RO-1 GM57260 to A.S.A. B.J.P. is a Damon Runyon Fellow (DRG#1888-05) and A.S.A. is a Howard Hughes Medical Institute Investigator. Part of this research was conducted in a Forsyth Institute facility renovated with support from Research Facilities Improvement Grant Number C06RR11244 from the National Center for Research Resources, NIH. NR 60 TC 37 Z9 38 U1 0 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD SEP-OCT PY 2008 VL 1 IS 2-3 BP 131 EP 143 DI 10.1242/dmm.000117 PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 474AH UT WOS:000268254100013 PM 19048075 ER PT J AU Rosengren, DB Hartzler, B Baer, JS Wells, EA Dunn, CW AF Rosengren, David B. Hartzler, Bryan Baer, John S. Wells, Elizabeth A. Dunn, Christopher W. TI The video assessment of simulated encounters-revised (VASE-R): Reliability and validity of a revised measure of motivational interviewing skills SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE motivational interviewing; training evaluation; skill assessment; evaluation instruments ID CLINICAL-SIGNIFICANCE; VALIDATION AB The video assessment of simulated encounters-revised (VASE-R) is a video-based method. administered in individual or group settings, for assessing motivational interviewing (MI) skills. The 18-item instrument includes three video-based vignettes. in which actors portray substance abusers, with each vignette followed by questions that prompt examinees to write responses that are then scored against MI standards. The VASE-R was administered to two independent samples: (1) substance abuse practitioners participating in a study of MI training methods, and (2) MI training facilitators with a high level of MI skill and expertise. This multi-study report describes basic VASE-R psychometric properties - including scoring reliability, internal consistency, concurrent validity, and sensitivity to the effects of training - and then presents proficiency standards based oil administration to a sample of MI training facilitators (MI Experts). The findings indicate excellent inter-rater reliability using intra-class correlations for the full-scale score (.85) and acceptable levels for subscales (.44 to .73). The instrument displayed strong concurrent validity with the Helpful Responses Questionnaire (HRQ) and a behavioral sample of clinician behavior with a standardized patient scored using the MI Treatment Integrity (MITI) system. as well as good sensitivity to improvement in MI skill as a result of training. The findings provide an empirical basis for suggesting VASE-R benchmarks for beginning proficiency and expert MI practice. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Rosengren, David B.; Hartzler, Bryan; Baer, John S.; Wells, Elizabeth A.; Dunn, Christopher W.] Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98195 USA. [Baer, John S.] Univ Washington, Dept Psychol, Seattle, WA 98108 USA. [Baer, John S.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Wells, Elizabeth A.] Univ Washington, Sch Social Work, Seattle, WA 98195 USA. [Dunn, Christopher W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Rosengren, DB (reprint author), Univ Washington, Inst Alcohol & Drug Abuse, 1107 NE 45th St,Suit 120, Seattle, WA 98195 USA. EM dhr@u.washington.edu FU NIDA NIH HHS [L30 DA020240, R01 DA 016360, R01 DA016360, R01 DA016360-03, L30 DA020240-01] NR 19 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2008 VL 97 IS 1-2 BP 130 EP 138 DI 10.1016/j.drugalcdep.2008.03.018 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 335RQ UT WOS:000258308100013 PM 18499356 ER PT J AU Najavits, LM Lester, KM AF Najavits, Lisa M. Lester, Kristin M. TI Gender differences in cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine dependence; psychopathology; gender; treatment ID NATIONAL-INSTITUTE; COOCCURRING DISORDERS; ABUSERS; TRAUMA; WOMEN AB Aims: This study examined gender differences among treatment-seeking cocaine-dependent outpatients (e.g., on demographics, psychopathology, and substance abuse). Participants: Participants were 2376 adults with cocaine dependence entering a multisite randomized controlled trial of psychosocial therapies. Findings: Women, compared to men, had less severe lifetime substance use problems but a higher pattern of psychiatric. medical, social/family, and employment problems: they also had more positive expectations and opinions about treatment. Conclusions: Women tray be willing to engage in treatment but (nay have challenging economic and psychosocial concerns over and above their addiction. Published by Elsevier Ireland Ltd. C1 [Najavits, Lisa M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Najavits, Lisa M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Najavits, Lisa M.] McLean Hosp, Belmont, MA 02478 USA. [Najavits, Lisa M.] Harvard Univ, Sch Med, Belmont, MA 02478 USA. RP Najavits, LM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM lisa.najavits@va.gov FU NIDA NIH HHS [U01 DA007693, U01 DA007693-07] NR 23 TC 27 Z9 27 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2008 VL 97 IS 1-2 BP 190 EP 194 DI 10.1016/j.drugalcdep.2008.04.012 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 335RQ UT WOS:000258308100020 PM 18571340 ER PT J AU Fan, D Makaryus, AN Hamik, A Finn, AV Isselbacher, EM AF Fan, Dali Makaryus, Amgad N. Hamik, Anne Finn, Aloke V. Isselbacher, Eric M. TI Prosthetic valve dysfunction presenting as intermittent acute aortic regurgitation SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Editorial Material DE aortic regurgitation; intermittent; echocardiography AB We describe the case of a 43 year old man with a history of aortic stenosis, for which he had undergone aortic valve replacement in 1991 with a 25-mm Medtronic Hall prosthesis. He presented with several acute episodes of dyspnea and flash pulmonary edema. Transthoracic and transesophageal echocardiography performed to evaluate prosthetic valve function revealed evidence of "intermittent" episodes of AI, documented on color M-mode flow mapping to have a variable duration of diastolic flow (early vs. pandiastolic) across the left ventricular outflow tract and the pulse wave Doppler in the descending thoracic aorta showed similar variability in the duration of diastolic flow reversal. C1 [Fan, Dali; Makaryus, Amgad N.] N Shore Univ Hosp, Div Cardiol, Manhasset, NY 11030 USA. [Hamik, Anne; Finn, Aloke V.; Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fan, D (reprint author), N Shore Univ Hosp, Div Cardiol, 300 Community Dr Manhasset, Manhasset, NY 11030 USA. EM dfan@nshs.edu OI Makaryus, Amgad/0000-0003-2104-7230 NR 4 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD SEP PY 2008 VL 25 IS 8 BP 925 EP 927 DI 10.1111/j.1540-8175.2008.00693.x PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 347NC UT WOS:000259147300019 PM 18476977 ER PT J AU Friedman, CS O'Donnell, MA Legarda-Addison, D Ng, A Cardenas, WB Yount, JS Moran, TM Basler, CF Komuro, A Horvath, CM Xavier, R Ting, AT AF Friedman, Constantin S. O'Donnell, Marie Anne Legarda-Addison, Diana Ng, Aylwin Cardenas, Washington B. Yount, Jacob S. Moran, Thomas M. Basler, Christopher F. Komuro, Akihiko Horvath, Curt M. Xavier, Ramnik Ting, Adrian T. TI The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response SO EMBO REPORTS LA English DT Article DE cylindromatosis; interferon; IRF3; RIG-I; ubiquitin ID NF-KAPPA-B; GENE-EXPRESSION; INNATE IMMUNITY; IKK-EPSILON; ACTIVATION; INDUCTION; PATHWAY; A20 AB On detecting viral RNAs, the RNA helicase retinoic acid-inducible gene I (RIG-I) activates the interferon regulatory factor 3 (IRF3) signalling pathway to induce type I interferon (IFN) gene transcription. How this antiviral signalling pathway might be negatively regulated is poorly understood. Microarray and bioinformatic analysis indicated that the expression of RIG-I and that of the tumour suppressor CYLD (cylindromatosis), a deubiquitinating enzyme that removes Lys 63-linked polyubiquitin chains, are closely correlated, suggesting a functional association between the two molecules. Ectopic expression of CYLD inhibits the IRF3 signalling pathway and IFN production triggered by RIG-I; conversely, CYLD knockdown enhances the response. CYLD removes polyubiquitin chains from RIG-I as well as from TANK binding kinase 1 (TBK1), the kinase that phosphorylates IRF3, coincident with an inhibition of the IRF3 signalling pathway. Furthermore, CYLD protein level is reduced in the presence of tumour necrosis factor and viral infection, concomitant with enhanced IFN production. These findings show that CYLD is a negative regulator of RIG-I-mediated innate antiviral response. C1 [Friedman, Constantin S.; O'Donnell, Marie Anne; Legarda-Addison, Diana; Ting, Adrian T.] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA. [Ng, Aylwin; Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Cardenas, Washington B.; Yount, Jacob S.; Moran, Thomas M.; Basler, Christopher F.] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. [Komuro, Akihiko; Horvath, Curt M.] Northwestern Univ, Dept Med, Evanston, IL 60208 USA. [Komuro, Akihiko; Horvath, Curt M.] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. RP Ting, AT (reprint author), Mt Sinai Sch Med, Inst Immunol, Box 1630,1 Gustave L Levy Pl, New York, NY 10029 USA. EM adrian.ting@mssm.edu RI Yount, Jacob/F-9905-2014; OI Cardenas, Washington/0000-0001-6829-1295 FU National Institutes of Health (NIH) [AI052417, AI057997, AI059536, AI041111, AI062623, AI073919, AI062773, T32 AI07647]; Crohn's and Colitis Foundation of America; Northeast Biodefense Center-Lipkin [AI057158]; NIH Ruth L. Kirschstein NRSA Postdoctoral Award [AI065058] FX We thank C. Lopez for her critical reading of the manuscript and S.-C. Sun, A. Garcia-Sastre, J. Hiscott, D. Thanos, J. Chen and T. Fujita for providing crucial reagents. This paper is dedicated to the memory of the late P. Leibson, whose passion for science, teaching and life remains a great inspiration to many others (A.T.T.). This study was supported in part by National Institutes of Health (NIH) grants AI052417 ( A.T.T.), AI057997 (A.T.T.), AI059536 (C.F.B.), AI041111 (T.M.M.), AI062623 (T.M.M.), AI073919 (C.M.H.) and AI062773 (R.X.). C. S. F.was supported in part by the NIH T32 AI07647- Training Program: Mechanisms of Virus-Host Interactions. M.A.O'D. and A.N. are recipients of Research Fellowship Awards from the Crohn's and Colitis Foundation of America. W. B. C. was supported in part by a fellowship awarded through grant AI057158 (Northeast Biodefense Center-Lipkin). D.L.-A. is supported by an NIH Ruth L. Kirschstein NRSA Postdoctoral Award AI065058. A. T. T. is a recipient of the Irma T. Hirschl Career Scientist Award. NR 25 TC 146 Z9 159 U1 3 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD SEP PY 2008 VL 9 IS 9 BP 930 EP 936 DI 10.1038/embor.2008.136 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 344GR UT WOS:000258915400022 PM 18636086 ER PT J AU Tilly, JL Rueda, BR AF Tilly, Jonathan L. Rueda, Bo R. TI Minireview: Stem cell contribution to ovarian development, function, and disease SO ENDOCRINOLOGY LA English DT Review ID ADULT-MOUSE OVARY; BONE-MARROW; GERM-CELLS; SIDE POPULATION; IN-VITRO; HEMATOLOGICAL MALIGNANCIES; CANCER-CELLS; OOGENESIS; OOCYTES; MICE AB By virtue of the fact that oocytes not only serve to produce embryos after fertilization but also can effectively reprogram adult somatic cell nuclei to a pluripotent state, much of the interest in the role of stem cells in ovarian biology has been focused on the germline. However, very recent studies have revealed that somatic stem cells may also be of considerable relevance to the study of normal ovarian function. Furthermore, stem cell dysfunction may underlie or contribute to disease states such as ovarian cancer and polycystic ovary syndrome. Our objective is to explore these concepts in greater detail, with the hope of stimulating further research efforts into understanding what role stem cells may play in the physiology and pathology of the mammalian female gonads. C1 [Tilly, Jonathan L.; Rueda, Bo R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, THR-901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU National Institutes of Health [R01-AG024999, R37-AG012279, R01-CA98333]; Advanced Medical Research Foundation; Shulsky Philanthropic Fund; Rosenberg Philanthropic Fund; Vincent Memorial Research Funds FX Work conducted in the authors' laboratories discussed herein was supported by the National Institutes of Health (R01-AG024999 and R37-AG012279 to J.L.T.; R01-CA98333 to B.R.R.), Advanced Medical Research Foundation, Shulsky Philanthropic Fund, Rosenberg Philanthropic Fund, and Vincent Memorial Research Funds. NR 70 TC 16 Z9 20 U1 0 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2008 VL 149 IS 9 BP 4307 EP 4311 DI 10.1210/en.2008-0458 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QT UT WOS:000258660800011 PM 18556344 ER PT J AU Schneyer, AL Sidis, Y Gulati, A Sun, JL Keutmann, H Krasney, PA AF Schneyer, Alan L. Sidis, Yisrael Gulati, Anisha Sun, Jie L. Keutmann, Henry Krasney, Philip A. TI Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin SO ENDOCRINOLOGY LA English DT Article ID SKELETAL-MUSCLE MASS; CELL DIFFERENTIATION; TRANSGENIC MICE; BINDING; DEFECTS; OVEREXPRESSION; EXPRESSION; DEFICIENT; RECEPTORS; CACHEXIA AB Follistatin binds and neutralizes members of the TGF beta superfamily including activin, myostatin, and growth and differentiation factor 11 (GDF11). Crystal structure analysis of the follistatin-activin complex revealed extensive contacts between follistatin domain (FSD)-2 and activin that was critical for the high-affinity interaction. However, it remained unknown whether follistatin residues involved with myostatin and GDF11 binding were distinct from those involved with activin binding. If so, this would allow development of myostatin antagonists that would not inhibit activin actions, a desirable feature for development of myostatin antagonists for treatment of muscle-wasting disorders. We tested this hypothesis with our panel of point and domain swapping follistatin mutants using competitive binding analyses and in vitro bioassays. Our results demonstrate that activin binding and neutralization are mediated primarily by FSD2, whereas myostatin binding is more dependent on FSD1, such that deletion of FSD2 or adding an extra FSD1 in place of FSD2 creates myostatin antagonists with vastly reduced activin antagonism. However, these mutants also bind GDF11, indicating that further analysis is required for creation of myostatin antagonists that will not affect GDF11 activity that could potentially elicit GDF11-induced side effects in vivo. C1 [Schneyer, Alan L.; Sidis, Yisrael; Gulati, Anisha; Sun, Jie L.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Keutmann, Henry] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Krasney, Philip A.] Pfizer Global Res & Dev, Groton, CT 06340 USA. RP Schneyer, AL (reprint author), Pioneer Valley Life Sci Inst, 3601 Main St, Springfield, MA 01107 USA. EM alan.schneyer@bhs.org FU NIDDK NIH HHS [R01 DK075058, R01DK075058] NR 29 TC 41 Z9 49 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2008 VL 149 IS 9 BP 4589 EP 4595 DI 10.1210/en.2008-0259 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 340QT UT WOS:000258660800042 PM 18535106 ER PT J AU Artifon, ELA da Silveira, EB Lopes, RI Kumar, A Bhutani, MS Mesquita, JL Souza, T Dall'oglio, M Lucon, AM Couto, D Sakai, P Srougi, M AF Artifon, E. L. A. da Silveira, E. B. Lopes, R. I. Kumar, A. Bhutani, M. S. Mesquita, J. L. Souza, T. Dall'oglio, M. Lucon, A. M. Couto, D. Sakai, P. Srougi, M. TI Endoscopic ultrasound-guided ureterosigmoidostomy in malignant ureteral obstruction: description of a new method SO ENDOSCOPY LA English DT Editorial Material ID DIVERSION; QUALITY; STENTS; LIFE C1 [da Silveira, E. B.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Gastroenterol, Div Gastroenterol, Portland, OR 97239 USA. [Artifon, E. L. A.; Kumar, A.; Souza, T.; Couto, D.; Sakai, P.] Univ Sao Paulo, Sch Med, Dept Gastroenterol, Sao Paulo, Brazil. [Lopes, R. I.; Mesquita, J. L.; Dall'oglio, M.; Lucon, A. M.; Srougi, M.] Univ Sao Paulo, Sch Med, Dept Urol, Sao Paulo, Brazil. [Bhutani, M. S.] Univ Texas MD Anderson Canc Ctr, Div Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. RP da Silveira, EB (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Gastroenterol, Div Gastroenterol, 3710 SW US Vet Hosp,Blvd MC,P3GI, Portland, OR 97239 USA. EM eda_silveira@hotmail.com OI Dall'Oglio, Marcos Francisco/0000-0002-9611-6846; Lopes, Roberto/0000-0002-6636-7679 NR 6 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD SEP PY 2008 VL 40 IS 9 BP 769 EP 772 DI 10.1055/s-2008-1077447 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 351EX UT WOS:000259408400012 PM 18668473 ER PT J AU Sharma, R Tsuchiya, M Bartlett, JD AF Sharma, Ramaswamy Tsuchiya, Masahiro Bartlett, John D. TI Fluoride induces endoplasmic reticulum stress and inhibits protein synthesis and secretion SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE ameloblasts; eIF2 alpha; enamel; endoplasmic reticulum; ER stress; fluoride; LS8 cells; SEAP; UPR ID DENTAL FLUOROSIS; SODIUM-FLUORIDE; ULTRASTRUCTURAL-CHANGES; BIOLOGICAL MECHANISMS; TREATED RATS; ER STRESS; ENAMEL; CELLS; EXPOSURE; PATHWAY AB BACKGROUND: Exposure to excessive amounts of fluoride (F-) causes dental fluorosis in susceptible individuals; however, the mechanism of F--induced toxicity is unclear. Previously, we have shown that high-dose F- activates the unfolded protein response (UPR) in ameloblasts that are responsible for dental enamel formation. The UPR is a signaling pathway responsible for either alleviating endoplasmic reticulum (ER) stress or for inducing apoptosis of the stressed cells. OBJECTIVES: In this study we determined if low-dose F- causes ER stress and activates the UPR, and we also determined whether F- interferes with the secretion of proteins from the ER. METHODS: We stably transfected the ameloblast-derived LS8 cell line with secreted alkaline phosphatase (SEAP) and determined activity and localization of SEAP and F--mediated induction of UPR proteins. Also, incisors from mice given drinking water containing various concentrations of F- were examined for eucaryotic initiation factor-2, subunit alpha (eIF2 alpha) phosphorylation. RESULTS: We found that F- decreases the extracellular secretion of SEAP in a linear, dose-dependent manner. We also found a corresponding increase in the intracellular accumulation of SEAP after exposure to F-. These changes are associated with the induction of UPR proteins such as the molecular chaperone BiP and phosphorylation of the UPR sensor PKR-like ER kinase, and its substrate, eIF2 alpha. Importantly, F--induced phosphorylation of eIF2 alpha was confirmed in vivo. CONCLUSIONS: These data suggest that F- initiates an ER stress response in ameloblasts that interferes with protein synthesis and secretion. Consequently, ameloblast function during enamel development may be impaired, and this may culminate in dental fluorosis. C1 [Sharma, Ramaswamy; Bartlett, John D.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Sharma, Ramaswamy; Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Tsuchiya, Masahiro] Tohoku Univ, Grad Sch Dent, Div Aging & Geriatr Dent, Sendai, Miyagi 980, Japan. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM jbartlett@forsyth.org RI Sharma, Ramaswamy/F-8401-2012; OI Tsuchiya, Masahiro/0000-0002-7000-4547 FU National Institute of Dental and Craniofacial Research [DE016276] FX This work was supported in part by grant DE016276 from the National Institute of Dental and Craniofacial Research to J.D.B. NR 43 TC 49 Z9 60 U1 0 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2008 VL 116 IS 9 BP 1142 EP 1146 DI 10.1289/ehp.11375 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 345TP UT WOS:000259020100025 PM 18795154 ER PT J AU Giraldez, R Wiviott, SD Giugliano, RG Nicolau, JC Mohanavelu, S Morrow, DA Antman, EM Braunwald, E AF Giraldez, R. Wiviott, S. D. Giugliano, R. G. Nicolau, J. C. Mohanavelu, S. Morrow, D. A. Antman, E. M. Braunwald, E. TI Fibrinolytic therapy with streptokinase and enoxaparin is associated with improved outcomes compared to fibrin-specific lytics and unfractionated heparin - an ExTRACT-TIMI 25 analysis SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Giraldez, R.; Wiviott, S. D.; Giugliano, R. G.; Mohanavelu, S.; Morrow, D. A.; Antman, E. M.; Braunwald, E.] Brigham & Womens Hosp, Dept Cardiol, TIMI Study Grp, Boston, MA 02115 USA. [Nicolau, J. C.] Inst Coracao InCor HCFMUSP, Sao Paulo, Brazil. RI Nicolau, Jose/E-1487-2012 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 75 EP 75 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702500285 ER PT J AU Merlini, PA Berzuini, C Mannucci, PM Tubaro, M Lina, D Notarangelo, MF Buratti, S Altshuler, D Kathiresan, S Ardissino, D AF Merlini, P. A. Berzuini, C. Mannucci, P. M. Tubaro, M. Lina, D. Notarangelo, M. F. Buratti, S. Altshuler, D. Kathiresan, S. Ardissino, D. CA Italian Atherosclerosis Investiga Thrombosis Vasc Biol Investigators TI Genetic variants on chromosomal region 9p21.3 associate with early-onset myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Merlini, P. A.] Azienda Osped Niguarda Ca Granda, Div Cardiol, Milan, 02114, Italy. [Berzuini, C.] MRC, Cambridge, England. [Mannucci, P. M.] Fdn IRCCS Osped Maggiore, Milan, Italy. [Tubaro, M.] Osped S Filippo Neri, Rome, Italy. [Lina, D.; Notarangelo, M. F.; Buratti, S.; Ardissino, D.] Azienda Osped Univ, Parma, Italy. [Altshuler, D.; Kathiresan, S.] Massachusetts Gen Hosp, Boston, MA USA. RI Altshuler, David/A-4476-2009; Mannucci, Pier/C-3102-2014 OI Altshuler, David/0000-0002-7250-4107; NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 112 EP 113 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702500434 ER PT J AU Ardissino, D Merlini, PA Berzuini, C Mannucci, PM Tubaro, M Lina, D Notarangelo, MF Marzialiano, N Bernardinelli, L Kathiresan, S AF Ardissino, D. Merlini, P. A. Berzuini, C. Mannucci, P. M. Tubaro, M. Lina, D. Notarangelo, M. F. Marzialiano, N. Bernardinelli, L. Kathiresan, S. CA Italian Atherosclerosis Thrombosis TI Influence of the 9p21.3 genetic variant rs1333040 on the severity of coronary artery disease in early-onset myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Ardissino, D.; Lina, D.; Notarangelo, M. F.] Azienda Osped Univ Parma, Div Cardiol, Parma, Italy. [Merlini, P. A.] Azienda Osped Niguarda Ca Granda, Div Cardiol, Milan, Italy. [Berzuini, C.] MRC, Cambridge, England. [Mannucci, P. M.] Fdn IRCCS Osped Maggiore, Milan, Italy. [Tubaro, M.] Osped S Filippo Neri, Rome, Italy. [Marzialiano, N.] Fdn IRCCS Policlin S Matteo, Pavia, Italy. [Bernardinelli, L.] Univ Pavia, I-27100 Pavia, Italy. [Kathiresan, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Mannucci, Pier/C-3102-2014 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 114 EP 114 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702500441 ER PT J AU Kiernan, TJ Boilson, B Yan, BP Simari, R AF Kiernan, T. J. Boilson, B. Yan, B. P. Simari, R. TI Vasoprotective effects of human CD34+cells in an immunodeficient rat model of arterial injury SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Kiernan, T. J.; Boilson, B.; Simari, R.] Mayo Clin, Rochester, MN USA. [Yan, B. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 237 EP 237 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702501148 ER PT J AU Feuchtner, GM Dichtl, W Bonatti, J Mueller, S Jodocy, D Friedrich, G Bartel, T Pachinger, O Jaschke, W Cury, R AF Feuchtner, G. M. Dichtl, W. Bonatti, J. Mueller, S. Jodocy, D. Friedrich, G. Bartel, T. Pachinger, O. Jaschke, W. Cury, R. TI Diagnostic accuracy of cardiac 64-slice ECG-gated computed tomography in detecting atrial thrombi: comparative study with transesophageal echocardiography and cardiac surgery SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Feuchtner, G. M.; Dichtl, W.; Bonatti, J.; Mueller, S.; Jodocy, D.; Friedrich, G.; Bartel, T.; Pachinger, O.; Jaschke, W.] Med Univ Innsbruck, A-6020 Innsbruck, Austria. [Cury, R.] Massachussets Gen Hosp, Boston, MA 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 245 EP 245 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702501180 ER PT J AU Gonzalez, IC Chia, S Raffel, OC Senatore, F Jang, IK AF Gonzalez, I. Cruz Chia, S. Raffel, O. C. Senatore, F. Jang, I. K. TI Hyperglycemia on admission predicts larger infarct size in patients undergoing percutaneous coronary intervention for acute ST-segment elevation myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Gonzalez, I. Cruz; Chia, S.; Raffel, O. C.; Jang, I. K.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Senatore, F.] Mitsubishi Pharma Amer Inc, Warren, NJ 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 448 EP 448 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702502221 ER PT J AU Grabowski, M Szymanski, FM Januzzi, J Wu, AHB Hrynkiewicz, A Filipiak, KJ Opolski, G AF Grabowski, M. Szymanski, F. M. Januzzi, J. Wu, A. H. B. Hrynkiewicz, A. Filipiak, K. J. Opolski, G. TI Baseline concentrations of the interleukin receptor family member ST2 add independent prognostic information to risk scores in STEMI patients treated with PCI SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Grabowski, M.; Szymanski, F. M.; Hrynkiewicz, A.; Filipiak, K. J.; Opolski, G.] Med Univ Warsaw, Dept Cardiol 1, Warsaw, Poland. [Januzzi, J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Wu, A. H. B.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 449 EP 450 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702502228 ER PT J AU Chua, S Levine, R Yosefy, C Handschumacher, M Chu, J Ton-Nu, T Qureshi, A Neary, J Fu, M Hung, J AF Chua, S. Levine, R. Yosefy, C. Handschumacher, M. Chu, J. Ton-Nu, T. Qureshi, A. Neary, J. Fu, M. Hung, J. TI Assessment of right ventricular function by real-time three-dimensional echocardiography improves accuracy and decreases interobserver variability compared with conventional two-dimensional views SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Chua, S.; Levine, R.; Yosefy, C.; Handschumacher, M.; Chu, J.; Ton-Nu, T.; Qureshi, A.; Neary, J.; Hung, J.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Fu, M.] Chang Gung Mem Hosp KMC, Kaohsiung Hsien, Taiwan. 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 520 EP 520 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702502492 ER PT J AU Grabowski, M Szymanski, FM Januzzi, J Wu, AHB Hrynkiewicz, A Filipiak, KJ Opolski, G AF Grabowski, M. Szymanski, F. M. Januzzi, J. Wu, A. H. B. Hrynkiewicz, A. Filipiak, K. J. Opolski, G. TI ST2 a novel biomarker with powerfully prognostic value for angiographic results, failure of intervention, and adverse cardiovascular events in STEMI patients treated with primary PCI SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Grabowski, M.; Szymanski, F. M.; Hrynkiewicz, A.; Filipiak, K. J.; Opolski, G.] Med Univ Warsaw, Dept Cardiol 1, Warsaw, Poland. [Januzzi, J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Wu, A. H. B.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 576 EP 577 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702503012 ER PT J AU Kiernan, TJ Yan, BP Cubeddu, RJ Cruz-Gonzalez, I Rosenfield, K Palacios, I AF Kiernan, T. J. Yan, B. P. Cubeddu, R. J. Cruz-Gonzalez, I. Rosenfield, K. Palacios, I. TI Coronary perforations during percutaneous coronary intervention: a contemporary analysis SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Kiernan, T. J.; Yan, B. P.; Cubeddu, R. J.; Cruz-Gonzalez, I.; Rosenfield, K.; Palacios, I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 583 EP 583 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702503038 ER PT J AU Meliga, E Garcia-Garcia, HM Valgimigli, M Chieffo, A Maree, AO Cook, S De Servi, S Windecker, S Colombo, A Serruys, PW AF Meliga, E. Garcia-Garcia, H. M. Valgimigli, M. Chieffo, A. Maree, A. O. Cook, S. De Servi, S. Windecker, S. Colombo, A. Serruys, P. W. TI Impact of DES selection on long-term clinical outcomes in patients treated for unprotected left main coronary artery disease: the Sirolimus vs Paclitaxel Drug Eluting stent for LeFT main registry SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Meliga, E.] Erasmus MC, Intervent Cardiol Dept, Rotterdam, Netherlands. [Garcia-Garcia, H. M.; Serruys, P. W.] Erasmus MC, Intervent Cardiol, Rotterdam, Netherlands. [Valgimigli, M.] St Anna Hosp, Ferrara, Italy. [Chieffo, A.; Colombo, A.] Hosp San Raffaele, I-20132 Milan, Italy. [Maree, A. O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cook, S.; Windecker, S.] Univ Hosp Bern, CH-3010 Bern, Switzerland. [De Servi, S.] Osped Civile Legnano, Legnano, Italy. 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 682 EP 682 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702503429 ER PT J AU Santos, RD Nasir, K Menghello, RS Carvalho, JAM Budoff, M Blumenthal, RS AF Santos, R. D. Nasir, K. Menghello, R. S. Carvalho, J. A. M. Budoff, M. Blumenthal, R. S. TI Peak exercise heart rate is inversely correlated with coronary artery calcification in asymptomatic subjec SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Santos, R. D.] Univ Sao Paulo, Heart Inst Incor, Lipid Clin, Sao Paulo, Brazil. [Nasir, K.] Harvard Univ, Sch Med, Mass Gen Hosp, PET CT MRI Program, Boston, MA USA. [Menghello, R. S.; Carvalho, J. A. M.] Albert Einstein Hosp, Prevent Med Ctr, Sao Paulo, Brazil. [Budoff, M.] Harbor UCLA, Torrance, CA USA. [Blumenthal, R. S.] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 750 EP 750 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702503687 ER PT J AU Tournoux, F Thibault, H Petersen, B Raher, MJ Halpern, E Picard, MH Scherrer-Crosbie, M AF Tournoux, F. Thibault, H. Petersen, B. Raher, M. J. Halpern, E. Picard, M. H. Scherrer-Crosbie, M. TI Validation of a non-invasive method to measure cardiac output in mice SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Tournoux, F.; Thibault, H.; Petersen, B.; Raher, M. J.; Halpern, E.; Picard, M. H.; Scherrer-Crosbie, M.] Mass Gen Hosp, Ultrasound Cardiac Lab, Boston, MA 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 793 EP 793 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702504022 ER PT J AU Tournoux, F Singh, JP Chan, RC Chen-Tournoux, AA Nandigam, V Manzke, R Ruskin, JN Cohen-Solal, A Picard, MH Weyman, AE AF Tournoux, F. Singh, J. P. Chan, R. C. Chen-Tournoux, A. A. Nandigam, V. Manzke, R. Ruskin, J. N. Cohen-Solal, A. Picard, M. H. Weyman, A. E. TI Absence of left ventricular apical rocking and atrial-ventricular dyssynchrony predicts non-response to cardiac resynchronization therapy SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Tournoux, F.; Cohen-Solal, A.] Hop Lariboisiere, F-75475 Paris, France. [Singh, J. P.; Chen-Tournoux, A. A.; Nandigam, V.; Ruskin, J. N.; Picard, M. H.; Weyman, A. E.] Mass Gen Hosp, Boston, MA USA. [Chan, R. C.; Manzke, R.] Philips Res North Amer, Boston, MA 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 804 EP 804 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702504062 ER PT J AU Giraldez, R Giugliano, RG Qin, J Buros, J Mccabe, CH Morrow, DA Antman, EM Braunwald, E AF Giraldez, R. Giugliano, R. G. Qin, J. Buros, J. Mccabe, C. H. Morrow, D. A. Antman, E. M. Braunwald, E. TI Gross national income per person accounts for global differences in mortality rates in STEMI patients undergoing fibrinolysis - ExTRACT-TIMI 25 analysis SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Giraldez, R.; Giugliano, R. G.; Qin, J.; Buros, J.; Mccabe, C. H.; Morrow, D. A.; Antman, E. M.; Braunwald, E.] Brigham & Womens Hosp, TIMI Study Grp, Dept Cardiol, 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 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 SU 1 BP 852 EP 852 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TG UT WOS:000208702504254 ER PT J AU Bankier, B Barajas, J Martinez-Rumayor, A Januzzi, JL AF Bankier, Bettina Barajas, Justine Martinez-Rumayor, Abelardo Januzzi, James L. TI Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients SO EUROPEAN HEART JOURNAL LA English DT Article DE C-reactive protein; generalized anxiety disorder; stable CHD ID CARDIOVASCULAR EVENTS; STATIN THERAPY; PHOBIC ANXIETY; CARDIAC EVENTS; RISK-FACTORS; DEPRESSION; SYMPTOMS; MEN; PREVALENCE; MARKERS AB Aims Comprehensive evaluation of major depressive disorder (MDD), anxiety disorder, and MDD in conjunction with anxiety disorder in stable coronary heart disease (CHD) patients, including cardiac biomarkers such as C-reactive protein (CRP), troponin T (TnT), and amino-terminal pro-B-type brain natriuretic peptide (NT-proBNP). Methods and results Cross-sectional study of a consecutive series of 120 stable CHD outpatients (n = 30 with MDD, n = 30 with anxiety disorder, n = 30 with MDD and anxiety disorder, n = 30 with no psychiatric disorder). Psychiatric diagnoses were established by using the structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV). Binomial logistic regression analyses using cut-off scores of biomarkers as dependent variables showed associations between CRP and generalized anxiety disorder (GAD) (P = 0.04), and education (P = 0.004), whereas MDD, and MDD and anxiety disorder did not reach the significance level. TnT showed relationships with hyperlipidaemia (P = 0.009), history of obesity or overweight (P = 0.04), and education (P = 0.04). NT-proBNP was associated with type II diabetes (P = 0.005). Conclusion After adjusting for relevant demographic, medical, and psychiatric co-variables, CRP was associated with GAD. C1 [Bankier, Bettina; Barajas, Justine; Martinez-Rumayor, Abelardo; Januzzi, James L.] Harvard Univ, Sch Med, Boston, MA USA. [Bankier, Bettina] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Barajas, Justine; Martinez-Rumayor, Abelardo; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Bankier, B (reprint author), Med Univ Vienna, Dept Psychiat & Psychotherapy, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM bettina.bankier@meduniwien.ac.at FU NARSAD [760-2339-5, 218960]; Mental Health Research Association, Great Neck, New York FX This work was fully supported by a NARSAD Young Investigator Award 2005, Mental Health Research Association, Great Neck, New York (NARSAD Fund No. 760-2339-5, Grant 218960 to B. B). NR 24 TC 34 Z9 35 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2008 VL 29 IS 18 BP 2212 EP 2217 DI 10.1093/eurheartj/ehn326 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 350BI UT WOS:000259327000007 PM 18603621 ER PT J AU Aliot, E Ruskin, JN AF Aliot, Etienne Ruskin, Jeremy N. TI Controversies in ablation of atrial fibrillation SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Review DE atrial fibrillation; catheter ablation; sinus rhythm; AF recurrence; mortality; quality of life; atrial flutter ID CONGESTIVE-HEART-FAILURE; PULMONARY VEIN ISOLATION; QUALITY-OF-LIFE; VENTRICULAR SYSTOLIC DYSFUNCTION; ARRHYTHMIA SUPPRESSION TRIAL; ANTIARRHYTHMIC-DRUG-THERAPY; RADIOFREQUENCY CATHETER ABLATION; ELECTRICAL CARDIOVERSION RACE; RHYTHM-MANAGEMENT AFFIRM; FOLLOW-UP STRATEGIES AB Catheter ablation is increasingly widely used to treat atrial. fibrillation (AF) and constantly evolving techniques and protocols have led to improved success rates and lower risks of complications in a broad range of patients. However, long-term clinical trial data are still limited and as a result many questions remain unanswered. Particularly in patients with symptomatic paroxysmal AF, high success rates in restoring sinus rhythm (SR) with a low risk of complications are reported by experienced centres. Nevertheless, the continued suppression of AF over time, particularly with regard to the recurrence of asymptomatic episodes of AF which could influence stroke risk, is not yet adequately documented and therefore the safety of discontinuing oral anticoagulation remains unclear. The risk of silent or subclinical complications associated with ablation procedures, the likelihood of autonomic modulation and the long-term impact of ablation on left. atrial. mechanical function have not yet been fully determined. Limited clinical trial data suggest that catheter ablation may be particularly beneficial for patients suffering from heart failure (HF) secondary to AF, indicating improved left. ventricular function and quality of Life with the restoration of SR. However, the processes underlying HF and the co-existing morbidities vary from one patient to another and the factors predicting a successful outcome of ablation have not yet been fully defined. Similarly, the consistently higher rates of AF suppression achieved with catheter ablation vs. antiarrhythmic drug therapy shown in comparative clinical trials encourage consideration of this treatment as a potential first-tine treatment in certain patients, but whether this is currently justifiable and if so, in which patient subsets, are open questions. This article reviews current approaches to catheter ablation and attempts to address some of the controversies regarding its use. C1 [Aliot, Etienne] Univ Nancy 1, Hop Brabois, Ctr Hosp, Nancy, France. [Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Aliot, E (reprint author), Univ Nancy 1, Hop Brabois, Ctr Hosp, Nancy, France. EM e.atiot@chu-nancy.fr FU sanofiaventis FX Funding for editorial support was provided by sanofiaventis. NR 115 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD SEP PY 2008 VL 10 IS H BP H32 EP H54 DI 10.1093/eurheartj/sun030 PG 23 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 356LX UT WOS:000259780800004 ER PT J AU Dorian, P Singh, BN AF Dorian, Paul Singh, Brarnah N. TI Upstream therapies to prevent atrial fibrillation SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Review DE atrial fibrillation; upstream therapy; angiotensin-converting enzyme inhibitors; angiotensin receptor blockers; statins; steroids; N-3 polyunsaturated fatty acids; fish oil ID C-REACTIVE PROTEIN; CONVERTING ENZYME-INHIBITORS; N-3 FATTY-ACIDS; LEFT-VENTRICULAR DYSFUNCTION; II RECEPTOR BLOCKERS; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; CARDIAC-SURGERY; RANDOMIZED-TRIAL; ELECTRICAL CARDIOVERSION AB Atrial fibrillation (AF) is the most common sustained arrhythmia in the western world. It is associated with increased morbidity and mortality and decreased quality of life. The absence of a clear benefit of a rhythm-control strategy over a rate-control strategy observed in recent trials may be due to the fact that none of the available membrane-acting antiarrhythmics is entirely satisfactory. In addition, ablative therapy is available only for a small number of patients. Besides research efforts to improve the efficacy and safety of conventional antiarrhythmic agents, therapies directed 'upstream' of the electrical aspects of AF, towards the underlying anatomical substrate (atrial. remodelling), have emerged as potential new pharmacological therapies. Potential upstream therapies for AF comprise a variety of agents such as those targeting the renin-angiotensin system [angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB)], statins, steroids, and N-3 polyunsaturated fatty acids. On the basis of suggestive experimental data, early phase clinical studies have been conducted and have provided exciting information on the potential of upstream therapy for the prevention of AF across a broad spectrum of cardiovascular patient groups. In some of these groups, such as patients with hypertension or heart failure, data may be considered to be sufficient to support the use of ACEI or ARB, at least in combination with membrane-acting antiarrhythmics. However, in most clinical settings examined, the evidence appears to be insufficient to drive changes in therapy management, and additional data from large-scale, randomized, double-blind, placebo-controlled trials with adequately defined endpoints are still needed. Numerous such trials are ongoing, reflecting the intense scientific interest in this field. The data derived from these trials may add to our understanding of the complex mechanisms that lead to AF and its maintenance, and may provide the necessary substantive evidence clarifying the benefit-to-risk ratio of these new therapeutic approaches. C1 [Singh, Brarnah N.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dorian, Paul] Univ Toronto, Div Cardiol, Toronto, ON, Canada. [Dorian, Paul] Univ Toronto, Div Clin Pharmacol, Toronto, ON, Canada. [Singh, Brarnah N.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Singh, BN (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM Bramah.Singh@va.gov FU sanofiaventis FX Funding for editorial support was provided by sanofiaventis. NR 104 TC 17 Z9 17 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD SEP PY 2008 VL 10 IS H BP H11 EP H31 DI 10.1093/eurheartj/sun033 PG 21 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 356LX UT WOS:000259780800003 ER PT J AU Singh, BN AF Singh, Bramah N. TI Recent advances in the management of atrial fibrillation SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Editorial Material C1 [Singh, Bramah N.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Singh, Bramah N.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Singh, BN (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM bramah.singh@va.gov NR 0 TC 1 Z9 3 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD SEP PY 2008 VL 10 IS H BP H2 EP H3 DI 10.1093/eurheartj/sun032 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 356LX UT WOS:000259780800001 ER PT J AU Bassing, CH Whitlow, S Mostoslovasky, R Yang-Iott, K Ranganath, S Alt, FW AF Bassing, Craig H. Whitlow, Scott Mostoslovasky, Raul Yang-Iott, Katherine Ranganath, Sheila Alt, Frederick W. TI V beta cluster sequences reduce the frequency of primary V beta 2 and V beta 14 rearrangements SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE gene-targeted mutation; T-cell receptor beta; V(D)J recombination ID CHROMOSOMAL V(D)J RECOMBINATION; T-CELL DEVELOPMENT; ALLELIC EXCLUSION; TRANSCRIPTIONAL REGULATION; GERMLINE TRANSCRIPTION; GENE ENHANCER; ALPHA-BETA; SEGMENTS; PROMOTER; DELETION AB T-cell receptor (TCR) beta variable region exons are assembled from numerous gene segments in a highly ordered and regulated manner. To elucidate mechanisms and identify cisacting elements that control V beta rearrangement, we generated an endogenous TCR-beta allele with only the V beta 2, V beta 4, and V beta 14 segments. We found that alpha beta T lineage cells containing this V beta(2-4-14) allele and a wild-type TCR-beta allele developed normally, but exhibited a significant increase in V beta 2(+) and V beta 14(+) cells. To quantify V beta rearrangements on the V beta(2-4-14) allele, we generated alpha beta T-cell hybridomas and analyzed TCR-beta rearrangements. Despite the deletion of almost all V beta segments and 234kb of V beta cluster sequences, the V beta(2-4-14) allele exhibited only a slight decrease in V beta rearrangement as compared with the wild-type TCR-beta allele. Thus, cis-acting control elements essential for directing V beta rearrangement across large chromosomal distances are not located within the V beta cluster. We also found a significant increase in the frequency of V beta rearrangements involving V beta 2 and V beta 14, but not V beta 4, on the V beta(2-4-14) allele. Collectively, our data suggest that V beta cluster sequences reduce the frequency of V beta 2 and V beta 14 rearrangements by competing with the productive coupling of accessible V beta 2 and V beta 14 segments with DJ beta 1 complexes. C1 [Alt, Frederick W.] Childrens Hosp, CBR Inst Biomed Res, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. [Bassing, Craig H.; Yang-Iott, Katherine] Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. [Bassing, Craig H.; Yang-Iott, Katherine] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Abramson Family Canc Res Inst,Ctr Childhood Canc, Philadelphia, PA 19104 USA. [Whitlow, Scott; Ranganath, Sheila; Alt, Frederick W.] Childrens Hosp, Immune Dis Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. [Whitlow, Scott; Mostoslovasky, Raul; Ranganath, Sheila; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Bassing, CH (reprint author), Childrens Hosp, CBR Inst Biomed Res, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. EM bassing@email.chop.edu FU National Institutes of Health Grant [AI20047]; Department of Pathology of the Children's Hospital of Philadelphia FX We thank Andrea Carpenter for helpful discussions of the manuscript and assistance for statistical analysis. C. H. B. is a Pew Scholar in the Biomedical Sciences. R. M. is a V Scholar. F. W. A. is an Investigator of the Howard Hughes Medical Institute. This work was supported by the National Institutes of Health Grant AI20047 (F. W. A.) and the Department of Pathology of the Children's Hospital of Philadelphia (C. H. B.). NR 26 TC 11 Z9 12 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2008 VL 38 IS 9 BP 2564 EP 2572 DI 10.1002/eji.200838347 PG 9 WC Immunology SC Immunology GA 355OQ UT WOS:000259718600020 PM 18792409 ER PT J AU Abbara, S Chow, BJW Pena, AJ Cury, RC Hoffmann, U Nieman, K Brady, TJ AF Abbara, Suhny Chow, Benjamin J. W. Pena, Antonio J. Cury, Ricardo C. Hoffmann, Udo Nieman, Koen Brady, Thomas J. TI Assessment of left ventricular function with 16-and 64-slice multi-detector computed tomography SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE left ventricular function; MDCT; echocardiography; SPECT; semi-automated MDCT data analysis ID M-MODE ECHOCARDIOGRAPHY; CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; DIAGNOSTIC-ACCURACY; EJECTION FRACTION; ANGINA-PECTORIS; HEART-DISEASE; HIGH-RISK; ROW CT; REPRODUCIBILITY AB Background: Important to the risk stratification and management of cardiac patients is the assessment of left ventricular function (LVEF), thus imaging modalities which can provide both anatomical and functional data is desirable. Electrocardiographic (ECG) gated multi-detector computed tomographic (MDCT) images may provide accurate assessment of LV ejection fraction, volume and dimensions but have shown systemic errors in the past due to slow gantry rotation speed. Methods: Between May 2004 and January 2005, 306 patients underwent ECG-gated cardiac CT studies at the Massachusetts General Hospital. Patients with available CT data sets and a recent (within 3 months) ECHO and/or SPECT perfusion imaging were included in the study. ECG-gated data sets were acquired either with a 16-slice or with a 64-slice MDCT. Functional MDCT data sets were reconstructed in 10 cardiac phases (5-95%) with 1.5 mm slices. Images were processed and interpreted by two observers blinded to ECHO and SPECT results. Results: A total of 69 patients had MDCT and ECHO or SPECT within 3 months (33 had 16-slice and 36 had 64-slice MDCT). There was fair correlation between LVEF measured by 16-slice MDCT and 'ECHO or SPECT' (62 +/- 10% vs. 62 +/- 10%; r = 0.56). There was poor correlation between LVEF measured by 16-slice MDCT and ECHO (64 +/- 10% vs. 59 +/- 11%; r = 0.26) and there was good correlation between LVEF measured by 16-slice MDCT and SPECT (62 +/- 11% and 64 +/- 9%, respectively; r = 0.76). There was very good correlation between LVEF measured by 64-slice MDCT and 'ECHO or SPECT' (57 +/- 15% vs. 58 +/- 13%; r = 0.86). There was very good correlation between LVEF measured by MDCT and ECHO (56 +/- 14% vs. 54 +/- 15%; r = 0.89) and between LVEF measured by 64-slice MDCT and SPECT (60 13% and 60 14%, respectively; r = 0.90). Conclusion: The assessment of LVEF and LV dimensions with 64-slice MDCT provide values which are similar to those obtained by echocardiography and Tc-99m gated SPECT. The accuracy of the 64-slice MDCT with a gantry rotation speed of 330 ms (when compared to ECHO and SPECT) may be superior to that of the 16-slice MDCT at 420 ms gantry rotation. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Abbara, Suhny; Chow, Benjamin J. W.; Pena, Antonio J.; Cury, Ricardo C.; Hoffmann, Udo; Nieman, Koen; Brady, Thomas J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abbara, Suhny; Chow, Benjamin J. W.; Pena, Antonio J.; Cury, Ricardo C.; Hoffmann, Udo; Nieman, Koen; Brady, Thomas J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chow, Benjamin J. W.] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON K1N 6N5, Canada. RP Abbara, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM Sabbara@partners.org NR 34 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD SEP PY 2008 VL 67 IS 3 BP 481 EP 486 DI 10.1016/j.ejrad.2007.07.022 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 351OQ UT WOS:000259434100016 PM 17826936 ER PT J AU Mischoulon, D Best-Popescu, C Laposata, M Merens, W Murakami, JL Wu, SL Papakostas, GI Dording, CM Sonawalla, SB Nierenberg, AA Alpert, JE Fava, M AF Mischoulon, David Best-Popescu, Catherine Laposata, Michael Merens, Wendelien Murakami, Jessica L. Wu, Shirley L. Papakostas, George I. Dording, Christina M. Sonawalla, Shamsah B. Nierenberg, Andrew A. Alpert, Jonathan E. Fava, Maurizio TI A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE eicosapentaenoic acid; docosahexaenoic acid; DHA; EPA; omega-3; n-3; depression ID PLACEBO-CONTROLLED TRIAL; BIPOLAR DEPRESSION; OPEN-LABEL; POSTPARTUM DEPRESSION; OMEGA-3-FATTY-ACIDS AB We examined the antidepressant efficacy and dose-response pattern of the n-3 docosahexaenoic acid (DHA). Thirty-five depressed adult outpatients (46% women; mean age 42 14 years) with a 17-item Hamilton-Depression Scale (HAM-D-17) score of > / = 18 were randomized into one of three double-blind dosing arms for 12 weeks. Group A (n = 14): 1 g/day of oral DHA; Group B (n = 11): 2 g/day; and Group C (n = 10): 4 g/day. We measured HAM-D-17 scores, plasma DHA, eicosapentaenoic acid (EPA), and n-6/n-3 ratio. Completer response rates (>/ = 50% decrease in HAM-D-17 score) were 83% for Group A, 40% for Group B, and 0% for Group C; Groups A and B had significant decreases in HAM-D-17 scores (p<0.05). For completers and intent-to-treat subjects, plasma DHA increased significantly (p<0.05), EPA had little change (p>0.05), and n-6/n-3 decreased significantly (p<0.05). DHA may be effective for depression at lower doses. (C) 2008 Elsevier B.V. and ECNP. All rights reserved. C1 [Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, WAC-812,15 Parkman St, Boston, MA 02114 USA. EM dmischoulon@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X NR 29 TC 43 Z9 45 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2008 VL 18 IS 9 BP 639 EP 645 DI 10.1016/j.euroneuro.2008.04.011 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 350FJ UT WOS:000259337800003 PM 18539007 ER PT J AU Dooley, KA Fraenkel, PG Langer, NB Schmid, B Davidson, AJ Weber, G Chiang, K Foott, H Dwyer, C Wingert, RA Zhou, Y Paw, BH Zon, LI AF Dooley, Kimberly A. Fraenkel, Paula G. Langer, Nathaniel B. Schmid, Bettina Davidson, Alan J. Weber, Gerhard Chiang, Ken Foott, Helen Dwyer, Caitlin Wingert, Rebecca A. Zhou, Yi Paw, Barry H. Zon, Leonard I. CA Tubingen 200 Screen Consortium TI montalcino, A zebrafish model for variegate porphyria SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BENZODIAZEPINE-RECEPTOR; POSITIONAL CLONING; HEME-SYNTHESIS; GENE; OXIDASE; ENZYME; PROTOPORPHYRIA; HEMATOPOIESIS; BIOSYNTHESIS; DEFICIENCY AB Objective. Inherited or acquired mutations in the heme biosynthetic pathway leads to a debilitating class of diseases collectively known as porphyrias, with symptoms that can include anemia, cutaneous photosensitivity, and neurovisceral dysfunction. In a genetic screen for hematopoietic mutants, we isolated a zebrafish mutant, montalcino (mno), which displays hypochromic anemia and porphyria. The objective of this study was to identify the defective gene and characterize the phenotype of the zebrafish mutant. Materials and Methods. Genetic linkage analysis was utilized to identify the region harboring the unto mutation. Candidate gene analysis together with reverse transcriptase polymerase chain reaction was utilized to identify the genetic mutation, which was confirmed via allele-specific oligo hybridizations. Whole mount in situ hybridizations and o-dianisidine staining were used to characterize the phenotype of the mno mutant. mRNA and morpholino micro-injections were performed to phenocopy and/or rescue the mutant phenotype. Results. Homozygous mno mutant embryos have a defect in the protoporphyrinogen oxidase (ppox) gene, which encodes the enzyme that catalyzes the oxidation of protoporphyrinogen. Homozygous mutant embryos are deficient in hemoglobin, and by 36 hours post-fertilization are visibly anemic and porphyric. The hypochromic anemia of mno embryos was partially rescued by human ppox, providing evidence for the conservation of function between human and zebrafish ppox. Conclusion. In humans, mutations in ppox result in variegate porphyria. At present, effective treatment for acute attacks requires the administration intravenous hemin and/or glucose. Thus, mno represents a powerful model for investigation, and a tool for future screens aimed at identifying chemical modifiers of variegate porphyria. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Dooley, Kimberly A.; Fraenkel, Paula G.; Schmid, Bettina; Davidson, Alan J.; Weber, Gerhard; Chiang, Ken; Foott, Helen; Dwyer, Caitlin; Wingert, Rebecca A.; Zhou, Yi; Zon, Leonard I.] Harvard Univ, Howard Hughes Med Inst, Sch Med, Div Hematol Oncol,Childrens Hosp, Boston, MA 02115 USA. [Dooley, Kimberly A.; Fraenkel, Paula G.; Schmid, Bettina; Davidson, Alan J.; Weber, Gerhard; Chiang, Ken; Foott, Helen; Dwyer, Caitlin; Wingert, Rebecca A.; Zhou, Yi; Zon, Leonard I.] Harvard Univ, Howard Hughes Med Inst, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Langer, Nathaniel B.; Paw, Barry H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. RP Zon, LI (reprint author), Harvard Univ, Howard Hughes Med Inst, Sch Med, Div Hematol Oncol,Childrens Hosp, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu OI Fraenkel, Paula/0000-0001-8894-0117 FU American Cancer Society; National Institutes of Health (NIH) FX K.A.D. was supported by a fellowship from the American Cancer Society and the National Institutes of Health (NIH). B.H.P. and L..LZ. were supported by the NIH. L.I.Z. is an investigator of the Howard Hughes Medical Institute. NR 35 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2008 VL 36 IS 9 BP 1132 EP 1142 DI 10.1016/j.exphem.2008.04.008 PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 344QT UT WOS:000258943100009 PM 18550261 ER PT J AU Armistead, PM Mohseni, M Gerwin, R Walsh, EC Iravani, M Chahardouli, B Rostami, S Zhang, WD Neuberg, D Rioux, J Ghavamzadeh, A Ritz, J Antin, JH Wu, CJ AF Armistead, Paul M. Mohseni, Mehrdad Gerwin, Roslyn Walsh, Emily C. Iravani, Masoud Chahardouli, Bahram Rostami, Shahrbano Zhang, Wandi Neuberg, Donna Rioux, John Ghavamzadeh, Ardeshir Ritz, Jerome Antin, Joseph H. Wu, Catherine J. TI Erythroid-lineage-specific engraftment in patients with severe hemoglobinopathy following allogeneic hematopoietic stem cell transplantation SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; INEFFECTIVE ERYTHROPOIESIS; BETA-THALASSEMIA; RISK-FACTORS; CHIMERISM; ANEMIA; BLOOD; FLUDARABINE; APLASIA AB Objective. We aimed to create a molecular assay to monitor erythroid (red blood cell [RBC]) engraftment in any patient following allogeneic hematopoietic stem cell transplantation, independent of disease-specific mutations. Materials and Methods. We identified 10 common single nucleotide polymorphisms (SNPs), expressed by genes encoding RBC antigens and structural proteins. These SNPs were polymerase chain reaction-amplified from total RNA extracted from peripheral blood, which contains nucleated erythroid progenitors. Mixing studies validated that each SNP can quantitatively measure donor/recipient DNA and RNA. Results. We directly genotyped 23 patients who underwent hematopoietic stem cell transplantation and their human leukocyte antigen-matched donors and found a median of three informative SNPs (i.e., discordant between donor and recipient) per pair. By using the informative RBC SNPs to quantify donor-derived RBC transcripts, we compared rates of RBC engraftment in 13 patients with hemoglobinopathies vs donor mononuclear cell (white blood cell [WBC]) engraftment. Consistent with known ineffective erythropoiesis associated with hemoglobinopathies, we detected up to threefold greater RBC-specific compared to overall WBC engraftment in five of eight patients who were mixed chimeras by transplant day 30. The remaining three of eight who received ABH-incompatible grafts, demonstrated at least 0.5-fold lower RBC compared to WBC engraftment that was related to persistence of host-derived anti-isohemagglutinin antibodies. Conclusion. This RNA-based assay can be used to monitor RBC-specific engraftment regardless of a patient's specific hemoglobin mutation or even diagnosis. We propose that panels of expressed SNPs informative for other cell lineages can be created to comprehensively assess the impact of novel stem cell-based therapies on lineage-specific engraftment. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Mohseni, Mehrdad; Gerwin, Roslyn; Zhang, Wandi; Ritz, Jerome; Antin, Joseph H.; Wu, Catherine J.] Harvard Univ, Inst Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Armistead, Paul M.; Ritz, Jerome; Antin, Joseph H.; Wu, Catherine J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Armistead, Paul M.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. [Walsh, Emily C.; Rioux, John] Broad Inst Harvard, Program Med & Populat Genet, Boston, MA USA. [Walsh, Emily C.; Rioux, John] MIT, Boston, MA USA. [Iravani, Masoud; Chahardouli, Bahram; Rostami, Shahrbano; Ghavamzadeh, Ardeshir] Univ Tehran, Sch Med Sci, Hematol Oncol & Bone Marrow Transplant Res Ctr, Tehran, Iran. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ritz, Jerome; Antin, Joseph H.; Wu, Catherine J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Wu, CJ (reprint author), Harvard Univ, Inst Med, Dana Farber Canc Inst, Dept Med Oncol, Room 416B,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org RI Rioux, John/A-9599-2015; OI Rioux, John/0000-0001-7560-8326; Ritz, Jerome/0000-0001-5526-4669 FU Doris Duke Charitable Foundation; DFCI; Cancer Research Institute; Pasquarello Tissue Bank FX This work is funded by the Doris Duke Charitable Foundation (CJ.W.), and the Friends of DFCI (CJ.W.). E.C.W. is a recipient of a Cancer Research Institute fellowship. We would like to acknowledge the generous support from the Pasquarello Tissue Bank, and from the clinical transplant teams at the Shariati Hospital in Tehran, Iran and at the DFCI, Boston. Finally, we thank Richard Kaufman for insightful discussions and suggestions. NR 39 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2008 VL 36 IS 9 BP 1205 EP 1215 DI 10.1016/j.exphem.2008.04.004 PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 344QT UT WOS:000258943100016 PM 18550258 ER PT J AU Keefe, DM Sonis, ST Bowen, JM AF Keefe, Dorothy M. Sonis, Stephen T. Bowen, Joanne M. TI Emerging drugs for chemotherapy-induced mucositis SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE chemotherapy; chemotherapy-induced diarrhea; medical foods; mucositis (oral and gastrointestinal); mucositis pathobiology; mucositis prevention ID STEM-CELL TRANSPLANTATION; INDUCED ORAL MUCOSITIS; CLINICAL-PRACTICE GUIDELINES; HIGH-DOSE CHEMOTHERAPY; CANCER-THERAPY; MUCOSAL INJURY; COLORECTAL-CANCER; GASTROINTESTINAL MUCOSITIS; INTESTINAL MUCOSITIS; ECONOMIC OUTCOMES AB Background: Chemotherapy-induced mucositis is an increasingly recognized problem in cancer management, preventing full doses of treatment being given, compromising cure rates and reducing quality of life. Symptoms include mouth pain and ulceration, esophagitis, abdominal pain, bloating, and diarrhea. It is associated with increased infections and occasional mortality, and its palliation is very expensive. The pathobiology of mucositis is complex, and agents that target mechanisms to prevent mucositis or accelerate healing are in high demand. Objectives: To review existing and potential treatments for chemotherapy-induced mucositis in the context of current knowledge of pathobiology. Methods: We searched for mucositis of any region of the gastrointestinal tract using Medline, the Pharmaprojects database and listed patents. Results/conclusions: There are many agents in varying stages of development for chemotherapy-induced mucositis. The field is complicated by the question of whether treatments should be developed as drugs or as medical foods, and whether the burden of proof of efficacy and safety should be different. C1 [Keefe, Dorothy M.] Royal Adelaide Hosp, Ctr Canc, Adelaide, SA 5000, Australia. [Sonis, Stephen T.] Harvard Farber Canc Ctr, Boston, MA USA. [Bowen, Joanne M.] Univ Adelaide, Fac Hlth Sci, Adelaide, SA, Australia. RP Keefe, DM (reprint author), Royal Adelaide Hosp, Ctr Canc, Adelaide, SA 5000, Australia. EM dorothy.keefe@health.sa.gov.au OI Bowen, Joanne/0000-0003-0876-0031 FU GlaxoSmithKline; Amgen and Novartis FX D Keefe is a consultant for Helsinn and Nestor, and has received grant support from GlaxoSmithKline and Amgen. S Sonis has received support from Amgen and Novartis. NR 82 TC 30 Z9 32 U1 1 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD SEP PY 2008 VL 13 IS 3 BP 511 EP 522 DI 10.1517/14728210802327831 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 353JR UT WOS:000259563100008 PM 18764726 ER PT J AU Taplin, ME AF Taplin, Mary-Ellen TI Androgen receptor: role and novel therapeutic prospects in prostate cancer SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE adrenal androgen; androgen receptor; androgen-deprivation therapy; antiandrogen; castration-resistant; prostate cancer ID HISTONE DEACETYLASE INHIBITORS; LIGAND-BINDING DOMAIN; N-TERMINAL DOMAIN; LEUKEMIA GROUP-B; PHASE-I; DEPRIVATION THERAPY; GENE AMPLIFICATION; ANTIANDROGEN WITHDRAWAL; ADRENAL ANDROGENS; HORMONAL-THERAPY AB Androgen receptor (AR) signaling is necessary for the development of prostate cancer. Androgen-deprivation therapy (ADT) for prostate cancer was described over 50 years ago and ADT remains the mainstay of systemic therapy. AR signaling remains intact as the disease evolves to castration-resistant prostate cancer (CRPC). Through cellular adaptations, CRPC continues to rely on androgens and AR growth signaling, and thus AR remains an important therapeutic target. CRPC cells upregulate enzymes used in androgen synthesis, thus providing an intracellular source of androgen despite systemic castration. Compounds in development, such as antiandrogens, lyase inhibitors, heat-shock protein-90 inhibitors, histone deacetylase inhibitors and others, will provide new tools to more effectively reduce ligand, inhibit AR and/or inhibit costimulatory pathways and result in improved clinical outcomes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Taplin, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM mtaplin@partners.org NR 118 TC 36 Z9 36 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD SEP PY 2008 VL 8 IS 9 BP 1495 EP 1508 DI 10.1586/14737140.8.9.1495 PG 14 WC Oncology SC Oncology GA 350DR UT WOS:000259333300019 PM 18759700 ER PT J AU Schernhammer, ES Ogino, S Fuchs, CS AF Schernhammer, Eva S. Ogino, Shuji Fuchs, Charles S. TI Folate and vitamin B-6 intake and risk of colon cancer in relation to p53 expression SO GASTROENTEROLOGY LA English DT Article ID CORONARY-HEART-DISEASE; COLORECTAL-CANCER; DIETARY-FOLATE; MICROSATELLITE INSTABILITY; MULTIVITAMIN USE; COMPETING RISKS; DNA METHYLATION; STRAND BREAKS; CELL-LINES; FOLIC-ACID AB Background & Aims: Considerable evidence suggests that a low-folate diet increases the risk of colorectal cancer, although the results of a recent randomized trial indicate that folate supplementation may not reduce the risk of adenoma recurrence. In laboratory models, folate deficiency appears to induce p53 mutation. Methods: We immunohistochemically assayed p53 expression in paraffin-fixed colon cancer specimens in a large prospective cohort of women with 22 years of follow-up to examine the relationship of folate intake and intake of other one-carbon nutrients to risks by tumor p53 expression. Results: A total of 399 incident colon cancers accessible for p53 expression were available. The effect of folate differed significantly according to p53 expression (P-heterogencity = .01). Compared with women reporting folate intake < 200 mu g/day, the multivariate relative risks (RRs) for p53-overexpressing (mutated) cancers were 0.54 (95% confidence interval [CI], 0.36-0.81) for women who consumed 200-299 mu g/day, 0.42 (95% CI, 0.24-0.76) for women who consumed 300-399 mu g/day, and 0.54 (95% CI, 0.35-0.83) for women who consumed >= 400 mu g/day. In contrast, total folate intake had no influence on wild-type tumors (RP, 1.05; 95% CI, 0.73-1.51; comparing >= 400 with < 200 mu g/day). Similarly, high vitamin B-6 intake conferred a protective effect on p53-overexpressing cancers (top versus bottom quintile: RP, 0.57; 95% CI, 0.35-0.94; P-heterogeneiry = .01) but had no effect on p53 vild-type tumors. Conclusions: We found that low folate and vitamin B-6 intake was associated with an increased risk of p53-overexpressing colon cancers but not wild-type tumors. C1 [Schernhammer, Eva S.; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Schernhammer, Eva S.] KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. [Schernhammer, Eva S.] Appl Canc Res Inst Translat Res Vienna, Vienna, Austria. [Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Schernhammer, ES (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eva.schernhammer@channing.harvard.edu FU NCI NIH HHS [CA55075, P01 CA087969, P01 CA087969-09, R01 CA042182, R01 CA058684, R01 CA070817, R01 CA070817-09, R01 CA090598, R01 CA058684-13, R01 CA042182-20, P01 CA055075-14, P01 CA055075, CA90598, CA87969, CA70817, CA58684, CA42812] NR 45 TC 35 Z9 38 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2008 VL 135 IS 3 BP 770 EP 780 DI 10.1053/j.gastro.2008.06.033 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 346WC UT WOS:000259099300016 PM 18619459 ER PT J AU Fujiki, K Duerr, EM Kikuchi, H Ng, A Xavier, RJ Mizukami, Y Imamura, T Kulke, MH Chung, DC AF Fujiki, Kotoyo Duerr, Eva-Maria Kikuchi, Hirotoshi Ng, Aylwin Xavier, Ramnik J. Mizukami, Yusuke Imamura, Takaaki Kulke, Matthew H. Chung, Daniel C. TI Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth SO GASTROENTEROLOGY LA English DT Article ID HOMEOBOX GENE; NEUROENDOCRINE TUMORS; PROSTATE-CANCER; EXPRESSION; MENIN; PROLIFERATION; PROTEIN; CELLS; AP-1; LEUKEMOGENESIS AB Background & Aim: The molecular alterations that underlie carcinoid tumor pathogenesis remain poorly defined. The homeobox gene HOXC6 was highly upregulated in human gastrointestinal carcinoid tumors, and we sought to define its pathogenic role. Methods: The functional and physical properties of Hoxc6 were investigated by establishing carcinoid cells that stably overexpressed Hoxc6 or were deficient in Hoxc6. Cellular proliferation assays, luciferase reporter assays, Western blotting, immunoprecipitation, DNA affinity precipitation, and DNA microarray studies were performed. Results: Expression of Hoxc6 in cultured human BON1 carcinoid cells enhanced their proliferation, and knock-down of Hoxc6 inhibited their growth. Hoxc6 activated the oncogenic activator protein-1 signaling pathway through a physical interaction with JunD. Mutations in the homeodomain of Hoxc6 blocked this interaction and inhibited proliferation of carcinoid cells. Of note, Hoxc6 induced the expression of genes that characteristically are up-regulated in carcinoid tumors, including neurotensin and connective tissue growth factor. Conclusions: A novel molecular pathway has been identified that links Hoxc6 with oncogenic signaling through the activator protein-1 pathway in carcinoid tumorigenesis. C1 [Fujiki, Kotoyo; Duerr, Eva-Maria; Kikuchi, Hirotoshi; Ng, Aylwin; Xavier, Ramnik J.; Mizukami, Yusuke; Imamura, Takaaki; Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ng, Aylwin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825,50 Blossom St, Boston, MA 02114 USA. EM dchung@partners.org FU Caring for Carcinoid Foundation; Stephen and Caroline Kaufer Fund; Deutsche Forschungsgemeinschaft; Crohn's and Colitis Foundation of America FX Supported by the Caring for Carcinoid Foundation, Stephen and Caroline Kaufer Fund for Neuroendocrine Tumor Research, by a fellowship from the Deutsche Forschungsgemeinschaft (E.-M.D.), and by a fellowship from the Crohn's and Colitis Foundation of America (A.N.). NR 34 TC 17 Z9 18 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2008 VL 135 IS 3 BP 907 EP 916 DI 10.1053/j.gastro.2008.06.034 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 346WC UT WOS:000259099300032 PM 18655788 ER PT J AU Leung, FW Schnelle, JF AF Leung, Felix W. Schnelle, John F. TI Urinary and fecal incontinence in nursing home residents SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article DE fecal incontinence; constipation; urinary incontinence ID LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIAL; RISK-FACTORS; ELDERLY-PATIENTS; INTERVENTION; MANAGEMENT; CONSTIPATION; QUALITY; CONTINENCE; EXERCISE AB Urinary and fecal incontinence are comorbid conditions affecting over 50% of nursing home residents. Management should focus on identifying and treating underlying causes. Despite appropriate management, residents may remain incontinent because of dementia and health- or restraint-related immobility. This article reviews the results of studies that have documented how prompted voiding programs can significantly reduce urinary and fecal incontinence, particularly if the intervention includes dietary and exercise components. Documentation of noninvasive and efficacious interventions by randomized, controlled trials and the labor costs of implementing these measures can lead to changes in how nursing home care is provided and funded. C1 [Schnelle, John F.] Vanderbilt Univ, Med Ctr, Dept Med, Ctr Qual Aging, Nashville, TN 37232 USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Leung, Felix W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA 91343 USA. RP Schnelle, JF (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Ctr Qual Aging, 1161 21st Ave S,S-1121 Med Ctr N, Nashville, TN 37232 USA. EM john.schnelle@vanderbilt.edu FU VA Clinical Merit Research Funds (FWL) and National Institutes of Health [1R02 AG 23,555-01A1] FX Supported in part by VA Clinical Merit Research Funds (FWL) and National Institutes of Health grant 1R02 AG 23,555-01A1 "Interventions to Improve Fecal Incontinence" (JFS). NR 59 TC 18 Z9 21 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 EI 1558-1942 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 2008 VL 37 IS 3 BP 697 EP + DI 10.1016/j.gtc.2008.06.005 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 357OH UT WOS:000259855500013 PM 18794004 ER PT J AU Wiik, AC Wade, C Biagi, T Ropstad, EO Bjerkas, E Lindblad-Toh, K Lingaas, F AF Wiik, Anne Caroline Wade, Claire Biagi, Tara Ropstad, Ernst-Otto Bjerkas, Ellen Lindblad-Toh, Kerstin Lingaas, Frode TI A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund SO GENOME RESEARCH LA English DT Article ID LEBER CONGENITAL AMAUROSIS; JOUBERT-SYNDROME; CENTROSOMAL PROTEIN; CANDIDATE GENES; MUTATIONS; RPGRIP1; LOCUS; NEPHROCYSTIN-4; DEGENERATION; ENCODES AB Cone-rod dystrophy is a retinal degenerative disorder occurring naturally in man and dog. Here we identify a novel gene for early-onset cone-rod dystrophy in the wire-haired dachshund. For the first time, we use genome- wide association-based Sibling Transmission Disequilibrium Test (sibTDT) analysis of only 13 discordant sib-pairs to identify a single significantly associated 6.5-Mb region (P(rawTDT) = 4.8 x 10(-5), P(genomeTDT) = 6 x 10(-4)) on canine chromosome 5, containing more than 70 genes. Segregation studies using microsatellites in the candidate region including additional meiosis supported the sibTDT analysis but could not further reduce the area. Candidate gene resequencing identified a 180-bp deletion in exon/intron 5 of NPHP4 (nephronophthisis 4, also known as nephroretinin). RT-PCR analysis of NPHP4 in cases and controls showed exon skipping of exon 5, resulting in a truncated protein that retains the binding domain interacting with nephronophthisis 1 (also known as nephrocystin-1) in the kidney but lacks the domain interacting with RPGRIP1 in retina. We suggest that this deletion in the canine NPHP4 gene is the cause of cone-rod dystrophy in the standard wire-haired dachshund. In humans, mutations in NPHP4 have been associated with simultaneous eye and kidney disease. Here we describe the first naturally occurring mutation in NPHP4 without additional kidney disease. Further studies will permit elucidation of the complex molecular mechanism of this retinopathy and the development of potential therapies. C1 [Wade, Claire; Biagi, Tara; Lindblad-Toh, Kerstin] Harvard & MIT, Broad Inst, Cambridge, MA 02141 USA. [Wiik, Anne Caroline; Lingaas, Frode] Norwegian Sch Vet Sci, Div Genet, Dept Basic Sci & Aquat Med, N-0033 Oslo, Norway. [Wade, Claire] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ropstad, Ernst-Otto; Bjerkas, Ellen] Norwegian Sch Vet Sci, Dept Compan Anim Clin Sci, N-0033 Oslo, Norway. [Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, S-75124 Uppsala, Sweden. RP Lindblad-Toh, K (reprint author), Harvard & MIT, Broad Inst, Cambridge, MA 02141 USA. EM kersli@broad.mit.edu; Frode.Lingaas@veths.no OI Wade, Claire/0000-0003-3413-4771 FU Norwegian School of Veterinary Science; Casey Gates and the Broad Institute Genetic analysis platform FX We acknowledge the Norwegian School of Veterinary Science for funding the project and Casey Gates and the Broad Institute Genetic analysis platform for performing the genotyping. We thank Michael C. Zody for comments on the manuscript and Leslie Gaffney for practical help with the manuscript preparation. NR 32 TC 50 Z9 51 U1 0 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2008 VL 18 IS 9 BP 1415 EP 1421 DI 10.1101/gr.074302.107 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 342AH UT WOS:000258756500004 PM 18687878 ER PT J AU Olawaiye, AB Rauh-Hain, JA Withiam-Leitch, M Rueda, BR Goodman, A del Carmen, MG AF Olawaiye, Alexander B. Rauh-Hain, Jose Alejandro Withiam-Leitch, Matthew Rueda, Bo R. Goodman, Annekathryn del Carmen, Marcela G. TI Utility of pre-operative serum CA-125 in the management of uterine papillary serous carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE endometrial cancer; papillary serous; CA-125 ID EPITHELIAL OVARIAN-CANCER; LYMPH-NODE METASTASIS; ENDOMETRIAL CANCER; CA 125; CLEAR-CELL; DIAGNOSIS; SURVIVAL; LEVEL; WOMEN; ADENOCARCINOMA AB Objective. To evaluate the usefulness of pre-operative serum CA-125 in the management of women diagnosed with uterine papillary serous carcinoma (UPSC). We hypothesized that elevated pre-operative levels of serum CA-125 correlate with higher disease stage and poorer prognosis. Methods. Patients diagnosed with UPSC and managed in our institution were identified over a period of 10 years, 1995 to 2005. All required information were extracted from their records. The nonparametric test applied for comparison of data included Kruskal Wallis H-test and Man-Whitney U-test. The chi(2) test and Spearman correlation test were used to examine the association of serum CA-125 with different parameters. Receiver operator characteristic curves (ROC) were used to quantify marker performance. Recurrence and survival were analyzed using Kaplan-Meier method. Multivariate analyses were performed with a Cox proportional regression method. Results. A total of 41 patients met the study criteria. Mean pre-operative serum CA-125 levels were significantly higher in patients with stage IV (1150 +/- 1297 U/mL), compared with stage III (181 +/- 232 U/mL; P<0.001), stage II (22 +/- 9; P<0.001), and stage I (14 +/- 1; P<0.001). CA-125 correlated strongly with stage (r=0.68, P<0.001). On the ROC, a cut-off of 35 lU/mL provided the best sensitivity and specificity (78% vs. 100% respectively) for extra-uterine disease. Disease free survival (DFS) and overall survival (OS) were longer in patients with CA-125<35 U/mL compared with CA-125 >= 35 U/mL [median DFS not reached during study vs. 21.2 months (P=0.009), and median OS not reached during study vs. 25 months, (P=0.0001) respectively]. Multivariate regression model showed CA-125 as the only variable associated with survival (P=0.05). Conclusion. Pre-operative serum CA-125 levels correlate with stage of disease in patients with UPSC. This tray be important for management planning, prognostication and counseling in these women. (C) 2008 Elsevier Inc. All rights reserved. C1 [Olawaiye, Alexander B.; Rauh-Hain, Jose Alejandro; Rueda, Bo R.; Goodman, Annekathryn; del Carmen, Marcela G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Vincent Obstet & Gynecol S, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, Boston, MA 02114 USA. [Withiam-Leitch, Matthew] Univ Buffalo, Womens & Childrens Hosp, Dept Gynecol & Obstet, Buffalo, NY 14222 USA. RP del Carmen, MG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Vincent Obstet & Gynecol S, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, 55 Fruit St, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 39 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2008 VL 110 IS 3 BP 293 EP 298 DI 10.1016/j.ygyno.2008.05.027 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 349XN UT WOS:000259316700005 PM 18644620 ER PT J AU Orezzoli, JP Russell, AH Oliva, E Del Carmen, MG Eichhorn, J Fuller, AF AF Orezzoli, J. P. Russell, A. H. Oliva, E. Del Carmen, M. G. Eichhorn, J. Fuller, A. F. TI Prognostic implication of endometriosis in clear cell carcinoma of the ovary SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Society-of-Gynecologic-Oncologists CY MAR 09-12, 2008 CL Tampa, FL SP Soc Gynecol Oncologists DE ovary; endometriosis; clear cell carcinoma; survival ID EXTRAOVARIAN ENDOMETRIOSIS; MALIGNANT-TRANSFORMATION; ATYPICAL ENDOMETRIOSIS; HORMONE-THERAPY; POOR-PROGNOSIS; CANCER; ADENOCARCINOMA; TUMORS; RISK; HETEROZYGOSITY AB Objective. The aim of this study is to investigate whether the presence of endometriosis is a prognostic factor in patients diagnosed with clear cell carcinoma (CCC) of the ovary. Methods. Retrospective chart review was performed to all patients diagnosed with CCC and endometriosis between 1975 and 2002. All pathology reports were reviewed and slides were reviewed when available. Cox regression analysis and Kaplan-Meier test were used to calculate survival prognostic factors. The level of significance seas set at 0.05. Results. Eighty-four patients with CCC were identified with a 49% rate of coexisting endometriosis. Patients with tumors arising in endometriosis (n = 15). with endometriosis found elsewhere in the specimen (n=26), and those without endometriosis (n=43) were analyzed comparatively. Patients with CCCs arising in endometriosis were 10 years younger (95% C. I. 0.6-18 years) than those with CCC not arising in endometriosis (P<0.05). Patients with endometriosis anywhere in the surgical specimen presented at early stage 66% of the times versus 42% for patients without endometriosis (p<0.05). Median overall survival (OS) for patients with endometriosis was 196 months (95%, C.I. 28-363) versus 34 months (95% C. I. 13-55) for patients without endometriosis (P=0.01). Advanced tumor stage at diagnosis (H R 13, 95% C. I. 5-29, P=0.001) and absence of endometriosis (HR 2, 95% C. I. 1-3.9, P=0.03) were the only significant prognostic factors associated with poor survival. Disease recurrence or death among optimally and completely cytoreduced patients was 31% and 59% for those with and without endometriosis respectively (P>0.05). Conclusions. Our study suggests that the presence of endometriosis in patients with CCC of the ovary is associated with progression free and OS advantages with no difference in initial resectability. (C) 2008 Elsevier Inc. All rights reserved. C1 [Orezzoli, J. P.; Del Carmen, M. G.] Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Boston, MA 02114 USA. [Orezzoli, J. P.; Russell, A. H.; Oliva, E.; Del Carmen, M. G.; Eichhorn, J.; Fuller, A. F.] Harvard Univ, Sch Med, Boston, MA USA. [Russell, A. H.] Massachusetts Gen Hosp, Div Radiat Oncol, Boston, MA 02114 USA. [Eichhorn, J.] Massachusetts Gen Hosp, Div Pathol, Boston, MA 02114 USA. [Fuller, A. F.] Winchester Hosp, Canc Care Ctr, Winchester, MA USA. RP Orezzoli, JP (reprint author), Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Yawkey 9E-522,55 Fruit St, Boston, MA 02114 USA. EM jporezzoli@inbox.com NR 54 TC 53 Z9 58 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2008 VL 110 IS 3 BP 336 EP 344 DI 10.1016/j.ygyno.2008.05.025 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 349XN UT WOS:000259316700012 PM 18639330 ER PT J AU Rini, C Manne, S DuHamel, K Austin, J Ostroff, J Boulad, F Parsons, SK Martini, R Williams, SE Mee, L Sexson, S Redd, WH AF Rini, Christine Manne, Sharon DuHamel, Katherine Austin, Jane Ostroff, Jamie Boulad, Farid Parsons, Susan K. Martini, Richard Williams, Sharon E. Mee, Laura Sexson, Sandra Redd, William H. TI Social support from family and friends as a buffer of low spousal support among mothers of critically ill children: A multilevel modeling approach SO HEALTH PSYCHOLOGY LA English DT Article DE pediatric hematopoietic stem cell transplant; pediatric bone marrow transplant; social support; maternal adjustment; multilevel model ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; POSTTRAUMATIC STRESS SYMPTOMS; CHILDHOOD-CANCER; PSYCHOLOGICAL ADJUSTMENT; DEPRESSIVE SYMPTOMS; LIFE EVENTS; PARENTS; SURVIVORS; HEALTH AB Objective: To investigate whether social support front family and friends (family/friend support) attenuated ("buffered") adverse effects of having low spouse support (spousal support) among mothers of children undergoing hematopoietic stem cell transplantation (HSCT). Design: One hundred sixty-three married mothers who were their child's primary caregiver during treatment completed assessments during the child's hospitalization for HSCT and 3-, 6-, and 12-months post-HSCT. Measures: Family/friend support and spousal support were assessed during hospitalization. Maternal physical and mental health-related functioning (the main Outcome measures) were assessed at all timepoints. Results: Multilevel modeling was used to analyze trajectories of maternal functioning. Findings indicated that mothers with low spousal support and low family/friend support demonstrated the worst functioning across all timepoints. Mothers with low spousal support and high family/friend support demonstrated significantly better functioning, supporting the hypothesized buffering effect. Their functioning compared to the functioning of mothers with high spousal support. Moreover, mothers with high family/friend support demonstrated trajectories of physical health-related functioning that were more stable than the trajectories of mothers with low family/friend support. Conclusion: These findings have clinical implications in addition to advancing knowledge of social support processes among couples coping with the shared stressor of a child's life-threatening illness and treatment. C1 [Rini, Christine; Austin, Jane; Redd, William H.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Manne, Sharon] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. [DuHamel, Katherine; Ostroff, Jamie; Boulad, Farid] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Parsons, Susan K.] Tufts Univ New England Med Ctr, Childrens Hosp Boston, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Parsons, Susan K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Martini, Richard] Northwestern Univ, Sch Med, Dept Psychiat, Childrens Mem Hosp, Chicago, IL 60611 USA. [Williams, Sharon E.] Stanford Univ, Med Ctr, Packard Childrens Hosp, Stanford, CA 94305 USA. [Mee, Laura; Sexson, Sandra] Emory Univ, Med Ctr, Atlanta, GA 30322 USA. RP Rini, C (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl,Box 1130, New York, NY 10029 USA. EM christine.rini@mssm.edu OI Ostroff, Jamie/0000-0003-2671-5680 FU National Cancer Institute [MH 57738]; National Institutes of Mental Health [98-450, K07CA104701] FX This work was supported by Grant MH 57738 awarded by file National Cancer Institute and the National Institutes of Mental Health. Christine Rini was supported by Grants 98-450 and K07CA104701 awarded by the National Cancer Institute. NR 60 TC 17 Z9 18 U1 6 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2008 VL 27 IS 5 BP 593 EP 603 DI 10.1037/0278-6133.27.5.593 PG 11 WC Psychology, Clinical; Psychology SC Psychology GA 350KC UT WOS:000259350300011 PM 18823186 ER PT J AU Raffel, OC Akasaka, T Jang, IK AF Raffel, O. C. Akasaka, T. Jang, I-K TI Cardiac optical coherence tomography SO HEART LA English DT Article ID BACKSCATTER INTRAVASCULAR ULTRASOUND; CORONARY-ARTERY-DISEASE; IN-VIVO; ATHEROSCLEROTIC PLAQUES; VULNERABLE PLAQUE; TISSUE CHARACTERIZATION; MYOCARDIAL-INFARCTION; NEOINTIMAL COVERAGE; DIAGNOSTIC-ACCURACY; ELUTING STENTS C1 [Raffel, O. C.; Jang, I-K] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Raffel, O. C.; Jang, I-K] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Boston, MA 02114 USA. [Akasaka, T.] Wakayama Med Univ, Wakayama, Japan. RP Jang, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Bigelow Gray 800, Boston, MA 02114 USA. EM ijang@partners.org NR 57 TC 28 Z9 28 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD SEP PY 2008 VL 94 IS 9 BP 1200 EP 1210 DI 10.1136/hrt.2007.130765 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 337PH UT WOS:000258447500024 PM 18703696 ER PT J AU Singal, AK AF Singal, Ashwani K. TI Silent Cirrhosis in Hepatitis B Virus Related Hepatocellular Carcinoma SO HEPATO-GASTROENTEROLOGY LA English DT Article DE Hepatitis B; Helpatocellular carcinoma; Silent cirrhosis; Liver cirrhosis; Person-years follow up ID SAUDI-ARABIA; INFECTION; PROGRESS; RISK AB Background/Aims: Prevalence of hepatitis B virus (HBV) related cirrhosis and hepatocellular carcinoma (HCC) is high in Saudi Arabia. However, thee relationship between these two presentations is not well studied. Methodology: Medical charts of 170 Saudi HBV patients (70 with HCC and 100 with cirrhosis without HCC) were reviewed. Results: Patients with HCC at presentation were older compared to those with cirrhosis without H CC at presentation (60.9 y vs. 51.2 y; p < 0.05). Right tipper quadrant pain (p < 0.001) and hepatic bruit (p < 0.0001) independently predicted the presence of HCC. Cirrhosis, present, in 76% of HCC patients, remained silent and only 4% (3 of 73) of all HCC cases had clinical manifest cirrhosis. Cirrhotics without HCC at presentation developed HCC at the rate of 0.67% per 100 person years follow up. Conclusions: Liver cirrhosis and HCC are distinct presentations of HBV in Saudi Arabia. Majority of patients with HCC at, presentation have silent cirrhosis. Rate of development of HCC in patients with HBV related cirrhosis is low. C1 [Singal, Ashwani K.] King Fahd Cent Hosp, Dept Med, Div Gastroenterol, Gizan, Saudi Arabia. RP Singal, AK (reprint author), James J Peters VA Med Ctr, Mt Sinai Sch Med, Dept Med, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ashwanisingal.com@gmail.com NR 25 TC 1 Z9 2 U1 0 U2 1 PU H G E UPDATE MEDICAL PUBLISHING S A PI ATHENS PA PO BOX 17257, ATHENS GR-10024, GREECE SN 0172-6390 J9 HEPATO-GASTROENTEROL JI Hepato-Gastroenterol. PD SEP-OCT PY 2008 VL 55 IS 86-87 BP 1734 EP 1737 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 371YK UT WOS:000260868400051 PM 19102380 ER PT J AU Major-Pedersen, A Ihlemann, N Hermann, TS Christiansen, B Kveiborg, B Dominguez, H Nielsen, D Rask-Madsen, C Svendsen, OL Kober, L Torp-Pedersen, C AF Major-Pedersen, A. Ihlemann, N. Hermann, T. S. Christiansen, B. Kveiborg, B. Dominguez, H. Nielsen, D. Rask-Madsen, C. Svendsen, O. L. Kober, L. Torp-Pedersen, C. TI Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: Is stimulation of first phase insulin secretion beneficial for the endothelial function? SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE insulin resistance; postprandial hyperglycemia; postprandial hyperinsulinemia; flow mediated dilation; impaired glucose tolerance; diabetes; 2hPG; atherosclerosis; cardiovascular disease ID ACUTE MYOCARDIAL-INFARCTION; SMOOTH-MUSCLE-CELLS; CARDIOVASCULAR-DISEASE; RISK-FACTOR; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; PLASMA-GLUCOSE; MORTALITY; DYSFUNCTION; ARTERY AB The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin-resistant subjects with the Flow-Mediated-Dilation (FMD) technique. We randomized subjects to intervention/control group, and examined the acute and chronic effect of nateglinide, an oral antidiabetic drug of rapid action. In the intervention group, postoral glucose-load (post-OGL) FMD delta values deteriorated when compared to pre-OGL values, most significantly at 3 h post-OGL, on the following days: on the first study day termed "Baseline day" (p=0.04); on both days after 3 months of nateglinide treatment with nateglinide administered on study-day "acute+chronic" (p=0.01); and without nateglinide on study-day "Closing day", p=0.001]. Post-OGL changes in the control group were nonsignificant both at Baseline and on Closing day. After a single dose of nateglinide "Acute day", post-OGL FMD deterioration was abolished. There was an increment in post-OGL FMD delta values most significant at 2 h post-OGL (p=0.02). Insulin concentrations increased while glucose concentrations decreased on study-days with nateglinide when compared to study-days without (p= <0.001 for both insulin and glucose). Comparisons for insulin and glucose concentrations between days with nateglinide, and likewise between days without, showed no significant difference. Postglucose load endothelial dysfunction call be prevented by administration of nateglinide, however, after 3 months of nateglinide treatment, this effect is abolished. Chronically increased insulin secretion could counteract the initial beneficial effect of reduced glucose excursions. We found no relationship between postprandial hyperglycemia and post-OGL FMD. C1 [Major-Pedersen, A.; Ihlemann, N.; Hermann, T. S.; Christiansen, B.; Kveiborg, B.; Nielsen, D.; Torp-Pedersen, C.] Bispebjerg Hosp, Dept Cardiol, Copenhagen NV, Denmark. [Dominguez, H.] Gentofte Univ Hosp, Copenhagen, Denmark. [Rask-Madsen, C.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Svendsen, O. L.] Bispebjerg Hosp, Endocrinol Clin, Copenhagen NV, Denmark. [Kober, L.] Rigshosp, DK-2100 Copenhagen, Denmark. RP Major-Pedersen, A (reprint author), Aftenabakken 27, DK-2870 Dyssegard, Denmark. EM atmp@heart.dk RI Torp-Pedersen, Christian/E-5931-2013; OI DOMINGUEZ, HELENA/0000-0002-7089-2636 FU Danish Diabetes Association FX This project was Supported by Novartis, Roche, and the Danish Diabetes Association. NR 32 TC 7 Z9 7 U1 0 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD SEP PY 2008 VL 40 IS 9 SI SI BP 607 EP 613 DI 10.1055/s-0028-1082327 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358OK UT WOS:000259927200004 PM 18792871 ER PT J AU Berndt, SI Potter, JD Hazra, A Yeager, M Thomas, G Makar, KW Welch, R Cross, AJ Huang, WY Schoen, RE Giovannucci, E Chan, AT Chanock, SJ Peters, U Hunter, DJ Hayes, RB AF Berndt, Sonja I. Potter, John D. Hazra, Aditi Yeager, Meredith Thomas, Gilles Makar, Karen W. Welch, Robert Cross, Amanda J. Huang, Wen-Yi Schoen, Robert E. Giovannucci, Edward Chan, Andrew T. Chanock, Stephen J. Peters, Ulrike Hunter, David J. Hayes, Richard B. TI Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER RISK; ADENOMATOUS POLYPS; LINKAGE PHASE; COLON-CANCER; C-MYC; METAANALYSIS; VARIANT; LOCUS; POPULATION AB Several different genetic variants at chromosome 8q24 have been related to prostate, breast and colorectal cancer risk with evidence of region-specific risk differentials for various tumor types. We investigated the association between 15 polymorphisms located in 8q24 regions associated with cancer risk in a pooled analysis of 2587 colorectal adenoma cases, 547 colorectal cancer cases and 2798 controls of European descent from four studies. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations. Three polymorphisms (rs10808555, rs6983267 and rs7837328) located between 128.47 and 128.54 Mb were found to be associated with colorectal tumor risk. The association was strongest for the previously reported rs6983267 variant and was similar for both adenoma (OR(per allele) = 1.16, 95% CI: 1.07-1.25, P = 0.0002) and cancer (OR(per allele) = 1.17, 95% CI: 1.01-1.35, P = 0.03). The strength of the association of the regional haplotype containing variant alleles at rs10808555, rs6983267 and rs7837328 but not rs10505476 was greater than that of any single variant of both adenoma (OR = 1.27, P = 0.0001) and cancer (OR = 1.26, P = 0.03). The risk associated with rs6983267 was stronger for multiple adenomas (OR(per allele) = 1.29, P = 5.6 x 10(-6)) than for single adenoma (ORper allele = 1.10, P = 0.03) with P(heterogeneity) = 0.008. This study confirms the association between colorectal neoplasia and the 8q24 polymorphisms located between 128.47 and 128.54 Mb and suggests a role for these variants in the formation of multiple adenomas. C1 [Berndt, Sonja I.; Yeager, Meredith; Thomas, Gilles; Welch, Robert; Cross, Amanda J.; Huang, Wen-Yi; Chanock, Stephen J.; Hayes, Richard B.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Potter, John D.; Makar, Karen W.; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Potter, John D.; Peters, Ulrike] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Hazra, Aditi; Giovannucci, Edward; Hunter, David J.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Yeager, Meredith; Welch, Robert] SAIC Frederick Inc, Adv Technol Program, Natl Canc Inst Frederick, Frederick, MD 21702 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Schoen, Robert E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. [Giovannucci, Edward; Hunter, David J.] Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward; Chan, Andrew T.; Hunter, David J.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Berndt, SI (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8116,MSC 7240, Bethesda, MD 20892 USA. EM berndts@mail.nih.gov OI Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health [N01-CO-12400, CA87969, CA55075, CA059045] FX This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; National Cancer Institute, National Institutes of Health under contract N01-CO-12400; and National Institutes of Health research grants CA87969, CA55075 and CA059045. NR 35 TC 51 Z9 53 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2008 VL 17 IS 17 BP 2665 EP 2672 DI 10.1093/hmg/ddn166 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 343PW UT WOS:000258867000008 PM 18535017 ER PT J AU Kiefer, SM Robbins, L Barina, A Zhang, ZH Rauchman, M AF Kiefer, Susan M. Robbins, Lynn Barina, Andrew Zhang, Zhihong Rauchman, Michael TI SALL1 truncated protein expression in Townes-Brocks syndrome leads to ectopic expression of downstream genes SO HUMAN MUTATION LA English DT Article DE Sall1; spalt; Townes-Brocks; Shox2; Nppa; derepression ID MESSENGER-RNA DECAY; NONSENSE-MEDIATED DECAY; TRANSCRIPTIONAL REPRESSOR; KIDNEY DEVELOPMENT; MURINE HOMOLOG; MOUSE LIMB; COMPLEX; MUTATIONS; HAPLOINSUFFICIENCY; PROLIFERATION AB Mutations in SALL1 lead to the dominant multiorgan congenital anomalies that define Townes-Brocks syndrome (TBS). The majority of these mutations result in premature termination codons that would be predicted to trigger nonsense-mediated decay (NMD) of mutant mRNA and cause haploinsufficiency. Our previous studies using a gene targeted mouse model (Sall1-Delta Zn) suggested that TBS phenotypes are due to expression of a truncated mutant protein, not haploinsufficiency. In this report, we strengthen this hypothesis by showing that expression of the mutant protein alone in transgenic mice is sufficient to cause limb phenotypes that are characteristic of TBS patients. We prove that the same pathogenetic mechanism elucidated in mice is occur-ring in humans by demonstrating that truncated SALL1 protein is expressed in cells derived from a TBS patient. TBS mutant protein is capable of dominant negative activity that results in ectopic activation of two downstream genes, Nppa and Shox2, in the developing heart and limb. We propose a model for the pathogenesis of TBS in which truncated Sall1 protein causes derepression of Sall-responsive target genes. C1 [Kiefer, Susan M.; Robbins, Lynn; Rauchman, Michael] US Dept Vet Affairs, Res & Educ Serv Line, St Louis VA Med Ctr, St Louis, MO 63106 USA. [Kiefer, Susan M.; Robbins, Lynn; Barina, Andrew; Zhang, Zhihong; Rauchman, Michael] St Louis Univ, Hlth Sci Ctr, Dept Internal Med, St Louis, MO 63103 USA. RP Rauchman, M (reprint author), US Dept Vet Affairs, Res & Educ Serv Line, St Louis VA Med Ctr, 915 N Grand Blvd,657-111B JC, St Louis, MO 63106 USA. EM Rauchman@slu.edu FU Veterans Administration Merit Award; VISN (Veterns Integrated Service Network); American Society of Nephrology Gottschalk Award; NIH FX We thank Juergen Kohlhase and Dan Hoft for the generous gifts of TBS and normal patient B-cell lines. Yiping Chen kindly provided the Hoxb6 promoter. Heart phenotypes were analyzed with the invaluable help of Jun Takeuchi (Tokyo). James Kiefer, Shannon Lauberth, and Sandy McLeskey gave valuable constructive comments on the data and manuscript and Amy Bilyeu and Emily Royse provided excellent technical assistance with genotyping. We thank BMJ Publishing group and Elsevier Limited for permission to reprint TBS patient figures. This work funded by a Veterans Administration Merit Award (to M.R.), a VISN (Veterns Integrated Service Network) 15 VA Award (to S.K.), an American Society of Nephrology Gottschalk Award (to S.K.), and an NIH grant (to M.R). NR 34 TC 15 Z9 16 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD SEP PY 2008 VL 29 IS 9 BP 1133 EP 1140 DI 10.1002/humu.20759 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 349KZ UT WOS:000259281000008 PM 18470945 ER PT J AU Hedley-Whyte, ET AF Hedley-Whyte, E. Tessa TI On being a pathologist: how does one plan a career, or does one? SO HUMAN PATHOLOGY LA English DT Editorial Material ID MULTIFOCAL LEUKOENCEPHALOPATHY; DISEASE; BRAIN; MOUSE C1 [Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Dept Pathol, Boston, MA 02114 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Boston, MA USA. RP Hedley-Whyte, ET (reprint author), Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Dept Pathol, Warren 325, Boston, MA 02114 USA. EM ehedleywhyte@partners.org NR 18 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2008 VL 39 IS 9 BP 1269 EP 1274 DI 10.1016/j.humpath.2008.05.002 PG 6 WC Pathology SC Pathology GA 340DO UT WOS:000258626500001 PM 18706348 ER PT J AU Chai, XY Li, LM Wu, KJ Zhou, CQ Cao, PJ Ren, QS AF Chai, Xinyu Li, Liming Wu, Kaijie Zhou, Chuanqing Cao, Pengjia Ren, Qiushi TI C-sight visual prostheses for the blind - Optic nerve stimulation with penetrating electrode array SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID ELECTRICAL-STIMULATION; RETINAL PROSTHESIS; VISION; CORTEX C1 [Ren, Qiushi] Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. [Ren, Qiushi] Harvard Univ, Sch Med, Ophthalm Laser Lab, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. [Ren, Qiushi] Univ Miami, Dept Biomed Engn, Coral Gables, FL 33124 USA. Univ Miami, Dept Ophthalmol, Coral Gables, FL 33124 USA. [Ren, Qiushi] Univ Miami, Bascom Palmer Eye Inst, Coral Gables, FL 33124 USA. [Ren, Qiushi] Minist Sci & Technol China, Natl Key Basic Res Project Project 973, Beijing, Peoples R China. [Ren, Qiushi] Shanghai Jiao Tong Univ, Dept Biomed Engn, Inst Laser Med & BioPhoton, Shanghai 200240, Peoples R China. RP Ren, QS (reprint author), Shanghai Jiao Tong Univ, Dept Biomed Engn, Inst Laser Med & BioPhoton, Room 423,Life Sci Bldg 2,800 Dong Chuan Rd, Shanghai 200240, Peoples R China. EM renqsh@sjtu.edu.cn RI Ren, Qiushi/D-1451-2012 FU National Basic Research Program of China [2005CB724300]; National Natural Science Foundation of China [60588101]; Shanghai Commission of Science and Technology [05DZ22318, 05DZ22325, 04DZ05114] FX This research is supported by the National Basic Research Program of China (973 Program, 2005CB724300), the National Science Fund for Distinguished Young Scholars from the National Natural Science Foundation of China (60588101), and the Shanghai Commission of Science and Technology (05DZ22318, 05DZ22325, and 04DZ05114). NR 22 TC 25 Z9 31 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD SEP-OCT PY 2008 VL 27 IS 5 BP 20 EP 28 DI 10.1109/MEMB.2008.923959 PG 9 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 356PH UT WOS:000259789600007 PM 18799386 ER PT J AU Salthouse, CD Weissleder, R Mahmood, U AF Salthouse, Christopher D. Weissleder, Ralph Mahmood, Umar TI Development of a Time Domain Fluorimeter for Fluorescent Lifetime Multiplexing Analysis SO IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS LA English DT Article DE Analog circuits; biomedical imaging; fluorescence; optical pulses AB We show that a portable, inexpensive USB-powered time domain fluorimeter (TDF) and analysis scheme were developed for use in evaluating a new class of fluorescent lifetime multiplexed dyes. Fluorescent proteins, organic dyes, and quantum dots allow the labeling of more and more individual features within biological systems, but the wide absorption and emission spectra of these fluorophores limit the number of distinct processes which may be simultaneously imaged using spectral separation alone. By additionally separating reporters in a second dimension, fluorescent lifetime multiplexing provides a means to multiply the number of available imaging channels. C1 [Salthouse, Christopher D.; Weissleder, Ralph; Mahmood, Umar] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Salthouse, CD (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM csalthouse@mgh.harvard.edu FU NIH [5R01EB001872-05, 5T32EB002102-26] FX Manuscript received December 22, 2007; revised April 09, 2008. Current version published October 24, 2008. This work was supported in part by the NIH Grants 5R01EB001872-05 "In Vivo Multichannel Fluorescent Imaging" and 5T32EB002102-26 "Postgraduate Program in Radiological Sciences." This paper was recommended by Associate Editor S. Hu. NR 14 TC 12 Z9 12 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1932-4545 J9 IEEE T BIOMED CIRC S JI IEEE Trans. Biomed. Circuits Syst. PD SEP PY 2008 VL 2 IS 3 BP 204 EP 211 DI 10.1109/TBCAS.2008.2003195 PG 8 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA V10PA UT WOS:000207474700007 PM 19830273 ER PT J AU Xia, Z Huang, XS Zhou, XB Sun, YX Ntziachristos, V Wong, STC AF Xia, Zheng Huang, Xishi Zhou, Xiaobo Sun, Youxian Ntziachristos, Vasilis Wong, Stephen T. C. TI Registration of 3-D CT and 2-d flat images of mouse via affine transformation SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE animal molecular imaging; fluorescence molecular tomography (FMT); registration; snake model ID POINT SETS; SHAPES; SNAKES AB It is difficult to directly coregister the 3-D fluorescence molecular tomography (FMT) image of a small tumor in a mouse whose maximal diameter is only a few millimeters with a larger CT image of the entire animal that spans about 10 cm. This paper proposes a new method to register 2-D flat and 3-D CT image first to facilitate the registration between small 3-D FMT images and large 3-D CT images. A novel algorithm combining differential evolution and improved simplex method for the registration between the 2-D flat and 3-D CT images is introduced and validated with simulated images and real images of mice. The visualization of the alignment of the 3-D FMT and CT image through 2-D registration shows promising results. C1 [Xia, Zheng; Sun, Youxian] Zhejiang Univ, State Key Lab Ind Control Technol, Hangzhou 310027, Zhejiang, Peoples R China. [Huang, Xishi] Univ Western Ontario, Biomed Engn Grad Program, London, ON N6A 5B8, Canada. [Huang, Xishi] Robarts Res Inst, Imaging Res Labs, London, ON N6A 5K8, Canada. [Zhou, Xiaobo; Wong, Stephen T. C.] Harvard Univ, Sch Med, HCNR, CBI, Boston, MA 02215 USA. [Zhou, Xiaobo; Wong, Stephen T. C.] Brigham & Womens Hosp, Boston, MA 02215 USA. [Zhou, Xiaobo; Wong, Stephen T. C.] Brigham & Womens Hosp, Funct Mol Imaging Ctr, Boston, MA 02115 USA. [Ntziachristos, Vasilis] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Xia, Z (reprint author), Zhejiang Univ, State Key Lab Ind Control Technol, Hangzhou 310027, Zhejiang, Peoples R China. EM zxia@iipc.zju.edu.cn; xhuang@imaging.robarts.ca; zhou@crystal.harvard.edu; yxsun@iipc.zju.edu.cn; vasilis@helix.mgh.harvard.edu; wong@crystal.harvard.edu RI Xia, Zheng/F-6561-2014 OI Xia, Zheng/0000-0003-3364-8324 FU Key Technologies R&D Program of Zhejiang Province [2005C21087]; Academician Foundation of Zhejiang Province [2005A1001-13]; Harvard Center for Neurodegeneration and Repair (HCNR) Center for Bioinformatics Research; Harvard Medical School; National Institutes of Health [R01 LM008696] FX The work of Z. Xia and Y. Sun was supported in part by the Key Technologies R&D Program of Zhejiang Province under Grant 2005C21087, and in part by the Academician Foundation of Zhejiang Province under Grant 2005A1001-13. The work of X. Zhou was supported in part by the Harvard Center for Neurodegeneration and Repair (HCNR) Center for Bioinformatics Research, Harvard Medical School under a Research Grant. The work of S. T. C. Wong was supported in part by the Harvard Center for Neurodegeneration and Repair (HCNR) Center for Bioinformatics Research, Harvard Medical School under a Research Grant, and in part by the National Institutes of Health under Grant R01 LM008696. NR 24 TC 11 Z9 12 U1 1 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1089-7771 EI 1558-0032 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD SEP PY 2008 VL 12 IS 5 BP 569 EP 578 DI 10.1109/TITB.2007.904631 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 353MI UT WOS:000259571700003 PM 18779071 ER PT J AU Markiewicz, MR Marincola, M Tovar, LA Margarone, JE Garlapo, DA Chuang, SK AF Markiewicz, Michael R. Marincola, Mauro Tovar, Luisa Arevalo Margarone, Joseph E., III Garlapo, Davis A. Chuang, Sung-Kiang TI Building on the proceedings of the McGill conference: Implant-retained overdentures in an area of South America SO IMPLANT DENTISTRY LA English DT Article DE dental implant; mandible; McGill consensus; overdenture ID RANDOMIZED CLINICAL-TRIAL; MANDIBULAR 2-IMPLANT OVERDENTURES; 8-YEAR FOLLOW-UP; CONVENTIONAL DENTURES; ENDOSSEOUS IMPLANTS; SUPPORTED OVERDENTURES; PATIENT SATISFACTION; MASTICATORY FUNCTION; ENDOSTEAL IMPLANTS; OSSEOINTEGRATED IMPLANTS AB Purpose: Since the McGill consensus conference, numerous reports have proposed the advantages of the 2-implant-retained overdenture over the conventional denture in the restorative management of the edentulous mandible. The purpose of this article was to demonstrate the use of the 2-implant-retained overdenture in the restorative management of patients with edentulous mandibles in an impoverished population. Materials: To address the study's purpose, the investigators initiated a retrospective cohort study and enrolled a sample of subjects who had mandibular 2-implant overdenture treatment using the protocol described within. The primary predictor variable was whether the patient had mandibular 2-implant overdenture treatment. The primary outcome variable was survival of mandibular 2-implant overdenture treatment as defined within. Results: The study sample included 35 patients each of whom had 2 mandibular implants placed for a total of 70 implants inserted with the purpose of retaining a mandibular overdenture. The mean clinical follow-up time was 74.7 months, during which there were no incidences of implant failure. Therefore, analytical and survival analyses could not be performed. Conclusion: Given the increase in quality of life and ease in implementation, clinicians should now be suggesting the mandibular 2-implant overdenture as the treatment of choice in the management of the edentulous mandible. C1 [Markiewicz, Michael R.] Oregon Hlth & Sci Univ, Dept Oral & Maxillofacial Surg, Portland, OR 97201 USA. [Marincola, Mauro; Tovar, Luisa Arevalo] Univ Cartagena, Dept Dent Med, Cartagena, Colombia. [Margarone, Joseph E., III] SUNY Buffalo, Sch Dent Med, Dept Oral & Maxillofacial Surg, Buffalo, NY 14260 USA. [Garlapo, Davis A.] SUNY Buffalo, Sch Dent Med, Dept Restorat Dent, Buffalo, NY 14260 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Markiewicz, MR (reprint author), Oral & Maxillofacial Surg SPC, 611 SW Campus Dr, Portland, OR 97239 USA. EM markiewm@ohsu.edu NR 83 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1056-6163 EI 1538-2982 J9 IMPLANT DENT JI Implant Dent. PD SEP PY 2008 VL 17 IS 3 BP 288 EP 293 DI 10.1097/ID.0b013e318182ed65 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 350XE UT WOS:000259386100007 PM 18784529 ER PT J AU LaRocque, RC Krastins, B Harris, JB Lebrun, LM Parker, KC Chase, M Ryan, ET Qadri, F Sarracino, D Calderwood, SB AF LaRocque, Regina C. Krastins, Bryan Harris, Jason B. Lebrun, Lauren M. Parker, Kenneth C. Chase, Michael Ryan, Edward T. Qadri, Firdausi Sarracino, David Calderwood, Stephen B. TI Proteomic analysis of Vibrio cholerae in human stool SO INFECTION AND IMMUNITY LA English DT Article ID SOLUBLE COLONIZATION FACTOR; TOXR REGULON; EL-TOR; EXPRESSION; INFECTION; BACTERIA; GENES; PILUS AB An effective vaccine for Vibrio cholerae is not yet available for use in the developing world, where the burden of cholera disease is highest. Characterizing the proteins that are expressed by V. cholerae in the human host environment may provide insight into the pathogenesis of cholera and assist with the development of an improved vaccine. We analyzed the V. cholerae proteins present in the stools of 32 patients with clinical cholera. The V. cholerae outer membrane porin, OmpU, was identified in all of the human stool samples, and many V. cholerae proteins were repeatedly identified in separate patient samples. The majority of V. cholerae proteins identified in human stool are involved in protein synthesis and energy metabolism. A number of proteins involved in the pathogenesis of cholera, including the A and B subunits of cholera toxin and the toxin-coregulated pilus, were identified in human stool. In a subset of stool specimens, we also assessed which in vivo expressed V. cholerae proteins were recognized uniquely by convalescent-phase as opposed to acute-phase serum from cholera patients. We identified a number of these in vivo expressed proteins as immunogenic during human infection. To our knowledge, this is the first characterization of the proteome of a pathogenic bacteria recovered from a natural host. C1 [LaRocque, Regina C.; Harris, Jason B.; Lebrun, Lauren M.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Krastins, Bryan; Parker, Kenneth C.; Chase, Michael; Sarracino, David] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Cambridge, MA 02138 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. [Ryan, Edward T.] Harvard Univ, Dept Immunol & Infect Dis, Sch Publ Hlth, Cambridge, MA 02138 USA. [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM rclarocque@partners.org OI Parker, Kenneth/0000-0002-6282-2478 FU Fogarty International Center [K01-TW07144, K01-TW07409]; Massachusetts General Hospital; National Institute of Allergy and Infectious Diseases [AI40725, U01-AI058935]; New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases [U54-AI057159]; ICDRR,B FX This research was supported by grants K01-TW07144 from the Fogarty International Center (R. C. L.), a Claflin Distinguished Scholar Award from the Massachusetts General Hospital (R. C. L.), K01-TW07409 from the Fogarty International Center (J.B.H.), AI40725 from the National Institute of Allergy and Infectious Diseases (E. T. R.), U01-AI058935 from the National Institute of Allergy and Infectious Diseases (S. B. C.), U54-AI057159 from the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (S. B. C., K. C. P., and D. S.), and by the ICDRR,B (F. Q.). NR 22 TC 17 Z9 17 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2008 VL 76 IS 9 BP 4145 EP 4151 DI 10.1128/IAI.00585-08 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 340TI UT WOS:000258667500035 PM 18591230 ER PT J AU Cornia, PB Lipsky, BA AF Cornia, Paul B. Lipsky, Benjamin A. TI Indwelling urinary catheters in hospitalized patients: When in doubt, pull it out SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID TRACT-INFECTION; UNITED-STATES; CARE; PHYSICIANS; BACTERIURIA; DURATION C1 [Cornia, Paul B.; Lipsky, Benjamin A.] Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Serv, Seattle, WA 98108 USA. [Cornia, Paul B.; Lipsky, Benjamin A.] Univ Washington, Sch Med, Seattle, WA USA. RP Cornia, PB (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM paul.cornia@med.va.gov RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 28 TC 3 Z9 3 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2008 VL 29 IS 9 BP 820 EP 822 DI 10.1086/590535 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 348MG UT WOS:000259214000003 PM 18700832 ER PT J AU Pollock, NR Campos-Neto, A Kashino, S Napolitano, D Behar, SM Shin, D Sloutsky, A Joshi, S Guillet, J Wong, M Nardell, E AF Pollock, Nira R. Campos-Neto, Antonio Kashino, Suely Napolitano, Danielle Behar, Samuel M. Shin, Daniel Sloutsky, Alex Joshi, Swati Guillet, Jasmine Wong, Michael Nardell, Edward TI Discordant QuantiFERON-TB Gold test results among US healthcare workers with increased risk of latent tuberculosis infection: A problem or solution? SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID BLOOD INTERFERON-GAMMA; SKIN-TEST; RELEASE ASSAYS; UNITED-STATES; DIAGNOSIS; PROGNOSIS; CONTACTS AB Objective. In late 2006, our hospital implemented use of the QuantiFERON-TB Gold (QFT-G) assay, a whole-blood interferon-gamma release assay, for detection of tuberculosis infection. All newly hired healthcare workers (HCWs) with positive Mantoux tuberculin skin test (TST) results were routinely tested with the QFT-G assay, to take advantage of its higher specificity. We then undertook a quality assurance review to evaluate the QFT-G test results in HCWs with multiple risk factors for latent tuberculosis infection (LTBI). Methods. The clinical records for TST-positive HCWs tested with the QFT-G assay were reviewed. HCWs with 2 or more risk factors commonly associated with LTBI were classified as "increased risk" (IR). IR HCWs who had negative QFT-G test results underwent repeat QFT-G testing and were offered testing with a different interferon-gamma release assay (T-SPOT.TB) and with extended T cell stimulation assays. Results. Of 143 TST-positive HCWs tested with the QFT-G assay, 26 (18%) had positive results, 115 (81%) had negative results, and 2 (1%) had indeterminate results. Of 82 IR HCWs, 23 (28%) had positive QFT-G test results, and 57 (70%) had negative results. Of the 57 IR HCWs with negative results, 43 underwent repeat QFT-G testing: 41 had negative results again, and 2 had positive results. These 43 HCWs were also offered additional testing with the T-SPOT.TB diagnostic, and 36 consented: 31/36 tested negative, and 5/36 tested positive. Extended assays using the antigens ESAT-6 and CFP-10 confirmed the positive results detected by the overnight assays and yielded positive results for an additional 7/36 (19%) of individuals; strikingly, all 36 HCWs had strongly positive test results with assays using purified protein derivative. Conclusions. The extreme discordance between the results of our clinical diagnostic algorithm and the results of QFT-G testing raises concern about the sensitivity of the QFT-G assay for detection of LTBI in our HCWs. Results of extended stimulation assays suggest that many of our IR HCWs have indeed been sensitized to Mycobacterium tuberculosis. It is possible that the QFT-G assay identifies those at higher reactivation risk rather than all previously infected, but, in the absence of long-term follow-up data, we should interpret negative QFT-G results with some caution. C1 [Pollock, Nira R.; Wong, Michael] Beth Israel Deaconess Med Ctr, Dept Infect Dis, Boston, MA 02215 USA. [Campos-Neto, Antonio; Kashino, Suely; Napolitano, Danielle] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Behar, Samuel M.; Shin, Daniel] Brigham & Womens Hosp, Dept Rheumatol, Boston, MA 02115 USA. [Nardell, Edward] Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. [Sloutsky, Alex; Joshi, Swati; Guillet, Jasmine] Massachusetts State Lab Inst, Boston, MA USA. RP Pollock, NR (reprint author), Beth Israel Deaconess Med Ctr, Dept Infect Dis, Lowry Med Bldg,110 Francis St,Suite GB, Boston, MA 02215 USA. EM npollock@bidmc.harvard.edu RI Kashino, Suely/F-4171-2012; OI Behar, Samuel/0000-0002-3374-6699 FU Pittsfield Anti-Tuberculosis Association; Clinical Investigator Training FX We thank the BIDMC EOHS team for their efforts in setting up QFT-G testing and for their flexible response to the data obtained in this study. We also thank the members of the Massachusetts Committee for Elimination of Tuberculosis for their review and discussion of the data.; Financial support. QuantiFERON-TB Gold kits were provided by Cellestis; T-SPOT.TB kits were provided by Oxford Immunotec. The project was supported by a grant from the Pittsfield Anti-Tuberculosis Association (to N.P.). N.P. is supported by the Clinical Investigator Training Program, which is a cooperative effort between the BIDMC and the Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, in collaboration with Pfizer and Merck & Co.; Potential conflict of interest. E.N. has served as a past consultant to Oxford Immunotec. S. M. B. has received technical support from Oxford Immunotec for performance of T-SPOT.TB assays in his laboratory. All other authors report no conflicts of interest relevant to this article. NR 40 TC 41 Z9 41 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2008 VL 29 IS 9 BP 878 EP 886 DI 10.1086/590262 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 348MG UT WOS:000259214000014 PM 18713053 ER PT J AU Aslam, S Trautner, BW Ramanathan, V Darouiche, RO AF Aslam, Saima Trautner, Barbara W. Ramanathan, Venkat Darouiche, Rabih O. TI Pilot trial of N-acetylcysteine and tigecycline as a catheter-lock solution for treatment of hemodialysis catheter-associated bacteremia SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT, 2007 CL San Diego, CA SP Infect Dis Soc Amer ID ANTIBIOTIC LOCK; INFECTIONS AB We evaluated a catheter-lock solution consisting of N-acetylcysteine, tigecycline, and heparin for catheter salvage in patients with hemodialysis catheter-associated bacteremia. Eighteen case patients received the catheter-lock solution for 14 days plus systemic antibiotic therapy. Treatment was successful for 15 (83%) of the 18 case patients within 90 days of follow-up, with a median catheter retention interval of 64.5 days. C1 [Aslam, Saima] Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. [Aslam, Saima; Trautner, Barbara W.; Darouiche, Rabih O.] Baylor Coll Med, Infect Dis Sect, Dept Med, Houston, TX 77030 USA. [Ramanathan, Venkat] Baylor Coll Med, Nephrol Sect, Dept Med, Houston, TX 77030 USA. [Darouiche, Rabih O.] Baylor Coll Med, Ctr Prostheses Infect, Houston, TX 77030 USA. RP Aslam, S (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, 2002 Holcombe Blvd,Room 4B-370, Houston, TX 77030 USA. EM saslam@bcm.tmc.edu FU NICHD NIH HHS [HD024014, HD43943-01A1]; NIDDK NIH HHS [DK077313] NR 10 TC 16 Z9 16 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2008 VL 29 IS 9 BP 894 EP 897 DI 10.1086/590192 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 348MG UT WOS:000259214000017 PM 18643743 ER PT J AU Hsiao, AF Wong, MD Miller, MF Ambs, AH Goldstein, MS Smith, A Ballard-Barbash, R Becerra, LS Cheng, EM Wenger, NS AF Hsiao, An-Fu Wong, Mitchell D. Miller, Melissa F. Ambs, Anita H. Goldstein, Michael S. Smith, Ashley Ballard-Barbash, Rachel Becerra, Lida S. Cheng, Eric M. Wenger, Neil S. TI Role of religiosity and spirituality in complementary and alternative medicine use among cancer survivors in California SO INTEGRATIVE CANCER THERAPIES LA English DT Article DE CAM; integrative medicine; spirituality; religiosity; survivors ID HEALTH-CARE; ETHNIC-DIFFERENCES; ONCOLOGY; PREVALENCE; ADULTS AB Objectives. Cancer survivors often turn to religion, spirituality, and complementary and alternative medicine (CAM) because they perceive these areas as being more holistic and patient-centered than conventional medicine. Because increased religiosity and spirituality have been found to be associated with higher CAM use in the general population, it was hypothesized that these factors would be important predictors of CAM use in cancer survivors. Design and Subjects. The study included a subsample of 1844 people with cancer or a history of cancer from the 2003 California Health Interview Survey of CAM, a cross-sectional survey of a population-based sample of adults in California. Prevalence and predictors of religious/spiritual forms of CAM (R/S CAM) and nonreligious/nonspiritual forms of CAM (non-R/S CAM) were compared. Multivariate logistic regression was used to identify the predictors of R/S CAM and non-R/S CAM. Results. Nearly two thirds of participants reported using at least 1 type of R/S CAM, and 85% reported ever using non-R/S CAM. The majority of cancer survivors reported that they were very/moderately religious or spiritual. Both religiosity and spirituality were strongly related to non-R/S CAM use, but in opposite directions. Very or moderately religious cancer survivors were less likely (odds ratio = 0.30; 95% confidence interval, 0.12-0.40) than nonreligious cancer survivors to use non-R/S CAM. In contrast, very or moderately spiritual cancer survivors were more likely (odds ratio = 2.42; 95% confidence interval, 1.16-6.02) than nonspiritual cancer survivors to use non-R/S CAM. Conclusions. The use of R/S CAM and non-R/S CAM is very high in cancer survivors. It may be helpful for clinicians to ascertain their patients' use of these types of CAM to integrate all forms of care used to managing their cancer. C1 [Hsiao, An-Fu] VA Long Beach Healthcare Syst, Long Beach, CA 90822 USA. [Hsiao, An-Fu] Univ Calif Irvine, Ctr Hlth Policy Res, Irvine, CA USA. [Wong, Mitchell D.] Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA USA. [Wong, Mitchell D.; Wenger, Neil S.] Univ Calif Los Angeles, Hlth Serv Res, Los Angeles, CA USA. [Miller, Melissa F.; Ambs, Anita H.; Smith, Ashley; Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Goldstein, Michael S.] Univ Calif Los Angeles, Dept Community Hlth Sci, Los Angeles, CA USA. [Becerra, Lida S.] Univ Calif Los Angeles, Ctr Hlth Policy & Res, Los Angeles, CA USA. [Cheng, Eric M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Hsiao, AF (reprint author), VA Long Beach Healthcare Syst, 5901 E 7th St,Mail Code 11-111, Long Beach, CA 90822 USA. EM anfu.hsiao@va.gov OI Wong, Mitchell/0000-0002-4800-8410 FU National Institutes of Health (NIH); National Center of Complementary and Alternative Medicine [R21 AT002248-01]; NCCAM [R21-AT002248-01]; National Cancer institute (NCI) [NO2-PC-95057] FX We thank Victor Gonzalez for his technical assistance. We thank UCLA Center for Health Policy Research for their assistance in carrying out the research. FUNDING/GRANT INFORMATION: Dr. Hsiao was supported by National Institutes of Health (NIH), National Center of Complementary and Alternative Medicine (R21 AT002248-01). This publication was made possible by Grant No. R21-AT002248-01 from NCCAM. The collection of data used in this study was supported by the National Cancer institute (NCI) under contract NO2-PC-95057 awarded to the UCLA Center for Health Policy Research. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, NCI, or the NIH. NR 36 TC 20 Z9 21 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-7354 J9 INTEGR CANCER THER JI Integr. Cancer Ther. PD SEP PY 2008 VL 7 IS 3 BP 139 EP 146 DI 10.1177/1534735408322847 PG 8 WC Oncology; Integrative & Complementary Medicine SC Oncology; Integrative & Complementary Medicine GA 351PQ UT WOS:000259436800004 PM 18815145 ER PT J AU Ferreira, JC Chipman, DW Kacmarek, RM AF Ferreira, Juliana C. Chipman, Daniel W. Kacmarek, Robert M. TI Trigger performance of mid-level ICU mechanical ventilators during assisted ventilation: a bench study SO INTENSIVE CARE MEDICINE LA English DT Article DE ventilators; mechanical; respiratory mechanics; respiration; artificial; intensive care units; equipment safety; models; biological ID LUNG MODEL; PRESSURE; HOME; TRANSPORT AB Objective: To compare the triggering performance of mid-level ICU mechanical ventilators with a standard ICU mechanical ventilator. Design: Experimental bench study. Setting: The respiratory care laboratory of a university-affiliated teaching hospital. Subject: A computerized mechanical lung model, the IngMar ASL5000. Interventions: Ten mid-level ICU ventilators were compared to an ICU ventilator at two levels of lung model effort, three combinations of respiratory mechanics (normal, COPD and ARDS) and two modes of ventilation, volume and pressure assist/control. A total of 12 conditions were compared. Measurements and main results: Performance varied widely among ventilators. Mean inspiratory trigger time was < 100 ms for only half of the tested ventilators. The mean inspiratory delay time (time from initiation of the breath to return of airway pressure to baseline) was longer than that for the ICU ventilator for all tested ventilators except one. The pressure drop during triggering (Ptrig) was comparable with that of the ICU ventilator for only two ventilators. Expiratory Settling Time (time for pressure to return to baseline) had the greatest variability among ventilators. Conclusions: Triggering differences among these mid-level ICU ventilators and with the ICU ventilator were identified. Some of these ventilators had a much poorer triggering response with high inspiratory effort than the ICU ventilator. These ventilators do not perform as well as ICU ventilators in patients with high ventilatory demand. C1 [Chipman, Daniel W.; Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv Ellison 401, Boston, MA 02114 USA. [Ferreira, Juliana C.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Ferreira, Juliana C.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Ferreira, Juliana C.] Univ Sao Paulo, Hosp Clin, Resp ICU, Div Pulm, Sao Paulo, Brazil. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv Ellison 401, 55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org RI Ferreira, Juliana/F-3455-2011 OI Ferreira, Juliana/0000-0001-6548-1384 NR 18 TC 19 Z9 20 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2008 VL 34 IS 9 BP 1669 EP 1675 DI 10.1007/s00134-008-1125-5 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 339FF UT WOS:000258562800018 PM 18542923 ER PT J AU Garakani, A Martinez, JM Marcus, S Weaver, J Rickels, K Fava, M Hirschowitz, J AF Garakani, Amir Martinez, Jose M. Marcus, Sue Weaver, James Rickels, Karl Fava, Maurizio Hirschowitz, Jack TI A randomized, double-blind, and placebo-controlled trial of quetiapine augmentation of fluoxetine in major depressive disorder SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE adjunct; atypical antipsychotic; depression; insomnia; selective serotonin reuptake inhibitor ID TREATMENT-RESISTANT DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; ANTIDEPRESSANT ACTION; CLINICAL-TRIALS; EARLY-ONSET; METAANALYSIS; STRATEGIES; SLEEP; THERAPY; ANXIETY AB The objective of this study was to investigate whether quetiapine, when compared with placebo, can speed the onset of action and improve the quality of response to fluoxetine treatment in patients suffering from major depressive disorder. A total of 114 patients with major depressive disorder were enrolled in an 8-week treatment study. Patients were initiated on a course of fluoxetine treatment and randomized to quetiapine or placebo. Quetiapine was flexibly dosed starting at 25 mg to a maximum of 100 mg daily. Mixed-effects regression showed that quetiapine plus fluoxetine did not achieve 50% reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale, Clinical Global Improvement (CGI)-Severity, and CGI-Improvement scores sooner than the fluoxetine plus placebo group; however both groups improved in all scores over time. Mixed-effects linear regression of insomnia scores showed that the quetiapine plus fluoxetine group improved significantly more rapidly compared with the fluoxetine plus placebo group. The study indicates that quetiapine plus fluoxetine did not achieve a reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale or CGI scores from baseline sooner than the fluoxetine plus placebo group. The combination of quetiapine and fluoxetine, however, improved sleep over fluoxetine alone over the first few weeks of treatment. C1 [Garakani, Amir; Martinez, Jose M.; Marcus, Sue; Weaver, James; Hirschowitz, Jack] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10075 USA. [Rickels, Karl] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. RP Hirschowitz, J (reprint author), Mt Sinai Sch Med, Dept Psychiat, 903 Pk Ave Suite 2A, New York, NY 10075 USA. EM jack.hirschowitz@mssm.edu RI Garakani, Amir/A-3936-2013 FU Investigator-Sponsored Study Program of AstraZeneca [IRUSQUET0287] FX The authors thank Dwight Evans, M.D. (University of Pennsylvania) and Jack Gorman, M.D. (Comprehensive Neuroscience, Inc., formerly of Mount Sinai School of Medicine) for their support to this study. The authors express deepest gratitude to Jessica Sohl, Carl Kessler, and Danielle Wolman (all formerly of Mount Sinai School of Medicine) for their assistance. This research was supported by a grant from the Investigator-Sponsored Study Program of AstraZeneca (IRUSQUET0287). NR 52 TC 23 Z9 23 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD SEP PY 2008 VL 23 IS 5 BP 269 EP 275 DI 10.1097/YIC.0b013e328301a74c PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 349KI UT WOS:000259279300004 PM 18703936 ER PT J AU Darouiche, RO AF Darouiche, R. O. TI Prevention of infections associated with vascular catheters SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Article DE Prevention; Catheter infection; Catheter colonization; Anti-infective approach ID CENTRAL VENOUS CATHETERS; BLOOD-STREAM INFECTION; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; DOUBLE-BLIND TRIAL; PROSPECTIVE RANDOMIZED-TRIAL; SILVER-SULFADIAZINE; ANTIMICROBIAL ACTIVITY; STAPHYLOCOCCUS-AUREUS; CLINICAL-TRIAL AB The expanding use of vascular catheters has increased the need to prevent hazardous infectious complications. Since bloodstream infection is the most common serious complication of indwelling vascular catheters, the proof that a potentially preventive approach is truly protective against clinical infection requires a significant reduction in the incidence of this infectious complication. Although catheter colonization is a prelude to infection, most colonized catheters do not result in catheter-related infection and, therefore, a mere reduction in catheter colonization does not, in and by itself, confirm protection against clinical infection. Adherence to optimal infection control guidelines is the primary measure for preventing infection, but in most instances the level of adherence to guidelines drops subsequent to the initial surge that follows the institutional adoption of educational programs. This explains the need to assess the potential clinical protection afforded by anti-infective technologies. In addition to improving patient care, a clinically protective anti-infective approach can also bring tremendous cost savings, (Int J Artif Organs 2008; 31: 810-19) C1 [Darouiche, R. O.] Baylor Coll Med, Ctr Prostheses Infect, Houston, TX 77030 USA. [Darouiche, R. O.] Baylor Coll Med, Michael E Debakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. RP Darouiche, RO (reprint author), Baylor Coll Med, Ctr Prostheses Infect, 1333 Moursund Ave,Suite A221, Houston, TX 77030 USA. EM rdarouiche@aol.com NR 68 TC 4 Z9 5 U1 1 U2 1 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD SEP PY 2008 VL 31 IS 9 BP 810 EP 819 PG 10 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 405SQ UT WOS:000263244900009 PM 18924093 ER PT J AU Thygesen, LC Gronbaek, M Johansen, C Fuchs, CS Willett, WC Giovannucci, E AF Thygesen, Lau Caspar Gronbaek, Morten Johansen, Christoffer Fuchs, Charles S. Willett, Walter C. Giovannucci, Edward TI Prospective weight change and colon cancer risk in male US health professionals SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colonic neoplasms/epidemiology; weight gain; weight loss ID IOWA WOMENS HEALTH; COLORECTAL-CANCER; BODY-SIZE; GENETIC-POLYMORPHISM; ADENOMATOUS POLYPS; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; OBESITY; MEN; MORTALITY AB Epidemiological studies are remarkably consistent, especially among men, in showing that overweight and obesity [body mass index (BMI) >25] are associated with increased risk of colon cancer. However, no prospective studies address the influence of weight change in adulthood on subsequent colon cancer risk. In this study, we investigated whether weight change influences colon cancer risk utilizing prospectively collected weight data. We included 46,349 men aged 40-75 participating in the Health Professionals Follow-Up Study. Questionnaires including items on weight were completed every second year during follow-up from 1986 to 2004. Updated weight change between consecutive questionnaires during follow-up and recalled weight gain since age 21 was evaluated. All eligible men were cancer-free at baseline. Proportional hazard and restricted spline regression models were implemented. Over an 18-year period, we documented 765 cases of colon cancer. Cumulative mean BMI >22.5 was associated with significantly increased risk of colon cancer. The short-term weight change in the prior 2 to 4 years was positively and significantly associated with risk [HR = 1.14 (95% confidence interval, 1.00-1.29) for 4.54 kg (10 pounds) increment, p = 0.04 for overall trend]. Weight gain per 10 years since age 21 was associated with significantly increased risk [HR = 1.33 (1.12-1.58) for 4.54 kg increase per 10 years, p = 0.001]. We estimated that 29.5% of all colon cancer cases was attributable to BMI above 22.5. Our results add support that overweight and obesity are modifiable risk factors for colon cancer among men and suggest that weight has an important influence on colon cancer risk even in later life. (C) 2008 Wiley-Liss, Inc. C1 [Thygesen, Lau Caspar; Gronbaek, Morten] Natl Inst Publ Hlth, Alcohol Res Ctr, DK-1399 Copenhagen, Denmark. [Thygesen, Lau Caspar; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Johansen, Christoffer] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Fuchs, Charles S.; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. [Fuchs, Charles S.; Willett, Walter C.; Giovannucci, Edward] Brigham & Womens Hosp, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Thygesen, LC (reprint author), Natl Inst Publ Hlth, Alcohol Res Ctr, Oster Farimagsgade 5, DK-1399 Copenhagen, Denmark. EM lct@niph.dk OI Thygesen, Lau/0000-0001-8375-5211 FU NCI NIH HHS [CA55075, P01 CA055075]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-13] NR 47 TC 40 Z9 41 U1 3 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2008 VL 123 IS 5 BP 1160 EP 1165 DI 10.1002/ijc.23612 PG 6 WC Oncology SC Oncology GA 334TE UT WOS:000258243300023 PM 18546286 ER PT J AU Rauh-Hain, JA Penson, RT AF Rauh-Hain, J. A. Penson, R. T. TI Potential benefit of Sunitinib in recurrent and refractory ovarian clear cell adenocarcinoma SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE ovarian clear cell adenocarcinoma; Sunitinib; angiogenesis; VEGF ID TYROSINE KINASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; CARCINOMA; SU11248; SUBTYPES; CANCER AB Ovarian clear cell adenocarcinoma (OCCA) is a unique biological subtype of epithelial ovarian cancer, with a similar gene profile to renal cell carcinoma (RCC). Sunitinib is a vascular endothelial growth factor receptor tyrosine kinase inhibitor with proven antitumor activity in RCC and a rational biological option for treatment of OCCA. A 60-year-old woman presented with recurrent and refractory stage IA OCCA, after 9 years of remission. Sunitinib was initiated as fifth-line chemotherapy, associated with cystic degeneration of liver metastasis and a short downward trend in her CA125 level. Recurrent and refractory OCCA may respond to Sunitinib. Clinical trials are needed to objectively confirm these findings, as benefit may be limited in patients with extensively pretreated tumors. C1 [Rauh-Hain, J. A.; Penson, R. T.] Massachusetts Gen Hosp, Div Clin Gynecol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Yawkey 9066,55 Fruit St, Boston, MA 02114 USA. EM rpenson@partners.org NR 15 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD SEP-OCT PY 2008 VL 18 IS 5 BP 934 EP 936 DI 10.1111/j.1525-1438.2007.01156.x PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 348LE UT WOS:000259211200009 PM 18081793 ER PT J AU Koon, EC Ma, PC Salgia, R Welch, WR Christensen, JG Berkowitz, RS Mok, SC AF Koon, E. C. Ma, P. C. Salgia, R. Welch, W. R. Christensen, J. G. Berkowitz, R. S. Mok, S. C. TI Effect of a c-Met-specific, ATP-competitive small-molecule inhibitor SU11274 on human ovarian carcinoma cell growth, motility, and invasion SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE c-Met; gynecological cancers; invasion; kinase inhibitors; metastasis; ovarian; protein kinase as targets for therapy; tumor progression ID RECEPTOR TYROSINE KINASE; THERAPEUTIC INHIBITION; LUNG-CANCER; MUTATIONS; HGF AB Increased expression of the receptor tyrosine kinase c-Met has been shown to correlate with enhanced cell proliferation, motility, and invasion. The objectives of this study were to characterize total and activated c-Met expression in both normal and malignant human ovarian epithelial cells and to determine the effects of inhibiting the activation of c-Met on ovarian epithelial cell growth, motility, and invasion. Total c-Met was overexpressed in 82 (68%) of 119 ovarian carcinomas, as shown by immunohistochemistry. Quantitative reverse transcription-polymerase chain reaction and Western blot analyses revealed that ovarian carcinoma cell lines had higher levels of c-Met messenger RNA, total protein, and activated protein expression compared to normal ovarian epithelial cell cultures. Using a specific adenosine triphosphate-competitive small-molecule inhibitor, SU11274, activated c-Met was decreased in normal and ovarian carcinoma cell lines. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that cell growth inhibition directly correlated to the level of activated c-Met detected in each cell line (r = -0.87, P = 0.012). Using modified Boyden chamber assays, ovarian carcinoma cells treated with SU11274 demonstrated significantly decreased cell motility and invasion compared to untreated cells (P = 0.003 and P < 0.001, respectively). These data indicate that c-Met is overexpressed in the majority of malignant ovarian epithelial cells both in vivo and in vitro and that decreasing activated c-Met in vitro can significantly decrease ovarian carcinoma cell growth, motility, and invasion. Developing therapies that specifically inhibit the activation of c-Met may represent a novel therapeutic modality for patients with ovarian carcinomas expressing high levels of c-Met. C1 [Mok, S. C.] Harvard Univ, Brigham & Womens Hosp, Lab Gynecol Oncol, Med Sch,Dept Obstet Gynecol & Reprod Biol,Div Gyn, Boston, MA 02115 USA. [Koon, E. C.; Welch, W. R.; Berkowitz, R. S.; Mok, S. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Ma, P. C.] Univ Hosp Case Med Ctr, Div Hematol Oncol, Cleveland, OH USA. [Ma, P. C.] Case Comprehens Canc Ctr, Ireland Canc Ctr, Cleveland, OH USA. [Salgia, R.] Univ Chicago, Pritzker Sch Med, Dept Med, Canc Res Ctr,Sect Hematol Oncol, Chicago, IL 60637 USA. [Welch, W. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Christensen, J. G.] Pfizer Global Res & Dev, San Diego, CA USA. RP Mok, SC (reprint author), Harvard Univ, Brigham & Womens Hosp, Lab Gynecol Oncol, Med Sch,Dept Obstet Gynecol & Reprod Biol,Div Gyn, BLI-447,221 Longwood Ave, Boston, MA 02115 USA. EM scmok@rics.bwh.harvard.edu FU National Institutes of Health [P50CA105009, R33CA103595]; Department of Health and Human Services; Gillette Center For Women's Cancer; Adler Foundation Inc.; Edgar Astrove Fund; Ovarian Cancer Research Fund Inc.; Morse Family Fund; Natalie Pihl Fund; Ruth N. White Research; Friends of Dana Farber Cancer Institute; Chemicon International Inc. FX This study was supported in part by Dana-Farber/Harvard Cancer Center Ovarian Cancer SPORE Grants P50CA105009 and R33CA103595 from National Institutes of Health, Department of Health and Human Services, Gillette Center For Women's Cancer, Adler Foundation Inc., Edgar Astrove Fund, the Ovarian Cancer Research Fund Inc., the Morse Family Fund, the Natalie Pihl Fund, the Ruth N. White Research Fellowship, and Friends of Dana Farber Cancer Institute. Chemicon International Inc., of Temecula, California, kindly provided the QCM Cell Invasion Assays. NR 19 TC 29 Z9 30 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD SEP-OCT PY 2008 VL 18 IS 5 BP 976 EP 984 DI 10.1111/j.1525-1438.2007.01135.x PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 348LE UT WOS:000259211200014 PM 18021219 ER PT J AU Arabi, Y Al-Shirawi, N Memish, Z Anzueto, A AF Arabi, Yaseen Al-Shirawi, Nehad Memish, Ziad Anzueto, Antonio TI Ventilator-associated pneumonia in adults in developing countries: a systematic review SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE ventilator-associated pneumonia; developing countries; intensive care; mechanical ventilation; complication; nosocomial infection; prevention ID INTENSIVE-CARE UNITS; INFECTION-CONTROL CONSORTIUM; NOSOCOMIAL INFECTIONS; RISK-FACTORS; MECHANICAL VENTILATION; RATES; MORTALITY; SURVEILLANCE; HOSPITALS; MICROBIOLOGY AB Background: Ventilator-associated pneumonia (VAP) is a leading cause of death in hospitalized patients, but there has been no systematic analysis of the incidence, microbiology, and outcome of VAP in developing countries or of the interventions most applicable in that setting. Methods: We reviewed MEDLINE (January 1966-April 2007) and bibliographies of the retrieved articles for all observational or interventional studies that examined the incidence, microbiology, outcome, and prevention of VAP in ventilated adults in developing countries. We evaluated the rates of VAP using the National Healthcare Safety Network (NHSN) definitions and the impact of VAP on the intensive care unit (ICU) length of stay (LOS) and mortality, and the impact of interventions used to reduce VAP rates. Results: The rates of VAP varied from 10 to 41.7 per 1000 ventilator-days and were generally higher than NHSN benchmark rates. Gram-negative bacilli were the most common pathogens (41-92%), followed-by Gram-positive cocci (6-58%). VAP was associated with a crude mortality that ranged from 16% to 94% and with increased ICU LOS. Only a small number of VAP intervention studies were performed; these found that staff education programs, implementation of hand hygiene, and VAP prevention practice guidelines, and/or implementation of sedation protocol were associated with a significant reduction in VAP rates. Only one interventional study was a randomized controlled trial comparing two technologies, the rest were sequential observational. This study compared a heat and moisture exchanger (HME) to a heated humidifying system (HHS) and found no difference in VAP rates. Conclusions: Based on the existing literature, the rate of VAP in developing countries is higher than NHSN benchmark rates and is associated with a significant impact on patient outcome. Only a few studies reported successful interventions to reduce VAP There is a clear need for additional epidemiologic studies to better understand the scope of the problem. Additionally, more work needs to be done on strategies to prevent VAP, probably with emphasis on practical, Low-cost, low technology, easily implemented measures. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. C1 [Arabi, Yaseen; Al-Shirawi, Nehad] King Abdul Aziz Med City, Dept Intens Care, Riyadh 11426, Saudi Arabia. [Memish, Ziad] King Abdul Aziz Med City, Infect Prevent & Control Program, Riyadh 11426, Saudi Arabia. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis Crit Care Med, Dept Med, Audie L Murphy Mem Vet Hosp, San Antonio, TX 78229 USA. RP Arabi, Y (reprint author), King Abdul Aziz Med City, Dept Intens Care, ICU 1425,POB 22490, Riyadh 11426, Saudi Arabia. EM arabi@ngha.med.sa NR 58 TC 49 Z9 63 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 EI 1878-3511 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD SEP PY 2008 VL 12 IS 5 BP 505 EP 512 DI 10.1016/j.ijid.2008.02.010 PG 8 WC Infectious Diseases SC Infectious Diseases GA 357LE UT WOS:000259846500013 PM 18502674 ER PT J AU Eisenstein, EM Eisenstein, DL Sarma, JSM AF Eisenstein, E. M. Eisenstein, D. L. Sarma, J. S. M. TI Does the behavioral homeostasis theory of habituation and sensitization apply to Pavlovian conditioning? SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Eisenstein, E. M.; Eisenstein, D. L.; Sarma, J. S. M.] VA Greater Los Angeles Healthcare Syst, Res & Dev 691 151, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 166 EP 167 DI 10.1016/j.ijpsycho.2008.05.429 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700101 ER PT J AU Mathalon, DH Calhoun, VD Kiehl, KA Pearlson, GD Mcglashan, TH Woods, SW AF Mathalon, D. H. Calhoun, V. D. Kiehl, K. A. Pearlson, G. D. Mcglashan, T. H. Woods, S. W. TI Abnormal sensory registration, deviance detection, and attention allocation in the schizophrenia prodrome SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 14th World Congress of Psychophysiology the Olympics of the Brain CY SEP 08-13, 2008 CL St Petersburg, RUSSIA SP Int Org Psychophysiol C1 [Mathalon, D. H.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Calhoun, V. D.; Kiehl, K. A.] Univ New Mexico, Albuquerque, NM 87131 USA. [Pearlson, G. D.] Yale Univ, Hartford Hosp, Inst Living, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2008 VL 69 IS 3 BP 186 EP 187 DI 10.1016/j.ijpsycho.2008.05.497 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 336VU UT WOS:000258393700169 ER PT J AU Basu, SK Schwartz, C Fisher, SG Hudson, MM Tarbell, N Muhs, A Marcus, KJ Mendenhall, N Mauch, P Kun, LE Constine, LS AF Basu, Swati K. Schwartz, Cindy Fisher, Susan G. Hudson, Melissa M. Tarbell, Nancy Muhs, Ann Marcus, Karen J. Mendenhall, Nancy Mauch, Peter Kun, Larry E. Constine, Louis S. TI Unilateral and bilateral breast cancer in women surviving pediatric Hodgkin's disease SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE pediatric Hodgkin's disease; bilateral breast cancer ID 2ND MALIGNANT NEOPLASMS; ATOMIC-BOMB SURVIVORS; LONG-TERM SURVIVORS; YOUNG-WOMEN; RADIATION-THERAPY; GERMLINE MUTATIONS; CHILDHOOD-CANCER; RISK-FACTORS; CHEMOTHERAPY; RADIOTHERAPY AB Purpose: To define demographic and therapeutic associations with the risk of breast cancer in children treated for Hodgkin's disease (HD), particularly the frequency and interval to the development of contralateral breast cancer. Methods and Materials: All 398 female patients (< 19 years) treated for HD in five institutions during the accrual period were evaluated. Mean follow-up was 16.9 years. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cases to the expected number of cases, estimated using age-matched controls from the Surveillance, Epidemiology, and End Results database. Results: A total of 29 women developed breast cancer (25 invasive, 4 ductal carcinoma in situ; SIR, 37.25; 95% confidence interval, 24.96-53.64). Time to diagnosis was 9.4 to 36.1 years. Cumulative incidence was 24% at 30 years. Ten patients (34%) had bilateral disease (9 metachronous, I synchronous). The interval to contralateral breast cancer was 12 to 34 months. On univariate analysis, significant variables included stage of HD, mantle radiation dose, pelvic radiation (protective), and follow-up time. On multivariate analysis, early stage and older age at diagnosis of HD (<= 12 vs. > 12 years) were significant predictors of secondary breast cancer. Conclusions: Women surviving pediatric HD were found to have a 37-fold increase in the risk of breast cancer and a high likelihood of rapidly developing bilateral disease. Early-stage HD and age greater than 12 years at diagnosis of HD were independent risk factors. Higher radiation doses may augment risk, and pelvic radiation may be protective. Breast cancer screening methodology and frequency, plus the role of prophylaxis in patients with unilateral disease, require definition. (C) 2008 Elsevier Inc. C1 [Muhs, Ann; Constine, Louis S.] Univ Rochester, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. [Basu, Swati K.; Fisher, Susan G.] Univ Rochester, James P Wilmot Canc Ctr, Dept Community & Preventat Med, Rochester, NY 14642 USA. [Constine, Louis S.] Univ Rochester, James P Wilmot Canc Ctr, Dept Pediat, Rochester, NY 14642 USA. [Schwartz, Cindy] Johns Hopkins Univ Hosp, Dept Hematol Oncol, Baltimore, MD 21287 USA. [Hudson, Melissa M.] St Jude Childrens Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. [Kun, Larry E.] St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. [Tarbell, Nancy] Massachusetts Gen Hosp, Dept Pediat Radiat Oncol, Boston, MA 02114 USA. [Marcus, Karen J.; Mauch, Peter] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Mendenhall, Nancy] Univ Florida, Ctr Med, Dept Radiat Oncol, Gainesville, FL USA. RP Constine, LS (reprint author), Univ Rochester, Med Ctr, Dept Radiat Oncol, 601 Elmwood Ave Box 647, Rochester, NY 14642 USA. EM louis_constine@urmc.rochester.edu OI Mendenhall, Nancy/0000-0003-2893-7703 FU NCI NIH HHS [P30 CA021765] NR 43 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2008 VL 72 IS 1 BP 34 EP 40 DI 10.1016/j.ijrobp.2008.04.068 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 341UX UT WOS:000258741700011 PM 18722264 ER PT J AU Rosenthal, DI Catalano, PJ Haller, DG Landry, JC Sigurdson, ER Spitz, FR Benson, AB AF Rosenthal, David I. Catalano, Paul J. Haller, Daniel G. Landry, Jerome C. Sigurdson, Elin R. Spitz, Francis R. Benson, Al B., III TI Phase I study of preoperative radiation therapy with concurrent infusional 5-fluorouracil and oxaliplatin followed by surgery and postoperative 5-fluorouracil plus leucovorin for T3/T4 rectal adenocarcinoma: ECOG E1297 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE rectal cancer; radiation therapy; chemoradiation; oxaliplatin; phase I; dose-escalation study; Eastern Cooperative Oncology Group ID TOTAL MESORECTAL EXCISION; COLORECTAL-CARCINOMA; TUMOR-REGRESSION; CANCER; RADIOTHERAPY; CHEMORADIOTHERAPY; RADIOCHEMOTHERAPY; SURVIVAL; IMPACT; TRIAL AB Purpose: Oxaliplatin is a platinum analog and radiosensitizer active in colorectal cancer. We performed a Phase I trial to test the safety and preliminary efficacy of adding oxaliplatin to standard preoperative chemoradiation therapy for rectal cancer. Methods and Materials: Eligible patients had T3 to T4 rectal adenocarcinoma. Patients received standard-dose radiation (50.4 Gy for 5.5 weeks) with concurrent infused 5-fluorouracil (5-FU) at 200 mg/m(2) per day, 7 days per week. Oxaliplatin was given three times at 14-day intervals at 55,70, or 85 mg/m(2) during the 5.5-week radiation period, before resection. Adjuvant therapy consisted of four cycles of 5-FU (500 mg/m(2) per week) with leucovorin (500 mg/m(2) per week) given every 6 weeks. The main goals were to identify the maximum tolerated dose of oxaliplatin and the dose-limiting toxicities when given with 5-FU and RT. Secondary goals were to determine resectability, pathologic response, sphincter preservation, and overall survival rates. Results: Twenty-one patients were enrolled, 5 at the 55 mg/m(2) oxaliplatin dose level, 5 at 70 mg/m(2), and 11 at 85 mg/m(2). All patients were able to complete the preoperative chemoradiation regimen with no dose adjustments. No dose-limiting toxicities or differences in the type or extent of toxicity were noted among the groups. Nineteen patients underwent surgery (three abdominopelvic resections and 16 low anterior resections), for an 84% sphincter preservation rate. The pathologic complete response rate was 26% (5 patients), and minimal microscopic residual tumor was found in 21% (4 additional patients). Conclusions: Oxaliplatin was well tolerated at 85 mg/m(2) given every 2 weeks in combination with standard preoperative chemoradiation for rectal cancer. The rates of major pathologic response and sphincter preservation are promising. (C) 2008 Elsevier Inc. C1 [Rosenthal, David I.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Unit 97, Houston, TX 77030 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haller, Daniel G.; Spitz, Francis R.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Landry, Jerome C.] Emory Univ, Atlanta, GA 30322 USA. [Sigurdson, Elin R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Benson, Al B., III] Northwestern Univ, Chicago, IL 60611 USA. RP Rosenthal, DI (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Unit 97, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dirosenthal@mdanderson.org FU NCI NIH HHS [U10 CA021115-34, U10 CA066636-15, U10 CA015488-36, U10 CA017145-33, CA21115, CA15488, U10 CA023318-32, U10 CA021115, CA17145, CA27525, CA23318, U10 CA015488, U10 CA027525, U10 CA023318, U10 CA027525-30, U10 CA017145, CA66636, U10 CA066636] NR 26 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2008 VL 72 IS 1 BP 108 EP 113 DI 10.1016/j.ijrobp.2008.05.054 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 341UX UT WOS:000258741700020 PM 18722265 ER PT J AU Jarlskog, CZ Paganetti, H AF Jarlskog, Christina Zacharatou Paganetti, Harald TI Risk of developing second cancer from neutron dose in proton therapy as function of field characteristics, organ, and patient age SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE proton therapy; neutron dose; secondary cancer risk; whole-body phantoms; pediatric radiation oncology ID MODULATED RADIATION-THERAPY; CHILDHOOD-CANCER SURVIVOR; INDUCED 2ND CANCERS; OUT-OF-FIELD; MONTE-CARLO; SECONDARY NEUTRONS; PEDIATRIC-PATIENTS; POOLED ANALYSIS; THYROID-CANCER; SOLID CANCER AB Purpose: To estimate the risk of a second malignancy after treatment of a primary brain cancer using passive scattered proton beam therapy. The focus was on the cancer risk caused by neutrons outside the treatment volume and the dependency on the patient's age. Methods and Materials: Organ-specific neutron-equivalent doses previously calculated for eight different proton therapy brain fields were considered. Organ-specific models were applied to assess the risk of developing solid cancers and leukemia. Results: The main contributors (>80%) to the neutron-induced risk are neutrons generated in the treatment head. Treatment volume can influence the risk by tip to a factor of similar to 2. Young patients are subject to significantly greater risks than are adult patients because of the geometric differences and age dependency of the risk models. Breast cancer should be the main concern for females. For males, the risks of lung cancer, leukemia, and thyroid cancer,were significant for pediatric patients. In contrast, leukemia was the leading risk for an adult. Most lifetime risks were <1 % (70-Gy treatment). The only exceptions were breast, thyroid, and lung cancer for females. For female thyroid cancer, the treatment risk can exceed the baseline risk. Conclusion: The risk of developing a second malignancy from neutrons from proton beam therapy of a brain lesion is small (i.e., presumably outweighed by the therapeutic benefit) but not negligible (i.e., potentially greater than the baseline risk). The patient's age at treatment plays a major role. (C) 2008 Elsevier Inc. C1 [Paganetti, Harald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Jarlskog, Christina Zacharatou] Univ Copenhagen Hosp, Dept Radiat Oncol, DK-2100 Copenhagen, Denmark. RP Jarlskog, CZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM hpaganetti@partners.org FU National Cancer Institute [R01 CA 116743] FX Supported in part by National Cancer Institute Grant R01 CA 116743. NR 44 TC 42 Z9 42 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2008 VL 72 IS 1 BP 228 EP 235 DI 10.1016/j.ijrobp.2008.04.069 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 341UX UT WOS:000258741700035 ER PT J AU Mori, S Chen, GTY AF Mori, Shinichiro Chen, George T. Y. TI Quantification and visualization of charged particle range variations SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE charged particle; four-dimensional computed tomography; 4D-CT; range uncertainty; radiotherapy; respiratory; water equivalent pathlength ID RESPIRATORY MOTION; RADIOTHERAPY; SCANS AB Purpose: Range variations during respiration affect the penetration of charged particle beams and can result in beam overshoot or undershoot to the target. We have developed analysis tools to quantify the water equivalent pathlength (WEL) variations resulting from respiration (WEL analyzer, Aqualyzer), as well as a data explorer to view WEL variations interactively. Methods and Materials: The metrics to characterize and quantify penetration of a charged particle beam during respiration were calculated semiautomatically. The analysis involved the generation of images that (1) encode the radiologic pathlength across a beam's eye view image during the respiratory phase, (2) display the variation of the radiologic pathlength relative to a reference respiratory phase, (3) display isopenetration as a function of breathing, and (4) show range fluctuation images for a compensating bolus when applied to four-dimensional computed tomography. Additional quantities relevant to the analysis of charged particle beams in a breathing patient that are calculated include the beam overshoot volume and beam overshoot distance. These quantities are calculated as a function of time, gantry angle, and position. Results: The software was applied to test cases to illustrate its utility in the analysis of range variations of charged particle beams in the treatment of lung tumors. Conclusion: WEL analysis is useful in the rapid assessment of range variations in the treatment of lung tumors and in determining the optimal gantry angle and respiratory gating window. The extension of encoding range fluctuations to a beam's eye view display is helpful in designing plans that are more robust in the presence of motion. (C) 2008 Elsevier Inc. C1 [Mori, Shinichiro] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mori, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 317, Boston, MA 02114 USA. EM shinshin@nirs.go.jp OI Mori, Shinichiro/0000-0002-0412-4399 FU National Cancer Institute [NCI PO1 CA 19139] FX Supported in part by Grant NCI PO1 CA 19139 front the National Cancer Institute. NR 13 TC 19 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2008 VL 72 IS 1 BP 268 EP 277 DI 10.1016/j.ijrobp.2008.05.011 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 341UX UT WOS:000258741700040 PM 18722277 ER PT J AU Knapp, H Anaya, HD Feld, JE AF Knapp, Herschel Anaya, Henry D. Feld, Jamie E. TI Expanding HIV rapid testing via point-of-care paraprofessionals SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE HIV; screening; health personnel; education; community outreach AB HIV counselling and testing has traditionally been performed by highly trained professionals in clinical settings. With HIV rapid testing, a reliable and easy to use diagnostic tool, paraprofessionals can be trained to administer on-site HIV testing in a variety of non-traditional settings, broadening the HIV detection rates. Our objective was to create a robust and sustainable paraprofessional training module to facilitate off-site HIV rapid testing in non-clinical settings. Trainees attended a series of training sessions involving HIV education, rapid test instructions and communication techniques. After these sessions, trainees competently carried out HIV rapid testing in homeless shelters throughout the Los Angeles county. Agencies motivated to expand HIV screening programmes may use trained paraprofessionals to administer a full range of services (recruitment, pretest counselling, test administration, interpretation of results, post-test counselling and documentation) through this training model and enabling more highly trained healthcare providers to focus efforts on patients identified as HIV-positive. C1 Vet Affairs VA Qual Enhancement Res Initiat HIV &, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, VA Greater Los Angeles Hlth Serv Res & Dev HRS&D, Ctr Study Healthcare Provider Behav, Ctr Excellence, Los Angeles, CA USA. RP Knapp, H (reprint author), 11301 Wilshire Blvd,111G,Bldg 500,Off 4681, Los Angeles, CA 90073 USA. EM Herschel.Knapp@va.gov FU US Department of Veteran's Affairs [RRP: 06-129] FX The authors wish to thank Rini Rajan and Mark Frank for their assistance with the project from which this work derived. This project was funded through a US Department of Veteran's Affairs grant (Implementing an HIV Rapid Testing Pilot Project among Homeless Veterans: RRP: 06-129) awarded to the second author. The OraQuick (R) Advance (TM) Rapid Tests used in this project were donated by OraSure Technologies, Inc. All views are expressly those of the authors and do not necessarily reflect those of the US government or of OraSure Technologies. NR 12 TC 4 Z9 4 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD SEP PY 2008 VL 19 IS 9 BP 629 EP 632 DI 10.1258/ijsa.2008.008027 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 350SZ UT WOS:000259374700012 PM 18725556 ER PT J AU Miksad, RA Zietemann, V Gothe, R Schwarzer, R Conrads-Frank, A Schnell-Inderst, P Stollenwerk, B Siebert, U AF Miksad, Rebecca A. Zietemann, Vera Gothe, Raffaella Schwarzer, Ruth Conrads-Frank, Annette Schnell-Inderst, Petra Stollenwerk, Bjoern Siebert, Uwe TI Progression-free survival as a surrogate endpoint in advanced breast cancer SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE Progression-free survival; Surrogate endpoint; Meta-analytic validation; Advanced breast cancer; Overall survival ID RANDOMIZED PHASE-III; INDIVIDUAL PATIENT DATA; COOPERATIVE-ONCOLOGY-GROUP; FRONT-LINE THERAPY; CLINICAL-TRIALS; 1ST-LINE CHEMOTHERAPY; COMBINATION CHEMOTHERAPY; COMPARING MITOXANTRONE; ESTROGENIC RECRUITMENT; CHEMOHORMONAL THERAPY AB Objectives: Progression-free survival (PFS) has not been validated as a surrogate endpoint for overall survival (OS) for anthracycline (A) and taxane-based (T) chemotherapy in advanced breast cancer (ABC). Using trial-level, meta-analytic approaches, we evaluated PFS as a surrogate endpoint. Methods: A literature review identified randomized, controlled A and T trials for ABC. Progression-based endpoints were classified by prospective definitions. Treatment effects were derived as hazard ratios for PFS (HRPFS) and OS (HROS). Kappa statistic assessed overall agreement. A fixed-effects regression model was used to predict HROS from observed HRPFS, Cross-validation was performed. Sensitivity and subgroup analyses were performed for PFS definition, year of last patient recruitment, line of treatment, and constant rate assumption. Results: Sixteen A and fifteen T trials met inclusion criteria, producing seventeen A (n 4,323) and seventeen T (n = 5,893) trial-arm pairs. Agreement (kappa statistic) between the direction of HROS and HRPFS was 0.71 for A (p = .0029) and 0.75 for T (p = .0028). While HRPFS was a statistically significant predictor of HROS for both A (p = .0019) and T (p = .012), the explained variances were 0.49 (A) and 0.35 (T). In cross-validation, 97 percent of the 95 percent prediction intervals crossed the equivalence line, and the direction of predicted HROS agreed with observed HROS in 82 percent (A) and 76 percent (T). Results were robust in sensitivity and subgroup analyses. Conclusions: This meta-analysis suggests that the trial-level treatment effect on PFS is significantly associated with the trial-level treatment effect on OS. However, prediction of OS based on PFS is surrounded with uncertainty. C1 [Miksad, Rebecca A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol & Oncol,Dept Med, Boston, MA 02215 USA. [Miksad, Rebecca A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Miksad, Rebecca A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Zietemann, Vera; Gothe, Raffaella; Schwarzer, Ruth; Conrads-Frank, Annette; Schnell-Inderst, Petra; Stollenwerk, Bjoern; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Eduard Wallnoefer Ctr 1, Med Decis Making & Hlth Technol Assessment, Dept Publ Hlth, A-6060 Hall In Tirol, Austria. RP Miksad, RA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol & Oncol,Dept Med, Shapiro 9,330 Brookline Ave, Boston, MA 02215 USA. EM rmiksad@bidmc.harvard.edu; public-health@umit.at; public-health@umit.at RI Miksad, Rebecca/B-8066-2009; Stollenwerk, Bjorn/G-5408-2013; OI Miksad, Rebecca/0000-0003-3194-5122 FU NCI NIH HHS [K23 CA139005, R25 CA 92203, R25 CA092203] NR 68 TC 47 Z9 48 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD FAL PY 2008 VL 24 IS 4 BP 371 EP 383 DI 10.1017/S0266462308080495 PG 13 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 362HX UT WOS:000260189900001 PM 18828930 ER PT J AU Michael, I Shmoish, M Walton, DS Levenberg, S AF Michael, Inbal Shmoish, Michael Walton, David S. Levenberg, Shulamit TI Interactions between trabecular meshwork cells and lens epithelial cells: A possible mechanism in infantile aphakic glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CONGENITAL CATARACT-SURGERY; GROWTH-FACTOR; PROTEIN EXPRESSION; AQUEOUS-HUMOR; EYES; COMPLICATIONS; TGF-BETA-2; OUTFLOW; LIBRARY; PATHWAY AB Infantile aphakic glaucoma may develop as a postoperative complication of early childhood cataract surgery. It has been associated with risk factors including surgery in early life and retained lens material; however, its cause and mechanism are poorly understood. This study focused on the potential role of retained lens material (specifically, exposed lens epithelial cells [LECs]) in undesired changes of the trabecular meshwork (TM) structure and function. METHODS. Interactions between LECs and TM cells were studied by analyzing structural changes and differential gene and protein expression in TM cells cocultured with LECs. RESULTS. Subjecting normal TM cells to the presence of LECs resulted in changes in their structural features (such as increase in volume and size, and decrease in cell-cell interactions), as well as in their protein expression (mainly cytoskeletal) and gene expression (such as genes related to organ and cell morphogenesis, inflammatory response, response to stimulus, ion homeostasis, and several signaling pathways). CONCLUSIONS. Many of the changes observed in TM cells after exposure to LECs resemble alternations seen in primary openangle glaucoma. This strengthens the suspected role of LECs in the development of aphakic glaucoma. C1 [Michael, Inbal; Levenberg, Shulamit] Technion Israel Inst Technol, Fac Biomed Engn, Lorry I Lokey Interdisciplinary Ctr Life Sci & En, IL-32000 Haifa, Israel. [Shmoish, Michael] Technion Israel Inst Technol, Bioinformat Knowledge Unit, Lorry I Lokey Interdisciplinary Ctr Life Sci & En, IL-32000 Haifa, Israel. [Walton, David S.] Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. [Walton, David S.] Harvard Univ, Sch Med, Boston, MA USA. RP Levenberg, S (reprint author), Technion Israel Inst Technol, Fac Biomed Engn, Lorry I Lokey Interdisciplinary Ctr Life Sci & En, Silver Bldg,Room 265, IL-32000 Haifa, Israel. EM shulamit@bm.technion.ac.il FU Children's Glaucoma Foundation; Russell Berrie Nanotechnology Institute at the Technion-Israel Institute of Technology FX Supported by the Children's Glaucoma Foundation, and in part by the Russell Berrie Nanotechnology Institute at the Technion-Israel Institute of Technology. NR 39 TC 11 Z9 13 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2008 VL 49 IS 9 BP 3981 EP 3987 DI 10.1167/iovs.08-1674 PG 7 WC Ophthalmology SC Ophthalmology GA 344AB UT WOS:000258896500033 PM 18469193 ER PT J AU Lee, DJ Benson, TE Brown, MC AF Lee, Daniel J. Benson, Thane E. Brown, M. Christian TI Diverse synaptic terminals on rat stapedius motoneurons SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article; Proceedings Paper CT 30th Midwinter Meeting of the Association-for-Research-in-Otolaryngology CY FEB 10-15, 2007 CL Denver, CO SP Assoc Res Otolaryngol DE stapedius muscle; acoustic reflex; vesicle; electron microscopy ID ANTEROVENTRAL COCHLEAR NUCLEUS; SPINAL ALPHA-MOTONEURONS; BUSHY CELL AXONS; TENSOR TYMPANI; GUINEA-PIG; OLIVOCOCHLEAR NEURONS; ACOUSTIC REFLEX; REACTION-PRODUCT; CAT; MUSCLE AB Stapedius motoneurons (SMN) mediate the contraction of the stapedius muscle, which protects the inner ear from injury and reduces the masking effects of background noise. A variety of inputs to SMNs are known to exist, but their terminal ultrastructure has not been investigated. We characterized the synaptic terminals on retrogradely labeled SMNs found just ventromedial to the facial motor nucleus. About 80% of the terminals contained round synaptic vesicles. One type (Sm Rnd) had small, round vesicles filling the terminal with occasional dense core vesicles and formed an asymmetric synapse. Sm Rnd terminals were small with lengths of apposition to the SMN less than 3 mu m. Partial reconstructions from serial sections demonstrated that these terminals formed up to three synapses per terminal. Another terminal type (Lg Rnd) had large, round vesicles and asymmetric synapses. Most Lg Rnd terminals were small but some were extensive, e.g., abutting the SMN for up to 10 mu m. One of these terminals formed at least seven synapses. Another terminal type (Pleo) had pleomorphic vesicles and symmetric active zones that, in some cases, were invaginated by spines from the SMN. A fourth uncommon terminal type (Het Rnd) had round vesicles of heterogeneous sizes and asymmetric synapses. A fifth rare terminal type (Cist) had large, round vesicles and an accompanying subsurface cistern in the SMN. These were generally the same kinds of terminals found on other motoneurons, but the high proportion of round vesicle synapses indicate that SMNs receive mostly excitatory inputs. C1 [Lee, Daniel J.; Benson, Thane E.; Brown, M. Christian] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, Boston, MA 02114 USA. [Lee, Daniel J.] UMass Mem Med Ctr, Dept Otolaryngol, Worcester, MA USA. [Lee, Daniel J.; Brown, M. Christian] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu FU NIDCD NIH HHS [1 K08 DC06285-01, R01 DC001089, K08 DC006285, R01 DC01089] NR 67 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD SEP PY 2008 VL 9 IS 3 BP 321 EP 333 DI 10.1007/s10162-008-0125-z PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 333MC UT WOS:000258155600006 PM 18563488 ER PT J AU Monnelly, EP LoCastro, JS Gagnon, D Young, M Fiore, LD AF Monnelly, Edward P. LoCastro, Joseph S. Gagnon, David Young, Melissa Fiore, Louis D. TI Quetiapine versus trazodone in reducing rehospitalization for alcohol dependence: A large data-base study SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE quetiapine; trazodone; alcohol dependence; rehospitalization; sleep disturbance ID NATIONAL COMORBIDITY SURVEY; DOUBLE-BLIND; ANTIPSYCHOTIC-DRUGS; GENERAL-POPULATION; SLEEP DISTURBANCE; CONTROLLED-TRIAL; SCHIZOPHRENIA; WITHDRAWAL; EFFICACY; PHARMACOTHERAPIES AB Clinicians commonly use nonindicated (or "off-label") medications for the treatment of alcoholism, although there is no clear evidence to Support this practice. Quetiapine and trazodone are 2 medications frequently used in this manner, especially to treat sleep disturbance associated with alcohol withdrawal. Using national administrative data front the Department of Veterans All, airs, we compared the differences among these medications in time to rehospitalization after discharge from in index hospitalization for alcohol dependence. Our outcome measure was the difference in time (weeks) to rehospitalization for patients given medications in 1 of 4 groups: quetiapine alone (median, 6.1 weeks); trazodone alone (median, 10.1 weeks); quetiapine combined (median, 7.1 weeks) and trazodone combined (median, 10.3 weeks) with other frequently used psychotropic drugs. Differences between groups were examined with Cox's proportional hazards regression using trazodone in combination with other medications as the reference category. Crude hazard ratios were determined first and then adjusted for covariates. There was no difference in the risk of rehospitalization when patients using quetiapine in combination were compared with the reference category (hazard ratio [HR] = 1.08; confidence interval [CI] 0.99-1.1 7; P < 0.0936). In contrast, when quetiapine was used alone there was a significantly higher risk of rehospitalization (HR = 1.22; CI = 1.06-1.41; P < 0.005). When trazodone was used alone there was no difference in risk in the unadjusted analysis (HR = 1.05 CI = 0.96-1.14: P < 0.3076): however, the HR increased to a significant level after adjusting for covariates (HR, 1.14: Cl 1.05-1.24 P < 0.0029) and for those with 2+ previous discharges (HR = 1.25; CI = 1.14-1.37; P < 0.0001). These findings suggest the need for additional Studies to better understand what symptoms of alcoholism benefit from the use of these medications, at what dose levels, and with what other medication combinations. C1 [Monnelly, Edward P.; LoCastro, Joseph S.; Gagnon, David; Young, Melissa; Fiore, Louis D.] Vet Affairs VA Boston Healthcare Syst, Boston, MA USA. [Gagnon, David; Young, Melissa; Fiore, Louis D.] MAVERIC, VA Cooperat Studies Program, Boston, MA USA. [Gagnon, David; Young, Melissa; Fiore, Louis D.] MAVERIC, Pharmacoepidemiol Res Grp, Boston, MA USA. [LoCastro, Joseph S.; Gagnon, David; Fiore, Louis D.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Monnelly, Edward P.; LoCastro, Joseph S.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Monnelly, EP (reprint author), VAOPC, 251 Causeway Street, Boston, MA 02114 USA. EM edward.monnelly@med.va.gov FU Health Services Research and Development Service; Cooperative Studies Program; US Department of Veterans Affairs FX This research was supported by the Health Services Research and Development Service, and the Cooperative Studies Program, US Department of Veterans Affairs. NR 39 TC 3 Z9 3 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD SEP PY 2008 VL 2 IS 3 BP 128 EP 134 DI 10.1097/ADM.0b013e318165cb56 PG 7 WC Substance Abuse SC Substance Abuse GA 345GJ UT WOS:000258984000003 PM 21768982 ER PT J AU Mosen, DM Schatz, M Magid, DJ Carnargo, CA AF Mosen, David M. Schatz, Michael Magid, David J. Carnargo, Carlos A., Jr. TI The relationship between obesity and asthma severity and control in adults SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; quality of life; obesity; hospitalization; inhaled; corticosleroids ID BODY-MASS INDEX; QUALITY-OF-LIFE; HEALTH-CARE UTILIZATION; WEIGHT-REDUCTION; ASSOCIATION; PREVALENCE; OVERWEIGHT; TRENDS; WOMEN AB Background: The association of obesity with asthma outcomes is not well understood. Objective: The objective of this study was to examine the association of obesity, as represented by a body mass index (BMI) of greater than 30 kg/m(2), with quality-of-life scores, asthma control problems, and asthma-related hospitalizations. Methods: The study followed a cross-sectional design. Questionnaires were completed at home by a random sample of 1113 members of a large integrated health care organization who were 35 years of age or older with health care use suggestive of active asthma. Outcomes included the mini-Asthma Quality of Life Questionnaire, the Asthma Therapy Assessment Questionnaire, and self-reported asthma-related hospitalization. Several other factors known to influence asthma outcomes also were collected: demographics, smoking status, oral corticosteroid use in the past month, evidence of gastroesophageal reflux disease, and inhaled corticosteroid use in the past month. Multiple logistic regression models were used to measure the association of BMI status with outcomes. Results: Even after adjusting for demographics, smoking status, oral corticosteroid use, evidence of gastroesophageal reflux disease, and inhaled corticosteroid use, obese adults were more likely than those with normal BMIs (<25 k g/m(2)) to report poor asthma-specific quality of life (odds ratio [OR], 2.8; 95% Cl, 1.6-4.9), poor asthma control (OR, 2.7; 95% Cl, 1.7-4.3), and a history of asthma-related hospitalizations (OR, 4.6; 95% Cl, 1.4-14.4). Conclusions: Our findings suggest that obesity is associated with worse asthma outcomes, especially an increased risk of asthma related hospitalizations. C1 [Schatz, Michael] Kaiser Permanente, Dept Allergy, San Diego, CA USA. [Magid, David J.] Kaiser Permanente, Clin Res Unit, Denver, CO USA. [Carnargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mosen, David M.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. RP Mosen, DM (reprint author), Kaiser Permanente NW, Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR USA. EM david.m.mosen@kpchr.org FU National Institutes of Health; Research Foundations; AstraZeneca; Critical Therapeutics; GlaxoSmithKline; Merck; Novartis; Respironics FX M. Schatz has consulting arrangements with GlaxoSmithKline and has received research support from GlaxoSmithKline and Merck. C. A. Camargo has consulting arrangements with AstraZeneca, Novartis, and Critical Therapeutics; is on the advisory board for Dey, Genentech. GlaxoSmithKline. Merck, Novartis, and Schering-Plough: is on the speakers bureau for AstraZeneca, GlaxoSmithKline, and Merck: and has received research support from the National Institutes of Health, Research Foundations. AstraZeneca. Critical Therapeutics. GlaxoSmithKline. Merck. Novartis. and Respironics. The rest of the authors have declared that they have no conflict of interest. NR 27 TC 132 Z9 137 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2008 VL 122 IS 3 BP 507 EP 511 DI 10.1016/j.jaci.2008.06.024 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 348TW UT WOS:000259234000010 PM 18774387 ER PT J AU Castells, MC Tennant, NM Sloane, DE Hsu, FI Barrett, NA Hong, DI Laidlaw, TM Legere, HJ Nallamshetty, SN Palis, RI Rao, JJ Berlin, ST Campos, SM Matulonis, UA AF Castells, Mariana C. Tennant, Nichole M. Sloane, David E. Hsu, F. Ida Barrett, Nora A. Hong, David I. Laidlaw, Tanya M. Legere, Henry J. Nallamshetty, Samridhi N. Palis, Ross I. Rao, Jayanti J. Berlin, Suzanne T. Campos, Susana M. Matulonis, Ursula A. TI Hypersensitivity reactions to chemotherapy: Outcomes and safety of rapid desensitization in 413 cases SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE anaphylaxis; chemotherapy agents; monoclonal antibodies; rapid desensitization; hypersensitivity reactions; carboplatin; paclitaxel; adverse drug reactions ID CARBOPLATIN HYPERSENSITIVITY; OVARIAN-CANCER; PROTOCOL; PACLITAXEL; SKIN; CISPLATIN; ALLERGY; TAXOL; EXPERIENCE AB Background: Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent. Objective: We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol. Methods: Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records. Results: Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective. Conclusions: Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs. C1 [Castells, Mariana C.; Tennant, Nichole M.; Sloane, David E.; Hsu, F. Ida; Barrett, Nora A.; Hong, David I.; Laidlaw, Tanya M.; Legere, Henry J.; Nallamshetty, Samridhi N.; Palis, Ross I.; Rao, Jayanti J.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Berlin, Suzanne T.; Campos, Susana M.; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Castells, MC (reprint author), 1 Jimmy Fund Way,Smith Bldg,Room 626D, Boston, MA 02115 USA. EM mcastells@partners.org FU Ovations for the Cure Desensitization Program; American Academy of Allergy, Asthma Immunology; National Institutes of Health; GlaxoSmithKline; Genentech; Novartis; Ortho-Biotechnology FX Supported by the Ovations for the Cure Desensitization Program.; Disclosure of potential conflict of interest: D. E. Sloane has received honoraria front Genentech F. I. Hsu has served as a coinvestigator for Dyax Corporation and has received a research grant front the American Academy of Allergy, Asthma & Immunology. N. A. Barrett has served as a coinvestigator for the National Institutes of Health and has served as a primary investigator for the American Academy of Allergy, Asthma & Immunology and Altana. D. I. Hong and T M. Laidlaw have received training grant salary from the National Institutes of Health. S. N. Nallamshetty has received training grant salary front the National Institutes of Health and research grants from the American Academy of Allergy, Asthma & Immunology and GlaxoSmithKline. S. M, Campos has served as a research consultant for Genentech and has received research support from Genentech, Novartis. and Ortho-Biotechnology. The rest of the authors have declared that they have no conflict of interest. NR 24 TC 180 Z9 187 U1 1 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2008 VL 122 IS 3 BP 574 EP 580 DI 10.1016/j.jaci.2008.02.044 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 348TW UT WOS:000259234000020 PM 18502492 ER PT J AU Schnyer, R Lao, LX Hammerschlag, R Wayne, P Langevin, HM Napadow, V Harris, R Park, J Milley, R Cohen, M MacPherson, H AF Schnyer, Rosa Lao, Lixing Hammerschlag, Richard Wayne, Peter Langevin, Helene M. Napadow, Vitaly Harris, Richard Park, Jongbae Milley, Ryan Cohen, Misha MacPherson, Hugh TI Society for Acupuncture Research: 2007 Conference Report: "The Status and Future of Acupuncture Research: 10 Years Post-NIH Consensus Conference" SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Editorial Material C1 [Napadow, Vitaly] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Napadow, Vitaly] Harvard Univ, Sch Med, Boston, MA USA. [Schnyer, Rosa; Wayne, Peter] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA USA. [Lao, Lixing] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. [Hammerschlag, Richard; Milley, Ryan] Oregon Coll Oriental Med, Portland, OR USA. [Langevin, Helene M.] Univ Vermont, Dept Neurol, Burlington, VT USA. [Harris, Richard] Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. [Park, Jongbae] Univ N Carolina, Dept Phys Med & Rehabil, Chapel Hill, NC USA. [Cohen, Misha] Quan Yin Healing Arts Ctr, San Francisco, CA USA. [MacPherson, Hugh] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. RP Napadow, V (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Bldg 149,13th St Room 2301 NMR Ctr, Charlestown, MA 02129 USA. EM vitaly@mnr.mgh.harvard.edu RI Lao, Lixing/I-7979-2013; OI Cohen, Misha/0000-0001-6362-6148; MacPherson, Hugh/0000-0003-4255-4768; Lao, Lixing/0000-0003-0198-9714 FU NCCIH NIH HHS [AT00414R13] NR 1 TC 3 Z9 4 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD SEP PY 2008 VL 14 IS 7 BP 859 EP 860 DI 10.1089/acm.2008.SAR-2 PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 363RD UT WOS:000260283500011 PM 18803494 ER PT J AU Napadow, V Ahn, A Longhurst, J Lao, LX Stener-Victorin, E Harris, R Langevin, HM AF Napadow, Vitaly Ahn, Andrew Longhurst, John Lao, Lixing Stener-Victorin, Elisabet Harris, Richard Langevin, Helene M. TI The Status and Future of Acupuncture Mechanism Research SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article; Proceedings Paper CT Annual Conference of the Society-for-Acupuncture-Research CY NOV 09-11, 2007 CL Univ Maryland, Baltimore, MD SP Soc Acupuncture Res, Natl Ctr Complementary Med, NCCAM HO Univ Maryland ID ROSTRAL VENTROLATERAL MEDULLA; IN-VITRO FERTILIZATION; LOW-FREQUENCY ELECTROACUPUNCTURE; MODALITY-RELATED MODULATION; INDUCED POLYCYSTIC OVARIES; FOS PROTEIN EXPRESSION; CARPAL-TUNNEL-SYNDROME; BLOOD-FLOW RESPONSES; CARDIOVASCULAR-RESPONSES; ANTI-HYPERALGESIA AB On November 8-9, 2007, the Society for Acupuncture Research (SAR) hosted an international conference to mark the tenth anniversary of the landmark NIH [National Institutes of Health] Consensus Development Conference on Acupuncture. More than 300 acupuncture researchers, practitioners, students, funding agency personnel, and health policy analysts from 20 countries attended the SAR meeting held at the University of Maryland School of Medicine, Baltimore, MD. This paper summarizes important invited lectures in the area of basic and translational acupuncture research. Specific areas include the scientific assessment of acupuncture points and meridians, the neural mechanisms of cardiovascular regulation by acupuncture, mechanisms for electroacupuncture applied to persistent inflammation and pain, basic and translational research on acupuncture in gynecologic applications, the application of functional neuroimaging to acupuncture research with specific application to carpal-tunnel syndrome and fibromyalgia, and the association of the connective tissue system to acupuncture research. In summary, mechanistic models for acupuncture effects that have been investigated experimentally have focused on the effects of acupuncture needle stimulation on the nervous system, muscles, and connective tissue. These mechanistic models are not mutually exclusive. Iterative testing, expanding, and perhaps merging of such models will potentially lead to an incremental understanding of the effects of manual and electrical stimulation of acupuncture needles that is solidly rooted in physiology. C1 [Napadow, Vitaly] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Napadow, Vitaly] Harvard Univ, Sch Med, Boston, MA USA. [Ahn, Andrew] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA USA. [Longhurst, John] Univ Calif Irvine, Susan Samueli Ctr Integrat Med, Irvine, CA USA. [Lao, Lixing] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. [Stener-Victorin, Elisabet] Univ Gothenburg, Dept Physiol, Inst Neurosci & Physiol, Gothenburg, Sweden. [Harris, Richard] Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. [Langevin, Helene M.] Univ Vermont, Dept Neurol, Burlington, VT USA. RP Napadow, V (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Bldg 149,13th St Room 2301 NMR Ctr, Charlestown, MA 02129 USA. EM vitaly@mnr.mgh.harvard.edu RI Harris, Richard/F-1307-2011; Lao, Lixing/I-7979-2013; OI Stener-Victorin, Elisabet/0000-0002-3424-1502 FU NCCIH NIH HHS [AT01111-01, K01-AT002166, K23-AT00323, P01-AT002048, P01-AT002605, P50-AT00084, R01 AT001415, R13AT004143]; NCRR NIH HHS [M01-RR000042]; NHLBI NIH HHS [R01 HL-63313, HL-72125] NR 78 TC 56 Z9 60 U1 0 U2 17 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD SEP PY 2008 VL 14 IS 7 BP 861 EP 869 DI 10.1089/acm.2008.SAR-3 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 363RD UT WOS:000260283500012 PM 18803495 ER PT J AU Hull, MJ Bierer, MF Griggs, DA Long, WH Nixon, AL Flood, JG AF Hull, Mindy J. Bierer, Michael F. Griggs, David A. Long, William H. Nixon, Andrea L. Flood, James G. TI Urinary buprenorphine concentrations in patients treated with Suboxone (R) as determined by liquid chromatography-mass spectrometry and CEDIA immunoassay SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID PHOTODIODE-ARRAY DETECTION; NORBUPRENORPHINE; CONFIRMATION; PHARMACOKINETICS; QUANTIFICATION; VALIDATION; ELISA; SERUM C1 [Hull, Mindy J.; Griggs, David A.; Long, William H.; Nixon, Andrea L.; Flood, James G.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bierer, Michael F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Bierer, Michael F.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Flood, JG (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. EM jflood@partners.org NR 17 TC 19 Z9 19 U1 1 U2 3 PU PRESTON PUBL INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP PY 2008 VL 32 IS 7 BP 516 EP 521 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 340IA UT WOS:000258638100009 PM 18713521 ER PT J AU Jiang, YD Liang, YF Kacmarek, RM AF Jiang, Yandong Liang, Yafen Kacmarek, Robert M. TI The principle of upper airway unidirectional flow facilitates breathing in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE pursed lip breathing; breathing efficiency; anatomical dead space; respiratory failure; panting ID TRACHEAL GAS INSUFFLATION; OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY DEAD SPACE; LUNG INJURY; TRACHEOSTOMY; VENTILATION; EXCHANGERS; EMPHYSEMA; MECHANICS; EFFICACY AB Upper airway unidirectional breathing, nose in and mouth out, is used by panting dogs to facilitate heat removal via water evaporation from the respiratory system. Why some humans instinctively employ the same breathing pattern during respiratory distress is still open to question. We hypothesized that 1) humans unconsciously perform unidirectional breathing because it improves breathing efficiency, 2) such an improvement is achieved by bypassing upper airway dead space, and 3) the magnitude of the improvement is inversely proportional to the tidal volume. Four breathing patterns were performed in random order in 10 healthy volunteers first with normal breathing effort, then with variable tidal volumes: mouth in and mouth out (MMB); nose in and nose out (NNB); nose in and mouth out (NMB); and mouth in and nose out (MNB). We found that unidirectional breathing bypasses anatomical dead space and improves breathing efficiency. At tidal volumes of similar to 380 ml, the functional anatomical dead space during NMB (81 +/- 31 ml) or MNB (101 +/- 20 ml) was significantly lower than that during MMB (148 +/- 15 ml) or NNB (130 +/- 13 ml) (all P < 0.001), and the breathing efficiency obtained with NMB (78 +/- 9%) or MNB (73 +/- 6%) was significantly higher than that with MMB (61 +/- 6%) or NNB (66 +/- 3%) (all P < 0.001). The improvement in breathing efficiency increased as tidal volume decreased. Unidirectional breathing results in a significant reduction in functional anatomical dead space and improvement in breathing efficiency. We suggest this may be the reason that such a breathing pattern is preferred during respiratory distress. C1 [Liang, Yafen; Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St,Ellison 401, Boston, MA 02114 USA. EM rkacmarek@partners.org FU Massachusetts Technology Transfer Center Investigation Award FX This work has been supported in part by a Massachusetts Technology Transfer Center Investigation Award 2007 to Y. Jiang. NR 22 TC 8 Z9 9 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2008 VL 105 IS 3 BP 854 EP 858 DI 10.1152/japplphysiol.90599.2008 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 345ZT UT WOS:000259038900012 PM 18599676 ER PT J AU Bozic, KJ Rubash, HE Sculco, TP Berry, DJ AF Bozic, Kevin J. Rubash, Harry E. Sculco, Thomas P. Berry, Daniel J. TI An analysis of Medicare payment policy for total joint arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE costs; revision hip; revision knee; outcomes ID TOTAL HIP-ARTHROPLASTY; HOSPITAL COST; REVISION AB Medicare facility payment policy for lower extremity total joint arthroplasty (TJA) has Undergone extensive changes since 2005. The purpose of this Study was to compare patient and procedure characteristics and resource use among TJA procedures and to identify predictors of resource use in TJA. Clinical, demographic, and economic data were analyzed from 6483 primary or revision TJA patients from 4 high-volume centers between October 2005 and June 2006. Descriptive analyses were conducted to evaluate differences between procedure types, and multivariable linear regression analyses were undertaken to identify predictors of resource use. Both patient severity of illness and Surgical complexity influenced resource use associated with TJA procedures. As the primary goal of Medicare payment policy is to set payment rates proportional to relative resource use, both severity of illness and surgical complexity should be incorporated for payment equity and to minimize incentives lot selection bias among hospitals that perform TJA procedures. C1 [Bozic, Kevin J.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Bozic, Kevin J.] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Sculco, Thomas P.] Hosp Special Surg, Dept Orthopaed Surg, New York, NY 10021 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,MU 320W, San Francisco, CA 94143 USA. FU Orthopaedic Research and Education Foundation FX Benefits or funds were received from Orthopaedic Research and Education Foundation. NR 12 TC 30 Z9 30 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2008 VL 23 IS 6 SU 1 BP 133 EP 138 DI 10.1016/j.arth.2008.04.013 PG 6 WC Orthopedics SC Orthopedics GA 349OU UT WOS:000259291000024 PM 18555644 ER PT J AU Gagnon, L Gauthier, C Hoge, RD Lesage, F Selb, J Boas, DA AF Gagnon, Louis Gauthier, Claudine Hoge, Rick D. Lesage, Frederic Selb, Juliette Boas, David A. TI Double-layer estimation of intra- and extracerebral hemoglobin concentration with a time-resolved system SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Biomedical optics; reflectance; optical properties ID NEAR-INFRARED SPECTROSCOPY; TISSUE OPTICAL-PROPERTIES; 2-LAYERED TURBID MEDIA; PHOTON MIGRATION; SCATTERING MEDIA; NONINVASIVE DETERMINATION; REFLECTANCE MEASUREMENTS; CEREBRAL HEMODYNAMICS; DIFFUSE-REFLECTANCE; FOCAL CHANGES AB We present in vivo measurements of baseline physiology from five subjects with a four-wavelength (690, 750, 800, and 850 nm) time-resolved optical system. The measurements were taken at four distances: 10, 15, 25, and 30 mm. All distances were fit simultaneously with a two-layered analytical model for the absorption and reduced scattering coefficient of both layers. The thickness of the first layer, comprising the skin, scalp, and cerebrospinal fluid, was obtained from anatomical magnetic resonance images. The fitting procedure was first tested with simulations before being applied to in vivo measurements and verified that this procedure permits accurate characterization of the hemoglobin concentrations in the extra- and intracerebral tissues. Baseline oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations and oxygen saturation were recovered from in vivo measurements and compared to the literature. We observed a noticeable intersubject variability of the hemoglobin concentrations, but constant values for the cerebral hemoglobin oxygen saturation. (C) 2008 Society of Photo-Optical Instrumentation Engineers. C1 [Gagnon, Louis; Gauthier, Claudine; Hoge, Rick D.; Lesage, Frederic] Ecole Polytech, Inst Genie Biomed, Montreal, PQ H3C 3A7, Canada. [Selb, Juliette; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Gagnon, L (reprint author), Ecole Polytech, Inst Genie Biomed, CP 6079,Succ Ctr Ville, Montreal, PQ H3C 3A7, Canada. EM louis-2.gagnon@polymtl.ca FU Natural Sciences and Engineering Council of Canada (NSERC); National Institutes of Health [P41-RR14075, R01-EB002482]; NSERC Discovery FX L. Gagnon is supported by a postgraduate scholarship from the Natural Sciences and Engineering Council of Canada (NSERC). This work was supported by the National Institutes of Health grants P41-RR14075 and R01-EB002482 and the NSERC Discovery grant. NR 58 TC 34 Z9 34 U1 1 U2 4 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2008 VL 13 IS 5 AR 054019 DI 10.1117/1.2982524 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 384SQ UT WOS:000261764900028 PM 19021399 ER PT J AU Huppert, TJ Diamond, SG Boas, DA AF Huppert, Theodore J. Diamond, Solomon G. Boas, David A. TI Direct estimation of evoked hemoglobin changes by multimodality fusion imaging SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE functional magnetic resonance imaging; near-infrared spectroscopy; diffuse optical tomography; multimodality imaging; Bayesian modeling ID DIFFUSE OPTICAL TOMOGRAPHY; HUMAN VISUAL-CORTEX; NEAR-INFRARED SPECTROSCOPY; CALIBRATED FUNCTIONAL MRI; VASCULAR-SPACE-OCCUPANCY; HUMAN BRAIN-FUNCTION; BALLOON MODEL; BOLD SIGNAL; HEMODYNAMIC-RESPONSE; OXIDATIVE-METABOLISM AB In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI signals. Using numerical simulations, we demonstrate that concurrent optical and BOLD measurements can be used to create cross-calibrated estimates of absolute micromolar deoxyhemoglobin changes. We apply this new analysis tool to experimental data acquired simultaneously with both DOT and BOLD imaging during a motor task, demonstrate the ability to more robustly estimate hemoglobin changes in comparison to DOT alone, and show how this approach can provide cross-calibrated estimates of hemoglobin changes. Using this multimodal method, we estimate the calibration of the 3 tesla BOLD signal to be -0.55% +/- 0.40% signal change per micromolar change of deoxyhemoglobin. (C) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.2976432] C1 [Huppert, Theodore J.] Univ Pittsburgh, UPMC Presbyterian Hosp, Dept Radiol, Pittsburgh, PA 15213 USA. [Huppert, Theodore J.; Diamond, Solomon G.; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Diamond, Solomon G.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Boas, David A.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Huppert, TJ (reprint author), Univ Pittsburgh, UPMC Presbyterian Hosp, Dept Radiol, Rm B804,200 Lothrop St, Pittsburgh, PA 15213 USA. EM huppertt@upmc.edu OI Diamond, Solomon/0000-0002-7589-2942 FU Howard Hughes Medical Institute; National Institutes of Health [R01-EB002482, RO1-EB001954, R01-EB006385, T32-CA09502, P41-RR14075] FX Huppert was funded by the Howard Hughes Medical Institute predoctorial fellowship program. This work was supported by the National Institutes of Health (R01-EB002482, RO1-EB001954, R01-EB006385, T32-CA09502, and P41-RR14075). The authors would like to thank Christiana Andre, Danny Joseph, Div Bolar, and Joe Mandeville, Rick Hoge, and Maria Franceschini for their help in collecting this data. The authors would also like to thank Ville Kolehmainen, Jari Kaipio, and Simon Arridge for useful discussions of this work. NR 82 TC 17 Z9 17 U1 0 U2 5 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2008 VL 13 IS 5 AR 054031 DI 10.1117/1.2976432 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 384SQ UT WOS:000261764900040 PM 19021411 ER PT J AU Laubach, HJ Chang, SK Lee, S Rizvi, I Zurakowski, D Davis, SJ Taylor, CR Hasan, T AF Laubach, Hans-Joachim Chang, Sung K. Lee, Seonkyung Rizvi, Imran Zurakowski, David Davis, Steven J. Taylor, Charles R. Hasan, Tayyaba TI In-vivo singlet oxygen dosimetry of clinical 5-aminolevulinic acid photodynamic therapy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE photodynamic therapy; singlet oxygen; luminescence ID NORMAL HUMAN SKIN; AMINOLEVULINIC ACID; ACTINIC KERATOSIS AB Photodynamic therapy (PDT) is a viable treatment option for a wide range of applications, including oncology, dermatology, and ophthalmology. Singlet oxygen is believed to play a key role in the efficacy of PDT, and on-line monitoring of singlet oxygen during PDT could provide a methodology to establish and customize the treatment dose clinically. This work is the first report of monitoring singlet oxygen luminescence in vivo in human subjects during PDT, demonstrating the correlation of singlet oxygen levels during PDT with the post-PDT photobiological response. (C) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.2981813] C1 [Laubach, Hans-Joachim; Chang, Sung K.; Rizvi, Imran; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lee, Seonkyung; Davis, Steven J.] Phys Sci Inc, Div Appl Sci, Andover, MA 01810 USA. [Rizvi, Imran] Dartmouth Coll, Dept Engn Sci, Hanover, NH 03755 USA. [Zurakowski, David] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Taylor, Charles R.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Laubach, HJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@partners.org OI Rizvi, Imran/0000-0001-9673-4700 FU NIH SBIR Phase II [R44 CA096243]; NIH [P01 CA84203] FX This work was supported by NIH SBIR Phase II grant R44 CA096243 and in part by NIH grant P01 CA84203. We also thank Oleg Akilov, Mehron Puoris'haag, Fernanda Sakamoto, and Kana Watanabe for evaluating the phototoxic response from the clinical photographs. NR 13 TC 26 Z9 29 U1 1 U2 11 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2008 VL 13 IS 5 AR 050504 DI 10.1117/1.2981813 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 384SQ UT WOS:000261764900004 PM 19021376 ER PT J AU Nadkarni, SK Bouma, BE Yelin, D Gulati, A Tearney, GJ AF Nadkarni, Seemantini K. Bouma, Brett E. Yelin, Dvir Gulati, Amneet Tearney, Guillermo J. TI Laser speckle imaging of atherosclerotic plaques through optical fiber bundles SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Biomedical optics; speckle; fiber optics; atherosclerosis; intracoronary; catheter ID VULNERABLE PLAQUES; THERMOGRAPHY AB Laser speckle imaging (LSI), a new technique that measures an index of plaque viscoelasticity, has been investigated recently to characterize atherosclerotic plaques. These prior studies demonstrated the diagnostic potential of LSI for detecting high-risk plaques and were conducted ex vivo. To conduct intracoronary LSI in vivo, the laser speckle pattern must be transmitted from the coronary wall to the image detector in the presence of cardiac motion. Small-diameter, flexible optical fiber bundles, similar to those used in coronary angioscopy, may be incorporated into an intravascular catheter for this purpose. A key challenge is that laser speckle is influenced by inter-fiber leakage of light, which may be exacerbated during bundle motion. In this study, we tested the capability of optical fiber bundles to transmit laser speckle patterns obtained from atherosclerotic plaques and evaluated the influence of motion on the diagnostic accuracy of fiber bundle-based LSI. Time-varying helium-neon laser speckle images of aortic plaques were obtained while cyclically moving the flexible length of the bundle to mimic coronary motion. Our results show that leached fiber bundles may reliably transmit laser speckle images in the presence of cardiac motion, providing a viable option to conduct intracoronary LSI. (C) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.2982529] C1 [Nadkarni, Seemantini K.; Bouma, Brett E.; Yelin, Dvir; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Nadkarni, Seemantini K.; Bouma, Brett E.; Yelin, Dvir; Gulati, Amneet; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Nadkarni, SK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, BAR 718,40 Blossom St, Boston, MA 02114 USA. EM snadkarni@hms.harvard.edu FU NHLBI NIH HHS [R01 HL119867, R21 HL088306, R21 HL088306-01A1] NR 11 TC 21 Z9 22 U1 0 U2 6 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2008 VL 13 IS 5 AR 054016 DI 10.1117/1.2982529 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 384SQ UT WOS:000261764900025 PM 19021396 ER PT J AU Oh, JW Feldman, MD Kim, J Sanghi, P Do, D Mancuso, JJ Kemp, N Cilingiroglu, M Milner, TE AF Oh, Junghwan Feldman, Marc D. Kim, Jihoon Sanghi, Pramod Do, Dat Mancuso, J. Jacob Kemp, Nate Cilingiroglu, Mehmet Milner, Thomas E. TI Detection of macrophages in atherosclerotic tissue using magnetic nanoparticles and differential phase optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE differential phase optical coherence tomography; macrophages; iron oxide nanoparticles; atherosclerosis; inflammation; vulnerable plaque; MIONs ID IN-VIVO; INTRAVASCULAR ULTRASOUND; VULNERABLE PLAQUE; IRON-OXIDE; MICROSCOPY; CONTRAST; REFLECTOMETRY; DISEASE AB We demonstrate the detection of iron oxide nanoparticles taken up by macrophages in atherosclerotic plaque with differential phase optical coherence tomography (DP-OCT). Magneto mechanical detection of nanoparticles is demonstrated in hyperlipidemic Watanabe and balloon-injured fat-fed New Zealand white rabbits injected with monocrystalline iron oxide nanoparticles (MIONs) of <40 nm diam. MIONs taken up by macrophages was excited by an oscillating magnetic flux density and resulting nanometer tissue surface displacement was detected by DP-OCT. Frequency response of tissue surface displacement in response to an externally applied magnetic flux density was twice the stimulus frequency as expected from the equations of motion for the nanoparticle cluster. (C) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.2985762] C1 [Oh, Junghwan; Feldman, Marc D.; Kim, Jihoon; Kemp, Nate; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Oh, Junghwan] Pukyong Natl Univ, Dept Mech Engn, Pusan 608739, South Korea. [Feldman, Marc D.; Sanghi, Pramod; Do, Dat; Mancuso, J. Jacob; Cilingiroglu, Mehmet] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Feldman, Marc D.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Feldman, MD (reprint author), Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. EM feldmanm@uthscsa.edu FU Veterans Administration FX This work was supported by a Veterans Administration Merit Grant to Dr. Marc D. Feldman. NR 36 TC 13 Z9 13 U1 0 U2 5 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2008 VL 13 IS 5 AR 054006 DI 10.1117/1.2985762 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 384SQ UT WOS:000261764900015 PM 19021386 ER PT J AU Ambrogini, E O'Brien, CA Martin-Millan, M Paik, J DePinho, RA Han, L Warren, A Shelton, RS Qui, X Goellner, J Jilka, RL Almeida, M Marrolagas, SC AF Ambrogini, E. O'Brien, C. A. Martin-Millan, M. Paik, J. DePinho, R. A. Han, L. Warren, A. Shelton, R. S. Qui, X. Goellner, J. Jilka, R. L. Almeida, M. Marrolagas, S. C. TI Loss or Gain of FoxO Function in Osteoclasts and Osteoblasts Alters the Rate of Apoptosis and BMD in Mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Ambrogini, E.; O'Brien, C. A.; Martin-Millan, M.; Han, L.; Warren, A.; Shelton, R. S.; Qui, X.; Goellner, J.; Jilka, R. L.; Almeida, M.; Marrolagas, S. C.] Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. [Paik, J.; DePinho, R. A.] Harvard Univ, Sch Med, Ctr Appl Canc Sci, Boston, MA USA. [Paik, J.; DePinho, R. A.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Dept Med, Boston, MA USA. [Paik, J.; DePinho, R. A.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S70 EP S70 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000248 ER PT J AU Aydin, C Mahon, MJ Bastepe, K AF Aydin, C. Mahon, M. J. Bastepe, K. TI The N-Terminally Extended XL alpha s (XXL alpha s) Acts as a Novel Heterotrimeric G Protein Subunit with an Ability to Transduce Receptor Activation into Intracellular Signaling SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S104 EP S104 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000372 ER PT J AU Bai, X Wang, D Luan, Y Kobayashi, T Kronenberg, HM Liu, C AF Bai, X. Wang, D. Luan, Y. Kobayashi, T. Kronenberg, H. M. Liu, C. TI ADAMTS-7, A Direct Targeting Molecule of PTHrP, Is a Novel Potent Mediator of Chondrogenesis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Bai, X.; Wang, D.; Luan, Y.; Liu, C.] NYU, New York, NY USA. [Kobayashi, T.; Kronenberg, H. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S73 EP S73 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000263 ER PT J AU Bergwitz, C Jaureguiberry, G Kremke, B Page, K Hiort, O Carpenter, T Insogna, K Forman, S Juppner, H AF Bergwitz, C. Jaureguiberry, G. Kremke, B. Page, K. Hiort, O. Carpenter, T. Insogna, K. Forman, S. Jueppner, H. TI The Human SLC34A3/NaPi-IIc Mutations T137M and L527del Uncouple Sodium-phosphate Co-transport SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Bergwitz, C.; Jaureguiberry, G.; Jueppner, H.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kremke, B.; Hiort, O.] Univ Klinikum Schleswig Holstein, D-23538 Lubeck, Germany. [Page, K.; Insogna, K.] Yale Univ, Sch Med, Endocrine Unit, New Haven, CT USA. [Carpenter, T.] Yale Univ, Dept Pediat, Sch Med, New Haven, CT 06520 USA. [Carpenter, T.] Yale Univ, Sch Med, Endocrine Unit, New Haven, CT USA. [Forman, S.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S127 EP S127 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000454 ER PT J AU Bischoff, DS Makhijani, NS Yamaguchi, DT AF Bischoff, D. S. Makhijani, N. S. Yamaguchi, D. T. TI Transient Expression of CXC Receptor 2 in Human Mesenchymal Stem Cells Stimulates Chemotaxis Toward CXC Ligand 8 and increased Mineralization in the Presence of Osteogenic Medium SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Bischoff, D. S.; Makhijani, N. S.; Yamaguchi, D. T.] VA Greater Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S167 EP S167 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000598 ER PT J AU Burnett-Bowie, SM Henao, MP Dere, ME Lee, H Leder, BZ AF Burnett-Bowie, S. M. Henao, M. P. Dere, M. E. Lee, H. Leder, B. Z. TI Effects of hPTH(1-34) Infusion on Circulating Serum Phosphate, 1,25-dihydroxyvitamin D and FGF-23 Levels in Healthy Men. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Burnett-Bowie, S. M.; Henao, M. P.; Dere, M. E.; Lee, H.; Leder, B. Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S282 EP S282 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001434 ER PT J AU Burnett-Bowie, SM Leder, BZ Henao, MP Mendoza, NT Finkelstein, JS AF Burnett-Bowie, S. M. Leder, B. Z. Henao, M. P. Mendoza, N. T. Finkelstein, J. S. TI The Effect of Treating Vitamin D Deficiency on FGF23 Levels in Humans SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Burnett-Bowie, S. M.; Leder, B. Z.; Henao, M. P.; Mendoza, N. T.; Finkelstein, J. S.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S174 EP S174 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001024 ER PT J AU Cackowski, FC Choksi, RJ Windle, JJ Roodman, D AF Cackowski, F. C. Choksi, R. J. Windle, J. J. Roodman, D. TI Angiogenic Potential of Osteoclasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Cackowski, F. C.; Choksi, R. J.; Roodman, D.] Univ Pittsburgh, Pittsburgh, PA USA. [Windle, J. J.] Virginia Commonwealth Univ, Richmond, VA USA. [Roodman, D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S261 EP S261 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001342 ER PT J AU Chillambhi, S Turan, S Hwang, D Chen, H Juppner, H Bastepe, M AF Chillambhi, S. Turan, S. Hwang, D. Chen, H. Jueppner, H. Bastepe, M. TI Deletion of the GNAS Antisense Transcript Results in Parent-Of-Origin Specific GNAS Imprinting Defects and Phenotypes Including PTH-H-Resistance. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Chillambhi, S.; Turan, S.; Jueppner, H.; Bastepe, M.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Chillambhi, S.; Turan, S.; Jueppner, H.; Bastepe, M.] Harvard Univ, Sch Med, Boston, MA USA. [Hwang, D.; Chen, H.] Kaohsiung Med Univ, Dept Nephrol, Kaohsiung, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S16 EP S16 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000053 ER PT J AU Conen, KL Nishimori, S Provot, S Kronenberg, HM AF Conen, K. L. Nishimori, S. Provot, S. Kronenberg, H. M. TI Overexpression of the Transcriptional Cofactor Lbh Impaires Angiogenesis and Endochondral Bone Formation During Fetal Bone Development in Chickens SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Conen, K. L.; Nishimori, S.; Kronenberg, H. M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Provot, S.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S244 EP S244 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001272 ER PT J AU Divieti, PP Powell, WF Kobayashi, T Harris, S Bringhurst, F AF Divieti, P. P. Powell, W. F. Kobayashi, T. Harris, S. Bringhurst, F. TI Target Ablation of PTH/PTHrP Receptor (PPR) in Osteocytes Induces Hypocalcemia and Impairs Bone Structure SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Divieti, P. P.; Powell, W. F.; Kobayashi, T.; Bringhurst, F.] Harvard Univ, Sch Med, Mass Gen Hosp, Endocrine Unit, Boston, MA USA. [Harris, S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S45 EP S45 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000159 ER PT J AU Finkelstein, JS Burnett-Bowie, SN Moore, AF Jones, BF Borges, LF Youngner, JM Hahn, CW Barry, CV Leder, BZ AF Finkelstein, J. S. Burnett-Bowie, S. N. Moore, A. F. Jones, B. F. Borges, L. F. Youngner, J. M. Hahn, C. W. Barry, C. V. Leder, B. Z. TI Toward a Physiologically-Based Definition of Hypogonadism in Men: Dose-Response Relationship Between Testosterone and Bone Resorption SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Finkelstein, J. S.; Burnett-Bowie, S. N.; Moore, A. F.; Jones, B. F.; Borges, L. F.; Youngner, J. M.; Hahn, C. W.; Barry, C. V.; Leder, B. Z.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S30 EP S30 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000103 ER PT J AU Gamer, L Tuji, K Cox, K Gagari, E Beppu, H Rosen, V AF Gamer, L. Tuji, K. Cox, K. Gagari, E. Beppu, H. Rosen, V. TI BMPR2 Is Dispensable for Formation of the Limb Skeleton. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Gamer, L.; Tuji, K.; Cox, K.; Gagari, E.; Rosen, V.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Beppu, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S276 EP S277 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001411 ER PT J AU Gori, F Demay, MB AF Gori, F. Demay, M. B. TI Wdr5 is Required for Chromatin Modifications at the Runx-2 Promoter. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Gori, F.; Demay, M. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S383 EP S383 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002176 ER PT J AU Grbic, J Black, D Lyles, K Reid, D Bucci-Rechtweg, C Mesenbrink, P Orwoll, E Eriksen, E AF Grbic, J. Black, D. Lyles, K. Reid, D. Bucci-Rechtweg, C. Mesenbrink, P. Orwoll, E. Eriksen, E. TI Osteonecrosis of the Jaw: Zoledronic Acid 5 mg Experience in a Variety of Osteoporosis Indications SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Grbic, J.] Columbia Univ, Coll Dent Med, New York, NY USA. [Black, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lyles, K.] VA Med Ctr, Durham, NC USA. [Reid, D.] Univ Aberdeen, Aberdeen, Scotland. [Bucci-Rechtweg, C.; Mesenbrink, P.] Novartis Pharmaceut, New Jersey, NJ USA. [Orwoll, E.] Portland VA Med Ctr, Portland, OR USA. [Eriksen, E.] Novartis Pharma AG, Basel, Switzerland. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S69 EP S69 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000247 ER PT J AU Guo, J Liu, M Yang, D Thomas, CC Schipani, E Bringhurst, FR Kronenberg, HM AF Guo, J. Liu, M. Yang, D. Thomas, C. C. Schipani, E. Bringhurst, F. R. Kronenberg, H. M. TI Suppression of Canonical wnt Signaling by Dkk1 Attenuates PTH-mediated Peritrabecular Stromal Cell Response and New Bone Formation in a Model of Secondary Hyperparathyroidism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S102 EP S103 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000367 ER PT J AU Hirai, T Chagin, AS Kobayashi, T Mackem, S Kronenberg, HM AF Hirai, T. Chagin, A. S. Kobayashi, T. Mackem, S. Kronenberg, H. M. TI Postnatal Deletion of PTH/PTHrP Receptor in Growth Plate Chondrocytes Leads to Growth Plate Fusion SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S95 EP S95 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000340 ER PT J AU Hiruma, Y Kurihara, N Zhou, H Subler, MA Dempster, DW Windle, JJ Roodman, GD AF Hiruma, Y. Kurihara, N. Zhou, H. Subler, M. A. Dempster, D. W. Windle, J. J. Roodman, G. D. TI Co-Expression of p62(P392L) and MVNP in Osteoclasts (OCL) precursors Increases the Formation of OCL that Express a Pagetic phenotype SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Hiruma, Y.; Kurihara, N.; Roodman, G. D.] Univ Pittsburgh, Pittsburgh, PA USA. [Zhou, H.; Dempster, D. W.] Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA. [Subler, M. A.; Windle, J. J.] Virginia Commonwealth Univ, Richmond, VA USA. [Roodman, G. D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S127 EP S127 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000456 ER PT J AU Hiruma, Y Kurihara, N Zhou, H Subler, MA Dempster, DW Windle, JJ Roodman, GD AF Hiruma, Y. Kurihara, N. Zhou, H. Subler, M. A. Dempster, D. W. Windle, J. J. Roodman, G. D. TI High Levels of IL-6 and Hyper-responsivity to 1,25-(OH)(2) D-3 Are Both Required for Development of Pagetic Osteoclasts (PD-OCL) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Hiruma, Y.; Kurihara, N.; Roodman, G. D.] Univ Pittsburgh, Pittsburgh, PA USA. [Zhou, H.; Dempster, D. W.] Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA. [Subler, M. A.; Windle, J. J.] Virginia Commonwealth Univ, Richmond, VA USA. [Roodman, G. D.] VA Pittsburgh Healthcare System, Pittsburgh, PA 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 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S128 EP S128 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000457 ER PT J AU Hiruma, Y Ishizuka, S Roodman, GD Kurihara, N AF Hiruma, Y. Ishizuka, S. Roodman, G. D. Kurihara, N. TI The Rapid-Nontransriptional Action of 1,25-(OH)(2)D-3 Induces IL-6 Production in Osteoclast Precursors Expressin Measles Virus Nucleocapsid Protein (MVNP) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Hiruma, Y.; Roodman, G. D.; Kurihara, N.] Univ Pittsburgh, Pittsburgh, PA USA. [Roodman, G. D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ishizuka, S.] Teijin Inst Biomed Res, Tokyo, Japan. 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 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S53 EP S53 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000187 ER PT J AU Huang, W Jarrahy, R Rudkin, GH Yamaguchi, DT Miller, TA AF Huang, W. Jarrahy, R. Rudkin, G. H. Yamaguchi, D. T. Miller, T. A. TI Synergistic Activation of Osteogenesis in Multi-Lineage Progenitor Cells by Oxysterols SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Huang, W.; Jarrahy, R.; Rudkin, G. H.; Yamaguchi, D. T.; Miller, T. A.] VA Greater LA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S252 EP S252 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001305 ER PT J AU Jones, MD Liu, JC Schoonmaker, J Barthel, TK Mulay, S Bouxsein, ML Stein, GS Mukherjee, S Lian, JB AF Jones, M. D. Liu, J. C. Schoonmaker, J. Barthel, T. K. Mulay, S. Bouxsein, M. L. Stein, G. S. Mukherjee, S. Lian, J. B. TI Bortezomib, a Proteasome Inhibitor, Prevents Metastatic Breast Cancer Osteolysis and Reduces Mammary Fat Pad Tumor Growth in Mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Jones, M. D.] Univ Massachusetts, Sch Med, Dept Orthoped & Phys Rehabil, Worcester, MA USA. [Liu, J. C.; Barthel, T. K.; Stein, G. S.; Mukherjee, S.; Lian, J. B.] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. [Liu, J. C.; Barthel, T. K.; Stein, G. S.; Mukherjee, S.; Lian, J. B.] Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA USA. [Schoonmaker, J.; Mulay, S.; Bouxsein, M. L.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Schoonmaker, J.; Mulay, S.; Bouxsein, M. L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S108 EP S108 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000388 ER PT J AU Kashiwagi, A Schipani, E Greer, PA McMahon, AP Shimada, M AF Kashiwagi, A. Schipani, E. Greer, P. A. McMahon, A. P. Shimada, M. TI Impact of Calpain Inhibition on Chondrocyte Development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Kashiwagi, A.; Schipani, E.; Shimada, M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kashiwagi, A.; Schipani, E.; Shimada, M.] Harvard Univ, Sch Med, Boston, MA USA. [Greer, P. A.] Queens Univ, Canc Res Inst, Kingston, ON, Canada. [McMahon, A. P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S410 EP S411 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002287 ER PT J AU Kiel, DP Hannan, MT Barton, BA Lang, TF Bouxsein, ML Brown, K Shane, E Magaziner, J Zimmerman, S Harris, T Rubin, CT AF Kiel, D. P. Hannan, M. T. Barton, B. A. Lang, T. F. Bouxsein, M. L. Brown, K. Shane, E. Magaziner, J. Zimmerman, S. Harris, T. Rubin, C. T. TI The "Vibes" Trial: Low Magnitude Mechanical Stimulation (LMMS) to Improve Bone Mineral Density (BMD). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Kiel, D. P.; Hannan, M. T.] Hebrew Rehab Ctr, IFAR, Boston, MA USA. [Barton, B. A.; Brown, K.] Maryland Med Res Inst, Baltimore, MD USA. [Lang, T. F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bouxsein, M. L.] BIDMC, Ortho Biomech Lab, Boston, MA USA. [Shane, E.] Columbia Univ, New York, NY USA. [Magaziner, J.] Univ MD, Baltimore, MD USA. [Zimmerman, S.] UNC, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. [Harris, T.] NIA, Washington, DC USA. [Rubin, C. T.] SUNY Stony Brook, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S474 EP S474 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002531 ER PT J AU Krum, SA Brown, M AF Krum, S. A. Brown, M. TI Cell Type Specific Regulation of Transcription by Estrogen. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Krum, S. A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Brown, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI krum, susan/D-7282-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S285 EP S285 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001444 ER PT J AU Kurihara, N Hiruma, Y Lorenzo, JA Roodman, GD AF Kurihara, N. Hiruma, Y. Lorenzo, J. A. Roodman, G. D. TI 1,25-dihydroxyvitamin D-3 Can Directly Induce Osteoclast Formation in Osteoclast Precursors in the Absence of RANKL SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Kurihara, N.; Hiruma, Y.; Roodman, G. D.] Univ Pittsburgh, Pittsburgh, PA USA. [Lorenzo, J. A.] Univ Connecticut, Farmington, CT USA. [Roodman, G. D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S259 EP S259 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001337 ER PT J AU Leder, BZ Dere, M Burnett-Bowie, SM AF Leder, B. Z. Dere, M. Burnett-Bowie, S. M. TI Effects of Aromatase Inhibitor Therapy on Bone Mineral Density in Hypogonadal Elderly Men SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Leder, B. Z.; Dere, M.; Burnett-Bowie, S. M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S39 EP S39 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000136 ER PT J AU Liu, F Gan, B Guan, J AF Liu, F. Gan, B. Guan, J. TI The Role of FIP200 in Osteoblast Differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Liu, F.] Univ Michigan, Sch Dent, BMS Dept, Ann Arbor, MI 48109 USA. [Gan, B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Guan, J.] Univ Michigan, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S396 EP S396 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002228 ER PT J AU Lu, G Hiruma, Y Cackowski, F Boykin, C Patrene, K Anderson, JL Del Prete, D Windle, JJ Roodman, GD AF Lu, G. Hiruma, Y. Cackowski, F. Boykin, C. Patrene, K. Anderson, J. L. Del Prete, D. Windle, J. J. Roodman, G. D. TI High Dose of RANKL Rescues Integrin alpha(-/-)(9) Osteoclast Phenotype SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Lu, G.; Hiruma, Y.; Cackowski, F.; Patrene, K.; Anderson, J. L.; Del Prete, D.; Roodman, G. D.] Univ Pittsburgh, Pittsburgh, PA USA. [Boykin, C.; Windle, J. J.] Virginia Commonwealth Univ, Richmond, VA USA. [Roodman, G. D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S92 EP S92 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000328 ER PT J AU Luderer, HF Demay, MB AF Luderer, H. F. Demay, M. B. TI Characterization of Interactions Between the Unliganded VDR and Effectors of the Canonical Wnt Signaling Pathway SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S52 EP S52 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000184 ER PT J AU Mandal, CC Ghosh-Choudhury, N AF Mandal, C. C. Ghosh-Choudhury, N. TI Simvastatin Induces Wnt Signaling and Reduces CSF-1 Secretion and RANKL/OPG Ratio to Block Osteoclast Differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Mandal, C. C.; Ghosh-Choudhury, N.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ghosh-Choudhury, N.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S266 EP S266 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001363 ER PT J AU Mandal, CC Choudhury, GG Ghosh-Choudhury, N AF Mandal, C. C. Choudhury, G. G. Ghosh-Choudhury, N. TI BMP-2 Stimulates a Feedback Activation loop for Expression of NFATc1 in Osteoblasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Mandal, C. C.; Choudhury, G. G.; Ghosh-Choudhury, N.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Choudhury, G. G.; Ghosh-Choudhury, N.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S86 EP S86 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000302 ER PT J AU Mannstadt, M Lorente, C Juppner, H AF Mannstadt, M. Lorente, C. Jueppner, H. TI Rapid Detection of Intact FGF-23 in Tumor Tissue from Patients with Oncogenic Osteomalacia SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Mannstadt, M.; Jueppner, H.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Lorente, C.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Lorente, C.] Harvard Vanguard Med Associates, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S173 EP S173 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001021 ER PT J AU Mannstadt, M Pulusani, SR Silve, C Jueppner, H AF Mannstadt, M. Pulusani, S. R. Silve, C. Jueppner, H. TI Dominant-negative GCMB Mutants Causing Autosomal-Dominant Hypoparathyroidism - Protein Expression and Cellular Localization SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Mannstadt, M.; Pulusani, S. R.; Jueppner, H.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Silve, C.] Univ Paris 05, Hop St Vincent de Paul, INSERM, U561,UFR Med, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S177 EP S177 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001033 ER PT J AU McDonough, AK Teng, GG Abott, J Nair, R Amling, C Colli, J Fiveash, JB Lopez, R Urban, D Curtis, JR Saag, K AF McDonough, A. K. Teng, G. G. Abott, J. Nair, R. Amling, C. Colli, J. Fiveash, J. B. Lopez, R. Urban, D. Curtis, J. R. Saag, K. TI Effects of Androgen Deprivation Therapy on Bone Health in Prostate Cancer SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [McDonough, A. K.; Abott, J.; Nair, R.; Curtis, J. R.; Saag, K.] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Teng, G. G.] Natl Univ Singapore Hosp, Div Rheumatol, Singapore 117548, Singapore. [Amling, C.; Urban, D.] Univ Alabama Birmingham, Div Urol, Birmingham, AL USA. [Colli, J.] Birmingham VA Med Ctr, Birmingham, AL USA. [Fiveash, J. B.] Univ Alabama Birmingham, Dept Radiat Oncol, Birmingham, AL USA. [Lopez, R.] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S187 EP S187 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001070 ER PT J AU Miclea, RL Robanus-Maandag, FC Bosch, CAJ Kobayashi, T Kronenberg, HM Rawadi, G Lowik, CWGM Fodde, R Wit, JM Karperien, M AF Miclea, R. L. Robanus-Maandag, F. C. Bosch, C. A. J. Kobayashi, T. Kronenberg, H. M. Rawadi, G. Loewik, C. W. G. M. Fodde, R. Wit, J. M. Karperien, M. TI Apc-mediated Control of beta-catenin Is Essential for Both Chondrogenic and Osteogenic Differentiation of Skeletal Precursors SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Miclea, R. L.; Robanus-Maandag, F. C.; Bosch, C. A. J.; Loewik, C. W. G. M.; Wit, J. M.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Kobayashi, T.; Kronenberg, H. M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Rawadi, G.] Galapagos, Romainville, France. [Fodde, R.] Erasmus MC, Josephine Nefkens Inst, Rotterdam, Netherlands. [Karperien, M.] Univ Twente, Inst Biomed Technol, NL-7500 AE Enschede, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S159 EP S159 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000567 ER PT J AU Morse, LR Solomon, B Stashenko, P Battaglino, RA AF Morse, L. R. Solomon, B. Stashenko, P. Battaglino, R. A. TI Immediate Abnormalities at the Chondro-Osseous Junction due to Severe Spinal Cord Injury in Growing Rats SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Morse, L. R.] Harvard Univ, Sch Med, Boston, MA USA. [Solomon, B.; Stashenko, P.; Battaglino, R. A.] Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S232 EP S232 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001231 ER PT J AU Nagai, S Mahon, M Okazaki, N Potts, JT Juppner, H Gardella, T AF Nagai, S. Mahon, M. Okazaki, N. Potts, J. T. Jueppner, H. Gardella, T. TI Selective Removal of PLC Signaling in Novel PTH (1-28) Analogs Abolishes Regulation of NaPi-IIc but not Napi-IIa. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Nagai, S.; Mahon, M.; Okazaki, N.; Potts, J. T.; Jueppner, H.; Gardella, T.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S419 EP S419 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002323 ER PT J AU Nakamoto, T Mizoguchi, F Izu, Y Hayata, T Ezura, Y Mathis, D Benoist, C Miyasaka, N Noda, M AF Nakamoto, T. Mizoguchi, F. Izu, Y. Hayata, T. Ezura, Y. Mathis, D. Benoist, C. Miyasaka, N. Noda, M. TI Deficiency of the Nucleocytoplasmic Shuttling Protein CIZ Suppresses K/BxN Serum-Induced Model of Rheumatoid Arthritis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Nakamoto, T.; Mizoguchi, F.; Izu, Y.; Hayata, T.; Ezura, Y.; Miyasaka, N.; Noda, M.] Tokyo Med & Dent Univ, Tokyo, Japan. [Mathis, D.; Benoist, C.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S487 EP S487 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002580 ER PT J AU Nishimori, S Kobayashi, T Kronenberg, HM AF Nishimori, S. Kobayashi, T. Kronenberg, H. M. TI Gene Expression Profiling within Murine Growth Plates Using DNA Microarrays. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Nishimori, S.; Kobayashi, T.; Kronenberg, H. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S412 EP S412 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002293 ER PT J AU O'Brien, CA Galli, C Plotkin, L Vyas, K Cazer, P Goellner, JJ Berryhill, S Webb, W Robling, A Bouxsein, M Schipani, E Turner, CH Weinstein, RS Jilka, RL Manolagas, SC Bellido, TM AF O'Brien, C. A. Galli, C. Plotkin, L. Vyas, K. Cazer, P. Goellner, J. J. Berryhill, S. Webb, W. Robling, A. Bouxsein, M. Schipani, E. Turner, C. H. Weinstein, R. S. Jilka, R. L. Manolagas, S. C. Bellido, T. M. TI PTH Receptor Signaling in Osteocytes Increases Bone Mass and the Rate of Bone Remodeling Through Wnt/LRP5-dependent and -independent Mechanisms, Respectively SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [O'Brien, C. A.; Galli, C.; Plotkin, L.; Vyas, K.; Cazer, P.; Goellner, J. J.; Berryhill, S.; Webb, W.; Weinstein, R. S.; Jilka, R. L.; Manolagas, S. C.; Bellido, T. M.] Univ Arkansas Med Sci, Dept Internal Med, Little Rock, AR 72205 USA. [Robling, A.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Bouxsein, M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Schipani, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Turner, C. H.] Indiana Univ, Sch Med, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S12 EP S12 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000039 ER PT J AU Ohishi, M Chiusaroli, R Asuncion, F Ominsky, M Kostenuik, P Schipani, E AF Ohishi, M. Chiusaroli, R. Asuncion, F. Ominsky, M. Kostenuik, P. Schipani, E. TI OPG and Bispbosphonates Had Differential Effects on Osteoclast Numbers, Bone Marrow Fibrosis and Cortical Porosity in a Mouse Model of Constitutive Activation of the PTH/PTHrP Receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Ohishi, M.; Chiusaroli, R.; Schipani, E.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Asuncion, F.; Ominsky, M.; Kostenuik, P.] Amgen Inc, Metab Disorders, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S392 EP S392 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002213 ER PT J AU Ohishi, M Purton, LE Schipani, E AF Ohishi, M. Purton, L. E. Schipani, E. TI Expansion of Mesenchymal Progenitors in an in vivo Model of Constitutive Activation of the PTH/PTHrP Receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Ohishi, M.; Purton, L. E.; Schipani, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S74 EP S74 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000264 ER PT J AU Okazaki, M Potts, JT Gardella, TJ AF Okazaki, M. Potts, J. T. Gardella, T. J. TI Identification and Optimization of Residues in PTH and PTHrP that Determine Altered Modes of Binding to the PTH/PTHrP Receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Okazaki, M.; Potts, J. T.; Gardella, T. J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S103 EP S103 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000371 ER PT J AU Okazaki, M Potts, JT Gardella, TJ AF Okazaki, M. Potts, J. T. Gardella, T. J. TI A Long-Acting PTH Ligand that Binds to a Distinct PTH Receptor Conformation (R0) Call Stimulate Increases in Markers of Both Bone Resorption and Bone Formation in Mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Okazaki, M.; Potts, J. T.; Gardella, T. J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S103 EP S103 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000370 ER PT J AU Pozzi, S Yan, H Vallet, S Vaghela, N Cirstea, D Santo, L Mukheriee, S Hideshima, T Schirtzinger, L Kuhstoss, S Anderson, KC Scadden, D Raje, N AF Pozzi, S. Yan, H. Vallet, S. Vaghela, N. Cirstea, D. Santo, L. Mukheriee, S. Hideshima, T. Schirtzinger, L. Kuhstoss, S. Anderson, K. C. Scadden, D. Raje, N. TI Preclinical Validation of a Novel Dkk-1 Neutralizing Antibody for the Treatment of Multiple Myeloma Related Bone Disease. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Pozzi, S.; Vallet, S.; Vaghela, N.; Raje, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA USA. [Schirtzinger, L.; Kuhstoss, S.] Eli Lilly & Co, Indianapolis, IN 46285 USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S300 EP S300 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001503 ER PT J AU Rached, M Ogita, M DePinho, RA Bilezikian, JP Kousteni, S AF Rached, M. Ogita, M. DePinho, R. A. Bilezikian, J. P. Kousteni, S. TI FOXO1 Signaling in the Control of Bone Mass SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Rached, M.; Ogita, M.; Bilezikian, J. P.; Kousteni, S.] Columbia Univ, Dept Med, Div Endocrinol, Coll Phys & Surg, New York, NY USA. [DePinho, R. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S32 EP S32 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000113 ER PT J AU Schafer, AL Silva, R Yafai, M Shoback, D AF Schafer, A. L. Silva, R. Yafai, M. Shoback, D. TI Diffuse Sclerosing Osteomyelitis of the Mandible: Case Report and Literature Review. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S508 EP S508 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002644 ER PT J AU Schafer, AL Silva, R Yafai, M Shoback, D AF Schafer, A. L. Silva, R. Yafai, M. Shoback, D. TI Diffuse Sclerosing Osteomyelitis of the Mandible: Case Report and Literature Review. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S489 EP S489 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411002586 ER PT J AU Shalom, SI Kenan, Y Matsumoto, T Neer, R AF Shalom, S. Ish Kenan, Y. Matsumoto, T. Neer, R. TI Repetitive Rapid Delivery of Pharmacologically-Active hPTH 1-34 Across Human Skin Without Injection SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Shalom, S. Ish] Rambam Med Ctr, Metab Bone Dis Unit, Haifa, Israel. [Kenan, Y.] TransPharma Med Ltd, Lod, Israel. [Matsumoto, T.] Univ Tokushima, Dept Med & Bioregulatory Sci, Grad Sch Med Sci, Tokushima 770, Japan. [Neer, R.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S207 EP S207 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001143 ER PT J AU Shimizu, M Ichikawa, F Noda, H Okazaki, M Nakagawa, C Tamura, T Gardella, TJ Potts, JT Ogata, E Kuromaru, O Kawabe, Y AF Shimizu, M. Ichikawa, F. Noda, H. Okazaki, M. Nakagawa, C. Tamura, T. Gardella, T. J. Potts, J. T. Ogata, E. Kuromaru, O. Kawabe, Y. TI A New Long-Acting PTH/PTHrP Hybrid Analog that Binds to a Distinct PTHR Conformation has Superior Efficacy in a Rat Model of Hypoparathyroidism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Shimizu, M.; Ichikawa, F.; Noda, H.; Okazaki, M.; Nakagawa, C.; Tamura, T.; Kuromaru, O.; Kawabe, Y.] Chugai Pharmaceut Co Ltd, Pharmaceut Res Dept 1, Shizuoka, Japan. [Gardella, T. J.; Potts, J. T.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Ogata, E.] Canc Inst Hosp, Tokyo, Japan. NR 0 TC 4 Z9 4 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S128 EP S128 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000459 ER PT J AU Smith, MR Morton, RA Hancock, ML Barnette, G Rodriguez, D Veverka, KA Steiner, M AF Smith, M. R. Morton, R. A. Hancock, M. L. Barnette, G. Rodriguez, D. Veverka, K. A. Steiner, M. TI C-telopeptide and Bone Alkaline Phosphatase Predict Morphometric Vertebral Fracture Risk in a Pivotal Phase III Trial of Toremifene in Men on ADT SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Smith, M. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Morton, R. A.; Hancock, M. L.; Barnette, G.; Rodriguez, D.; Veverka, K. A.; Steiner, M.] GTx Inc, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S82 EP S82 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000293 ER PT J AU Solomon, DH Finkelstein, JS Shadick, N LeBoff, MS Winalski, C Stedman, M Glass, R Brookhart, MA Weinblattt, ME Gravallese, EM AF Solomon, D. H. Finkelstein, J. S. Shadick, N. LeBoff, M. S. Winalski, C. Stedman, M. Glass, R. Brookhart, M. A. Weinblattt, M. E. Gravallese, E. M. TI The Relationship Between Focal Erosions and Generalized Osteoporosis in Postmenopausal Women with Rheumatoid Arthritis: The Osteoporosis in Rheumatoid Arthritis (OPiRA) Cohort Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Solomon, D. H.; Shadick, N.; LeBoff, M. S.; Stedman, M.; Glass, R.; Brookhart, M. A.; Weinblattt, M. E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Finkelstein, J. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winalski, C.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Gravallese, E. M.] Univ Massachusetts, Med Ctr, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S202 EP S203 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001125 ER PT J AU Tye, CE Pham, CT Bartlett, JD AF Tye, C. E. Pham, C. T. Bartlett, J. D. TI Identification of Dipeptidyl Peptidase I as a Potential Activator of Kallikrein-4 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Tye, C. E.; Bartlett, J. D.] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Pham, C. T.] Washington Univ, Sch Med, Div Rheumatol, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S164 EP S164 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000586 ER PT J AU Tye, CE Ding, Y Li, YP Bartlett, JD AF Tye, C. E. Ding, Y. Li, Y. P. Bartlett, J. D. TI Cathepsin K Expression During Enamel Formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Tye, C. E.; Ding, Y.; Li, Y. P.; Bartlett, J. D.] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 SU S BP S164 EP S164 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000585 ER PT J AU Vallet, S Mukherjee, S Vaghela, N Hideshima, T Pozzi, S Santo, L Cirstea, D Seehra, J Scadden, DT Anderson, KC Raje, N AF Vallet, S. Mukherjee, S. Vaghela, N. Hideshima, T. Pozzi, S. Santo, L. Cirstea, D. Seehra, J. Scadden, D. T. Anderson, K. C. Raje, N. TI Activin A Mediates Multiple Myeloma (MM) Bone Disease which Is Reversed by RAP-011. a Soluble Activin Receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Vallet, S.; Vaghela, N.; Pozzi, S.; Raje, N.] Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. [Seehra, J.] Acceleron Pharma Inc, Cambridge, MA USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S65 EP S65 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000232 ER PT J AU Wang, Y Long, RK Elalieh, HZ Bikle, DD AF Wang, Y. Long, R. K. Elalieh, H. Z. Bikle, D. D. TI Ablation of IGF-1 Signaling in Osteoprogenitors; Decreases Bone Formation and Blunts the Skeletal Response to PTH SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Wang, Y.; Long, R. K.; Elalieh, H. Z.; Bikle, D. D.] Univ Calif San Francisco, San Francisco VA Med Ctr, Endocrine Unit, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S55 EP S55 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000194 ER PT J AU Ward, LM Pinto, T Lawrence, S Lawson, M Bastepe, M Juppner, H Rauch, F AF Ward, L. M. Pinto, T. Lawrence, S. Lawson, M. Bastepe, M. Jueppner, H. Rauch, F. TI Hypothyroidism and Autism Combined with Pseudohypoparathyroidism in the Absence of Albright's Hereditary Osteodystrophy and GNAS Imprinting Changes: A Novel Clinical Syndrome? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Ward, L. M.; Pinto, T.; Lawrence, S.; Lawson, M.] Childrens Hosp Eastern Ontario, Div Endocrinol, Ottawa, ON K1H 8L1, Canada. [Bastepe, M.; Jueppner, H.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Rauch, F.] Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S183 EP S183 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001056 ER PT J AU Wu, JY Maes, C Chen, M Weinstein, LS Kronenberg, HM AF Wu, J. Y. Maes, C. Chen, M. Weinstein, L. S. Kronenberg, H. M. TI Deletion of the G Protein Subunit Gs alpha in Early Osteoblasts Leads to Accelerated Osteoblast Maturation and Formation of Woven Bone with Abnormal Osteocytes, Resulting in Severe Osteoporosis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Wu, J. Y.; Maes, C.; Kronenberg, H. M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Chen, M.; Weinstein, L. S.] NIDDK, Metab Dis Branch, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S71 EP S71 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000255 ER PT J AU Wu, Y Ackerman, JL Cao, H Reese, TG Hrovat, MI Glimcher, MJ AF Wu, Y. Ackerman, J. L. Cao, H. Reese, T. G. Hrovat, M. I. Glimcher, M. J. TI In vivo Bone Matrix Density Measurements by Water and Fat Suppressed Projection MRI (WASPI) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Wu, Y.; Cao, H.; Glimcher, M. J.] Childrens Hosp, Boston, MA 02115 USA. [Ackerman, J. L.; Reese, T. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hrovat, M. I.] Mirtech Inc, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S154 EP S154 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000548 ER PT J AU Yang, S Chen, W Chen, L Li, N Li, Y AF Yang, S. Chen, W. Chen, L. Li, N. Li, Y. TI CNBP Conditional Knockout Mice Show Severe Osteoporosis-like Phenotype SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Yang, S.; Chen, W.; Li, Y.] Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. RI Yang, Shuying/G-4599-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S87 EP S87 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000308 ER PT J AU Yano, F Chung, U Ikeda, T Kawasaki, Y Kawayuchi, H Tawfeek, HAW Mahon, MJ Segre, GV Ogata, N AF Yano, F. Chung, U. Ikeda, T. Kawasaki, Y. Kawayuchi, H. Tawfeek, H. A. W. Mahon, M. J. Segre, G. V. Ogata, N. TI beta-catenin Directly Binds to a Specifc Intracellular Domain of PTH/PTHrP Receptor and Regulates the Signaling in Chondrocytes during Endochondral Ossification SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Yano, F.; Chung, U.; Ikeda, T.; Kawasaki, Y.; Kawayuchi, H.; Ogata, N.] Univ Tokyo, Tokyo, Japan. [Tawfeek, H. A. W.; Mahon, M. J.; Segre, G. V.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S5 EP S5 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411000014 ER PT J AU Zalutskaya, AA Demay, MB AF Zalutskaya, A. A. Demay, M. B. TI Phosphate Regulates Chondrocyte Differentiation, Proliferation and Apoptosis in a Model of Embryonic Endochondral Bone Formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Zalutskaya, A. A.; Demay, M. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S272 EP S272 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001391 ER PT J AU Zhu, S Zhu, E Provot, S Gori, F AF Zhu, S. Zhu, E. Provot, S. Gori, F. TI Role of Wdr5 in Endochondral Bone Formation During Chicken Limb Development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 12-16, 2008 CL Montreal, CANADA SP Amer Soc Bone & Mineral Res C1 [Zhu, S.; Zhu, E.; Gori, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Provot, S.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2008 VL 23 BP S271 EP S271 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351FX UT WOS:000259411001388 ER PT J AU Shuhaiber, JH Gunnar, W AF Shuhaiber, Jeffrey H. Gunnar, William TI Intra-cardiac thrombosis following aortic valve replacement SO JOURNAL OF CARDIAC SURGERY LA English DT Article C1 [Shuhaiber, Jeffrey H.; Gunnar, William] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Sect Thorac & Cardiovasc Surg, Hines, IL 60141 USA. RP Shuhaiber, JH (reprint author), 614 G Laflin, Chicago, IL 60607 USA. EM jeffrey01@mac.com 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 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD SEP-OCT PY 2008 VL 23 IS 5 BP 552 EP 552 DI 10.1111/j.1540-8191.2008.00703.x PG 1 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 339SG UT WOS:000258597000034 PM 18928493 ER PT J AU Karasawa, T Wang, Q Fu, Y Cohen, DM Steyger, PS AF Karasawa, Takatoshi Wang, Qi Fu, Yi Cohen, David M. Steyger, Peter S. TI TRPV4 enhances the cellular uptake of aminoglycoside antibiotics SO JOURNAL OF CELL SCIENCE LA English DT Article DE gentamicin; ototoxicity; aminoglycosides; cochlea; hair cells; stria vascularis; TRPV4; drug permeability ID CATION CHANNEL TRPV4; SENSORY HAIR-CELLS; STRIA VASCULARIS; EPITHELIAL-CELLS; INNER-EAR; IN-VITRO; GENTAMICIN; EXPRESSION; KIDNEY; ENDOCYTOSIS AB The cochlea and kidney are susceptible to aminoglycoside-induced toxicity. The non-selective cation channel TRPV4 is expressed in kidney distal tubule cells, and hair cells and the stria vascularis in the inner ear. To determine whether TRPV4 is involved in aminoglycoside trafficking, we generated a murine proximal-tubule cell line (KPT2) and a distal-tubule cell line (KDT3). TRPV4 expression was confirmed in KDT3 cells but not in KPT2 cells. Removal of extracellular Ca(2+) significantly enhanced gentamicin-Texas-Red (GTTR) uptake by KDT3, indicative of permeation through non-selective cation channels. To determine whether TRPV4 is permeable to GTTR, stable cell lines were generated that express TRPV4 in KPT2 (KPT2-TRPV4). KPT2-TRPV4 cells took up more GTTR than control cell lines (KPT2-pBabe) in the absence of extracellular Ca(2+). TRPV4-dependent GTTR uptake was abolished by a point mutation within the crucial pore region of the channel, suggesting that GTTR permeates the TRPV4 channel. In an endolymph-like extracellular environment, clearance of GTTR was attenuated from KPT2-TRPV4 cells in a TRPV4-dependent fashion. We propose that TRPV4 has a role in aminoglycoside uptake and retention in the cochlea. C1 [Karasawa, Takatoshi; Wang, Qi; Steyger, Peter S.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97239 USA. [Fu, Yi; Cohen, David M.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97201 USA. [Fu, Yi; Cohen, David M.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Steyger, PS (reprint author), Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, 3181 Sam Jackson Pk Rd, Portland, OR 97239 USA. EM steygerp@ohsu.edu OI Steyger, Peter/0000-0002-6103-5237 FU NIH NIDCD [DC04555, P30 DC05983, T32 DC005945, F32 DC008465]; Oregon Medical Research Foundation FX We thank Stefan Heller for anti-TRPV4 antibody and Wolfgang Liedtke for TRPV4 cDNA and TRPV4- knockout mice. This work was supported by NIH NIDCD grants DC04555 (P. S. S.), P30 DC05983, T32 DC005945 and F32 DC008465 (T. K.), and by the Oregon Medical Research Foundation. NR 50 TC 34 Z9 36 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP 1 PY 2008 VL 121 IS 17 BP 2871 EP 2879 DI 10.1242/jcs.023705 PG 9 WC Cell Biology SC Cell Biology GA 339SC UT WOS:000258596600010 PM 18682499 ER PT J AU You, ZR Savitz, SI Yang, JS Degterev, A Yuan, JY Cuny, GD Moskowitz, MA Whalen, MJ AF You, Zerong Savitz, Sean I. Yang, Jinsheng Degterev, Alexei Yuan, Junying Cuny, Gregory D. Moskowitz, Michael A. Whalen, Michael J. TI Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE necroptosis; necrostatin; traumatic brain injury; mice; necrosis; inflammation ID TRAUMATIC BRAIN-INJURY; TUMOR-NECROSIS-FACTOR; NECROTIC CELL-DEATH; FAS RECEPTOR; NECROPTOSIS INHIBITORS; UP-REGULATION; L929 CELLS; APOPTOSIS; CASPASE-3; CULTURES AB Necroptosis is a newly identified type of programmed necrosis initiated by the activation of tumor necrosis factor alpha (TNF alpha)/Fas. Necrostatin-1 is a specific inhibitor of necroptosis that reduces ischemic tissue damage in experimental stroke models. We previously reported decreased tissue damage and improved functional outcome after controlled cortical impact (CCI) in mice deficient in TNFa and Fas. Hence, we hypothesized that necrostatin-1 would reduce histopathology and improve functional outcome after CCI in mice. Compared with vehicle-/inactive analog-treated controls, mice administered necrostatin-1 before CCI had decreased propidium iodide-positive cells in the injured cortex and dentate gyrus (6 h), decreased brain tissue damage (days 14, 35), improved motor (days 1 to 7), and Morris water maze performance (days 8 to 14) after CCI. Improved spatial memory was observed even when drug was administered 15 mins after CCI. Necrostatin-1 treatment did not reduce caspase-3-positive cells in the dentate gyrus or cortex, consistent with a known caspase-independent mechanism of necrostatin-1. However, necrostatin-1 reduced brain neutrophil influx and microglial activation at 48 h, suggesting a novel anti-inflammatory effect in traumatic brain injury (TBI). The data suggest that necroptosis plays a significant role in the pathogenesis of cell death and functional outcome after TBI and that necrostatin-1 may have therapeutic potential for patients with TBI. C1 [You, Zerong; Savitz, Sean I.; Yang, Jinsheng; Moskowitz, Michael A.; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Crit Care Med,Neurosci Ctr, Charlestown, MA 02129 USA. [You, Zerong; Yang, Jinsheng; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. [Savitz, Sean I.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Degterev, Alexei; Yuan, Junying] Harvard Univ, Sch Med, Dept Cell Biol, Charlestown, MA 02129 USA. [Cuny, Gregory D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Drug Discovery Neurodegenerat, Cambridge, MA 02138 USA. [Moskowitz, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Whalen, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Crit Care Med,Neurosci Ctr, 149 13th St, Charlestown, MA 02129 USA. EM MWhalen@Partners.org RI Moskowitz, Michael/D-9916-2011 FU NIH/NINDS [RO1NS47447, P30NS45776] FX This work was supported by grants from NIH/NINDS (RO1NS47447 to MJW) and P30NS45776. NR 32 TC 116 Z9 130 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2008 VL 28 IS 9 BP 1564 EP 1573 DI 10.1038/jcbfm.2008.44 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 341LQ UT WOS:000258716400005 PM 18493258 ER PT J AU Magnee, MJCM de Gelder, B van Engeland, H Kemner, C AF Magnee, Maurice J. C. M. de Gelder, Beatrice van Engeland, Herman Kemner, Chantal TI Audiovisual speech integration in pervasive developmental disorder: evidence from event-related potentials SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE multisensory integration; language and communication; autism; EEG; visual; auditory ID AUDITORY-VISUAL INTEGRATION; AUTISM; RECOGNITION; INFORMATION AB Background: Integration of information from multiple sensory sources is an important prerequisite for successful social behavior, especially during face-to-face conversation. It has been suggested that communicative impairments among individuals with pervasive developmental disorders (PDD) might be caused by an inability to integrate synchronously presented visual and auditory cues. Method: We investigated audiovisual integration of speech stimuli among a group of high-functioning adult PDD individuals and age- and IQ-matched controls using electroencephalography, measuring both early pre-phonological, as well as late phonologically driven integration. Results: Pre-phonological AV interactions are intact, while AV interactions corresponding to more complex phonological processes are impaired in individuals with PDD. Conclusions: The present findings argue for a pattern of impairments on tasks related to complex audiovisual integration combined with relative sparing of low-level integrational abilities. This combination may very well contribute to the communicative disabilities which are typical for the disorder. C1 [Magnee, Maurice J. C. M.; van Engeland, Herman; Kemner, Chantal] Univ Med Ctr Utrecht, Dept Child & Adolescent Psychiat, Rudolf Magnus Inst Neurosci, NL-3584 CX Utrecht, Netherlands. [Magnee, Maurice J. C. M.; de Gelder, Beatrice] Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands. [Kemner, Chantal] Maastricht Univ, Fac Psychol, Sect Biol Dev Psychol, Maastricht, Netherlands. [de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [de Gelder, Beatrice] Harvard Univ, Sch Med, Charlestown, MA USA. RP Magnee, MJCM (reprint author), Univ Med Ctr Utrecht, Dept Child & Adolescent Psychiat, Rudolf Magnus Inst Neurosci, B01-201,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM M.J.C.M.Magnee@umcutrecht.nl FU Netherlands Organization for Scientific Research [402-01-094] FX This research was funded by an Innovational Research Incentives grant of the Netherlands Organization for Scientific Research (NWO; VIDI-scheme, 402-01-094) to Chantal Kemner. NR 20 TC 35 Z9 35 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD SEP PY 2008 VL 49 IS 9 BP 995 EP 1000 DI 10.1111/j.1469-7610.2008.01902.x PG 6 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 342KL UT WOS:000258782900012 PM 18492039 ER PT J AU Kupelian, V Hayes, FJ Link, CL Rosen, R McKinlay, JB AF Kupelian, Varant Hayes, Frances J. Link, Carol L. Rosen, Raymond McKinlay, John B. TI Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-BINDING GLOBULIN; ENDOGENOUS SEX-HORMONES; MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE; BODY-COMPOSITION; MUSCLE STRENGTH; SERUM TESTOSTERONE; PROVISIONAL REPORT; DIABETES-MELLITUS; ADIPOSE-TISSUE AB Context: Low sex hormone levels have been associated with the metabolic syndrome (MetS). Objectives: Our objective was to determine whether the association between sex hormone levels and MetS varies by race/ethnicity among men and to investigate the relationship of sex hormones and individual components of MetS. Design: We conducted a population-based observational survey. Participants: A multistage stratified design was used to recruit a random sample of 2301 racially/ethnically diverse men age 30-79 yr. Blood samples were obtained on 1899 men. Analyses were conducted on 1885 men with complete data on total testosterone ( T), free T, and SHBG. Interventions: There were no interventions. Main Outcome Measure: MetS was defined using a modification of the Adult Treatment Panel III guidelines. The association between MetS and sex hormone levels was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models. Results: A strong inverse association was observed, in both bivariate and multivariate analyses, between hormone levels and MetS. The odds of MetS increased about two-fold with a 1 SD decrease in hormone levels. The association between sex hormones and MetS was statistically significant across racial/ethnic groups. Although the magnitude of this association was largest among White men, racial/ethnic differences were not statistically significant. The strength of the association of sex hormones with individual components of MetS varied; stronger associations were observed with waist circumference and dyslipidemia and more modest associations with diabetes and elevated blood sugar. Conclusions: A robust, dose-response relationship between sex hormone levels and odds of the metabolic syndrome in men is consistent across racial/ethnic groups. C1 [Kupelian, Varant; Link, Carol L.; Rosen, Raymond; McKinlay, John B.] New England Res Inst, Watertown, MA 02472 USA. [Hayes, Frances J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kupelian, V (reprint author), 9 Galen St, Watertown, MA 02472 USA. EM bach@neriscience.com RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU National Institute of Diabetes and Digestive and Kidney Diseases ( National Institutes of Health) [DK 56842]; Solvay Pharmaceuticals FX This work was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases ( National Institutes of Health) DK 56842, and a grant from Solvay Pharmaceuticals. NR 45 TC 57 Z9 61 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2008 VL 93 IS 9 BP 3403 EP 3410 DI 10.1210/jc.2008-0054 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344TV UT WOS:000258951100023 PM 18559915 ER PT J AU Triant, VA Brown, TT Lee, H Grinspoon, SK AF Triant, Virginia A. Brown, Todd T. Lee, Hang Grinspoon, Steven K. TI Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large US healthcare system SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; ANTIRETROVIRAL THERAPY; AIDS PATIENTS; WOMEN; MEN; OSTEOPOROSIS; OSTEOPENIA; RISK; ASSOCIATION; EVOLUTION AB Context: Reduced bone mineral density has been demonstrated among HIV-infected patients, but fracture prevalence is unknown. Objective: The objective of the study was to compare fracture prevalence in HIV-infected and non-HIV-infected patients. Design: This was a population-based study. Setting: The study was conducted at a large U. S. health care system. Patients: A total of 8525 HIV-infected and 2,208,792 non-HIV-infected patients with at least one inpatient or outpatient encounter between October 1, 1996, and March 21, 2008, was compared. Main Outcome Measure: Fracture prevalence using specific International Classification of Diseases, Ninth Revision, Clinical Modification fracture codes was measured. Results: The overall fracture prevalence was 2.87 vs. 1.77 patients with fractures per 100 persons in HIV-infected, compared with non-HIV-infected patients (P < 0.0001). Among females, the overall fracture prevalence was 2.49 vs. 1.72 per 100 persons in HIV-infected vs. non-HIV-infected patients (P = 0.002). HIV-infected females had a higher prevalence of vertebral (0.81 vs. 0.45; P = 0.01) and wrist (1.31 vs. 0.83; P = 0.01) fractures per 100 persons, compared with non-HIV-infected females but had a similar prevalence of hip fractures (0.47 vs. 0.56; P = 0.53). Among males, the fracture prevalence per 100 persons was higher in HIV-infected vs. non-HIV-infected patients for any fracture (3.08 vs. 1.83; P < 0.0001), vertebral fractures (1.03 vs. 0.49; P < 0.0001), hip fractures (0.79 vs. 0.45; P = 0.001), and wrist fractures (1.46 vs. 0.99; P = 0.001). Fracture prevalence was higher relative to non-HIV-infected patients among African-American and Caucasian females and Caucasian males. Conclusions: Fracture prevalence is increased in HIV-infected compared with non-HIV-infected patients. C1 [Triant, Virginia A.; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Triant, Virginia A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Brown, Todd T.] Johns Hopkins Univ, Div Endocrinol & Metab, Baltimore, MD 21287 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,Longfellow 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU Massachusetts General Hospital [T32 AI07387, K24 DK064545]; Johns Hopkins Medical Center [K23 AT002862] FX This work was supported in part by Grants T32 AI07387 (to V. A. T., Massachusetts General Hospital), K23 AT002862 (to T. T. B., Johns Hopkins Medical Center), and K24 DK064545 (to S. K. G., Massachusetts General Hospital). NR 24 TC 247 Z9 250 U1 1 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2008 VL 93 IS 9 BP 3499 EP 3504 DI 10.1210/jc.2008-0828 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344TV UT WOS:000258951100037 PM 18593764 ER PT J AU Cole, LW Sidis, Y Zhang, C Quinton, R Plummer, L Pignatelli, D Hughes, VA Dwyer, AA Raivio, T Hayes, FJ Seminara, SB Huot, C Alos, N Speiser, P Takeshita, A Van Vliet, G Pearce, S Crowley, WF Zhou, QY Pitteloud, N AF Cole, Lindsay W. Sidis, Yisrael Zhang, ChengKang Quinton, Richard Plummer, Lacey Pignatelli, Duarte Hughes, Virginia A. Dwyer, Andrew A. Raivio, Taneli Hayes, Frances J. Seminara, Stephanie B. Huot, Celine Alos, Nathalie Speiser, Phyllis Takeshita, Akira Van Vliet, Guy Pearce, Simon Crowley, William F., Jr. Zhou, Qun-Yong Pitteloud, Nelly TI Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: Molecular genetics and clinical spectrum SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; DOMINANT KALLMANN-SYNDROME; OLFACTORY-BULB; MICE LACKING; PROTEIN; RECEPTOR; IDENTIFICATION; FAMILY; HETEROGENEITY; ANGIOGENESIS AB Context: Mice deficient in prokineticin 2 (PROK2) and prokineticin receptor 2 (PROKR2) exhibit variable olfactory bulb dysgenesis and GnRH neuronal migration defects reminiscent of human GnRH deficiency. Objectives: We aimed to screen a large cohort of patients with Kallmann syndrome (KS) and normosmic idiopathic hypogonadotropic hypogonadism (IHH) for mutations in PROK2/PROKR2, evaluate their prevalence, define the genotype/phenotype relationship, and assess the functionality of these mutant alleles in vitro. Design: Sequencing of the PROK2 and PROKR2 genes was performed in 170 KS patients and 154 nIHH. Mutations were examined using early growth response 1-luciferase assays in HEK 293 cells and aequorin assays in Chinese hamster ovary cells. Results: Four heterozygous and one homozygous PROK2 mutation (p. A24P, p. C34Y, p. I50M, p. R73C, and p. I55fsX1) were identified in five probands. Four probands had KS and one nIHH, and all had absent puberty. Each mutant peptide impaired receptor signaling in vitro except the I50M. There were 11 patients who carried a heterozygous PROKR2 mutation (p. R85C, p. Y113H, p. V115M, p. R164Q, p. L173R, p. W178S, p. S188L, p. R248Q, p. V331M, and p. R357W). Among them, six had KS, four nIHH, and one KS proband carried both a PROKR2 (p. V115M) and PROK2 (p. A24P) mutation. Reproductive phenotypes ranged from absent to partial puberty to complete reversal of GnRH deficiency after discontinuation of therapy. All mutant alleles appear to decrease intracellular calcium mobilization; seven exhibited decreased MAPK signaling, and six displayed decreased receptor expression. Nonreproductive phenotypes included fibrous dysplasia, sleep disorder, synkinesia, and epilepsy. Finally, considerable variability was evident in family members with the same mutation, including asymptomatic carriers. Conclusion: Loss-of-function mutations in PROK2 and PROKR2 underlie both KS and nIHH. C1 [Cole, Lindsay W.; Sidis, Yisrael; Plummer, Lacey; Hughes, Virginia A.; Dwyer, Andrew A.; Raivio, Taneli; Hayes, Frances J.; Seminara, Stephanie B.; Crowley, William F., Jr.; Pitteloud, Nelly] Massachusetts Gen Hosp, Harvard Ctr Reprod Endocrine Sci, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Cole, Lindsay W.; Sidis, Yisrael; Plummer, Lacey; Hughes, Virginia A.; Dwyer, Andrew A.; Raivio, Taneli; Hayes, Frances J.; Seminara, Stephanie B.; Crowley, William F., Jr.; Pitteloud, Nelly] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zhang, ChengKang; Zhou, Qun-Yong] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA. [Quinton, Richard] Univ Newcastle Upon Tyne, Inst Human Genet, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Quinton, Richard] Univ Newcastle Upon Tyne, Sch Clin Med Sci, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Pignatelli, Duarte; Pearce, Simon] Univ Porto, Fac Med, Lab Cell & Mol Biol, San Joao Hosp,Endocrinol Dept, P-4200319 Oporto, Portugal. [Pignatelli, Duarte; Pearce, Simon] Univ Porto, Inst Mol Pathol & Immunol, P-4200319 Oporto, Portugal. [Huot, Celine; Alos, Nathalie] CHU St Justine, Ctr Rech, Montreal, PQ H3T 1C5, Canada. [Speiser, Phyllis] Schneider Childrens Hosp, Div Pediat Endocrinol, New York, NY 11040 USA. [Takeshita, Akira] Toranomon Gen Hosp, Endocrine Ctr, Tokyo 1058470, Japan. [Takeshita, Akira] Okinaka Mem Inst Med Res, Tokyo 1058470, Japan. [Van Vliet, Guy] St Justine Hosp, Serv Endocrinol, Montreal, PQ H3T 1C5, Canada. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Harvard Ctr Reprod Endocrine Sci, Reprod Endocrine Unit, Dept Med, Bartlett Hall Extens 5, Boston, MA 02114 USA. EM npitteloud@partners.org RI ZHANG, CHENGKANG/A-8141-2008; Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Pearce, Simon/0000-0001-8384-8063; Pignatelli, Duarte/0000-0002-5555-7004 FU National Institutes of Health [R01HD015788-21, U54HD028138-16] FX This work was supported by National Institutes of Health Grants R01HD015788-21 and U54HD028138-16. NR 35 TC 104 Z9 111 U1 2 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2008 VL 93 IS 9 BP 3551 EP 3559 DI 10.1210/jc.2007-2654 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344TV UT WOS:000258951100045 PM 18559922 ER PT J AU Mannstadt, M Bertrand, G Muresan, M Weryha, G Leheup, B Pulusani, SR Grandchamp, B Juppner, H Silve, C AF Mannstadt, Michael Bertrand, Guylene Muresan, Mihaela Weryha, Georges Leheup, Bruno Pulusani, Sirish R. Grandchamp, Bernard Jueppner, Harald Silve, Caroline TI Dominant-negative GCMB mutations cause an autosomal dominant form of hypoparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FAMILIAL ISOLATED HYPOPARATHYROIDISM; CALCIUM-SENSING RECEPTOR; PREPROPARATHYROID HORMONE GENE; PARATHYROID-GLAND DEVELOPMENT; TRANSCRIPTION FACTOR; DNA-BINDING; SIGNAL PEPTIDE; HUMAN HOMOLOG; DROSOPHILA; EXPRESSION AB Context: Hypoparathyroidism (HP) is characterized by low PTH levels, hypocalcemia, and hyperphosphatemia. Heterozygous mutations in pre-pro-PTH or the calcium-sensing receptor (CaSR) cause some forms of autosomal dominant HP (AD-HP). Furthermore, homozygous mutations in glial cells missing B (GCMB) have been implicated in autosomal recessive HP (AR-HP). In most other HP patients, however, the molecular defect remains undefined. Objective: Our objectives were to determine the genetic defect in the affected members of two unrelated families with AD-HP and define the underlying disease mechanism. Subjects: Several family members affected by AD-HP were investigated. The proband in family A had low calcium detected on routine blood testing, whereas the proband in family B had symptomatic hypocalcemia. Methods: Mutational analysis of the genes encoding pre-pro-PTH, CaSR, and GCMB was performed using PCR-amplified genomic DNA of the probands and other available members of each family. The identified GCMB mutants were characterized by Western blot analysis and luciferase reporter assay using DF-1 fibroblasts. Results: Two novel heterozygous mutations located in the last GCMB exon (c. 1389delT and c. 1399delC in families A and B, respectively) were identified that both lead to frame-shifts and replacement of the putative second transactivation domain within carboxyl-terminal region by unrelated amino acid sequence. The mutant GCMB proteins were well expressed, and both showed dose-dependent inhibition of the transactivation capacity of wild-type protein in luciferase reporter assays. Conclusions: The dominant-negative effect observed in vitro for both GCMB mutations provides a plausible explanation for the impaired PTH secretion observed in the two unrelated families with AD-HP. C1 [Mannstadt, Michael; Pulusani, Sirish R.; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bertrand, Guylene; Grandchamp, Bernard; Silve, Caroline] Univ Paris 07, UFR Med, Hop Bichat Claude Bernard, Serv Biochim Hormonale & Genet,AP HP, F-75018 Paris, France. [Silve, Caroline] Univ Paris 05, Hop St Vincent de Paul, UFR Med, INSERM U561, F-75014 Paris, France. [Muresan, Mihaela; Weryha, Georges; Leheup, Bruno] CHU Nancy, Serv Endocrinol, F-54003 Nancy, France. [Muresan, Mihaela; Weryha, Georges; Leheup, Bruno] CHU Nancy, Serv Med Infantile 3, F-54003 Nancy, France. [Muresan, Mihaela; Weryha, Georges; Leheup, Bruno] CHU Nancy, Genet Clin, F-54003 Nancy, France. [Muresan, Mihaela; Weryha, Georges; Leheup, Bruno] Univ Henri Poincare, Nancy Univ, Fac Med, F-54003 Nancy, France. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,55 Fruit St, Boston, MA 02114 USA. EM hjueppner@partners.org OI WERYHA, Georges/0000-0003-2062-3419 FU National Institute of Diabetes and Digestive and Kidney Disease [RO1-46718-10, K08-DK081669-01]; Institut National de la Sante et de la Recherche Medicale and reseaux DHOS FX This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Disease (RO1-46718-10 to H. J. and K08-DK081669-01 to M. M.) and from Institut National de la Sante et de la Recherche Medicale and reseaux DHOS (to C. S. and B. G.). NR 28 TC 35 Z9 37 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2008 VL 93 IS 9 BP 3568 EP 3576 DI 10.1210/jc.2007-2167 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 344TV UT WOS:000258951100047 PM 18583467 ER PT J AU Yong, PL Russo, P Sullivan, KE AF Yong, Pierre L. Russo, Pierre Sullivan, Kathleen E. TI Use of sirolimus in IPEX and IPEX-like children SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE IPEX; enteropathy; regulatory T cells; sirolimus; rapamycin ID X-LINKED SYNDROME; BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; IMMUNE DYSREGULATION; AUTOIMMUNE ENTEROPATHY; PROTRACTED DIARRHEA; POLYENDOCRINOPATHY; INFANCY; IMMUNODYSREGULATION; AUTOANTIBODIES AB Introduction IPEX (immune dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome), a rare inflammatory disease caused by mutations of Foxp3, destroys the immunoregulatory environment of affected male infants. Data on optimal therapy are limited. Methods We reviewed the effect of sirolimus use in our cohort of IPEX and IPEX-like patients (n=7). Results and Discussion Our patients exhibited features of enteropathy and recurrent infections with bacterial and viral pathogens. Before initiating sirolimus, six patients were treated with corticosteroids. Several also received other immunosuppressive agents. After starting sirolimus, six patients had improvement in diarrhea, and two were able to decrease corticosteroid dosages. Several also had significantly decreased number of infections after treatment. Of the three patients with post-treatment duodenal biopsies, two showed improvement in villous architecture. No significant adverse events occurred. Our experience suggests that sirolimus is a clinically effective and safe therapeutic option in IPEX and IPEX-like patients. C1 [Yong, Pierre L.] Univ Penn, Sch Med, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Yong, Pierre L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Yong, Pierre L.] Hosp Univ Penn, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Russo, Pierre] Childrens Hosp Philadelphia, Div Pathol, Philadelphia, PA 19104 USA. [Sullivan, Kathleen E.] Childrens Hosp Philadelphia, Div Allergy & Immunol, Philadelphia, PA 19104 USA. RP Yong, PL (reprint author), Univ Penn, Sch Med, Robert Wood Johnson Clin Scholars Program, 423 Guardian Dr,1303A Blockley Hall, Philadelphia, PA 19104 USA. EM pyong@mail.med.upenn.edu OI Sullivan, Kathleen/0000-0003-4018-1646 FU Philadelphia Veterans Affairs Medical Center; Robert Wood Johnson Clinical Scholars Program FX Dr. Pierre Yong is supported by a training grant from the Philadelphia Veterans Affairs Medical Center and the Robert Wood Johnson Clinical Scholars Program at the University of Pennsylvania. NR 24 TC 32 Z9 36 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2008 VL 28 IS 5 BP 581 EP 587 DI 10.1007/s10875-008-9196-1 PG 7 WC Immunology SC Immunology GA 345OV UT WOS:000259007000020 PM 18481161 ER PT J AU Ziegler, DS Wright, RD Kesari, S Lemieux, ME Tran, MA Jain, M Zawel, L Kung, AL AF Ziegler, David S. Wright, Renee D. Kesari, Santosh Lemieux, Madeleine E. Tran, Mary A. Jain, Monish Zawel, Leigh Kung, Andrew L. TI Resistance of human glioblastoma multiforme cells to growth factor inhibitors is overcome by blockade of inhibitor of apoptosis proteins SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ALPHA-DEPENDENT APOPTOSIS; HUMAN-MALIGNANT GLIOMA; X-LINKED INHIBITOR; PHASE-II TRIAL; FACTOR RECEPTOR; IMATINIB MESYLATE; KINASE INHIBITOR; CANCER-CELLS; SELECTIVE INHIBITOR; AKT INACTIVATION AB Multiple receptor tyrosine kinases (RTKs), including PDGFR, have been validated as therapeutic targets in glioblastoma multiforme (GBM), yet inhibitors of RTKs have had limited clinical success. As various antiapoptotic mechanisms render GBM cells resistant to chemo- and radiotherapy, we hypothesized that these antiapoptotic mechanisms also confer resistance to RTK inhibition. We found that in vitro inhibition of PDGFR in human GBM cells initiated the intrinsic pathway of apoptosis, as evidenced by mitochondrial outer membrane permeabilization, but downstream caspase activation was blocked by inhibitor of apoptosis proteins (IAPs). Consistent with this, inhibition of PDGFR combined with small molecule inactivation of IAPs induced apoptosis in human GBM cells in vitro and had synergistic antitumor effects in orthotopic mouse models of GBM and in primary human GBM neurospheres. These results demonstrate that concomitant inhibition of IAPs can overcome resistance to RTK inhibitors in human malignant GBM cells, and suggest that blockade of IAPs has the potential to improve treatment outcomes in patients with GBM. C1 [Ziegler, David S.; Wright, Renee D.; Lemieux, Madeleine E.; Kung, Andrew L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ziegler, David S.; Wright, Renee D.; Lemieux, Madeleine E.; Kung, Andrew L.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Kesari, Santosh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Kesari, Santosh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA 02115 USA. [Kesari, Santosh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Tran, Mary A.; Jain, Monish; Zawel, Leigh] Novartis Inst BioMed Res, Cambridge, MA USA. RP Kung, AL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Mayer 649, Boston, MA 02115 USA. EM andrew_kung@dfci.harvard.edu RI Kesari, Santosh/E-8461-2013; OI Lemieux, Madeleine/0000-0001-6355-8691; Kung, Andrew/0000-0002-9091-488X FU Dana-Farber Cancer Institute; Royal Australasian College of Physicians Rowden White Fellowship; Hagerty Fund Research Award; Leonard Florence Brain Tumor Fund; Australian-American Fulbright Commission FX This work was supported by grants From the Dana-Farber Cancer Institute-Novartis Drug Discovery Program (to A.L. Kung), the Royal Australasian College of Physicians Rowden White Fellowship (to D.S. Ziegler), the Hagerty Fund Research Award (to D.S. Ziegler, S. Kesari, and A.L. Kung), the Leonard Florence Brain Tumor Fund (to S. Kesari), and the Australian-American Fulbright Commission (to D.S. Ziegler). NR 62 TC 53 Z9 54 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2008 VL 118 IS 9 BP 3109 EP 3122 DI 10.1172/JCI34120 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 344OF UT WOS:000258936500015 PM 18677408 ER PT J AU Goldstein, LJ O'Neill, A Sparano, JA Perez, EA Shulman, LN Martino, S Davidson, NE AF Goldstein, Lori J. O'Neill, Anne Sparano, Joseph A. Perez, Edith A. Shulman, Lawrence N. Martino, Silvana Davidson, Nancy E. TI Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American breast cancer intergroup trial E 2197 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID PHASE-III TRIAL; COOPERATIVE-ONCOLOGY-GROUP; COLONY-STIMULATING FACTOR; ADJUVANT CHEMOTHERAPY; COMBINATION CHEMOTHERAPY; 1ST-LINE CHEMOTHERAPY; ESTROGEN-RECEPTOR; PATIENTS PTS; FOLLOW-UP; PACLITAXEL AB Purpose The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant regimen. Doxorubicin and docetaxel (AT) is one of the most active cytotoxic regimens for metastatic breast cancer. The purpose of this trial was to determine whether adjuvant AT improved disease-free survival compared with AC in operable breast cancer. Patients and Methods Women with invasive breast cancer were eligible if there were one to three positive lymph nodes or if the node-negative tumor was greater than 1 cm. Patients were randomly assigned after surgery to receive doxorubicin (60 mg/ m(2)) plus either cyclophosphamide (600 mg/ m(2); AC) or docetaxel (60 mg/ m(2); AT) given every 3 weeks for four cycles, followed by hormone therapy for patients with estrogen receptor (ER) and/ or progesterone receptor (PR)-positive tumors. Results There were 2,882 eligible patients enrolled. After a median follow-up of 79.5 months, there was no significant difference in disease-free survival (DFS; 85% in both arms) or overall survival (91% v 92%) at 5 years. The hazard ratio for AC versus AT was 1.02 (95% Cl for DFS, 0.86 to 1.22; P =.78). In an exploratory analysis of prespecified stratification factors by ER and PR expression there were trends toward improved DFS for AT in ER/ PR-negative disease. Grade 3 neutropenia associated with fever or infection occurred more often with AT (26% v 10%; P <.05). Conclusion AT did not improve DFS or overall survival in this population, and was associated with more toxicity. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Mayo Clin, Jacksonville, FL 32224 USA. Angeles Clin & Res Inst, Santa Monica, CA USA. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Goldstein, Lori J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Goldstein, LJ (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM lori.goldstein@fccc.edu FU NCI NIH HHS [CA14958, CA16116, CA21115, CA027525, CA23318, CA25224, CA27525, CA32102, CA32291, CA66636, P30-CA006927] NR 36 TC 72 Z9 75 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2008 VL 26 IS 25 BP 4092 EP 4099 DI 10.1200/JCO.2008.16.7841 PG 8 WC Oncology SC Oncology GA 350KB UT WOS:000259350200007 PM 18678836 ER PT J AU Meyerhardt, JA Niedzwiecki, D Hollis, D Saltz, LB Mayer, RJ Nelson, H Whittom, R Hantel, A Thomas, J Fuchs, CS AF Meyerhardt, Jeffrey A. Niedzwiecki, Donna Hollis, Donna Saltz, Leonard B. Mayer, Robert J. Nelson, Heidi Whittom, Renaud Hantel, Alexander Thomas, James Fuchs, Charles S. TI Impact of body mass index and weight change after treatment on cancer recurrence and survival in patients with stage III colon cancer: Findings from cancer and leukemia group B 89803 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR-I; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; BREAST-CANCER; RECTAL-CANCER; RISK; OBESITY; INSULIN; WOMEN; MEN AB Purpose Obesity is a risk factor for the development of colon cancer. However, the influence of body mass index (BMI) on the outcome of patients with established colon cancer remains uncertain. Moreover, the impact of change in body habitus after diagnosis has not been studied. Patients and Methods We conducted a prospective, observational study of 1,053 patients who had stage III colon cancer and who were enrolled on a randomized trial of adjuvant chemotherapy. Patients reported on height and weight during and 6 months after adjuvant chemotherapy. Patients were observed for cancer recurrence or death. Results In this cohort of patients with stage III cancer, 35% of patients were overweight (BMI, 25 to 29.9 kg/m(2)), and 34% were obese (BMI >= 30 kg/m(2)). Increased BMI was not significantly associated with a higher risk of colon cancer recurrence or death (P trend =.54). Compared with normal-weight patients (BMI, 21 to 24.9 kg/m(2)), the multivariate hazard ratio for disease-free survival was 1.00 (95% CI, 0.72 to 1.40) for patients with class I obesity (BMI, 30 to 34.9 kg/m(2)) and 1.24 (95% CI, 0.84 to 1.83) for those with class II to III obesity (BMI >= 35 kg/m(2)) after analysis was adjusted for tumor-related prognostic factors, physical activity, tobacco history, performance status, age, and sex. Similarly, after analysis was controlled for BMI, weight change (either loss or gain) during the time period between ongoing adjuvant therapy and 6 months after completion of therapy did not significantly impact on cancer recurrence and/or mortality. Conclusion Neither BMI nor weight change was significantly associated with an increased risk of cancer recurrence and death in patients with colon cancer. C1 [Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Leukemia Grp Stat Ctr B, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. Ohio State Univ, Columbus, OH 43210 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jmeyerhardt@partners.org OI Saltz, Leonard/0000-0001-8353-4670 FU National Cancer Institute [CA32291, CA33601, CA77651, CA25224, CO15, CA38926, CA32101, CA46282, CA21076, P50CA127003, R01 CA 118553-01A2, K07CA097992]; Pharmacia Upjohn Co FX Supported by Grants No. CA32291; CA33601; CA77651; CA25224; CO15; CA38926, CA32101, CA46282; CA21076; P50CA127003; R01 CA 118553- 01A2; and K07CA097992 from the National Cancer Institute. Also supported by Pharmacia & Upjohn Co, now Pfizer Oncology. NR 41 TC 113 Z9 113 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2008 VL 26 IS 25 BP 4109 EP 4115 DI 10.1200/JCO.2007.15.6687 PG 7 WC Oncology SC Oncology GA 350KB UT WOS:000259350200009 PM 18757324 ER PT J AU Herndon, JE Kornblith, AB Holland, JC Paskett, ED AF Herndon, James E. Kornblith, Alice B. Holland, Jimmie C. Paskett, Electra D. TI Patient education level as a predictor of survival in lung cancer clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LEUKEMIA GROUP-B; NON-SMALL-CELL; AFRICAN-AMERICAN PATIENTS; QUALITY-OF-LIFE; PHASE-III TRIAL; SOCIOECONOMIC-STATUS; BREAST-CANCER; PROGNOSTIC-FACTORS; PROSTATE-CANCER; STAGE AB Purpose To investigate the effect of socioeconomic status, as measured by education, on the survival of 1,577 lung cancer patients treated on 11 studies conducted by the Cancer and Leukemia Group B. Patients and Methods Sociodemographic data, including education, was reported by the patient at the time of clinical trial accrual. Cox proportional hazards model stratified by treatment arm/ study was used to examine the effect of education on survival after adjustment for known prognostic factors. Results The patient population included 1,177 patients diagnosed with non-small-cell lung cancer (NSCLC; stage III or IV) and 400 patients diagnosed with small-cell lung cancer (SCLC; extensive or limited). Patients with less than an eighth grade education (13% of patients) were significantly more likely to be male, nonwhite, and older; have a performance status (PS) of 1 or 2; and have chest pain. Significant predictors of poor survival in the final model included male sex, PS of 1 or 2, dyspnea, weight loss, liver or bone metastases, unmarried, presence of adrenal metastases and high alkaline phosphatase levels among patients with NSCLC, and high WBC levels among patients with advanced disease. Education was not predictive of survival. Conclusion The physical condition of patients with low education who enroll onto clinical trials is worse than patients with higher education. Once enrolled onto a clinical trial, education does not affect the survival of patients with SCLC or stage III or IV NSCLC. The standardization of treatment and follow-up within a clinical trial, regardless of education, is one possible explanation for this lack of effect. C1 [Herndon, James E.] Duke Univ, Med Ctr, Canc Stat Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Herndon, JE (reprint author), Duke Univ, Med Ctr, Canc Stat Ctr, Dept Biostat & Bioinformat, Hock Plaza,Ste 802,Box 2717, Durham, NC 27710 USA. EM james.herndon@duke.edu FU National Cancer Institute [CA32291, CA77651, CA77658] FX Supported by Grants No. CA32291, CA77651, and CA77658 from the National Cancer Institute. NR 52 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2008 VL 26 IS 25 BP 4116 EP 4123 DI 10.1200/JCO.2008.16.7460 PG 8 WC Oncology SC Oncology GA 350KB UT WOS:000259350200010 PM 18757325 ER PT J AU Smith, AK McCarthy, EP Paulk, E Balboni, TA Maciejewski, PK Block, SD Prigerson, HG AF Smith, Alexander K. McCarthy, Ellen P. Paulk, Elizabeth Balboni, Tracy A. Maciejewski, Paul K. Block, Susan D. Prigerson, Holly G. TI Racial and ethnic differences in advance care planning among patients with cancer: Impact of terminal illness acknowledgment, religiousness, and treatment preferences SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OF-LIFE CARE; BLACK-AND-WHITE; NURSING-HOME RESIDENTS; NOT-RESUSCITATE ORDERS; AFRICAN-AMERICAN; SUSTAINING TREATMENTS; RACE MATTERS; HOSPICE USE; END; DIRECTIVES AB Purpose Despite well-documented racial and ethnic differences in advance care planning (ACP), we know little about why these differences exist. This study tested proposed mediators of racial/ethnic differences in ACP. Patients and Methods We studied 312 non-Hispanic white, 83 non-Hispanic black, and 73 Hispanic patients with advanced cancer in the Coping with Cancer study, a federally funded multisite prospective cohort study designed to examine racial/ethnic disparities in ACP and end-of-life care. We assessed the impact of terminal illness acknowledgment, religiousness, and treatment preferences on racial/ethnic differences in ACP. Results Compared with white patients, black and Hispanic patients were less likely to have an ACP (white patients, 80%; black patients, 47%; Hispanic patients, 47%) and more likely to want life-prolonging care even if he or she had only a few days left to live (white patients, 14%; black patients, 45%; Hispanic patients, 34%) and to consider religion very important (white patients, 44%; black patients, 88%; Hispanic patients, 73%; all P < .001, comparison of black or Hispanic patients with white patients). Hispanic patients were less likely and black patients marginally less likely to acknowledge their terminally ill status (white patients, 39% v Hispanic patients, 11%; P < .001; white v black patients, 27%; P = .05). Racial/ethnic differences in ACP persisted after adjustment for clinical and demographic factors, terminal illness acknowledgment, religiousness, and treatment preferences (has ACP, black v white patients, adjusted relative risk, 0.64 [ 95% Cl, 0.49 to 0.83]; Hispanic v white patients, 0.65 [ 95% Cl, 0.47 to 0.89]). Conclusion Although black and Hispanic patients are less likely to consider themselves terminally ill and more likely to want intensive treatment, these factors did not explain observed disparities in ACP. C1 [Smith, Alexander K.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Brookline, MA 02446 USA. Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Univ Texas SW Med Ctr Dallas, Palliat Care Serv, Dallas, TX 75390 USA. Yale Univ, Sch Med, Dept Psychiat, Womens Hlth Res & Magnet Resonance Res Ctr, New Haven, CT USA. RP Smith, AK (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 1309 Beacon St, Brookline, MA 02446 USA. EM asmith7@bidmc.harvard.edu FU National Institutes of Health [MH63892, CA106370]; institutional National Research Service Award [5 T32 HP11001-19] FX Supported by the National Institutes of Health Grants No. MH63892 and CA106370 (grants to the Coping with Cancer study) and by an institutional National Research Service Award (Grant No. 5 T32 HP11001-19 to A. K. S.). NR 47 TC 89 Z9 89 U1 2 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2008 VL 26 IS 25 BP 4131 EP 4137 DI 10.1200/JCO.2007.14.8452 PG 7 WC Oncology SC Oncology GA 350KB UT WOS:000259350200012 PM 18757326 ER PT J AU Carlson, JW Miron, A Jarboe, EA Parast, MM Hirsch, MS Lee, YH Muto, MG Kindelberger, D Crum, CP AF Carlson, Joseph W. Miron, Alexander Jarboe, Elke A. Parast, Mana M. Hirsch, Michelle S. Lee, Yonghee Muto, Michael G. Kindelberger, David Crum, Christopher P. TI Serous tubal Intraepithelial carcinoma: Its potential role in primary peritoneal serous carcinoma and serous cancer prevention SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID REDUCING SALPINGO-OOPHORECTOMY; FALLOPIAN-TUBE; MUTATION CARRIERS; OVARIAN-CARCINOMA; PROPHYLACTIC OOPHORECTOMY; PATHOLOGICAL FINDINGS; CANDIDATE PRECURSOR; BRCA MUTATIONS; WOMEN; SPECIMENS AB Purpose A diagnosis of primary peritoneal serous carcinoma (PPSC) requires exclusion of a source in other reproductive organs. Serous tubal intraepithelial carcinoma (STIC; stage 0) has been described in asymptomatic women with BRCA mutations and linked to a serous cancer precursor in the fimbria. This study examined the frequency of STIC in PPSC and its clinical outcome in BRCA-positive women. Patients and Methods Presence or absence of STIC was recorded in consecutive cases meeting the 2001 WHO criteria for PPSC, including 26 patients with nonuniform sampling of the fallopian tubes (group 1) and 19 patients with complete tubal examination (group 2; sectioning and extensively examining the fimbriated end, or SEE-FIM protocol). In selected cases, STIC or its putative precursor and the peritoneal tumor were analyzed for p53 mutations (exons 1 to 11). Outcome of STIC was ascertained by literature review. Result Thirteen (50%) of 26 PPSCs in group 1 involved the endosalpinx, with nine STICs (35%). Fifteen (79%) of 19 cases in group 2 contained endosalpingeal involvement, with nine STICs (47%). STIC was typically fimbrial and unifocal, with variable invasion of the tubal wall. In five of five cases, the peritoneal and tubal lesion shared an identical p53 mutation. Of 10 reported STICs in BRCA-positive women, all patients were without disease on follow-up. Conclusion The fimbria is the source of nearly one half of PPSCs, suggesting serous malignancy originates in the tubal mucosa but grows preferentially at a remote peritoneal site. The generally low risk of recurrence in stage 0 (STIC) disease further underscores STIC as a possible target for early serous cancer detection and prevention. C1 [Crum, Christopher P.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. EM ccrum@partners.org OI Carlson, Joseph/0000-0002-3006-4107 FU National Cancer Institute [P50 CA10500 [SPORE]]; D. Cramer, principal investigator [NCI KO8 CA108748]; R. Drapkin, principal investigator [NCI 1R21CA124688- 01A1]; C. P. C., principal investigator; Charlotte Geyer Foundation (C. P. C., principal investigator); Columbia Hospital for Women Research Foundation (C. P. C., principal investigator); Dana-Farber Cancer Institute; Francis Ward Paine; TSA Pemberton Funds from the Division of Women's and Perinatal Pathology, Brigham and Women's Hospital FX Supported by grants from the National Cancer Institute (Grants No. P50 CA10500 [SPORE]: D. Cramer, principal investigator; NCI KO8 CA108748, R. Drapkin, principal investigator; NCI 1R21CA124688- 01A1, C. P. C., principal investigator), the Charlotte Geyer Foundation (C. P. C., principal investigator), the Columbia Hospital for Women Research Foundation (C. P. C., principal investigator), the Dana- Farber Cancer Institute, and the Francis Ward Paine and TSA Pemberton Funds from the Division of Women's and Perinatal Pathology, Brigham and Women's Hospital. NR 28 TC 163 Z9 173 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2008 VL 26 IS 25 BP 4160 EP 4165 DI 10.1200/JCO.2008.16.4814 PG 6 WC Oncology SC Oncology GA 350KB UT WOS:000259350200016 PM 18757330 ER PT J AU Keedy, V Wang, W Schiller, J Chada, S Slovis, B Coffee, K Worrell, J Thet, LA Johnson, DH Carbone, DP AF Keedy, Vicki Wang, Wei Schiller, Joan Chada, Sunil Slovis, Bonnie Coffee, Keith Worrell, John Thet, Lyn A. Johnson, David H. Carbone, David P. TI Phase I study of adenovirus p53 administered by bronchoalveolar lavage in patients with bronchioloalveolar cell lung carcinoma: ECOG 6597 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL Chicago, IL SP Amer Soc Clin Oncol ID GENE-TRANSFER; CANCER; CHEMOTHERAPY; THERAPY AB Purpose This pilot phase I trial evaluated the safety and maximum- tolerated dose of p53 gene transfer using an adenovirus vector (Ad-p53) delivered via bronchoalveolar lavage (BAL) to patients with bronchioloalveolar lung carcinoma (BAC). Patients and Methods Patients were initially administered two treatments of Ad-p53 to a single involved lobe, beginning at 2 x 10(9) viral particles (vp) per dose and escalated to a maximum of 2 x 1012 vp. If a clinical benefit was seen and the treatment was well tolerated, additional doses could be administered to additional lobes. Results Twenty-five patients were treated at doses between 2 x 109 and 2 x 10(12) vp. At 2 x 10(12) vp, one patient experienced grade 4 pulmonary toxicity, and one patient died 25 days after his second cycle; therefore, a cohort of 10 patients was treated at the recommended phase II dose of 5 x 10(11) vp, with no grade 4 toxicity observed. The most frequent toxicities included low-grade fever, hypoxia, and dyspnea. Of the 23 assessable patients, 16 had stable disease as their best response. Subjective improvement in breathing was noted in eight patients. Limited distribution of vector was observed, with transient detection in patient sputum for 1 to 2 days after administration. Conclusion Ad-p53 can be administered safely by BAL at 5 x 10(11) vp with repeated dosing. Stabilization of disease and symptomatic improvement may warrant further studies of Ad-p53 or other adenoviruses administered by BAL in patients with BAC. C1 [Carbone, David P.] Vanderbilt Univ, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Introgen Therapeut Inc, Houston, TX USA. Univ Wisconsin, Ctr Canc, Madison, WI USA. RP Carbone, DP (reprint author), Vanderbilt Univ, Dept Med, Vanderbilt Ingram Canc Ctr, 2220 Pierce Ave,685 Preston Res Bldg, Nashville, TN 37232 USA. EM david.carbone@vanderbilt.edu RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA21076, CA21115, CA23318, CA49957, CA66636, CA68485, CA90949] NR 19 TC 15 Z9 17 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2008 VL 26 IS 25 BP 4166 EP 4171 DI 10.1200/JCO.2007.15.6927 PG 6 WC Oncology SC Oncology GA 350KB UT WOS:000259350200017 PM 18757331 ER PT J AU Adler, LA Goodman, DW Kollins, SH Weisler, RH Krishnan, S Zhang, YX Biederman, J AF Adler, Lenard A. Goodman, David W. Kollins, Scott H. Weisler, Richard H. Krishnan, Suma Zhang, Yuxin Biederman, Joseph TI Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; YOUNG-ADULTS; ADHD; METHYLPHENIDATE; CHILDREN; ADOLESCENTS; PREVALENCE; RELEASE; MISUSE AB Objective: To evaluate the efficacy and safety of 30, 50, and 70 mg/day lisdexamfetamine dimesylate compared with placebo in adults with attention-deficit/hyperactivity disorder (ADHD). Method: Following a 7- to 28-day washout, 420 adults aged 18 to 55 years with moderate to severe ADHD (DSM-IV-TR criteria) were treated with 30, 50, or 70 mg/day lisdexamfetamine or placebo, respectively, for 4 weeks (N = 119, 117, 122, and 62, respectively). The 50- and 70-mg/day groups underwent forced-dose titration. The primary efficacy measure was the clinician determined ADHD Rating Scale (ADHD-RS) total score. The study was conducted from May 2006 to November 2006. Results: Treatment groups were well matched at baseline, including in ADHD-RS scores. At endpoint, changes in ADHD-RS scores were significantly greater for each lisdexamfetamine dose than for placebo (placebo = -8.2, 30 mg/day lisdexamfetamine = -16.2, 50 mg/day lisdexamfetamine = -17.4, 70 mg/day lisdexamfetamine = -18.6; all p < .0001 vs. placebo), with no differences between doses. Significant differences relative to placebo were observed in each fisdexamfetamine group, beginning at week I and for each week throughout. The percentage of subjects who improved (Clinical Global Impressions-Improvement scale rating ! 2) was significantly greater for each lisdexamfetamine close than for placebo at each week and at endpoint (placebo 29%, 30 mg/day lisdexamfetamine = 57%, 50 mg/day lisdexamfetamine = 62%, 70 mg/day lisdexamfetamine = 61%; all p < .01). Adverse events were generally mild and included dry mouth, decreased appetite, and insomnia. Conclusion: All 3 lisdexamfetamine doses were significantly more effective than placebo in the treatment of adults with ADHD, with improvements noted within 1 week. Lisdexam-fetamine was generally well tolerated by these patients. C1 [Adler, Lenard A.] NYU, Dept Psychiat & Child & Adolescent Psychiat, Langone Sch Med, New York, NY 10016 USA. [Adler, Lenard A.] New York VA Harbor Healthcare Syst, New York, NY USA. [Goodman, David W.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Kollins, Scott H.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Weisler, Richard H.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Krishnan, Suma] New River Pharmaceut Inc, Belvedere, CA USA. [Zhang, Yuxin] XTiers Consulting Inc, Potomac, MD USA. [Biederman, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program Pediat Psychopharmacol, Boston, MA USA. RP Adler, LA (reprint author), NYU, Sch Med, Dept Psychiat, 530 1st Ave,7D, New York, NY 10016 USA. EM lenard.adler@med.nyu.edu RI Kollins, Scott/G-2965-2012 FU Shire Development Inc., Wayne, Pa; Shire Development Inc; Abbott; Cortex; Bristol-Myers Squibb; Merck; Novartis; Pfizer; Shire; Eli Lilly; Ortho-McNeii/Janssen/Johnson & Johnson, New River; Cephalon; National Institute on Drug Abuse; Organon; Sanofiaventis; Psychogenics; Forest; CoMentis; Addrenex; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; United States Environmental Protection Agency; AstraZeneca; Biovail; Burroughs Wellcome; Ciba Geigy; Corcept; Eisai; Janssen; Lundbeck; McNeil; Medicinova; Neurochem; Otsuka America; Pharmacia; Saegis; Sanofi; Sanofi-Synthelabo; Schwabe/Ingenix; Alza; National Institute of Child Health & Human Development; Celltech; National Alliance for Research on Schizophrenia and Depression; Noven; Neurosearch; Prechter Foundation; Stanley Foundation; Wyeth FX Supported by funding from Shire Development Inc., Wayne, Pa.; Members of the 303 Study Group are listed at the end of the article. Editorial assistance was provided by Richard Alexander, Ph.D., of Health Learning Systems, part of Common Health, and George Brown, Ph.D., formerly of Health Learning Systems, and funded by Shire Development Inc. Drs. Alexander and Brown report no additional financial or other relationships relevant to the subject of this article.; Dr. Adler has received grant/research support from Abbott, Cortex, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Shire, Eli Lilly, Ortho-McNeii/Janssen/Johnson & Johnson, New River, Cephalon, National Institute on Drug Abuse, Organon, sanofiaventis, and Psychogenics; is a member of the speakers bureaus for Eli Lilly and Shire; and is a member of the advisory boards and consultant for Abbott, Cortex, Novartis, Pfizer, Shire, Eli Lilly, Ortho-McNeil/Janssen/Johnson & Johnson, New River, Cephalon, Merck, Organon, and sanofi-aventis. Dr. Goodman has received grant/research support from Forest, Shire, McNeil, Cephalon, and New River; has received honoraria from and is a member of the speakers bureaus for GlaxoSmithKline, Forest, Eli Lilly, Shire, McNeil, Wyeth, and Novartis; and is a consultant for GlaxoSmithKline, Forest, Eli Lilly, Shire, McNeil, New River, and Novartis. Dr. Kollins is a consultant for Shire, CoMentis. Eli Lilly, National Institute on Drug Abuse, and Addrenex and has received grant/research support from Shire, CoMentis, Addrenex, PsychoGenics, National Institute on Drug Abuse, National Institute of Mental Health, National Institute of Environmental Health Services, National Institute of Neurological Disorders and Stroke, and the United States Environmental Protection Agency. Dr. Weisler is or has been a consultant to, a member of the speakers bureaus for, and/or received research support from the National Institute of Mental Health, Abbott, AstraZeneca, Biovail, Bristol-Myers Squibb, Burroughs Wellcome, Cephalon, Ciba Geigy, CoMentis, Corcept, Eisai, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson, Lundbeck, McNeil, Medicinova, Merck, Neurochem, New River, Novartis, Organon, Otsuka America, Pfizer, Pharmacia, Saegis, Sanofi, Sanofi-Synthelabo, Schwabe/Ingenix, Shire. Solvay, Synaptic, TAP, UCB Pharma, Vela, and Wyeth and has been a stock shareholder in Bristol-Myers Squibb, Cortex, Merck, and Pfizer. Ms. Krishnan is a former employee of New River. Dr. Biederman currently receives research support from Alza, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, McNeil, Merck, Organon, Otsuka, Shire, National Institute of Mental Health, and National Institute of Child Health and Human Development; is a consultant/advisory board member for Janssen, McNeil, Novartis, and Shire; is a member of the speakers bureaus for Janssen, McNeil, Novartis, Shire, and UCB Pharma; and has in previous years received research support, consultation fees, or speaker's fees from Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly, Eisai, Forest, Glaxo, Gliatech, National Alliance for Research on Schizophrenia and Depression, National Institute on Drug Abuse, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, Prechter Foundation, Stanley Foundation, and Wyeth. Dr. Zhang reports no additional financial or other relationship relevant to the subject of this article. NR 32 TC 115 Z9 116 U1 0 U2 13 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2008 VL 69 IS 9 BP 1364 EP + PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 355NV UT WOS:000259716500003 PM 19012818 ER PT J AU Spencer, TJ Adler, LA Weisler, RH Youcha, SH AF Spencer, Thomas J. Adler, Lenard A. Weisler, Richard H. Youcha, Sharon H. TI Triple-bead mixed amphetamine salts (SPD465), a novel, enhanced extended-release amphetamine formulation for the treatment of adults with ADHD: A randomized, double-blind, multicenter, placebo-controlled study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; CHILDREN; IMPAIRMENTS; DIAGNOSIS; EFFICACY AB Introduction: The efficacy and safety of triple-bead mixed amphetamine salts (MAS), an oral, once-daily, enhanced extended-re lease amphetamine formulation designed for a duration of action up to 16 hours, were evaluated in adults with attention-deficit/hyperactivity disorder (ADHD). Method: In this phase 3, 7-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, dose-optimization study of 272 adults with ADHD (DSM-IV-TR criteria), subjects (aged 18 to 55 years) were randomly assigned to triple-bead MAS (starting dose 12.5 mg) or placebo. The primary outcome measure was change in ADHD Rating Scale-IV (ADHD-RS-IV). Secondary outcome measures included Clinical Global Impressions (CGI) scale, Time-Sensitive ADHD Symptom Scale (TASS) (measuring extended duration), Brown Attention-Deficit Disorder Scale (BADDS) (measuring executive function), Adult ADHD Impact Module (AIM-A) (measuring quality of life [QOL]), and ADHD-RS-IV hyperactivity-impulsivity and inattentiveness subscales. Adverse events (AEs), vital signs, electrocardiograms (ECGs), and laboratory data were collected. The trial was conducted from January 2005 to June 2005. Results: Triple-bead MAS resulted in significantly greater improvement versus placebo in mean ADHD-RS-IV total score change (p < .0001), CGI-Improvement (p < .0001), TASS total score at 13-16 hours postdose (p = .002), BADDS total score (p < .0001), all AIM-A domains (p <= .01), and ADHD-RS-IV subscales (p <= .01), demonstrating extended duration of efficacy and improvements in executive function and QOL. The most common treatment-emergent AEs included insomnia, dry mouth, decreased appetite and weight, and headache. Most treatment-emergent AEs were mild or moderate in severity. Conclusions: Triple-bead MAS was significantly more effective than placebo in treating adult ADHD. The extended duration of action up to 16 hours and significant improvements in executive function and QOL address unique treatment needs of adults with ADHD. Treatment-emergent AEs with triple-bead MAS were consistent with amphetamine treatment. C1 [Spencer, Thomas J.] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Dept Psychiat, Boston, MA 02114 USA. [Spencer, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Adler, Lenard A.] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Weisler, Richard H.] Duke Univ, Med Ctr, Dept Psychiat, Raleigh, NC USA. [Weisler, Richard H.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Youcha, Sharon H.] Shire Dev Inc, Wayne, PA USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Dept Psychiat, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM spencer@helix.mgh.harvard.edu FU Shire Development Inc FX Supported by funding from Shire Development Inc. NR 34 TC 36 Z9 36 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2008 VL 69 IS 9 BP 1437 EP 1448 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 355NV UT WOS:000259716500011 PM 19012813 ER PT J AU Mischoulon, D Fava, M AF Mischoulon, David Fava, Maurizio TI Are nutritional supplements ready for prime time? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID NATURAL REMEDIES; UNITED-STATES; TRIAL; OMEGA-3-FATTY-ACIDS; METAANALYSIS; DEPRESSION; PSYCHIATRY; METHIONINE; DISORDERS; MEDICINE C1 [Mischoulon, David; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. NR 23 TC 8 Z9 8 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2008 VL 69 IS 9 BP 1497 EP 1498 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 355NV UT WOS:000259716500018 PM 19193349 ER PT J AU Cantwell, CP Setty, BN Holalkere, N Sahani, DV Fischman, AJ Blake, MA AF Cantwell, Colin Patrick Setty, Bindit N. Holalkere, Nagaraj Sahani, Dushyant V. Fischman, Alan J. Blake, Michael A. TI Liver Lesion Detection and Characterization in Patients With Colorectal Cancer: A Comparison of Low Radiation Dose Non-enhanced PET/CT, Contrast-enhanced PET/CT, and Liver MRI SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE colorectal carcinoma; PET/CT; MRI; characterization; detection ID POSITRON-EMISSION-TOMOGRAPHY; FDG-PET; METASTASES; CT; RESECTION; ADENOCARCINOMA; ACCURACY; LYMPHOMA; SYSTEM; IMPACT AB Objectives: To compare low-radiation dose nonenhanced fluorine 18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) (NE-PET/CT), contrast-enhanced fluorine 18 fluorodeoxyglucose PET/CT (CE-PET/CT), and gadolinium-enhanced liver magnetic resonance imaging (MRI) for the detection and characterization of liver lesions in patients with colorectal cancer (CRC). Methods: In this retrospective review of imaging database of CRC patients with suspected liver metastases, 33 patients (22 men, I I women mean age, 63 years) evaluated with low-radiation dose NE-PET/CT, CE-PET/CT, and liver MRI were studied. The final diagnosis was established either by pathological examination or follow-up imaging over a period of at least 6 months for lesion stability or growth. The liver lesions were characterized on an ordinal scale of 0 to 6 (0 = absent, 1 - definitely benign, and 6 = definitely malignant). Receiver operating characteristic analysis was performed to compare performance of the 3 imaging methods. Results: A total of I 10 lesions were present on follow-up. The detection rate on low-radiation dose NE-PET/CT, CE-PET/CT, and MRI was 73.6%, 90.9%, and 95.4%, respectively. Magnetic resonance imaging (P < 0.001) and CE-PET/CT (P < 0.001) had a higher detection rate than low-radiation dose NE-PET/CT. There was no significant statistical difference in lesion detection between MRI and CE-PET/CT (P = 0.11). The sensitivity, specificity, and accuracy for characterization of detected liver lesions on low-radiation dose NE-PET/CT were 67%, 60%, and 66%, respectively; those on CE-PET/CT were 85%, 100%. and 86%, respectively and those on MRI were 98%, 100%, and 98%, respectively Comparative receiver operating characteristic analysis showed an area under curve of 0.74 for low-radiation dose NE-PET/CT, 0.86 for CE-PET/CT, and 0.97 for MRI. There were statistically significant differences in the accuracy of MRI, low-radiation dose NE-PET/CT, and CE-PET/CT for lesion characterization. Conclusions: When performing PET/CT, optimal detection and characterization of liver lesions require the use of a fused contrast-enhanced CT. Magnetic resonance imaging and CE-PET/CT have similar lesion detection rates. Magnetic resonance imaging is the best test for liver lesion characterization in patients with CRC. C1 [Cantwell, Colin Patrick; Setty, Bindit N.; Holalkere, Nagaraj; Sahani, Dushyant V.; Blake, Michael A.] Massachusetts Gen Hosp, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. [Fischman, Alan J.] Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. [Fischman, Alan J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cantwell, CP (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, White Bldg,Room 270,55 Fruit St, Boston, MA 02114 USA. EM ccanty@gofree.indigo.ie NR 20 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2008 VL 32 IS 5 BP 738 EP 744 DI 10.1097/RCT.0b013e3181591d33 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 360SQ UT WOS:000260078400011 PM 18830103 ER PT J AU Hui, GC Legasto, A Wittram, C AF Hui, Gladwin C. Legasto, Alan Wittram, Conrad TI The Prevalence of Symptomatic and Coincidental Pulmonary Embolism on Computed Tomography SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE pulmonary embolism; CTPA; coincidental findings ID NATURAL-HISTORY; HELICAL CT; PHASE-II; DIAGNOSIS; CANCER AB Purpose: To investigate the proportion of pulmonary embolism (PE) on computed tomographic pulmonary angiography (CTPA) and the proportion of coincidental PE on regular contrast-enhanced CT in oncological and nononcological patients. Methods: This study received internal review board approval and was Health Insurance Portability and Accountability Act compliant. All consecutive adult patients who had contrast-enhanced chest CT or dedicated CTPA during January 2005 were studied. procedural codes were used to identify cases, and all CT images were reviewed. Clinical data collected included oncology status, chemotherapy regimen, site of tumor, and location of PE. X 2 Tests were used for statistical analysis. Results: Two hundred twenty-nine patients had CTPA, and 27 (11.8%) of them were positive for PE. Of 1168 patients who had contrast-enhanced CT for other indications, coincidental PE was found in 21 patients (1.8%). The proportions of coincidental PE were 3.3% of patients with progressive cancer, 2.5% of patients with stable cancer, 0.7% of patients with no evidence of cancer posttreatment, and 1.0% of nononcological patients. Coincidental PE was found more frequently in patients with progressive cancer compared with nononcological patients (P = 0.035). Patients who were on chemotherapy also had a higher risk of coincidental PE (P = 0.019). Conclusions: The prevalence of symptomatic PE on dedicated CTPA was 11.8%, and the rate of coincidental PE on contrast-enhanced CT was 1.8%. Coincidental PE was significantly higher in patients with progressive cancer or those receiving chemotherapy. C1 [Hui, Gladwin C.] Univ Toronto, Dept Med Imaging, Toronto, ON M5S 3E2, Canada. [Hui, Gladwin C.] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wittram, Conrad] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hui, GC (reprint author), Univ Toronto, Dept Med Imaging, 150 Coll St,Room 112A, Toronto, ON M5S 3E2, Canada. EM gladwin.hui@utoronto.ca NR 26 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2008 VL 32 IS 5 BP 783 EP 787 DI 10.1097/RCT.0b013e31815a7aea PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 360SQ UT WOS:000260078400020 PM 18830112 ER PT J AU Eap, S DeGarmo, DS Kawakami, A Hara, SN Hall, GCN Teten, AL AF Eap, Sopagna DeGarmo, David S. Kawakami, Ayaka Hara, Shelley N. Hall, Gordon C. N. Teten, Andra L. TI Culture and personality among European American and Asian American men SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article DE Asian Americans; loss of face; acculturation; Big Five personality ID ACCULTURATION SCALE; CHINESE; TRAITS; BIG-5; VALIDATION; PSYCHOLOGY; INVENTORY; PROFILES AB Personality differences between Asian American (N = 320) and European American men (N = 242) and also among Asian American ethnic groups (Korean, Chinese, Japanese, Filipino, and mixed Asian) are examined on the Big Five personality dimension. Personality structures for Asian Americans and European Americans closely replicate established norms. However, congruence is greater for European American and highly acculturated Asian American men than for low acculturated Asian American men. Similar patterns are found for the construct loss of face (LOF). Asian American men with a high concern for LOF are less similar in their personality structure to European American men than Asian American men with low LOF concern. Mean differences are also found among Asian American and European American men, who differ significantly on Extraversion, Conscientiousness, Openness, and Neuroticism. Results indicate that acculturation and LOF are significantly associated with these four personality dimensions for both Asian American and European American men. C1 [Eap, Sopagna] Univ Oregon, Eugene, OR 97403 USA. [DeGarmo, David S.] Oregon Social Learning Ctr, Eugene, OR 97401 USA. [Hara, Shelley N.] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Teten, Andra L.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Eap, S (reprint author), 1227 Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. EM seap@uoregon.edu FU NICHD NIH HHS [R01 HD042115, R01 HD042115-04]; NIDA NIH HHS [P20 DA017592-057874, P20 DA017592]; NIMH NIH HHS [P50 MH073511-02, R01 MH058726, R01 MH058726-03, P50 MH073511] NR 40 TC 16 Z9 16 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD SEP PY 2008 VL 39 IS 5 BP 630 EP 643 DI 10.1177/0022022108321310 PG 14 WC Psychology, Social SC Psychology GA 340QO UT WOS:000258660300006 PM 19169434 ER PT J AU Tseng, AS Levin, M AF Tseng, A. -S. Levin, M. TI Tail regeneration in Xenopus laevis as a model for understanding tissue repair SO JOURNAL OF DENTAL RESEARCH LA English DT Review DE Xenopus; frog; tadpole; tail; regeneration; growth factor; bioelectricity; ion pump ID LEFT-RIGHT ASYMMETRY; AMPHIBIAN LIMB REGENERATION; ZEBRAFISH FIN REGENERATION; I-SCEI MEGANUCLEASE; MATRIX METALLOPROTEINASES; TADPOLE TAIL; STEM-CELLS; SUSTAINED DEPOLARIZATION; MUSCLE REGENERATION; TRANSGENIC XENOPUS AB Augmentation of regenerative ability is a powerful strategy being pursued for the biomedical management of traumatic injury, cancer, and degeneration. While considerable attention has been focused on embryonic stem cells, it is clear that much remains to be learned about how somatic cells may be controlled in the adult organism. The tadpole of the frog Xenopus laevis is a powerful model system within which fundamental mechanisms of regeneration are being addressed. The tadpole tail contains spinal cord, muscle, vasculature, and other terminally differentiated cell types and can fully regenerate itself through tissue renewal - a process that is most relevant to mammalian healing. Recent insight into this process has uncovered fascinating molecular details of how a complex appendage senses injury and rapidly repairs the necessary morphology. Here, we review what is known about the chemical and bioelectric signals underlying this process and draw analogies to evolutionarily conserved pathways in other patterning systems. The understanding of this process is not only of fundamental interest for the evolutionary and cell biology of morphogenesis, but will also generate information that is crucial to the development of regenerative therapies for human tissues and organs. C1 [Levin, M.] Harvard Univ, Sch Dent Med, Ctr Regenerat & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Ctr Regenerat & Dev Biol, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NSF [IBN0347295]; NHTSA [DTNH22-06-G-00001]; DARPA [W911NF-07-1-0572]; NIH [HD055850]; Research Facilities Improvement [CO6RR11244] FX We thank the members of the FCRDB for many useful discussions. The authors gratefully acknowledge support from the NSF (IBN#0347295), NHTSA (DTNH22-06-G-00001), DARPA (W911NF-07-1-0572), and NIH (HD055850). This review was prepared in a Forsyth Institute facility renovated with support from Research Facilities Improvement Grant Number CO6RR11244 from the National Center for Research Resources, NIH. NR 127 TC 35 Z9 35 U1 2 U2 11 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2008 VL 87 IS 9 BP 806 EP 816 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 340SD UT WOS:000258664400007 PM 18719206 ER PT J AU Rezende, TMB Veira, LQ Sobrinho, APR Oliveira, RR Taubman, MA Kawai, T AF Berto Rezende, Taia Maria Veira, Leda Quercia Ribeiro Sobrinho, Antonio Paulino Oliveira, Ricardo Reis Taubman, Martin A. Kawai, Toshihisa TI The influence of mineral trioxide aggregate on adaptive immune responses to endodontic pathogens in mice SO JOURNAL OF ENDODONTICS LA English DT Article DE bacteria; cytokine; immunoglobulin antibody; mineral trioxide aggregate; T cells ID RAT PERIAPICAL LESIONS; CYTOKINE PRODUCTION; BONE-RESORPTION; IN-VITRO; MACROPHAGES; CELLS; IDENTIFICATION; COMPONENTS; INFECTION; ADJUVANTS AB This study assessed the influence of mineral trioxide aggregate (MTA) on adaptive immune responses. BALB/c mice were immunized with heat-killed Fusobacterium nucleatum (Fn) in MTA or other control adjuvants, and serum IgG responses to Fn were measured. Either Fn- or Peptostreptococcus anaerobius (Pa)-reactive memory T cells (Tm) were preincubated in vitro with/without MTA and restimulated with Fn or Pa. Tm proliferation and cytokine production were assessed. Compared with control groups, immunoglobulin G-antibody responses were upregulated in mice immunized with Fn in MTA in a similar manner to animals immunized with Fn in Freund's adjuvant or aluminum hydroxide adjuvant. Although MTA did not affect the upregulated expression of interleukin 10, tumor necrosis factor a, or RANKL by Tm, it suppressed the proliferation of Pa- or Fn-Tm and inhibited their production of Th1- or Th2-signature cytokines. MTA upregulated the adaptive humoral immune responses but had little or no effect on pro- or anti-inflammatory cytokine production by Tm. C1 [Berto Rezende, Taia Maria; Taubman, Martin A.; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. [Berto Rezende, Taia Maria; Ribeiro Sobrinho, Antonio Paulino; Oliveira, Ricardo Reis] Univ Fed Minas Gerais, Fac Odontol, Dept Dent Restauradora, Belo Horizonte, MG, Brazil. [Veira, Leda Quercia] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. EM tkawai@forsyth.org RI Sobrinho, Antonio/H-3245-2012; Rezende, Taia/D-3732-2015 FU NIDCR NIH HHS [DE 03420, K22 DE014551, K22 DE014551-04, R37 DE003420, R01 DE003420, R21 DE018310, DE 14551, DE18310, R01 DE003420-31, R21 DE018310-02] NR 20 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 0099-2399 J9 J ENDODONT JI J. Endod. PD SEP PY 2008 VL 34 IS 9 BP 1066 EP 1071 DI 10.1016/j.joen.2008.06.006 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 344BU UT WOS:000258901200006 PM 18718367 ER PT J AU Berry, AM Korkes, F Ferreira, M Hu, JC AF Berry, Alexander M. Korkes, Fernando Ferreira, Marcos Hu, Jim C. TI Robotic Urethrovesical Anastomosis: Combining Running and Interrupted Sutures SO JOURNAL OF ENDOUROLOGY LA English DT Article ID LAPAROSCOPIC RADICAL PROSTATECTOMY C1 [Hu, Jim C.] Harvard Univ, Sch Med, Dana Faber Canc Ctr, Div Urol,Brigham & Womens Hosp, Boston, MA 02155 USA. RP Hu, JC (reprint author), Harvard Univ, Sch Med, Dana Faber Canc Ctr, Div Urol,Brigham & Womens Hosp, Boston, MA 02155 USA. EM jhu@partners.org NR 3 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 2008 VL 22 IS 9 BP 2127 EP 2129 DI 10.1089/end.2008.0099 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 358EG UT WOS:000259899300091 PM 18811567 ER PT J AU Takizawa, M Tolarova, H Li, Z Dubois, W Lim, S Callen, E Franco, S Mosaico, M Feigenbaum, L Alt, FW Nussenzweig, A Potter, M Casellas, R AF Takizawa, Makiko Tolarova, Helena Li, Zhiyu Dubois, Wendy Lim, Susan Callen, Elsa Franco, Sonia Mosaico, Maria Feigenbaum, Lionel Alt, Frederick W. Nussenzweig, Andre Potter, Michael Casellas, Rafael TI AID expression levels determine the extent of cMyc oncogenic translocations and the incidence of B cell tumor development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS-SWITCH RECOMBINATION; INDUCED CYTIDINE DEAMINASE; ACTIVATION-INDUCED DEAMINASE; SOMATIC HYPERMUTATION; DNA BREAKS; CHROMOSOME BREAKS; PATHWAY; REGION; MICRORNA-155; MECHANISMS AB Immunoglobulin (Ig) isotype switching is a recombination event that changes the constant domain of antibody genes and is catalyzed by activation-induced cytidine deaminase (AID). Upon recruitment to Ig genes, AID deaminates cytidines at switch (S) recombination sites, leading to the formation of DNA breaks. In addition to their role in isotype switching, AID-induced lesions promote Igh-cMyc chromosomal translocations and tumor development. However, cMyc translocations are also present in lymphocytes from healthy humans and mice, and thus, it remains unclear whether AID directly contributes to the dynamics of B cell transformation. Using a plasmacytoma mouse model, we show that AID(+/-) mice have reduced AID expression levels and display haploinsufficiency both in the context of isotype switching and plasmacytomagenesis. At the Ig loci, AID(+/-) lymphocytes show impaired intra- and inter-switch recombination, and a substantial decrease in the frequency of S mutations and chromosomal breaks. In AID(+/-) mice, these defects correlate with a marked decrease in the accumulation of B cell clones carrying Igh-cMyc translocations during tumor latency. These results thus provide a causality link between the extent of AID enzymatic activity, the number of emerging Igh-cMyc-translocated cells, and the incidence of B cell transformation. C1 [Dubois, Wendy; Potter, Michael] NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. [Takizawa, Makiko; Tolarova, Helena; Li, Zhiyu; Lim, Susan; Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA. [Franco, Sonia; Alt, Frederick W.] Childrens Hosp, CBR Inst Biomed Res, Boston, MA 02115 USA. [Franco, Sonia; Alt, Frederick W.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Mosaico, Maria; Feigenbaum, Lionel] NCI, Lab Anim Sci Program, SAIC, NIH, Frederick, MD 21702 USA. RP Potter, M (reprint author), NCI, Genet Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM potter@helix.nih.gov; casellar@mail.nih.gov FU NIAMS; NCI; NIH FX This research was supported in part by the Intramural Research Program of NIAMS and NCI of the NIH. NR 35 TC 90 Z9 93 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 2008 VL 205 IS 9 BP 1949 EP 1957 DI 10.1084/jem.20081007 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 354RI UT WOS:000259656300002 PM 18678733 ER PT J AU Chauhan, AK Kisucka, J Brill, A Walsh, MT Scheiflinger, F Wagner, DD AF Chauhan, Anil K. Kisucka, Janka Brill, Alexander Walsh, Meghan T. Scheiflinger, Friedrich Wagner, Denisa D. TI ADAMTS13: a new link between thrombosis and inflammation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID VON-WILLEBRAND-FACTOR; VONWILLEBRAND-FACTOR MULTIMERS; SELECTIN-DEFICIENT MICE; ROLLING IN-VIVO; THROMBOCYTOPENIC PURPURA; SHEAR-STRESS; P-SELECTIN; PLATELET-ADHESION; FACTOR-VIII; DISEASE AB von Willebrand factor (VWF) levels are elevated and a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) activity is decreased in both acute and chronic inflammation. We hypothesized that by cleaving hyperactive ultralarge VWF (ULVWF) multimers, ADAMTS13 down-regulates both thrombosis and inflammation. Using intravital microscopy, we show that ADAMTS13 deficiency results in increased leukocyte rolling on unstimulated veins and increased leukocyte adhesion in inflamed veins. Both processes were dependent on the presence of VWF. Depletion of platelets in Adamts13(-/-) mice reduced leukocyte rolling, suggesting that platelet interaction with ULVWF contributes to this process. Increased levels of endothelial P-selectin and plasma VWF in Adamts13(-/-) compared with wild-type (WT) mice indicated an elevated release of Weibel-Palade bodies. ULVWF multimers released upon stimulation with histamine, a secretagogue of Weibel-Palade bodies, slowed down leukocyte rolling in Adamts13(-/-) but not in WT mice. Furthermore, in inflammatory models, ADAMTS13 deficiency resulted in enhanced extravasation of neutrophils, and this process was also dependent on VWF. Our findings reveal an important role for ADAMTS13 in preventing excessive spontaneous Weibel-Palade body secretion, and in the regulation of leukocyte adhesion and extravasation during inflammation. C1 [Chauhan, Anil K.; Kisucka, Janka; Brill, Alexander; Walsh, Meghan T.; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Chauhan, Anil K.; Kisucka, Janka; Brill, Alexander; Walsh, Meghan T.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chauhan, Anil K.; Kisucka, Janka; Brill, Alexander; Wagner, Denisa D.] Baxter Biosci, A-1220 Vienna, Austria. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM wagner@idi.harvard.edu FU National Heart, Lung, and Blood Institute [R37 HL041002, P01 HL066105] FX This work was supported by a Sponsored Research Agreement from Baxter Bioscience (to A. K. Chauhan and D. D. Wagner), and National Heart, Lung, and Blood Institute grants R37 HL041002 and P01 HL066105 ( to D. D. Wagner). NR 44 TC 94 Z9 102 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 2008 VL 205 IS 9 BP 2065 EP 2074 DI 10.1084/jem.20080130 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 354RI UT WOS:000259656300012 PM 18695007 ER PT J AU Kleinman, RE AF Kleinman, R. E. TI Protection of the gastrointestinal tract epithelium against damage from low pH beverages SO JOURNAL OF FOOD SCIENCE LA English DT Review DE acid/low pH; beverages; gastrointestinal epithelium; gastrointestinal mucosa; gastrointestinal mucosal protection/defenses ID MUCOSAL ALKALINE SECRETION; GASTRIC MUCUS GLYCOPROTEIN; NECTURUS ANTRAL MUCOSA; ACID-INDUCED INCREASE; POTENTIAL DIFFERENCE; HYDROCHLORIC-ACID; INTRACELLULAR PH; BICARBONATE SECRETION; HCO3-SECRETION; BLOOD-FLOW AB Extensive consumption of low pH beverages such as citrus juices (pHs 2.3 to 4.3), alcoholic beverages (pHs 2.7 to 4.5), and soft drinks (pHs 2.3 to 4.2) has raised the question of whether exposure of the gastrointestinal (GI) tract to acidic beverages will cause damage to the epithelial lining. To evaluate the potential effects of low pH beverages on the GI tract epithelium, a detailed examination of the literature was undertaken. In some animal models, there is evidence of damage to GI epithelial cells following exposure to low pH beverages; however, In these studies there is no definitive relationship between acidity and the amount or severity of damage. Results from several other studies, conducted in both animals and humans, indicate a lack of adverse effects on epithelial cells. Furthermore, there is no evidence that damage is irreversible. Permanent damage from routine exposure to acidic beverages in humans would not be expected because of repair mechanisms that are available to maintain a healthy epithelium. Additionally, numerous physical, chemical, and biological mechanisms are in place to prevent damage to the epithelial cells. Finally, the safe history of consumption of low pH beverages, including various fruit juices, supports the conclusion that low pH beverage Ingestion does not cause damage to the GI epithelium. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kleinman, RE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rkleinman@partners.org NR 95 TC 3 Z9 3 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD SEP PY 2008 VL 73 IS 7 BP R99 EP R105 DI 10.1111/j.1750-3841.2008.00863.x PG 7 WC Food Science & Technology SC Food Science & Technology GA 348MR UT WOS:000259215100003 PM 18803726 ER PT J AU Hermsen, JL Dobrescu, C Kudsk, KA AF Hermsen, Joshua L. Dobrescu, Cosmin Kudsk, Kenneth A. TI Clostridium difficile infection: A surgical disease in evolution SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Clostridium difficile; colitis; colectomy ID HOSPITALIZED-PATIENTS; DIARRHEA; COLITIS; CLINDAMYCIN; COLONIZATION; RESTRICTION; FACILITY; TOXIN AB Introduction Several recent publications suggest an increase in the incidence of Clostridium difficile colitis. However, such studies commonly lack denominators over which to index this rise. There is also concern in the literature that disease virulence is increasing. Methods Billing, admission, operative, and infection databases at a single tertiary care center identified patients admitted from 1990 to 2006 with a diagnosis of C. difficile infection. Grouped by era, case numbers were indexed against overall hospital, operative, and laboratory volumes. C. difficile colectomy cases were individually examined and analyzed. Results The number of hospitalized patients diagnosed with C. difficile colitis increased in a linear fashion during the study period (1990, 14 cases; 2006, 927 cases). The colectomy per C. difficile case ratio did not change over the study period (era 1, 0.17%; era 2, 0.20%; era 3, 0.16%). Thirteen patients underwent colectomy with 54% surviving. The increase in patients admitted with a diagnosis of C. difficile was significantly associated with hospital volume (p=0.04), operative volume (p<0.001), and lab testing volume (p=0.008). Conclusion The number of C. difficile patients admitted to our hospital is rising at an alarming rate. This reflects national trends and urgent action seems warranted to prevent a C. difficile epidemic. C1 [Hermsen, Joshua L.; Dobrescu, Cosmin; Kudsk, Kenneth A.] Univ Wisconsin, Coll Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), Univ Wisconsin, Coll Med & Publ Hlth, Dept Surg, 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu NR 30 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP PY 2008 VL 12 IS 9 BP 1512 EP 1517 DI 10.1007/s11605-008-0569-9 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 339FP UT WOS:000258563800007 PM 18612709 ER PT J AU LaFemina, J Sokal, SM Chang, Y McGrath, D Berger, DL AF LaFemina, Jennifer Sokal, Suzanne M. Chang, Yuchiao McGrath, Deborah Berger, David L. TI Effect of medical or surgical admission on outcome of patients with gallstone pancreatitis and common bile duct stones SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE common bile duct stones; gallstone pancreatitis; admitting team; outcome; cost ID TERM-FOLLOW-UP; COST-EFFECTIVE MANAGEMENT; SINGLE-STAGE MANAGEMENT; TRIAL COMPARING 2-STAGE; GALLBLADDER IN-SITU; ENDOSCOPIC SPHINCTEROTOMY; LONG-TERM; LAPAROSCOPIC CHOLECYSTECTOMY; RANDOMIZED-TRIAL; CHOLEDOCHOLITHIASIS AB Introduction Management of uncomplicated common bile duct stone (CBDS) and gallstone pancreatitis (GP) presumably varies based on whether a patient is admitted to medicine or surgery. This study evaluates the impact of admitting team on outcome and cost. Methods Three hundred seventy patients admitted to the Massachusetts General Hospital for CBDS or GP were retrospectively analyzed for demographics, insurance status, procedures, complications, length of stay, readmission, and cost. A multivariable analysis was conducted for outcome and cost measures. Results Patients admitted to a surgical service were younger than those admitted to a medical service. Gender, race, tobacco use, and the presence of chronic obstructive pulmonary disease and chronic renal insufficiency were not significantly different between groups. Patients admitted to a medical service had a higher incidence of coronary artery disease and diabetes. Despite lower readmission rates for surgical patients, there was no difference in total hospital days between groups. Though total cost of an initial surgical admission was greater than a medical admission, total cost attributable to the index admission diminished over time and ultimately was not significant in follow-up. Conclusions Despite variations in uncomplicated management of CBDS and GP, there is no difference, in long-term follow-up, in the total number of hospital days or cost for the management of CBDS or GP based on admitting team practices. C1 [Berger, David L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [LaFemina, Jennifer; Sokal, Suzanne M.; Chang, Yuchiao; McGrath, Deborah; Berger, David L.] Harvard Univ, Sch Med, Boston, MA USA. [Sokal, Suzanne M.] Massachusetts Gen Hosp, Decis Support & Qual Management Unit, Boston, MA USA. [LaFemina, Jennifer; McGrath, Deborah; Berger, David L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WAC 4-460, Boston, MA 02114 USA. EM dberger@partners.org NR 28 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP PY 2008 VL 12 IS 9 BP 1554 EP 1560 DI 10.1007/s11605-008-0580-1 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 339FP UT WOS:000258563800014 PM 18622658 ER PT J AU Raut, CP Ashley, SW AF Raut, Chandrajit P. Ashley, Stanley W. TI How i do it: Surgical management of gastrointestinal stromal tumors SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE gastrointestinal stromal tumor; surgery; adjuvant therapy; metastases; sarcoma ID IMATINIB MESYLATE; RESIDUAL DISEASE; TARGETED THERAPY; SURGERY; RESECTION; GIST; SURVIVAL; STOMACH; ERA AB The surgical management of gastrointestinal stromal tumors (GISTs) has been impacted by the development of tyrosine kinase inhibitors (TKIs), advances in surgical technique, and a better understanding of the natural history of this unique disease. In this article, we review the technical aspects of the operations, the expanding role of laparoscopy, and the indications for neoadjuvant and neoadjuvant TKI therapy in primary GIST. Furthermore, we explore the rationale for and incorporation of surgery in the multidisciplinary management of advanced GIST. C1 [Raut, Chandrajit P.; Ashley, Stanley W.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Raut, Chandrajit P.; Ashley, Stanley W.] Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 28 TC 15 Z9 21 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP PY 2008 VL 12 IS 9 BP 1592 EP 1599 DI 10.1007/s11605-008-0501-3 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 339FP UT WOS:000258563800021 PM 18317848 ER PT J AU Ginde, AA Cagliero, E Nathan, DM Camargo, CA AF Ginde, Adit A. Cagliero, Enrico Nathan, David M. Camargo, Carlos A., Jr. TI Value of risk stratification to increase the predictive validity of HbA1c in screening for undiagnosed diabetes in the US population SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE diabetes mellitus; glycohemoglobin; screening; validity; NHANES ID NUTRITION EXAMINATION SURVEY; IMPAIRED FASTING GLUCOSE; PLASMA-GLUCOSE; GHB HBA(1C); GLYCOSYLATED HEMOGLOBIN; DIAGNOSTIC-CRITERIA; NATIONAL-HEALTH; BLOOD-GLUCOSE; MELLITUS; PREVALENCE AB BACKGROUND: Opportunistic screening using hemoglobin A1c (HbA1c) may improve detection of undiagnosed diabetes but remains controversial. OBJECTIVE: To evaluate the predictive validity of HbA1c as a screening test for undiagnosed diabetes in a risk-stratified sample of the US population. DESIGN: Weighted cross-sectional analysis of diabetes risk factors, HbA1c, and fasting plasma glucose (FPG) in National Health and Nutrition Examination Survey (NHANES), 1999-2004. SUBJECTS: Six thousand seven hundred and twenty-three NHANES participants from morning examination session, aged >= 18 years and without prior physician-diagnosed diabetes. MEASUREMENTS: HbA1c and undiagnosed diabetes defined by FPG >= 7.0 mmol/l (126 mg/dl). RESULTS: The estimated prevalence of undiagnosed diabetes in the US population was 2.8% (5.5 million people). HbA1c had strong correlation with undiagnosed diabetes, with an area under the receiver-operating characteristic curve of 0.93. Independent predictors of undiagnosed diabetes were older age, male sex, black race, hypertension, elevated waist circumference, elevated triglycerides, and low high-density lipoprotein cholesterol. We derived a risk score for undiagnosed diabetes and stratified participants into low (0.44% prevalence), moderate (4.1% prevalence), and high (11.1% prevalence) risk subgroups. In moderate and high risk groups, a threshold HbA1c value >= 6.1% identified patients requiring confirmatory FPG; HbA1c <= 5.4% identified patients for whom diabetes could be reliably excluded. Intermediate HbA1c (5.5-6.0%) may exclude diabetes in moderate, but not high risk groups). CONCLUSIONS: Risk stratification improves the predictive validity of HbA1c in screening for undiagnosed diabetes in the US population. Although opportunistic screening with HbA1c would improve detection of undiagnosed diabetes, cost-effectiveness studies are needed before implementation of specific screening strategies using HbA1c. C1 [Ginde, Adit A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. [Ginde, Adit A.] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Cagliero, Enrico; Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Ginde, AA (reprint author), Univ Colorado, Denver Sch Med, Dept Emergency Med, 12401 E 17th Ave,B-215, Aurora, CO 80045 USA. EM adit.ginde@uchsc.edu RI Siry, Bonnie/D-7189-2017 FU Emergency Medicine Foundation Research Fellowship grant (Dallas, TX) FX Dr. Ginde was supported by the Emergency Medicine Foundation Research Fellowship grant (Dallas, TX). NR 40 TC 23 Z9 24 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2008 VL 23 IS 9 BP 1346 EP 1353 DI 10.1007/s11606-008-0661-6 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 339LJ UT WOS:000258578800009 PM 18543044 ER PT J AU Isaac, T Jha, AK AF Isaac, Thomas Jha, Ashish K. TI Are patient safety indicators related to widely used measures of hospital quality? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient safety indicators (PSIs); hospital quality scores; unsafe medical care ID ADMINISTRATIVE DATA; ADVERSE EVENTS; OF-CARE; COMPLICATIONS; PROGRAM AB CONTEXT: Patient safety indicators (PSIs) are screening tools that use administrative data to identify potential complications of care and are being increasingly used as measures of hospital safety. It is unknown whether PSIs are related to standard quality metrics. OBJECTIVE: To examine the relationship between select PSIs and measures of hospital quality. DESIGN, SETTING, AND PARTICIPANTS: We used the 2003 MedPAR dataset to examine the performance of 4,504 acute-care hospitals on four medical PSIs among Medicare enrollees. MAIN OUTCOME MEASURES: We used bivariate and multivariate techniques to examine the relationship between PSI performance and quality scores from the Hospital Quality Alliance program, risk-adjusted mortality rates, and selection as a top hospital by US News & World Report. RESULTS: We found inconsistent and usually poor associations among the PSIs and other hospital quality measures with the exception of "failure to rescue," which was consistently associated with better performance on all quality measures tested. For example, hospitals in the top quartile of failure to rescue performance had a 0.9% better summary performance score in acute myocardial infarction (AMI) processes and a 22% lower mortality rate in AMI compared to hospitals in the bottom quartile of failure to rescue (p < 0.01 for both comparisons). Death in low mortality DRG, decubitus ulcer, and infection due to medical care generally had poor or often inverse relationships with the other quality measures. CONCLUSIONS: With the exception of failure to rescue, we found poor or inverse relationships between PSIs and other measures of healthcare quality. Whether the lack of relationship is due to the limitations of the PSIs is unknown, but suggests that PSIs need further validation before they are employed broadly. C1 [Isaac, Thomas; Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA 02115 USA. [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. RP Isaac, T (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02115 USA. EM txi001@gmail.com FU Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System FX We are grateful to E. John Orav, PhD, for his statistical input, Jeffery Geppert, JD, for his help with the PSI software and Drs. Saul Weingart and Lisa Iezzoni for their insightful comments on earlier versions of the manuscript.; This material is the result of work supported with resources and the use of facilities at the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System. NR 25 TC 25 Z9 26 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2008 VL 23 IS 9 BP 1373 EP 1378 DI 10.1007/s11606-008-0665-2 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 339LJ UT WOS:000258578800013 PM 18574640 ER PT J AU Ross, JT TenHave, T Eakin, AC Difilippo, S Oslin, DW AF Ross, Jennifer T. TenHave, Thomas Eakin, April C. Difilippo, Suzanne Oslin, David W. TI A randomized controlled trial of a close monitoring program for minor depression and distress SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE minor depression; close monitoring; telephone care management ID PRIMARY-CARE PATIENTS; GENERAL-POPULATION; SYMPTOMS; RELIABILITY; PREVALENCE; TELEPHONE; MANAGEMENT; DISORDERS; DYSTHYMIA; VALIDITY AB BACKGROUND: Minor depression is almost twice as common in primary care (PC) as major depression. Despite the high prevalence, few evidence-based algorithms exist for managing patients with minor depression or patients presenting solely with distress. OBJECTIVES: The aim of this study was to test the effectiveness of a telephone-based close monitoring program to manage PC patients with minor depression or distress. DESIGN: Subjects were randomly assigned to either the control arm (usual care; UC) or the intervention arm (close monitoring; CM). We hypothesized that those randomized to CM would exhibit less depression and be less likely to have symptoms progress to the point of meeting diagnostic criteria. SUBJECTS: Overall, 223 PC subjects with minor depression or distress consented to participation in this trial. MEASUREMENTS: At baseline, subjects completed a telephone-based evaluation comprised of validated diagnostic assessments of depression and other MH disorders. Outcomes were assessed at six months utilizing this same battery. Chart reviews were conducted to track care received, such as prescribed antidepressants and MH and primary care visits. RESULTS: Subjects in the CM arm exhibited fewer psychiatric diagnoses than those in the UC arm (chi(2) = 4.04, 1 df, p = 0.04). In addition, the intervention group showed improved overall physical health (SF-12 PCS scores) (M = 45.1, SD = 11.8 versus M = 41.5, SD = 12.4) (chi(2) = 5.90, 1 df, p = .02). CONCLUSIONS: Those randomized to CM exhibited less MH problems at the conclusion of the trial, indicating that the close monitoring program is effective, feasible and valuable. The findings of this study will allow us to enhance clinical care and support the integration of mental health services and primary care. C1 [Ross, Jennifer T.; Eakin, April C.; Oslin, David W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Ross, Jennifer T.; Eakin, April C.; Oslin, David W.] VISN 4 Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Oslin, David W.] Philadelphia VA Ctr Excellence Subst Abuse Treatm, Philadelphia, PA USA. [Ross, Jennifer T.; Difilippo, Suzanne; Oslin, David W.] Univ Penn, Dept Psychiat, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. [TenHave, Thomas] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Oslin, David W.] Univ Penn, Dept Psychiat, Ctr Study Addict, Philadelphia, PA 19104 USA. RP Oslin, DW (reprint author), Philadelphia Vet Affairs Med Ctr, Mail Stop 116,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM oslin@mail.med.upenn.edu FU Philadelphia Veterans Affairs Medical Center (PVAMC); Robert Wood Johnson foundation; Veterans Integrated Service Network 4 Mental Illness Research Education and Clinical Center; Behavioral Health Laboratory staff FX Supported by Robert Wood Johnson and VISN 4 the Mental Illness Research, Education, and Clinical Center (MIRECC) at the Philadelphia Veterans Affairs Medical Center (PVAMC).; This work was supported by a grant from the Robert Wood Johnson foundation and support from the Veterans Integrated Service Network 4 Mental Illness Research Education and Clinical Center. We acknowledge the support and dedication of the Primary Care Clinicians at the Philadelphia Veterans Affairs Medical Center and the Behavioral Health Laboratory staff. NR 27 TC 18 Z9 18 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2008 VL 23 IS 9 BP 1379 EP 1385 DI 10.1007/s11606-008-0663-4 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 339LJ UT WOS:000258578800014 PM 18498013 ER PT J AU Pippins, JR Gandhi, TK Hamann, C Ndumele, CD Labonville, SA Diedrichsen, EK Carty, MG Karson, AS Bhan, I Coley, CM Liang, CL Turchin, A McCarthy, PC Schnipper, JL AF Pippins, Jennifer R. Gandhi, Tejal K. Hamann, Claus Ndumele, Chima D. Labonville, Stephanie A. Diedrichsen, Ellen K. Carty, Marcy G. Karson, Andrew S. Bhan, Ishir Coley, Christopher M. Liang, Catherine L. Turchin, Alexander McCarthy, Patricia C. Schnipper, Jeffrey L. TI Classifying and predicting errors of inpatient medication reconciliation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medication errors; medication systems; hospital; continuity of patient care; inpatients ID ADVERSE DRUG EVENTS; HOSPITAL ADMISSION; DISCREPANCIES; DISCHARGE; CARE; MANAGEMENT; HISTORIES AB BACKGROUND: Failure to reconcile medications across transitions in care is an important source of potential harm to patients. Little is known about the predictors of unintentional medication discrepancies and how, when, and where they occur. OBJECTIVE: To determine the reasons, timing, and predictors of potentially harmful medication discrepancies. DESIGN: Prospective observational study. PATIENTS: Admitted general medical patients. MEASUREMENTS: Study pharmacists took gold-standard medication histories and compared them with medical teams' medication histories, admission and discharge orders. Blinded teams of physicians adjudicated all unexplained discrepancies using a modification of an existing typology. The main outcome was the number of potentially harmful unintentional medication discrepancies per patient (potential adverse drug events or PADEs). RESULTS: Among 180 patients, 2066 medication discrepancies were identified, and 257 (12%) were unintentional and had potential for harm (1.4 per patient). Of these, 186 (72%) were due to errors taking the preadmission medication history, while 68 (26%) were due to errors reconciling the medication history with discharge orders. Most PADEs occurred at discharge (75%). In multivariable analyses, low patient understanding of preadmission medications, number of medication changes from preadmission to discharge, and medication history taken by an intern were associated with PADEs. CONCLUSIONS: Unintentional medication discrepancies are common and more often due to errors taking an accurate medication history than errors reconciling this history with patient orders. Focusing on accurate medication histories, on potential medication errors at discharge, and on identifying high-risk patients for more intensive interventions may improve medication safety during and after hospitalization. C1 [Pippins, Jennifer R.; Gandhi, Tejal K.; Ndumele, Chima D.; Carty, Marcy G.; Liang, Catherine L.; Schnipper, Jeffrey L.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02120 USA. [Labonville, Stephanie A.] Brigham & Womens Hosp, Serv Pharm, Boston, MA 02115 USA. [Carty, Marcy G.; Schnipper, Jeffrey L.] Brigham & Womens Hosp, Brigham & Womens Faulkner Hospitalist Serv, Boston, MA 02115 USA. [Carty, Marcy G.] Brigham & Womens Hosp, Ctr Clin Excellence, Boston, MA 02115 USA. [Hamann, Claus; Karson, Andrew S.; Bhan, Ishir; Coley, Christopher M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hamann, Claus] Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. [Diedrichsen, Ellen K.] Massachusetts Gen Hosp, Serv Pharm, Boston, MA 02114 USA. [McCarthy, Patricia C.] Massachusetts Gen Hosp, Decis Support & Qual Management Unit, Boston, MA 02114 USA. [Turchin, Alexander] Partners Informat Syst Clin Informat Res & Dev, Boston, MA USA. [Pippins, Jennifer R.; Gandhi, Tejal K.; Hamann, Claus; Carty, Marcy G.; Karson, Andrew S.; Bhan, Ishir; Coley, Christopher M.; Turchin, Alexander; Schnipper, Jeffrey L.] Harvard Univ, Sch Med, Boston, MA USA. RP Schnipper, JL (reprint author), Brigham & Womens Hosp, Div Gen Med, 1620 Tremont St, Boston, MA 02120 USA. EM jschnipper@partners.org FU Harvard Risk Management Foundation; Massachusetts General Hospital, Brigham and Women's Hospital, and Partners Healthcare; Health Resources and Services Administration [T32 HP11001-18]; National Heart, Lung, and Blood Institute [K08 HL072806] FX Portions of this work were presented as a poster at the 2007 Summer Meeting of the American Society of Health-System Pharmacists, June 24 27, 2007, San Francisco, CA and as a poster at the 2008 Annual Meeting of the Society of General Internal Medicine, April 9-12, 2008, Pittsburgh, PA. This study was supported in part by an investigator-initiated grant from the Harvard Risk Management Foundation, and by internal support from Massachusetts General Hospital, Brigham and Women's Hospital, and Partners Healthcare. Dr. Pippins was supported by a National Research Service Award from the Health Resources and Services Administration (T32 HP11001-18). Dr. Schnipper is supported by a Mentored Clinical Scientist Award from the National Heart, Lung, and Blood Institute (K08 HL072806). NR 25 TC 143 Z9 151 U1 1 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2008 VL 23 IS 9 BP 1414 EP 1422 DI 10.1007/s11606-008-0687-9 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 339LJ UT WOS:000258578800019 PM 18563493 ER PT J AU Covinsky, KE Lin, F Bittner, V Hlatky, MA Knight, SJ Vittinghoff, E AF Covinsky, Kenneth E. Lin, Feng Bittner, Vera Hlatky, Mark A. Knight, Sara J. Vittinghoff, Eric TI Health-related quality of life following coronary artery bypass graft surgery in post-menopausal women SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE coronary artery bypass graft; health related quality of life; physical function; post-menopausal women ID OPEN-HEART OPERATIONS; ESTROGEN/PROGESTIN REPLACEMENT; DEPRESSIVE SYMPTOMS; RANDOMIZED-TRIAL; OLDER-ADULTS; OUTCOMES; QUESTIONNAIRE; DISEASE; OCTOGENARIANS; ANGIOPLASTY AB OBJECTIVES: To describe the impact of coronary artery bypass graft (CABG) surgery on health related quality of life (HRQOL) in post-menopausal women. DESIGN: Prospective cohort study. SETTING: Women enrolled in the Heart and Estrogen/progestin Replacement Study (HERS). PARTICIPANTS: One hundred and thirty-seven women (mean age 66.6) who had CABG surgery while enrolled in HERS. MEASUREMENTS: Physical function was assessed using the 12-item Duke Activity Status Index (DASI), energy-fatigue with the four-item RAND scale, and mental health with the RAND mental health inventory each year. We defined baseline HRQOL from the interview that preceded the CABG (mean 4.6 months pre-CABG). To assess post-CABG HRQOL, we used the first interview that was obtained at least 6 months following the CABG (mean 11.5 months post-CABG). RESULTS: For all three measures of HRQOL, mean scores post-CABG were virtually identical to mean scores pre-CABG (mean pre and post scores were 20.8, 20.4 for physical function, 49.3, 49.2 for energy-fatigue, and 71.9 and 72.3 for mental health). After adjusting for demographic and clinical characteristics and the expected temporal change in HRQOL, differences between pre and post-operative HRQOL remained minimal. However, on an individual patient level, there was significant variability in HRQOL outcomes. For example, while mean physical function scores changed little, 32% of women were at least moderately better (scores improved by at least 0.5 standard deviations) following surgery, while 26% were at least moderately worse (scores declined by at least 0.5 standard deviations). CONCLUSION: Following CABG surgery in post-menopausal women, on average, HRQOL is virtually identical to the pre-operative baseline. However, there is significant variability, as substantial numbers of women are significantly better or significantly worse. C1 [Covinsky, Kenneth E.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Covinsky, Kenneth E.; Knight, Sara J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lin, Feng; Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bittner, Vera] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hlatky, Mark A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Hlatky, Mark A.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Covinsky, KE (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement, San Francisco, CA 94121 USA. EM covinsky@medicine.ucsf.edu OI Bittner, Vera/0000-0001-9456-850X FU National Institute on Aging [5 R01 AG023626-03, 1K24AG029812-01A1]; Wyeth Pharmaceuticals FX Supported in part by grants from the National Institute on Aging (5 R01 AG023626-03 and 1K24AG029812-01A1). The HERS study was funded by Wyeth Pharmaceuticals. Wyeth Pharmaceuticals was not involved in the plans to use the HERS database to conduct this study, and was not involved in the data analysis, preparation of the manuscript, or decision to publish this manuscript. NR 34 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2008 VL 23 IS 9 BP 1429 EP 1434 DI 10.1007/s11606-008-0691-0 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 339LJ UT WOS:000258578800021 PM 18574638 ER PT J AU Silberman, J Tentler, A Ramgopal, R Epstein, RM AF Silberman, Jordan Tentler, Aleksey Ramgopal, Rajeev Epstein, Ronald M. TI Recall-promoting physician behaviors in primary care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE communication skills; medical education-communication skills; patient education ID CONTROLLED-TRIAL; COMMUNICATION; PATIENT; INFORMATION; SATISFACTION; DOCTORS; ADVICE AB BACKGROUND: Effective treatments can be rendered useless by poor patient recall of treatment instructions. Studies suggest that patients forget a great deal of important information and that recall can be increased through recall-promoting behaviors (RPBs) like repetition or summarization. OBJECTIVE: To assess how frequently RPBs are used in primary care, and to reveal how they might be applied more effectively. DESIGN: Recordings of 49 unannounced standardized patient (SP) visits were obtained using hidden audiorecorders. All SPs presented with typical gastroesophageal reflux disease symptoms. Transcripts were coded for treatment recommendations and RPBs. PARTICIPANTS: Forty-nine primary care physicians. RESULTS: Of 1,140 RPBs, 53.7% were repetitions, 28.2% were communication of the rationale for a treatment, 11.7% were categorizations of treatments (i.e., stating that a treatment could be placed into a treatment category, such as medication-related or lifestyle-related categories), and 3.8% were emphasis of a recommendation's importance. Physicians varied substantially in their use of most RPBs, although no physicians summarized or asked patients to restate recommendations. The number of RPBs was positively correlated with visit length. CONCLUSIONS: Primary care physicians apply most RPBs inconsistently, do not utilize several RPBs that are particularly helpful, and may use RPBs inefficiently. Simple principles guiding RPB use may help physicians apply these communication tools more effectively. C1 [Silberman, Jordan; Tentler, Aleksey; Epstein, Ronald M.] Univ Rochester, Med Ctr, Rochester Ctr Improve Commun Hlth Care, Rochester, NY 14610 USA. [Ramgopal, Rajeev] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Silberman, J (reprint author), Univ Rochester, Med Ctr, Rochester Ctr Improve Commun Hlth Care, 1381 S Ave, Rochester, NY 14610 USA. EM jordan_silberman@urmc.rochester.edu RI Tentler, Aleksey/I-6404-2013 OI Tentler, Aleksey/0000-0001-7741-3776 FU AHRQ HHS [R01-HS1610-01A1] NR 20 TC 12 Z9 12 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2008 VL 23 IS 9 BP 1487 EP 1490 DI 10.1007/s11606-008-0597-x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 339LJ UT WOS:000258578800031 PM 18548316 ER PT J AU Schillerstrom, JE Royall, DR Palmer, RF AF Schillerstrom, Jason E. Royall, Donald R. Palmer, Raymond F. TI Depression, disability and intermediate pathways: A review of longitudinal studies in elders SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE depression; disability; functional status; longitudinal study; cohort ID PREDICT FUNCTIONAL DECLINES; PHYSICAL-DISABILITY; OLDER-ADULTS; LATE-LIFE; EXECUTIVE DYSFUNCTION; GERIATRIC DEPRESSION; VASCULAR DEMENTIA; METHYLPHENIDATE TREATMENT; CARDIOVASCULAR HEALTH; DISABLEMENT PROCESS AB Cross-sectional studies demonstrate depression is associated with disability in elders. These studies also report that disability in depressed elders is associated with greater medical illness burden, cognitive impairment, and behavioral changes. Only longitudinal Studies, however, can determine the impact of depression and its comorbidities on functional decline. This review summarizes the findings of 20 longitudinal Studies examining the relationship between baseline or incident depression and functional decline. However, the mediational effects of potential risk factors identified by cross-sectional studies cannot be derived from the current literature. We propose a mediational effects model for future longitudinal studies, incorporating measures sensitive to both mood symptoms and the medical, cognitive, and behavioral comorbidities of depression to better understand the impact of each on functional decline and to focus future clinical interventions. C1 [Schillerstrom, Jason E.; Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Royall, Donald R.] Audie Murphy Div GRECC, S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Schillerstrom, JE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM schillerstr@uthscsa.edu NR 78 TC 40 Z9 42 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2008 VL 21 IS 3 BP 183 EP 197 DI 10.1177/0891988708320971 PG 15 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 347TN UT WOS:000259164100004 PM 18838741 ER PT J AU Scangas, G Lozano-Calderon, S Ring, D AF Scangas, George Lozano-Calderon, Santiago Ring, David TI Disparity between popular (Internet) and scientific illness concepts of carpal tunnel syndrome causation SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE carpal tunnel syndrome; media; Internet; quality of information ID SUBSYNOVIAL CONNECTIVE-TISSUE; BODY-MASS INDEX; RISK-FACTORS; MEDIAN NERVE; MUSCULOSKELETAL DISORDERS; OCCUPATIONAL FACTORS; SENSORY CONDUCTION; GENERAL-POPULATION; DIABETES-MELLITUS; WORK AB Purpose To determine whether there are notable disparities between popular (Internet) and scientific (Index Medicus) theories of carpal tunnel syndrome (CTS) causation. Methods Reports from 3 sources were evaluated with regard to support for etiological theories of CTS: 1) patient-oriented information on CTS from the Internet, 2) recent physician-oriented information on CTS from medical journals indexed on Index Medicus, and 3) articles addressing the etiology of CTS from the 1997 National Institute for Occupational Safety and Health report. Multiple logistic regression analyses evaluated differences in etiological theories from the 3 sources. Results Internet sites implicated vitamin B-6 deficiency, tenosynovitis, and typing or computer use as causes for idiopathic CTS considerably more often and genetic predisposition considerably less often than recent Index Medicus scientific reports and reports reviewed by the National Institute for Occupational Safety and Health. Conclusions There are notable disparities between popular (Internet) and scientific (Index Medicus) theories of CTS causation. C1 [Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU AD Foundation; Wright Medical; Joint Active Systems; Smith and Nephew; Small Bone Innovations; Biomet FX Supported by unrestricted research grants from AD Foundation, Wright Medical, Joint Active Systems, Smith and Nephew, Small Bone Innovations, and Biomet. NR 63 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2008 VL 33A IS 7 BP 1076 EP 1080 DI 10.1016/j.jhsa.2008.03.001 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 347VH UT WOS:000259168900007 PM 18762100 ER PT J AU Ring, D AF Ring, David TI Mini-incision fixation of nondisplaced scaphoid fracture nonunions SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 [Ring, David] Harvard Univ, Sch Med, Dept Orthoped Surg, Hand & Upper Extrem Serv, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 2 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2008 VL 33A IS 7 BP 1121 EP 1121 DI 10.1016/j.jhsa.2008.03.014 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 347VH UT WOS:000259168900014 PM 18762107 ER PT J AU Jupiter, JB AF Jupiter, Jesse B. TI Tendon stabilization of the distal ulna SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE distal ulna; instability; combined tenodesis; Darrach resection ID CARPI ULNARIS AB The technique of a combined extensor and flexor carpi ulnaris tenodesis to stabilize the distal ulna, especially after a Darrach resection, is presented in detail. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Suite 2100 Yawkey Bldg, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 4 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2008 VL 33A IS 7 BP 1196 EP 1200 DI 10.1016/j.jhsa.2008.06.021 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 347VH UT WOS:000259168900026 PM 18762119 ER PT J AU Lundgren, K Brownell, H Cayer-Meade, C AF Lundgren, Kristine Brownell, Hiram Cayer-Meade, Carol TI Theory of mind training following traumatic brain injury: A pilot study SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Meeting Abstract C1 [Lundgren, Kristine] Univ N Carolina, Chapel Hill, NC 27515 USA. [Brownell, Hiram] Boston Coll, Chestnut Hill, MA 02167 USA. [Cayer-Meade, Carol] Boston Univ, Sch Med, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD SEP-OCT PY 2008 VL 23 IS 5 MA 0045 BP 354 EP 355 DI 10.1097/01.HTR.0000336886.45646.ce PG 2 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 357GN UT WOS:000259834400050 ER PT J AU Hauer, KE Landefeld, CS AF Hauer, Karen E. Landefeld, C. Seth TI CHAMP Trains Champions: Hospitalist-Educators Develop New Ways to Teach Care for Older Patients SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID GENERAL INTERNAL-MEDICINE; GERIATRICS; PHYSICIANS; OUTCOMES; IMPROVE; FACULTY C1 [Hauer, Karen E.] Univ Calif San Francisco, Dept Med, Div Hosp Med, San Francisco, CA 94143 USA. [Landefeld, C. Seth] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Landefeld, C. Seth] San Francisco VA Med Ctr, San Francisco, CA USA. RP Hauer, KE (reprint author), Univ Calif San Francisco, Dept Med, Div Hosp Med, 533 Parnassus Ave,U137,Box 0131, San Francisco, CA 94143 USA. EM khauer@medicine.ucsf.edu NR 15 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD SEP-OCT PY 2008 VL 3 IS 5 BP 357 EP 360 DI 10.1002/jhm.357 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 369JK UT WOS:000260690300001 PM 18951398 ER PT J AU Li, YM Chen, FQ Putt, M Koo, YK Madaio, M Cambier, JC Cohen, PL Eisenberg, RA AF Li, Yongmei Chen, Fangqi Putt, Mary Koo, Yumee K. Madaio, Michael Cambier, John C. Cohen, Philip L. Eisenberg, Robert A. TI B cell depletion with anti-CD79 mAbs ameliorates autoimmune disease in MRL/lpr mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MURINE LUPUS; IG-BETA; IN-VIVO; ACTIVATION; RECEPTOR; ALPHA/BETA; ROLES; CD79 AB MRL/lpr mice develop a spontaneous systemic lupus erythematosus-like autoimmune syndrome due to a dysfunctional Fas receptor, with contributions from other less well-defined genetic loci. The removal of B cells by genetic manipulation not only prevents autoantibody formation, but it also results in substantially reduced T cell activation and kidney inflammation. To determine whether B cell depletion by administration of Abs is effective in lupus mice with an intact immune system and established disease, we screened several B cell-specific mAbs and found that a combination of anti-CD79 alpha and anti-CD79 beta Abs was most effective at depleting B cells in vivo. Anti-CD79 therapy started at 4-5 mo of age in MRL/lpr mice significantly decreased B cells (B220(+)CD19(+)) in peripheral blood, bone marrow, and spleens. Treated mice also had a significant increase in the number of both double-negative T cells and naive CD4(+) T cells, and a decreased relative abundance of CD4(+) memory cells. Serum anti-chromatin IgG levels were significantly decreased compared with controls, whereas serum anti-dsDNA IgG, total IgG, or total IgM were unaffected. Overall, survival was improved with lower mean skin scores and significantly fewer focal inflammatory infiltrates in submandibular salivary glands and kidneys. Anti-CD79 mAbs show promise as a potential treatment for systemic lupus erythematosus and as a model for B cell depletion in vivo. C1 [Eisenberg, Robert A.] Univ Penn, Div Rheumatol, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Putt, Mary] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Koo, Yumee K.] Univ Sci Philadelphia, Dept Chem & Biochem, Philadelphia, PA 19104 USA. [Madaio, Michael] Temple Univ, Philadelphia, PA 19140 USA. [Cambier, John C.] Univ Colorado, Denver Sch Med, Denver, CO 80206 USA. [Cambier, John C.] Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. [Cohen, Philip L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Eisenberg, RA (reprint author), Univ Penn, Div Rheumatol, Sch Med, Dept Med, Room 747,BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM raemd@mail.med.upenn.edu OI Cambier, John/0000-0002-7803-242X FU Lupus Research Institute; Arthritis Foundation and the Alliance for Lupus Research; Lupus Foundation of South New Jersey; Department of Veterans Affairs; National Institutes of Health [R01-AR-34156, U19-AI-46358, R01-AI063626, R01-DE017590] FX Supported by the Lupus Research Institute, the Arthritis Foundation and the Alliance for Lupus Research, the Lupus Foundation of South New Jersey, the Department of Veterans Affairs, and the National Institutes of Health (Grants R01-AR-34156, U19-AI-46358, R01-AI063626, and R01-DE017590). NR 27 TC 36 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2008 VL 181 IS 5 BP 2961 EP 2972 PG 12 WC Immunology SC Immunology GA 352QJ UT WOS:000259511800004 PM 18713966 ER PT J AU Kawamura, K McLaughlin, KA Weissert, R Forsthuber, TG AF Kawamura, Kazuyuki McLaughlin, Katherine A. Weissert, Robert Forsthuber, Thomas G. TI Myelin-reactive type B T cells and T cells specific for low-affinity MHC-binding myelin peptides escape tolerance in HLA-DR transgenic mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; HISTOCOMPATIBILITY COMPLEX-BINDING; BASIC-PROTEIN EPITOPE; CLASS-II MOLECULES; MULTIPLE-SCLEROSIS; AUTOIMMUNE-DISEASES; NEGATIVE SELECTION; HLA-DR15 HAPLOTYPE; EFFECTOR FUNCTIONS; MEMORY CELLS AB Genes of the MHC show the strongest genetic association with multiple sclerosis (MS), but the underlying mechanisms have remained unresolved. In this study, we asked whether the MS-associated MHC class 11 molecules, HLA-DRB1*1501, HLA-DRB5*0101, and HLA-DRB1*0401, contribute to autoimmune CNS demyelination by promoting pathogenic T cell responses to human myelin basic protein (hMBP), using three transgenic (Tg) mouse lines expressing these MHC molecules. Unexpectedly, profound T cell tolerance to the high-affinity MHC-binding hMBP82-100 epitope was observed in all Tg mouse lines. T cell tolerance to hMBP82-100 was abolished upon back-crossing the HLA-DR Tg mice to MBP-deficient mice. In contrast, T cell tolerance was incomplete for low-affinity MHC-binding hMBP epitopes. Furthermore, hMBP82-100-specific type B T cells escaped tolerance in HLA-DRB5*0101 Tg mice. Importantly, T cells specific for low-affinity MHC-binding hMBP epitopes and hMBP82-100-specific type B T cells were highly encephalitogenic. Collectively, the results show that MS-associated MHC class 11 molecules are highly efficient at inducing T cell tolerance to high-affinity MHC-binding epitope, whereas autoreactive T cells specific for the low-affinity MHC-binding epitopes and type B T cells can escape the induction of T cell tolerance and may promote MS. C1 [Kawamura, Kazuyuki; Forsthuber, Thomas G.] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA. [McLaughlin, Katherine A.] Harvard Univ, Boston, MA 02115 USA. [McLaughlin, Katherine A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weissert, Robert] Univ Tubingen, Dept Gen Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany. RP Forsthuber, TG (reprint author), Univ Texas San Antonio, Dept Biol, 1 UTSA Circle, San Antonio, TX 78249 USA. EM thomas.forsthuber@utsa.edu RI Weissert, Robert/B-2585-2009 OI Weissert, Robert/0000-0002-1295-1271 FU National Institutes of Health [NS-428846]; National Multiple Sclerosis Society [RG3499, RG3701]; National Multiple Sclerosis Society FX This work was supported by Grant NS-428846 from the National Institutes of Health, and Grants RG3499 and RG3701 from the National Multiple Sclerosis Society (to T.G.F.). K.K. is recipient of a Postdoctoral Fellowship float the National Multiple Sclerosis Society, NR 49 TC 13 Z9 13 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2008 VL 181 IS 5 BP 3202 EP 3211 PG 10 WC Immunology SC Immunology GA 352QJ UT WOS:000259511800029 PM 18713991 ER PT J AU Wegmann, KW Wagner, CR Whitham, RH Hinrichs, DJ AF Wegmann, Keith W. Wagner, Cynthia R. Whitham, Ruth H. Hinrichs, David J. TI Synthetic peptide dendrimers block the development and expression of experimental allergic encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REGULATORY T-CELLS; PROTEOLIPID PROTEIN; TOLERANCE INDUCTION; MULTIPLE-SCLEROSIS; IN-VIVO; ENCEPHALITOGENIC PEPTIDES; PERIPHERAL TOLERANCE; DELIVERY VEHICLES; TRANSGENIC MICE AB Multiple Ag peptides (MAPS) containing eight proteolipid protein (PLP)(139-151) peptides arranged around a dendrimeric branched lysine core were used to influence the expression and development of relapsing experimental allergic encephalomyelitis (EAE) in SJL mice. The PLP139-151 MAN were very efficient agents in preventing the development of clinical disease when administered after immunization with the PLP139-151 monomeric encephalitogenic peptide in CFA. The treatment effect with these MAPs was peptide specific; irrelevant multimeric peptides such as guinea pig myelin basic protein GPBP(72-84) MAP (a dendrimeric octamer composed of the 72-84 peptide) and PLP178-191 MAP (a dendrimeric octamer composed of the PLP178-191 peptide) bad no treatment effect on PLP139-151-induced EAE. PLP139-151 MAP treatment initiated after clinical signs of paralysis also altered the subsequent course of EAE; it limited developing signs of paralysis and effectively limited the severity and number of disease relapses in MAP-treated mice over a 60-day observation period. PLP139-151 MAP therapy initiated before disease onset acts to limit the numbers of Th17 and IFN-gamma-producing cells that enter into the CNS. However, Foxp3(+) cells entered the CNS in numbers equivalent for nontreated and PLP139-151 MAP-treated animals. The net effect of PLP139-151 MAP treatment dramatically increases the ratio of Foxp3(+) cells to Th17 and IFN-gamma-producing cells in the CNS of PLP139-151. MAP-treated animals. C1 [Wegmann, Keith W.; Wagner, Cynthia R.; Whitham, Ruth H.; Hinrichs, David J.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97239 USA. [Wegmann, Keith W.; Wagner, Cynthia R.; Hinrichs, David J.] Oregon Hlth & Sci Univ, Immunol Res Grp, Portland, OR 97239 USA. [Whitham, Ruth H.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Wagner, Cynthia R.] Oregon Hlth & Sci Univ, Dept Cardiol, Portland, OR 97239 USA. RP Hinrichs, DJ (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, R&D 21, Portland, OR 97201 USA. EM hinrichs@ohsu.edu FU Department of Veterans Affairs FX This work was supported by Merit Review funds from the Department of Veterans Affairs. NR 60 TC 22 Z9 22 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2008 VL 181 IS 5 BP 3301 EP 3309 PG 9 WC Immunology SC Immunology GA 352QJ UT WOS:000259511800040 PM 18714002 ER PT J AU Permar, SR Kang, HH Carville, A Mansfield, KG Gelman, RS Rao, SS Whitney, JB Letvin, NL AF Permar, Sallie R. Kang, Helen H. Carville, Angela Mansfield, Keith G. Gelman, Rebecca S. Rao, Srinivas S. Whitney, James B. Letvin, Norman L. TI Potent simian immunodeficiency virus-specific cellular immune responses in the breast milk of simian immunodeficiency virus-infected, lactating rhesus monkeys SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TO-CHILD TRANSMISSION; LYMPHOCYTE-RESPONSES; HUMAN COLOSTRUM; HIV-1-INFECTED WOMEN; HIV TRANSMISSION; DENDRITIC CELLS; POOLED ANALYSIS; MACACA-MULATTA; TYPE-1; MASTITIS AB Breast milk transmission of HIV is a leading cause of infant HIV/AIDS in the developing world. Remarkably, only a small minority of breastfeeding infants born to HIV-infected mothers contract HIV via breast milk exposure, raising the possibility that immune factors in the breast milk confer protection to the infants who remain uninfected. To model HIV-specific immunity in breast milk, lactation was pharmacologically induced in Mamu-A*01(+) female rhesus monkeys. The composition of lymphocyte subsets in hormone-induced lactation breast milk was found to be similar to that in natural lactation breast milk. Hormone-induced lactating monkeys were inoculated i.v. with SIVmac251 and CD8(+) T lymphocytes specific for two immunodominant SIV epitopes, Gag p11C and Tat TL8, and SIV viral load were monitored in peripheral blood and breast milk during acute infection. The breast milk viral load was 1-2 logs lower than plasma viral load through peak and set point of viremia. Surprisingly, whereas the kinetics of the SIV-specific cellular immunity in breast milk mirrored that of the blood, the peak magnitude of the SIV-specific CD8(+) T lymphocyte response in breast milk was more than twice as high as the cellular immune response in the blood. Furthermore, the appearance of the SIV-specific CD8(+) T lymphocyte response in breast milk was associated with a reduction in breast milk viral load, and this response remained higher than that in the blood after viral set point. This robust viral-specific cellular immune response in breast milk may contribute to control of breast milk virus replication. C1 [Permar, Sallie R.; Kang, Helen H.; Whitney, James B.; Letvin, Norman L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. [Permar, Sallie R.] Harvard Univ, Sch Med, Div Infect Dis, Childrens Hosp Boston, Boston, MA 02115 USA. [Carville, Angela; Mansfield, Keith G.] Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Gelman, Rebecca S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rao, Srinivas S.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Permar, SR (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, 330 Brookline Ave,Res E, Boston, MA 02115 USA. EM sallie.permar@childrens.harvard.edu FU Center for HIV/AIDS Vaccine Immunology [R01AI067854]; Fred Lovejoy Research and Education Fund; Children's Hospital House Officer Research Award; Pediatric Infectious Disease Society/St. Jude Children's Hospital Basic Science Research Award; Harvard Center for AIDS Research [P30AI060354] FX This work was supported by the Center for HIV/AIDS Vaccine Immunology (to S.R.P. and N.L.L.; R01AI067854), the Fred Lovejoy Research and Education Fund (to S.R.P.), the Children's Hospital House Officer Research Award (to S.R.P.), the Pediatric Infectious Disease Society/St. Jude Children's Hospital Basic Science Research Award (to S.R.P.), and the Harvard Center for AIDS Research (to R.S.G.: P30AI060354). NR 55 TC 23 Z9 23 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2008 VL 181 IS 5 BP 3643 EP 3650 PG 8 WC Immunology SC Immunology GA 352QJ UT WOS:000259511800077 PM 18714039 ER PT J AU Patel, AM Heist, EK Chevalier, J Holmvang, G D'Avila, A Mela, T Ruskin, JN Mansour, MC AF Patel, Anshul M. Heist, E. Kevin Chevalier, Jianping Holmvang, Godtfred D'Avila, Andre Mela, Theofanie Ruskin, Jeremy N. Mansour, Moussa C. TI Effect of presenting rhythm on image integration to direct catheter ablation of atrial fibrillation SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; image integration; electroanatomic mapping ID ELECTROANATOMIC MAPPING SYSTEM; RADIOFREQUENCY ABLATION; PULMONARY VEINS; HEART RHYTHM; CT IMAGE; ACCURACY; IMPACT; MANAGEMENT AB Introduction Magnetic resonance (MR) imaging of the left atrium (LA) can be integrated with electroanatomic mapping systems to guide catheter ablation of atrial fibrillation (AF). The usefulness of this technique is dependent on the accuracy of image integration. Objective The aim of this study is to determine the effect of heart rhythm at the time of pre-procedure MR imaging and heart rhythm at the time of ablation on integration error. Methods Fifty-two consecutive patients who underwent catheter ablation for AF were included. All patients underwent MR imaging of LA and pulmonary veins and image integration with real-time electroanatomic mapping. The rhythm at the time of MR imaging and on the day of ablation was recorded. CARTO-Merge software (BiosenseWebster) was used to calculate the average accuracy of integration of electroanatomic points with MR-derived reconstructions. Results There was no significant difference in integration error between patients who were in AF at the time of their MR vs. those who were in sinus rhythm at the time of their MR (1.76 +/- 0.26 vs. 1.88 +/- 0.31 mm, p=0.15). There was also no significant difference in integration error between patients who were in concordant vs. discordant rhythms at the time of MR vs. day of ablation (1.81 +/- 0.23 vs. 1.89 +/- 0.32 mm, p=0.40). There was a trend toward less integration error between patients who were in AF on the day of ablation vs. those in sinus rhythm (1.74 +/- 0.26 vs. 1.89 +/- 0.31 mm, p=0.07). Conclusions Image integration can be performed to direct catheter ablation of AF regardless of the rhythm at the time of imaging and ablation. C1 [Patel, Anshul M.; Heist, E. Kevin; Chevalier, Jianping; Holmvang, Godtfred; D'Avila, Andre; Mela, Theofanie; Ruskin, Jeremy N.; Mansour, Moussa C.] Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mansour, Moussa C.] Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Mansour, MC (reprint author), Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 23 TC 8 Z9 10 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD SEP PY 2008 VL 22 IS 3 BP 205 EP 210 DI 10.1007/s10840-008-9265-7 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 337CW UT WOS:000258414100007 PM 18506606 ER PT J AU Kiernan, TJ Ajani, AE Yan, BP AF Kiernan, Thomas J. Ajani, Andrew E. Yan, Bryan P. TI Management of Access Site and Systemic Complications of Percutaneous Coronary and Peripheral Interventions SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Review AB The role of endovascular therapy for the treatment of coronary and peripheral vascular diseases (including carotid, renal and lower extremity arteries) is expanding. The steady growth in the volume of endovascular procedures is likely to result in an absolute increase in the incidence of procedural complications. Knowledge of common and specific procedural complications and their management are critical to successful outcomes. Complications can be classified as (i) access site-related and (ii) systemic. C1 [Yan, Bryan P.] Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Royal Melbourne Hosp, Dept Cardiol, Melbourne, Vic, Australia. Univ Melbourne, Melbourne, Vic, Australia. RP Yan, BP (reprint author), Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, 55 Fruit St,GRB-800, Boston, MA 02114 USA. EM bryan.p.yan@gmail.com RI Yan, Bryan/P-5928-2015 NR 75 TC 6 Z9 6 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD SEP PY 2008 VL 20 IS 9 BP 463 EP 469 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V14MT UT WOS:000207739200009 PM 18762676 ER PT J AU Chien, W McKenna, MJ Rosowski, JJ Merchant, SN AF Chien, W. McKenna, M. J. Rosowski, J. J. Merchant, S. N. TI Isolated fracture of the manubrium of the malleus SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article DE malleus; fracture; conductive deafness ID TYMPANIC MEMBRANE; HANDLE FRACTURE; DIAGNOSIS AB Objective: To describe a series of five patients with isolated fracture of the manubrium of the malleus. Design: Retrospective case series. Subjects: Five patients aged 44-64 years with isolated fracture of the manubrium who presented to our institution over a five-year period (2000-2005). Results: All patients presented with a history of digitally manipulating the external auditory canal, leading to the manubrial fracture, which we presume was due to a suction-type mechanism. Otomicroscopy often revealed a break in the smooth contour of the manubrium. All patients had air-bone gaps on audiometry, especially at higher frequencies. Tympanometry showed hypermobility of the tympanic membrane in four patients who were tested. Laser-Doppler vibrometry revealed increased umbo velocity in four out of five patients. Four patients were treated conservatively. One patient underwent exploratory tympanotomy with successful ossiculoplasty. Conclusions: Isolated fracture of the manubrium is a rare condition which may present as sudden-onset hearing loss after digital manipulation of the external auditory canal. The diagnosis can be made on the basis of otomicroscopy, audiometry, tympanometry and laser-Doppler vibrometry. Conservative treatment is often successful. C1 [Chien, W.; McKenna, M. J.; Rosowski, J. J.; Merchant, S. N.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Chien, W.; McKenna, M. J.; Rosowski, J. J.; Merchant, S. N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Rosowski, J. J.; Merchant, S. N.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Chien, W (reprint author), 243 Charles St, Boston, MA 02114 USA. EM wadechien@hotmail.com FU National Institutes of Health [DC04798]; Silverstein Young Investigator Award FX We thank Mike Ravicz, Melissa Wood and Jocelyn Songer for assistance with laser vibrometry measurements, and Richard Cortese for computer graphics assistance. The authors were supported in part by the National Institutes of Health grant number DC04798 (to SNM), the Silverstein Young Investigator Award (to WC), and Mr Lakshmi Mittal. NR 9 TC 13 Z9 14 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0022-2151 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD SEP PY 2008 VL 122 IS 9 BP 898 EP 904 DI 10.1017/S0022215107000990 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 350CU UT WOS:000259331000005 PM 18036285 ER PT J AU Al-Turkmani, MR Andersson, C Alturkmani, R Katrangi, W Cluette-Brown, JE Freedman, SD Laposata, M AF Al-Turkmani, M. Rabie Andersson, Charlotte Alturkmani, Ragheed Katrangi, Waddah Cluette-Brown, Joanne E. Freedman, Steven D. Laposata, Michael TI A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA SO JOURNAL OF LIPID RESEARCH LA English DT Article DE arachidonic acid; docosahexaenoic acid; fatty acid alterations; lipid classes; n-6 pathway; phospholipids; supplementation; uptake ID EPITHELIAL-CELLS; FATTY-ACIDS; PHOSPHOLIPIDS; DEFICIENCY; ABNORMALITIES; EXPRESSION; DIAGNOSIS; PANCREAS; CHILDREN; MUTATION AB Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The principal alterations include decreased levels of linoleic acid (LA) and docosahexaenoic acid (DHA). We investigated the potential mechanisms of these alterations by studying the cellular uptake of LA and DHA, their distribution among lipid classes, and the metabolism of LA in a human bronchial epithelial cell model of CF. CF (antisense) cells demonstrated decreased levels of LA and DHA compared with wild type (WT, sense) cells expressing normal CFTR. Cellular uptake of LA and DHA was higher in CF cells compared with WT cells at 1 h and 4 h. Subsequent incorporation of LA and DHA into most lipid classes and individual phospholipids was also increased in CF cells. The metabolic conversion of LA to n-6 metabolites, including 18: 3n-6 and arachidonic acid, was upregulated in CF cells, indicating increased flux through the n-6 pathway. Supplementing CF cells with DHA inhibited the production of LA metabolites and corrected the n-6 fatty acid defect. In conclusion, the evidence suggests that low LA level in cultured CF cells is due to its increased metabolism, and this increased LA metabolism is corrected by DHA supplementation.-Al-Turkmani, M. R., C. Andersson, R. Alturkmani, W. Katrangi, J. E. Cluette- Brown, S. D. Freedman, and M. Laposata. A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA. C1 [Al-Turkmani, M. Rabie; Alturkmani, Ragheed; Katrangi, Waddah; Cluette-Brown, Joanne E.; Laposata, Michael] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Andersson, Charlotte; Freedman, Steven D.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM michael.laposata@vanderbilt.edu FU National Institutes of Health [R01 DK-52765]; The Cystic Fibrosis Foundation [FREEDM06A0] FX This study was funded by National Institutes of Health Grant R01 DK-52765 (S.D.F.) and The Cystic Fibrosis Foundation (Grant FREEDM06A0) (S.D.F.). NR 29 TC 24 Z9 25 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2008 VL 49 IS 9 BP 1946 EP 1954 DI 10.1194/jlr.M800035-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 337YX UT WOS:000258472500010 PM 18480495 ER PT J AU Balmana, J Balaguer, F Castellvi-Bel, S Steyerberg, EW Andreu, M Llor, X Jover, R Castells, A Syngal, S AF Balmana, J. Balaguer, F. Castellvi-Bel, S. Steyerberg, E. W. Andreu, M. Llor, X. Jover, R. Castells, A. Syngal, S. CA Spanish Gastroenterological Assoc TI Comparison of predictive models, clinical criteria and molecular tumour screening for the identification of patients with Lynch syndrome in a population-based cohort of colorectal cancer patients SO JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID REVISED BETHESDA GUIDELINES; MISMATCH-REPAIR GENES; MICROSATELLITE INSTABILITY; COLON-CANCER; HEREDITARY; MUTATIONS; RISK; FAMILIES; CARRIERS; HOMOLOG AB Background: Several models have recently been developed to predict mismatch repair (MMR) gene mutations. Their comparative performance with clinical criteria or universal molecular screening in a population based colorectal cancer (CRC) cohort has not been assessed. Methods: All 1222 CRC from the EPICOLON cohort underwent tumour MMR testing with immunohistochemistry and microsatellite instability, and those with MMR deficiency (n= 91) underwent MLH1/ MSH2 germline testing. Sensitivity, specificity and positive predictive value (PPV) of the PREMM(1,2) and the Barnetson models for identification of MLH1/ MSH2 mutation carriers were evaluated and compared with the revised Bethesda guidelines (RBG), Amsterdam II criteria, and tumour analysis for MMR deficiency. Overall discriminative ability was quantified by the area under the ROC curve (AUC), and calibration was assessed by comparing the average predictions versus the observed prevalence. Results: Both models had similar AUC (0.93 and 0.92, respectively). Sensitivity of the RBG and a PREMM1,2 score > 5% was 100% (95% CI 71% to 100%); a Barnetson score.0.5% missed one mutation carrier (sensitivity 87%, 95% CI 51% to 99%). PPVs of all three strategies were 2 - 3%. Presence of MMR deficiency increased specificity and PPV of predictive scores ( 97% and 21% for PREMM(1,2) score > 5%, and 98% and 21% for Barnetson > 0.5%, respectively). Conclusions: The PREMM(1,2) and the Barnetson models offer a quantitative systematic approach to select CRC patients for identification of MLH1/MSH2 mutation carriers with a similar performance to the RBG. C1 [Balaguer, F.; Castellvi-Bel, S.; Castells, A.] Univ Barcelona, IDIBAPS, CIBERehd,Hosp Clin, Dept Gastroenterol,Inst Malalties Digest & Metab, Barcelona, Spain. Univ Autonoma Barcelona, Hosp Vall Hebron, Dept Med, Dept Med Oncol, Barcelona, Spain. [Steyerberg, E. W.] Univ MC, Erasmus Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands. [Andreu, M.] Hosp del Mar, Dept Gastroenterol, Barcelona, Spain. [Llor, X.] Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL USA. [Jover, R.] Hosp Gen Univ Alicante, Dept Gastroenterol, Alicante, Spain. [Syngal, S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Gastroenterol, Div Populat Sci, Boston, MA 02115 USA. [Syngal, S.] Harvard Univ, Sch Med, Boston, MA USA. RP Balmana, J (reprint author), Hosp Univ Vall Hebron, Dept Med Oncol, Paseo Vall Hebron 119-129, Barcelona 08035, Spain. EM jbalmana@vhebron.net RI Andreu, Montserrat/D-9911-2015; BALAGUER, FRANCESC/G-2389-2016; QUINTERO, ENRIQUE/C-3841-2017; OI Andreu, Montserrat/0000-0003-4286-1098; QUINTERO, ENRIQUE/0000-0002-7244-8125; Sanchez Hernandez, Eloy/0000-0003-2493-8303; Castells, Antoni/0000-0001-8431-2033; Bujanda, Luis/0000-0002-4353-9968; CUBIELLA, JOAQUIN/0000-0002-9994-4831; Steyerberg, Ewout/0000-0002-7787-0122 FU NCI NIH HHS [CA 113433] NR 27 TC 43 Z9 43 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2008 VL 45 IS 9 BP 557 EP 563 DI 10.1136/jmg.2008.059311 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 343CD UT WOS:000258829300002 PM 18603628 ER PT J AU Tarpey, P Dibbens, LM Hynes, K Smith, R Edkins, S Teague, J Mckee, S Ryan, S Kivity, S Schafer, IE Afawi, Z Turner, SJ Gusella, JF Sutton, E Lev, D Sutherland, GR Futreal, PA Stratton, MR Mulley, JC Gecz, J AF Tarpey, Patrick Dibbens, L. M. Hynes, K. Smith, R. Edkins, S. Teague, J. McKee, S. Ryan, S. Kivity, S. Schafer, I. E. Afawi, Z. Turner, S. J. Gusella, J. F. Sutton, E. Lev, D. Sutherland, G. R. Futreal, P. A. Stratton, M. R. Mulley, J. C. Gecz, J. TI X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment SO JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT British Human Genetics Conference CY SEP 15-17, 2008 CL Univ York, York, ENGLAND HO Univ York C1 [Tarpey, Patrick; Smith, R.; Edkins, S.; Teague, J.; Futreal, P. A.; Stratton, M. R.] Wellcome Trust Sanger Inst, Hinxton, 5006, England. [Dibbens, L. M.; Hynes, K.; Sutherland, G. R.; Gecz, J.] Womens & Childrens Hosp, Dept Med Genet, Adelaide BT9 7AD, SA, Australia. [McKee, S.] Belfast City Hosp, No Ireland Reg Genet Serv, Belfast, Antrim 19803, North Ireland. [Ryan, S.] AstraZeneca, IL-49202 Wilmington, DE USA. [Kivity, S.] Schneider Childrens Med Ctr, Dept Neurol, Petaq Tikvah, 3081, Israel. [Schafer, I. E.; Turner, S. J.] Univ Melbourne, Heidelberg Repatriat Hosp, Epilepsy Res Ctr, Heidelberg, Vic 3081, Australia. [Schafer, I. E.; Turner, S. J.] Univ Melbourne, Heidelberg Repatriat Hosp, Dept Med, IL-64239 Heidelberg, Vic, Australia. [Afawi, Z.] Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, 02114, Israel. [Gusella, J. F.; Sutton, E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02115 USA. [Gusella, J. F.; Sutton, E.] Harvard Univ, Sch Med, Dept Genet, IL-58100 Boston, MA USA. [Lev, D.] Wolfson Med Ctr, Metab Neurogenet Clin, Holon, Israel. EM pst@sanger.ac.uk RI Sutherland, Grant/D-2606-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2008 VL 45 SU 1 BP S17 EP S17 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 351PM UT WOS:000259436400008 ER PT J AU Mohile, NA Forsyth, P Stewart, D Raizer, JJ Paleologos, N Kewalramani, T Louis, DN Cairncross, JG Abrey, LE AF Mohile, Nimish A. Forsyth, Peter Stewart, Douglas Raizer, Jeffrey J. Paleologos, Nina Kewalramani, Tarun Louis, David N. Cairncross, J. Gregory Abrey, Lauren E. TI A phase II study of intensified chemotherapy alone as initial treatment for newly diagnosed anaplastic oligodendroglioma: an interim analysis SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE anaplastic oligodendroglioma; chemotherapy; 1p; 19q; procarbazine ID HIGH-DOSE CHEMOTHERAPY; STEM-CELL RESCUE; THERAPY; RADIOTHERAPY; PROCARBAZINE; VINCRISTINE; IRRADIATION; PROGRESSION; TRIAL AB Background Anaplastic oligodendrogliomas (AO) and anaplastic oligoastrocytomas (AOA) are currently treated with a combination of surgery, radiotherapy and chemotherapy. Myeloablative therapy with autologous peripheral blood progenitor cell rescue (APBPCR) is one strategy to exploit the chemosensitivity of these tumors while deferring cranial radiation in an effort to avoid radiation-related neurotoxicity. Methods Twenty patients (16 AO, 4 AOA) with a median age of 46 years (range, 19-60) and KPS of 90 (range, 70-100) were treated with 4 cycles of procarbazine, Lomustine (CCNU) and vincristine (I-PCV) every six weeks. Responding patients were eligible for myeloablative therapy with busulfan and thiotepa followed by APBPCR. 1p and 19q chromosomes were analyzed prospectively but patients were enrolled without regard to deletion status. Results Fifteen patients (75%) had a response to I-PCV and 14 underwent transplant. Median disease-free and overall survival of the transplanted patients has not been reached but is at least 36 months. No patients required dose reduction or termination of I-PCV due to toxicity. Hepatic veno-occlusive disease (VOD) was a complication of transplant in three patients and resulted in one death. Patients with and without deletions of 1p and 19q had durable responses. Conclusions This regimen conferred durable responses in more than one-half of patients, allowing deferral of radiotherapy for three years or longer. The major limitation of this approach is the acute toxicity associated with both the induction and consolidation regimens; temozolomide has replaced I-PCV for the current trial and the incidence and severity of VOD is being followed closely. C1 [Mohile, Nimish A.; Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Forsyth, Peter; Stewart, Douglas] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Raizer, Jeffrey J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Paleologos, Nina] Northwestern Univ, Evanston, IL USA. [Kewalramani, Tarun] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY USA. [Louis, David N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Louis, David N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abrey, LE (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. EM abreyl@mskcc.org NR 15 TC 7 Z9 7 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2008 VL 89 IS 2 BP 187 EP 193 DI 10.1007/s11060-008-9603-8 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 333LV UT WOS:000258154900008 PM 18458821 ER PT J AU Fadul, CE Wen, PY Kim, L Olson, JJ AF Fadul, Camilo E. Wen, Patrick Y. Kim, Lyndon Olson, Jeffrey J. TI Cytotoxic chemotherapeutic management of newly diagnosed glioblastoma multiforme SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article ID HIGH-GRADE GLIOMAS; OPERATED ASTROCYTOMAS GRADE-3; EXTERNAL-BEAM-RADIOTHERAPY; RESISTANCE IN-VITRO; FACTOR-KAPPA-B; MALIGNANT GLIOMA; PHASE-II; RADIATION-THERAPY; RANDOMIZED TRIAL; POSTOPERATIVE TREATMENT C1 [Olson, Jeffrey J.] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA. [Fadul, Camilo E.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Neurooncol Program, Dartmouth Med Sch, Lebanon, NH 03766 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Kim, Lyndon] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. RP Olson, JJ (reprint author), Emory Univ, Sch Med, Dept Neurosurg, 1365B Clifton Rd,NE,Ste 6200, Atlanta, GA 30322 USA. EM jeffrey.olson@emoryhealthcare.org RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 79 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2008 VL 89 IS 3 BP 339 EP 357 DI 10.1007/s11060-008-9615-4 PG 19 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 339XW UT WOS:000258611600006 PM 18712284 ER PT J AU Signore, AP Zhang, F Weng, ZF Gao, YQ Chen, J AF Signore, Armando P. Zhang, Feng Weng, Zhongfang Gao, YanQin Chen, Jun TI Leptin neuroprotection in the CNS: mechanisms and therapeutic potentials SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE neurodegeneration; stroke; epilepsy; mitogen-activated protein kinase kinase/extracellular signal-regulated kinase; phosphatidylinositol 3-kinase ID BLOOD-BRAIN-BARRIER; HIPPOCAMPAL SYNAPTIC PLASTICITY; STREPTOZOTOCIN-DIABETIC RATS; DOPAMINERGIC CELL-DEATH; PITUITARY-ADRENAL AXIS; RECEPTOR MESSENGER-RNA; LONG-TERM POTENTIATION; NF-KAPPA-B; GENE-EXPRESSION; OB/OB MICE AB Leptin is well known as a hormone important in the central control of appetitive behaviors via receptor-mediated actions in the hypothalamus, where leptin adjusts food intake to maintain homeostasis with the body's energy stores. Recent evidence has shown that leptin and its receptors are widespread in the CNS and may provide neuronal survival signals. This review summarizes our current knowledge of how leptin functions in the brain and then focuses on the ability of leptin to mitigate neuronal damage in experimental models of human neurological disorders. Damage to the brain by acute events such as stroke, or long-term loss of neurons associated with neurodegenerative diseases, including Parkinson's and Alzheimer's disease, may be amenable to treatment using leptin to limit death of susceptible cells. Leptin-mediated pro-survival signaling is now known to prevent the death of neurons in these models. The signaling cascades that leptin generates are shared by other neuroprotective molecules including insulin and erythropoietin, and are thus a component of the neurotrophic effects mediated by endogenous hormones. Coupled with evidence that leptin dysregulation in human disease also results in enhanced neuronal susceptibility to damage, development of leptin as a therapeutic methodology is an attractive and viable possibility. C1 [Signore, Armando P.; Zhang, Feng; Weng, Zhongfang; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Gao, YanQin; Chen, Jun] Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507 Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU NINDS NIH HHS [R01 NS043802-05, NS36736, NS43802, NS44178, NS45048, NS56118, R01 NS036736, R01 NS036736-10, R01 NS043802, R01 NS044178, R01 NS044178-05, R01 NS045048, R01 NS045048-05, R01 NS056118] NR 142 TC 74 Z9 83 U1 2 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2008 VL 106 IS 5 BP 1977 EP 1990 DI 10.1111/j.1471-4159.2008.05457.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 336JL UT WOS:000258360000001 PM 18466320 ER PT J AU Snuderl, M Chi, SN De Santis, SM Stemmer-Rachamimov, AO Betensky, RA De Girolami, U Kieran, MW AF Snuderl, Matija Chi, Susan N. De Santis, Stacia M. Stemmer-Rachamimov, Anat O. Betensky, Rebecca A. De Girolami, Umberto Kieran, Mark W. TI Prognostic value of tumor microinvasion and metalloproteinases expression in intracranial pediatric ependymomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE bcl-2; ependymoma; ezrin; microinvasion; MMP2; MMP14 ID CENTRAL-NERVOUS-SYSTEM; HUMAN GLIOMA-CELLS; MATRIX METALLOPROTEASE-2; EZRIN IMMUNOREACTIVITY; BCL-2; MIGRATION; INVASION; BRAIN; CHILDREN; SURVIVAL AB Ependymomas are common pediatric intracranial neoplasms that often appear well circumscribed on imaging but may recur when they are treated by Surgical resection alone. The current World Health Organization histological grading system does not accurately predict clinical behavior. The aim of this Study was to identify histological and immunohistochemical features that correlate with clinical Course in patients with ependymomas treated by gross total resection. We analyzed 41 pediatric ependymomas for microinvasion and correlated immunostaining for the metalloproteinase (MMP)-2 and MMP14 and for ezrin and bcl-2 with clinical outcome. Gross total resection had a significantly positive effect on overall survival and progression-free survival. In 28 patients who underwent gross total resection, microinvasion correlated with poor overall survival (p = 0.003) and progression-free survival (p = 0.03). Gross totally resected tumors with high expression of MMP2 and MMP14 had significantly shorter overall survival. Ezrin staining, identified tumor cells invading the adjacent white matter that were not identified by routine stains, but Ezrin staining and bcl-2 staining did not provide strong prognostic correlations. The data indicate that tumor microinvasion into adjacent brain and tumor expression of MMP2 and MMP 14 predict both overall and progression-free survival in pediatric ependymomas, and these are useful prognostic markers that may help stratify patients for adjuvant therapies. C1 [Snuderl, Matija; Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [De Girolami, Umberto] Childrens Hosp, Div Neuropathol, Boston, MA 02115 USA. [Chi, Susan N.; Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [De Santis, Stacia M.; Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Snuderl, M (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St, Boston, MA 02114 USA. EM MSnuderl@partners.org OI Kieran, Mark/0000-0003-2184-7692; Snuderl, Matija/0000-0003-0752-0917 FU Stop & Shop Pediatric Brain Tumor Brain Tumor Program; Pediatric Brain Tumor Research and Clinical Fund of the Dana-Farber Cancer Institute. FX The costs of this study were supported by the Stop & Shop Pediatric Brain Tumor Brain Tumor Program and the Pediatric Brain Tumor Research and Clinical Fund of the Dana-Farber Cancer Institute. NR 42 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 2008 VL 67 IS 9 BP 911 EP 920 DI 10.1097/NEN.0b013e318184f413 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 344PA UT WOS:000258938600009 PM 18716553 ER PT J AU Larsen, E Cedolin, L Delgutte, B AF Larsen, Erik Cedolin, Leonardo Delgutte, Bertrand TI Pitch representations in the auditory nerve: Two concurrent complex tones SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VENTRAL COCHLEAR NUCLEUS; STEADY-STATE VOWELS; FUNDAMENTAL-FREQUENCY; HEARING-LOSS; GUINEA-PIG; DISCHARGE PATTERNS; F0 DISCRIMINATION; SOUND SEGREGATION; HARMONIC NUMBER; IDENTIFICATION AB Pitch differences between concurrent sounds are important cues used in auditory scene analysis and also play a major role in music perception. To investigate the neural codes underlying these perceptual abilities, we recorded from single fibers in the cat auditory nerve in response to two concurrent harmonic complex tones with missing fundamentals and equal-amplitude harmonics. We investigated the efficacy of rate-place and interspike-interval codes to represent both pitches of the two tones, which had fundamental frequency (F0) ratios of 15/14 or 11/9. We relied on the principle of scaling invariance in cochlear mechanics to infer the spatiotemporal response patterns to a given stimulus from a series of measurements made in a single fiber as a function of F0. Templates created by a peripheral auditory model were used to estimate the F0s of double complex tones from the inferred distribution of firing rate along the tonotopic axis. This rate-place representation was accurate for F0s greater than or similar to 900 Hz. Surprisingly, rate-based F0 estimates were accurate even when the two-tone mixture contained no resolved harmonics, so long as some harmonics were resolved prior to mixing. We also extended methods used previously for single complex tones to estimate the F0s of concurrent complex tones from interspike-interval distributions pooled over the tonotopic axis. The interval-based representation was accurate for F0s less than or similar to 900 Hz, where the two-tone mixture contained no resolved harmonics. Together, the rate-place and interval-based representations allow accurate pitch perception for concurrent sounds over the entire range of human voice and cat vocalizations. C1 [Larsen, Erik; Cedolin, Leonardo; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Larsen, Erik; Cedolin, Leonardo; Delgutte, Bertrand] Harvard Univ, MIT, Speech & Hearing Biosci & Technol Program, Div Hlth Sci & Technol, Cambridge, MA USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Delgutte, B (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM bertrand_delgutte@meei.harvard.edu OI , /0000-0003-1349-9608 FU National Institute on Deafness and Other Communication Disorders (NIDCD) [R01 DC-002258, P30 DC-005209, T32 DC-00038] FX This work was supported by National Institute on Deafness and Other Communication Disorders (NIDCD) Grants R01 DC-002258 and P30 DC-005209. E. Larsen was partly supported by NIDCD Training Grant T32 DC-00038. This article is based on a thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in the Department of Electrical Engineering and Computer Science at the Massachusetts Institute of Technology in September 2008. NR 93 TC 29 Z9 29 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2008 VL 100 IS 3 BP 1301 EP 1319 DI 10.1152/jn.01361.2007 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 345YR UT WOS:000259034900015 PM 18632887 ER PT J AU Elman, I Chi, WH Gurvits, TV Ryan, ET Lasko, NB Lukas, SE Pitman, RK AF Elman, Igor Chi, Won H. Gurvits, Tamara V. Ryan, Elizabeth T. Lasko, Natasha B. Lukas, Scott E. Pitman, Roger K. TI Impaired Reproduction of Three-Dimensional Objects by Cocaine-Dependent Subjects SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NEW-YORK-CITY; NEUROPSYCHOLOGICAL DEFICITS; COGNITIVE PERFORMANCE; ALCOHOL DEPENDENCE; PARIETAL CORTEX; CRACK-COCAINE; DRUG-USE; ABUSERS; INDIVIDUALS AB This study employed a perceptual-motor task of figure copying in 27 cocaine-dependent, 26 marijuana-abusing or dependent, and 33 healthy subjects. Cocaine-dependent and healthy individuals did not differ in their scores on the copying of a two-dimensional diamond and a cross. In contrast, cocaine-dependent subjects displayed significantly poorer ability to copy a three-dimensional Necker cube, a smoking pipe, a hidden line elimination cube, a pyramid, and a dissected pyramid. Marijuana users' performance on all copied figures was comparable to that of the healthy comparison subjects. Considering that decreased three-dimensional copying ability has been found to be associated with fatal injuries, further studies are needed to investigate possible underlying mechanisms (e.g., parietal lobe damage) and their role in the pathophysiology of cocaine dependence. C1 [Elman, Igor] Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Belmont, MA 02478 USA. [Gurvits, Tamara V.; Lasko, Natasha B.; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Elman, I (reprint author), Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM ielman@partners.org FU National Institute on Drug Abuse [DA 017959] FX This work was supported by grant DA # 017959 (IE) from the National Institute on Drug Abuse. NR 40 TC 6 Z9 6 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2008 VL 20 IS 4 BP 478 EP 484 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 399CV UT WOS:000262778900012 PM 19196934 ER PT J AU Codd, PJ Mitha, AP Ogilvy, CS AF Codd, Patrick J. Mitha, Alim P. Ogilvy, Christopher S. TI A recurrent cerebral arteriovenous malformation in an adult - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE arteriovenous malformation; postoperative angiography; recurrent arteriovenous malformation ID SURGICAL EXCISION; CHILDREN; MANAGEMENT; EXPERIENCE; RESECTION; ANGIOMAS; BRAIN; AVMS AB Arteriovenous malformations are generally considered to be cured following angiographically proven complete resection. However, rare instances of AVM recurrence despite negative findings on postoperative angiography have been reported in both children and adults. In this paper, the authors present the case of a 33-year-old woman with 2 AVM recurrences. This patient represents the oldest case of recurrent AVM, and the first adult double recurrence reported in the literature. The case is presented, the radiological and surgical features are considered, and the literature on recurrent AVMs is reviewed. C1 [Codd, Patrick J.; Mitha, Alim P.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,VBK 710, Boston, MA 02114 USA. EM cogilvy@partners.org NR 28 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2008 VL 109 IS 3 BP 486 EP 491 DI 10.3171/JNS/2008/109/9/0486 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 344CX UT WOS:000258904400020 PM 18759581 ER PT J AU Upenieks, VV Needleman, J Soban, L Pearson, ML Parkerton, P Yee, T AF Upenieks, Valda V. Needleman, Jack Soban, Lynn Pearson, Marjorie L. Parkerton, Pat Yee, Tracy TI The relationship between the volume and type of Transforming Care at the Bedside innovations and changes in nurse vitality SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID HOSPITALS; UNITS; MAGNET; WORK C1 [Upenieks, Valda V.] Univ Calif Los Angeles, Sch Nursing, Nursing Adm Grad Program, Los Angeles, CA 90095 USA. [Needleman, Jack; Parkerton, Pat; Yee, Tracy] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Soban, Lynn] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Excellence Study Healthcare, Los Angeles, CA USA. [Pearson, Marjorie L.] RAND Corp, Santa Monica, CA USA. RP Upenieks, VV (reprint author), Univ Calif Los Angeles, Sch Nursing, Nursing Adm Grad Program, 3-242 Factor Bldg,Box 956917, Los Angeles, CA 90095 USA. EM vupeniek@ucla.edu RI Needleman, Jack/I-5461-2013 OI Needleman, Jack/0000-0002-2875-0589 FU Robert Wood Johnson Foundation; Veterans Affairs Health Services Research and Development FX Funding for this work was provided by the Robert Wood Johnson Foundation. Dr Soban is currently funded by a Career Development Award from the Veterans Affairs Health Services Research and Development program. The conclusions are those of the authors and do not necessarily reflect the opinions of the Robert Wood Johnson Foundation or the Veterans Health Administration. NR 20 TC 12 Z9 12 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD SEP PY 2008 VL 38 IS 9 BP 386 EP 394 DI 10.1097/01.NNA.0000323959.52415.86 PG 9 WC Nursing SC Nursing GA 354UY UT WOS:000259665700005 PM 18791422 ER PT J AU Markiewicz, MR Brady, MF Ding, EL Dodson, TB AF Markiewicz, Michael R. Brady, Mark F. Ding, Eric L. Dodson, Thomas B. TI Corticosteroids reduce postoperative morbidity after third molar surgery: A systematic review and meta-analysis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Review ID BILATERAL ORAL-SURGERY; CONTROLLED-TRIAL; CLINICAL-TRIALS; POSTSURGICAL SEQUELAE; RANDOMIZED-TRIALS; SURGICAL REMOVAL; DOUBLE-BLIND; METHYLPREDNISOLONE; DEXAMETHASONE; EXTRACTION AB Purpose: The purpose of this study was to apply meta-analytical methods to measure the effect of corticosteroids (CS) on edema, trismus, and pain at early and late postoperative periods after third molar (M3) removal. Materials and Methods: A systematic search of the literature was carried out to identify eligible articles. The primary predictor variable was perioperative CS exposure (yes or no). The 3 outcome variables were edema, trismus, and pain assessed during the early (1-3 days) and late (>3 days) postoperative time periods. Standardized mean differences (SMD) for edema and weighted mean differences (WMD) for trismus and pain were pooled across studies. Differences between the 2 treatment groups were assessed using random effects models and metaregressions for both early and late postoperative assessments. Results: Twelve trials met the inclusion criteria. Subjects receiving CS had significantly less edema during both early (SMD, 1.4; 95% confidence interval [CI], 0.6, 2.2; P < .001) and late (SMD, 1.1; 95% CI, 0.1, 2.0; P = .03) time periods after surgery and less trismus than controls during the early and late postoperative periods (early WMD, 4.1 mm; 95% CI, 2.8 mm, 5.5 mm; P < .001; late WMD, 2.7 mm; 95% Cl, 0.8 mm, 4.6 mm; P = .005). Average pain levels were not significantly different between the 2 groups (early WMD, 0.4 visual analog scale [VAS]; 95% CI, -0.04 VAS, 0.9 VAS; P = .07; late WMD, 0.5 VAS; 95% CI, -0.6 VAS, 1.5 VAS; P = .4). Conclusions: The findings of this study suggest that perioperative administration of corticosteroids produces a mild to moderate reduction in edema and improvement in range of motion after M3 removal. (C) 2008 American Association of Oral and Maxillofacial Surgeons. C1 [Brady, Mark F.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Markiewicz, Michael R.] SUNY Buffalo, Sch Dent Med, Buffalo, NY USA. [Brady, Mark F.] Johns Hopkins Sch Publ Hlth, Natl Inst Hlth, Lima, Peru. RP Markiewicz, MR (reprint author), Oregon Hlth & Sci Univ, SDOMS, 611 SW Campus Dr, Portland, OR 97239 USA. EM michaelmarkiewicz@gmail.com OI Ding, Eric/0000-0002-5881-8097 FU OMS Foundation Student Research Training Award; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund; Center for Applied Clinical Investigation; Massachusetts General Physicians Organization FX The authors thank Dr Rob Van Dam, Harvard School of Public Health, for his guidance in the initial stages of this project. The authors appreciate the kind responses of the authors contacted during the literature review of this study including: Drs Roger E. Alexander, O. Ross Beirne, Raymond Dionne, Marc Leone, A. Markovic, Paul S. Tiwana, and Yakup Ustun. The authors thank Dr Raymond White, Jr, for providing an insightful review of this manuscript. The authors thank Dr Ceib Phillips for her constructive and critical review of this manuscript. This project was supported in part by the OMS Foundation Student Research Training Award (M.R.M.), Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund and Center for Applied Clinical Investigation (T.B.D., M.R.M.), and Massachusetts General Physicians Organization (T.B.D.). NR 74 TC 50 Z9 55 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2008 VL 66 IS 9 BP 1881 EP 1894 DI 10.1016/j.joms.2008.04.022 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 343YC UT WOS:000258891300015 PM 18718396 ER PT J AU Mudgal, CS Jupiter, JB AF Mudgal, Chaitanya S. Jupiter, Jesse B. TI Plate fixation of osteoporotic fractures of the distal radius SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article ID INTERNAL-FIXATION; EXTERNAL FIXATION; INTRAARTICULAR FRACTURES; SCAPHOLUNATE DIASTASIS; UNSTABLE FRACTURES; COLLES FRACTURES; OPEN REDUCTION; PATIENTS OLDER; DORSAL; END AB Fractures of the distal radius in patients with osteoporosis constitute a unique challenge for the surgeon. They are by nature most commonly seen in the elderly Population. Our understanding of the age, physiology, and functionality of the elderly has evolved considerably over the last two decades. Often these fractures simply affect a patient's already-compromised functional status. However, in active elderly adults they can also Substantially reduce the functionality and this can have a significant impact on their ability to care for themselves, pursue avocational activities, or both. In carefully selected patients, even in the face of osteoporosis, plate fixation of these fractures has satisfying outcomes for both the patient and the surgeon and must be considered part of a Surgeon's armamentarium in the contemporary treatment of osteoporotic fractures of the distal radius. C1 [Mudgal, Chaitanya S.; Jupiter, Jesse B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 44 TC 10 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD SEP PY 2008 VL 22 IS 8 SU S BP S106 EP S115 PG 10 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 347ZY UT WOS:000259181700009 PM 18753886 ER PT J AU Morone, NE Lynch, CS Greco, CM Tindle, HA Weiner, DK AF Morone, Natalia E. Lynch, Cheryl S. Greco, Carol M. Tindle, Hilary A. Weiner, Debra K. TI "I Felt Like a New Person." The effects of mindfulness meditation on older adults with chronic pain: Qualitative narrative analysis of diary entries SO JOURNAL OF PAIN LA English DT Article DE qualitative research; meditation; back pain; aging; mindfulness ID LOW-BACK-PAIN; STRESS REDUCTION MBSR; HEALTH-CARE; ATTENTION; BRAIN; STATE AB To identify the effects of mindfulness meditation on older adults with chronic low back pain (CLBP), we conducted a qualitative study based on grounded theory and used content analysis of diary entries from older adults who had participated in a clinical trial of an 8-week mindfulness meditation program. Participants were 27 adults >= 65 years of age with CLBP of at least moderate severity and of at least 3 months duration. We found several themes reflecting the beneficial effects of mindfulness meditation on pain, attention, sleep, and achieving well-being. Various methods of pain reduction were used, including distraction, increased body awareness leading to behavior change, better pain coping, and direct pain reduction through meditation. Participants described improved attention skills. A number of participants reported improved sleep latency as well as quality of sleep. Participants described achieving well-being during and after a meditation session that had immediate effects on mood elevation but also long-term global effects on improved quality of life. Several themes were identified related to pain reduction, improved attention, improved sleep, and achieving well-being resulting from mindfulness meditation that suggest it has promising potential as a nonpharmacologic treatment of chronic pain for older adults. Perspective: Community-dwelling older adults with chronic low back pain experience numerous benefits from mindfulness meditation including less pain, improved attention, better sleep, enhanced well-being, and improved quality of life. Additional research is needed to determine how mindfulness meditation works and how it might help with other chronic illnesses. (C) 2008 by the American Pain Society. C1 [Morone, Natalia E.; Lynch, Cheryl S.; Tindle, Hilary A.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Greco, Carol M.; Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Lynch, Cheryl S.; Weiner, Debra K.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Morone, NE (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM moronene@upmc.edu FU National Institutes of Health (NIH) [AG23641 K07]; National Center for Research Resources (NCRR) [1KL2RR024154-01]; National Institutes of Health [T32 AG 021885-05] FX Supported by grant AG23641 K07 to Dr. Stephanie Studenski from the National Institutes of Health (NIH). During the time of this work, Dr. Morone and Dr. Tindle were supported by the NIH Roadmap Multidisciplinary Clinical Research Career Development Award Grant (1KL2RR024154-01) from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Dr. Lynch was supported by grant T32 AG 021885-05 from the National Institutes of Health. NR 29 TC 53 Z9 55 U1 6 U2 59 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD SEP PY 2008 VL 9 IS 9 BP 841 EP 848 DI 10.1016/j.jpain.2008.04.003 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 347WN UT WOS:000259172200009 PM 18550444 ER PT J AU O'Neill, SM Ettner, SL Lorenz, KA AF O'Neill, Sean M. Ettner, Susan L. Lorenz, Karl A. TI Paying the Price at the End of Life: A Consideration of Factors that Affect the Profitability of Hospice SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PALLIATIVE CARE; NURSING-HOMES; HOSPITALS AB Objective: To evaluate factors that affect the financial performance of hospice. Methods: Using the California Office of Statewide Health Planning and Development 2003 survey, we evaluated the organizational attributes, clinical care, and financial performance of 185 operational hospices. As outcomes, we evaluated revenues, costs, and profits per patient and per patient-day, the intensity and skill mix of care, and the provision of charitable and special palliative services. We evaluated regression-adjusted differences by profit status controlling for other organizational features and aggregate patient characteristics. Results: Hospices reported median revenue of $6865 per patient and $138 per patient-day (for-profit-not-for profit [FP-NFP] difference -$20, p = 0.045), median cost of $6737 per patient, and $135 per patient-day (FP-NFP difference -$55, p = 0.002), and median pretax profit of $334 per patient and $6 per patient-day (FP-NFP difference $34, p = 0.026). Patients received a median of 29.9 total visits by all providers per patient (FP-NFP difference 8.8 visits, p = 0.010), but there was no difference in total visits per patient-day. A median of 50.8% of all nursing visits were registered nurse (RN) visits (FP-NFP difference -14.1%, p < 0.001). Few hospices provided charity care, and only 4% of hospices reported expenditures on chemotherapy and only 9% on radiation therapy. Conclusions: Overall hospice profitability is low. Length of stay is strongly associated with financial performance, and greater FP profitability is related to lower costs. FP hospices also provide less RN care as a proportion of nursing care. Few hospices provide charitable care or special costly services. The relationship of service patterns to patient quality needs to be examined. C1 [O'Neill, Sean M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Ettner, Susan L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lorenz, Karl A.] VA Greater Angeles Hlth Care Syst, Los Angeles, CA USA. RP O'Neill, SM (reprint author), Pardee RAND Grad Sch, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM soneill@prgs.edu OI O'Neill, Sean/0000-0001-7759-8942 FU NIA/AFAR; Lillian R. Gleitsman Summer Training Institute at UCLA; VA HSR&D Advanced Career Development Awardee FX Mr. O'Neill's work was supported by the NIA/AFAR and Lillian R. Gleitsman Summer Training Institute at UCLA. Dr. Lorenz is a VA HSR&D Advanced Career Development Awardee. NR 26 TC 15 Z9 15 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD SEP PY 2008 VL 11 IS 7 BP 1002 EP 1008 DI 10.1089/jpm.2007.0252 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 364XQ UT WOS:000260369400014 PM 18788962 ER PT J AU Williams, BR Allman, RM AF Williams, Beverly R. Allman, Richard M. TI Marital status and health: Exploring pre-widowhood (vol 11, pg 6, 2008) SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Correction C1 [Williams, Beverly R.; Allman, Richard M.] Birmingham VA Med Ctr, GRECC, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [Williams, Beverly R.; Allman, Richard M.] Univ Alabama, Div Gerontol Geriatr & Palliat Care, Dept Med, Birmingham, AL USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD SEP PY 2008 VL 11 IS 7 BP 1060 EP 1060 DI 10.1089/jpm.2008.9822 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 364XQ UT WOS:000260369400023 ER PT J AU Liegl, B Kepten, I Le, C Zhu, M Demetri, GD Heinrich, MC Fletcher, CDM Corless, CL Fletcher, JA AF Liegl, B. Kepten, I. Le, C. Zhu, M. Demetri, G. D. Heinrich, M. C. Fletcher, C. D. M. Corless, C. L. Fletcher, J. A. TI Heterogeneity of kinase inhibitor resistance mechanisms in GIST SO JOURNAL OF PATHOLOGY LA English DT Article DE imatinib; sunitinib; drug resistance mechanisms; GIST; heterogeneity ID GASTROINTESTINAL STROMAL TUMORS; CELL LUNG-CANCER; IMATINIB MESYLATE; GROWTH-FACTOR; KIT ACTIVATION; PHASE-II; IN-VITRO; MUTATIONS; SU11248; PROGRESSION AB Most GIST patients develop clinical resistance to KIT/PDGFRA tyrosine kinase inhibitors (TKI). However, it is unclear whether clinical resistance results from single or multiple molecular mechanisms in each patient. KIT and PDGFRA mutations were evaluated in 53 GIST metastases obtained from 14 patients who underwent surgical debulking after progression on imatinib or sunitinib. To interrogate possible resistance mechanisms across a broad biological spectrum of GISTs, inter- and intra-lesional heterogeneity of molecular drug-resistance mechanisms were evaluated in the following: conventional KIT (CD117)-positive GISTs with KIT mutations in exon 9, 11 or 13; KIT-negative GISTs; GISTs with unusual morphology; and KIT/PDGFRA wild-type GISTs. Genomic KIT and PDGFRA mutations were characterized systematically, using complementary techniques including D-HPLC for KIT exons 9, 11-18 and PDGFRA exons 12, 14, 18, and mutation-specific PCR (V654A, D820G, N822K, Y823D). Primary KIT oncogenic mutations were found in 11/14 patients (79%). Of these, 9/11 (83%), had secondary drug-resistant KIT mutations, including six (67%) with two to five different secondary mutations in separate metastases, and three (34%) with two secondary KIT mutations in the same metastasis. The secondary mutations clustered in the KIT ATP binding pocket and kinase catalytic regions. FISH analyses revealed KIT amplicons in 2/10 metastases lacking secondary KIT mutations. This study demonstrates extensive intra- and inter-lesional heterogeneity of resistance mutations and gene amplification in patients with clinically progressing GIST. KIT kinase resistance mutations were not found in KIT/PDGFP-4 wild-type GISTs or in KIT-mutant GISTs showing unusual morphology and/or loss of KIT expression by IHC, indicating that resistance mechanisms are fundamentally different in these tumours. Our observations underscore the heterogeneity of clinical TKI resistance, and highlight the therapeutic challenges involved in salvaging patients after clinical progression on TKI monotherapies. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Liegl, B.; Zhu, M.; Fletcher, C. D. M.; Fletcher, J. A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Liegl, B.; Zhu, M.; Demetri, G. D.; Fletcher, C. D. M.; Fletcher, J. A.] Harvard Univ, Sch Med, Boston, MA USA. [Liegl, B.] Med Univ Graz, Dept Pathol, Graz, Austria. [Kepten, I.; Le, C.; Corless, C. L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Demetri, G. D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Heinrich, M. C.] Oregon Hlth & Sci Univ, Inst Canc, Div Hematol & Oncol, Portland, OR USA. [Heinrich, M. C.] Portland VA Med Ctr, Portland, OR USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM bernadette.liegl-atzwanger@meduni-graz.at; jfletcher@partners.org FU GI SPORE [1P50CA127003-01]; Life Raft Group; Cesarini Team for the Pan-Massachusetts Challenge, the Virginia; Daniel K. Ludwig Trust for Cancer Research; Ronald O. Perelman Fund for Cancer Research; Stutman GIST Cancer Research Fund; BP Lester Foundation; Rubenstein Foundation; Leslie's Links; FWF Austrian Science Fund FX This work was supported by grants from an anonymous donor, GI SPORE 1P50CA127003-01, the Life Raft Group, the Cesarini Team for the Pan-Massachusetts Challenge, the Virginia and Daniel K. Ludwig Trust for Cancer Research, the Ronald O. Perelman Fund for Cancer Research, the Stutman GIST Cancer Research Fund, the BP Lester Foundation, the Rubenstein Foundation, Leslie's Links, a VA Merit Review Grant and the FWF Austrian Science Fund. NR 34 TC 183 Z9 192 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD SEP PY 2008 VL 216 IS 1 BP 64 EP 74 DI 10.1002/path.2382 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 345AS UT WOS:000258969000007 PM 18623623 ER PT J AU DuBois, SG Perez-Atayde, AR McLean, TW Grier, HE AF DuBois, Steven G. Perez-Atayde, Antonio R. McLean, Thomas W. Grier, Holcombe E. TI Late recurrence of Ewing sarcoma during pregnancy - A report of 2 cases SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE Ewing sarcoma; recurrence; pregnancy; estrogen; progesterone ID PRIMITIVE NEUROECTODERMAL TUMOR; GROWTH-FACTOR-I; HOSPITAL EXPERIENCE; CHEMOTHERAPY; SURVIVAL; EXPRESSION; CANCER; FAMILY; BONE AB Ewing sarcoma is the second most common type of malignant bone tumor in children and young adults. We report 2 patients with a history of Ewing sarcoma who were diagnosed with recurrent tumor during or immediately after pregnancy. To determine whether the hormonal milieu of pregnancy might have contributed to recurrence, we performed immunohistochemistry for estrogen and progesterone receptors on available tumor tissue. These receptors were not detected by immunohistochemistry. Increased medical surveillance during pregnancy may have resulted in ascertainment of recurrence in these 2 patients. C1 [DuBois, Steven G.] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [Perez-Atayde, Antonio R.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Grier, Holcombe E.] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [McLean, Thomas W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Pediat Hematol Oncol, Winston Salem, NC USA. RP DuBois, SG (reprint author), Univ Calif San Francisco, Sch Med, Dept Pediat, 505 Parnassus Ave,Box 0106, San Francisco, CA 94143 USA. EM duboiss@peds.ucsf.edu NR 20 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD SEP PY 2008 VL 30 IS 9 BP 716 EP 718 DI 10.1097/MPH.0b013e318175895f PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 346VS UT WOS:000259098300017 PM 18776769 ER PT J AU Polk-Williams, A Carr, BG Blinman, TA Masiakos, PT Wiebe, DJ Nance, ML AF Polk-Williams, Alison Carr, Brendan G. Blinman, Thane A. Masiakos, Peter T. Wiebe, Douglas J. Nance, Michael L. TI Cervical spine injury in young children: a National Trauma Data Bank review SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Trauma; Pediatric; Spine AB Background: Blunt cervical spine injury (CSI) is rare in the pediatric Population. The objective of this study was to better characterize the incidence and type of CSI in young children (age <3 years) using a large, trauma center-based data set. Methods: The National Trauma Data Bank (NTDB) was reviewed for the period January 2001 to December 2005 for patients Younger than 3 years of age with a blunt CSI (International Classification of Diseases, Ninth Revision, 805x, 806x, 952x). Demographic, injury, and Outcome information were reviewed. Data management was performed using SAS (SAS, Cary, NC) and Stata (Stata Corp, College Station, TX). Patients with CSI were compared to patients without CSI of similar age. Means were compared with the Wilcoxon rank sum test, medians were compared with a nonparametric test, and count data were compared with the chi(2) test, with significance set at < .05. Results: For the period of review, 95.654 young children (age <3 years) with blunt trauma were identified in the NTDB. The overall population had a median Injury Severity Score (ISS) of 4, and most patients (77.01%,) had a Glasgow Coma Score (GCS) of 15. There were 1523 (1.59%) patients with a CSI (spinal cord and/or column), including 366 patients (0.38%) with a spinal cord injury (with or without column injury) and 182 (0.19%) with an isolated spinal cord injury (SCIWORA). The CSI and non-CSI populations did not differ regarding median GCS (15 for both groups), but the CSI population had a significantly higher Median ISS (14 vs 4, respectively; P < .001). Compared to patients without CSI, the CSI Population was more likely to die in the emergency department (2.04% vs 1.25% P = .007) or be admitted to the intensive care unit (45.3% vs 16.9%; P < .001). Nearly half of all cervical spine fractures (48%) and more than half of cervical spinal cord injuries (53%) were in the lower cervical spine (C5-7). MVCs were the most common injury mechanism (66%) followed by falls (15%). A CSI was observed in 3.2% of all motor vehicle crashes (MVCs). Conclusions: In this trauma center population, these findings confirm the infrequency of blunt CSI in the youngest (age <3 years) trauma patients. The frequency of injuries to the lower cervical spine is higher than previously appreciated. MVCs are the most likely injury mechanism for this potentially devastating injury. (C) 2008 Elsevier Inc. All rights reserved. C1 [Nance, Michael L.] Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA 19104 USA. [Masiakos, Peter T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wiebe, Douglas J.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Carr, Brendan G.] Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA. RP Nance, ML (reprint author), Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA 19104 USA. EM nance@email.chop.edu NR 8 TC 23 Z9 24 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD SEP PY 2008 VL 43 IS 9 BP 1718 EP 1721 DI 10.1016/j.jpedsurg.2008.06.002 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 364TV UT WOS:000260359100024 PM 18779013 ER PT J AU Kratz, JR Deshpande, V Ryan, DP Goldstein, AM AF Kratz, Johannes R. Deshpande, Vikrarn Ryan, Daniel P. Goldstein, Allan M. TI Anal canal duplication associated with presacral cyst SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Anal canal duplication; Presacral cyst ID CHILDREN; INFANTS; SINUS AB Anal canal duplications are rare congenital malformations, with fewer than 50 reported cases in the literature. Anal canal duplications are noncommunicating second anal orifices located posterior to the true anus without other associated hindgut duplications. Typically, these are asymptomatic, tubular malformations that present in females before the age of 6 years. Here, we report on a 16-year-old girl with a symptomatic anal canal duplication associated with a presacral cystic component. This is an unusual presentation of an already rare entity. An overview of the clinical presentation, radiologic workup, surgical treatment, and histologic features of anal canal duplications is provided. (c) 2008 Elsevier Inc. All rights reserved. C1 [Ryan, Daniel P.; Goldstein, Allan M.] Harvard Univ, Sch Med, Dept Pediat Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kratz, Johannes R.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deshpande, Vikrarn] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Harvard Univ, Sch Med, Dept Pediat Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM agoldstein@partners.org NR 9 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD SEP PY 2008 VL 43 IS 9 BP 1749 EP 1752 DI 10.1016/j.jpedsurg.2008.05.026 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 364TV UT WOS:000260359100032 PM 18779021 ER PT J AU Kurtz, M Masiakos, PT AF Kurtz, Michael Masiakos, Peter T. TI Laparoscopic resection of a urachal remnant SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Urachus; Laparoscopy; VCUG ID MANAGEMENT; CHILDREN AB The surgical management of urachal remnants in children is evolving. This case is one example, with clear diagnostic imaging and excellent clinical results that were achieved laparoscopically. (c) 2008 Elsevier Inc. All rights reserved. C1 [Masiakos, Peter T.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Kurtz, Michael; Masiakos, Peter T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Masiakos, PT (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. EM pmasiakos@partners.org NR 7 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD SEP PY 2008 VL 43 IS 9 BP 1753 EP 1754 DI 10.1016/j.jpedsurg.2008.04.021 PG 2 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 364TV UT WOS:000260359100033 PM 18779022 ER PT J AU Wilens, TE Vitulano, M Upadhyaya, H Adamson, J Sawtelle, R Utzinger, L Biederman, J AF Wilens, Timoth E. Vitulano, Michael Upadhyaya, Himanshu Adamson, Joel Sawtelle, Robert Utzinger, Linsey Biederman, Joseph TI Cigarette smoking associated with attention deficit hyperactivity disorder SO JOURNAL OF PEDIATRICS LA English DT Article ID SUBSTANCE USE DISORDERS; DEFICIT/HYPERACTIVITY DISORDER; DRUG-USE; PSYCHIATRIC COMORBIDITY; YOUNG-ADULTS; ADOLESCENTS; ADHD; SYMPTOMS; CHILDREN; PATTERNS AB Objective To evaluate the association between attention deficit hyperactivity (ADHD) and severity of physical dependence on nicotine in a controlled study of adolescents and young adults with ADHD. Study design In controlled longitudinal family studies of ADHD, we examined self-reports on the modified Fagerstrom Tolerance Questionnaire (mFTQ) for degrees of physical dependence on nicotine. Results We obtained mFTQ data from 80 ADHD probands and 86 control probands (mean age, 19.2 years). The smokers with ADHD had significantly higher scores on the mFTQ, indicative of more severe physical dependence on nicotine. Similarly, in current smokers, a positive linear relationship was found between mFTQ score and both inattentive and hyperactive ADHD symptoms. Environmental factors, such as current parental smoking, peer smoking, and living with a smoker, all increased the risk for smoking in those with ADHD compared with controls. Conclusion Male and female smokers with ADHD manifest more severe physical dependence on smoking compared with controls. Important environmental factors appear to add to the risk of smoking associated with ADHD. C1 [Wilens, Timoth E.; Vitulano, Michael; Adamson, Joel; Sawtelle, Robert; Utzinger, Linsey; Biederman, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Program, Boston, MA USA. [Upadhyaya, Himanshu] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. RP Wilens, TE (reprint author), Pediat Psychopharmacol Unit, 55 Parkman St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org RI Price, Katie/H-1931-2012; OI Adamson, Joel/0000-0002-1399-5786 FU National Institute on Drug Abuse [R01 DA14419, DA016264, 5U10DA015831] FX Supported in part by the National Institute on Drug Abuse (grants R01 DA14419, DA016264, and 5U10DA015831). Potential conflict of interest information is available at www.jpeds.com. NR 31 TC 46 Z9 46 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2008 VL 153 IS 3 BP 414 EP 419 DI 10.1016/j.jpeds.2008.04.030 PG 6 WC Pediatrics SC Pediatrics GA 348JV UT WOS:000259207700024 PM 18534619 ER PT J AU Stearns, AT Balakrishnan, A Rhoads, DB Ashley, SW Tavakkolizadeh, A AF Stearns, Adam T. Balakrishnan, Anita Rhoads, David B. Ashley, Stanley W. Tavakkolizadeh, Ali TI Diurnal rhythmicity in the transcription of jejunal drug transporters SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Article DE diurnal rhythm; intestinal; drug efflux transporter ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN; COTRANSPORTER SGLT1; EFFLUX PROTEINS; EXPRESSION; BIOAVAILABILITY; PERIODICITY; INTESTINE AB Intestinal drug efflux proteins play a major role in the pharmacokinetics of many drugs. We assessed diurnal rhythmicity in the expression of ten major drug transporters. We acquired male Sprague-Dawley rats and harvested jejunal mucosa at 3-h intervals across a 24-h period. qPCR was performed for ten transporters: Mdr1, Mdr3, Mrp1-3, Mct1, Brcp, Pept1, Octn2, and Oatp-b. Rhythmicity was assessed with the cosinor procedure. Diurnal rhythmicity was observed for Mdr1, Mct1, Mrp2, Pept1, and Bcrp (1.6-5.4-fold-changes). Acrophases occurred during fasting hours. We conclude that many drug transporters display profound diurnal rhythms in transcription, which may underlie diurnal rhythms in drug pharmacokinetics. C1 [Stearns, Adam T.; Balakrishnan, Anita; Ashley, Stanley W.; Tavakkolizadeh, Ali] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Stearns, Adam T.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England. [Balakrishnan, Anita] Univ Liverpool, Div Gastroenterol, Sch Clin Sci, Liverpool L69 3GE, Merseyside, England. [Rhoads, David B.] Harvard Univ, Sch Med, MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Tavakkolizadeh, A (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM atavakkoli@partners.org OI Stearns, Adam/0000-0003-4327-7360 FU National Institute of Health [5 R01 DK047326]; Harvard Clinical Nutrition Center [P30-DK040561]; American Diabetes Association [7-05-RA-121]; Berkeley Fellowship; Nutricia Research Foundation FX We thank Jan Rounds for invaluable managerial assistance. This study is supported by National Institute of Health 5 R01 DK047326 (SWA), Harvard Clinical Nutrition Center Grant P30-DK040561 (AT), American Diabetes Association 7-05-RA-121 (DBR), Berkeley Fellowship (ATS), and the Nutricia Research Foundation (AB). NR 14 TC 27 Z9 31 U1 1 U2 2 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD SEP PY 2008 VL 108 IS 1 BP 144 EP 148 DI 10.1254/jphs.08100SC PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 355BJ UT WOS:000259683400019 PM 18787306 ER PT J AU Wolin, KY Heil, DP Askew, S Matthews, CE Bennett, GG AF Wolin, Kathleen Y. Heil, Daniel P. Askew, Sandy Matthews, Charles E. Bennett, Gary G. TI Validation of the International Physical Activity Questionnaire-Short Among Blacks SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE physical activity assessment; measurement; epidemiology; community-based research ID VALIDITY; RELIABILITY; PREVENTION; ADULTS; VARIABLES; EXERCISE; DISEASE; ISSUES; WOMEN; IPAQ AB Background: The International Physical Activity Questionnaire-Short Form (IPAQ-S) has been evaluated against accelerometer-determined physical activity measures in small homogenous samples of adults in the United States. There is limited information about the validity of the IPAQ-S in diverse US samples. Methods: 142 Blacks residing in low-income housing completed the IPAQ-S and wore an accelerometer for up to 6 days. Both 1- and 10-minute accelerometer bouts were used to define time spent in light, moderate, and vigorous physical activity. Results: We found fair agreement between the IPAQ-S and accelerometer-determined physical activity (r = .26 for 10-minute bout, r = .36 for 1-minute bout). Correlations were higher among men than women. When we classified participants as meeting physical activity recommendations, agreement was low (kappa = .04, 10-minute; kappa = .21, 1-minute); only 25% of individuals were classified the same by both instruments (10-minute bout). Conclusions: In one of the few studies to assess the validity of a self-reported physical activity measure among Blacks, we found moderate correlations with accelerometer data, though correlations were weaker for women. Correlations were smaller when IPAQ-S data were compared using a 10-versus a 1-minute bout definition. There was limited evidence for agreement between the instruments when classifying participants as meeting physical activity recommendations. C1 [Wolin, Kathleen Y.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Heil, Daniel P.] Montana State Univ, Dept Hlth & Human Dev, Bozeman, MT 59717 USA. [Askew, Sandy; Bennett, Gary G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Matthews, Charles E.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Nashville, TN 37232 USA. [Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Wolin, KY (reprint author), Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. RI matthews, Charles/E-8073-2015 OI matthews, Charles/0000-0001-8037-3103 FU NCI NIH HHS [3R01CA098864-02S1, 5R01CA098864-02, R01 CA098864, R01 CA098864-02, R25 CA100600] NR 30 TC 63 Z9 65 U1 0 U2 8 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD SEP PY 2008 VL 5 IS 5 BP 746 EP 760 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V18PA UT WOS:000208015500009 PM 18820348 ER PT J AU Aryee, MJA Quackenbush, J AF Aryee, Martin J. A. Quackenbush, John TI An optimized predictive strategy for interactome mapping SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE protein-protein interaction; interactome; yeast two-hybrid ID PROTEIN-PROTEIN INTERACTIONS; INTERACTION NETWORKS; DOMAIN INTERACTIONS; INTERACTION MAP; YEAST; ORGANISMS; RESOURCE; DATABASE AB We present an optimized experimental strategy that can accelerate progress toward identifying the majority of pairwise protein interactions. Our method involves applying a predictive algorithm, based on the existing data, to identify protein pairs likely to interact and prioritizing these for screening. The approach is iterative as additional data allows one to refine predictions directing the next stage of experimentation. C1 [Aryee, Martin J. A.; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Quackenbush, J (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu FU NHGRI NIH HHS [P50 HG004233] NR 28 TC 2 Z9 2 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP PY 2008 VL 7 IS 9 BP 4089 EP 4094 DI 10.1021/pr700858e PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 345RZ UT WOS:000259015500044 PM 18642945 ER PT J AU Leuchter, AE Lesser, IM Trivedi, MH Rush, AJ Morris, DW Warden, D Fava, M Wisniewski, SR Luther, JF Perales, M Gaynes, BN Stewart, JW AF Leuchter, Andrew F. Lesser, Ira M. Trivedi, Madhukar H. Rush, A. John Morris, David W. Warden, Diane Fava, Maurizio Wisniewski, Stephen R. Luther, James F. Perales, Mercedes Gaynes, Bradley N. Stewart, Jonathan W. TI An open pilot stud of the combination of escitalopram and bupropion-SR for outpatients with major depressive disorder SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE major depressive disorder; bupropion; escitalopram; medication combinations; adverse events ID SEROTONIN REUPTAKE INHIBITORS; STAR-ASTERISK-D; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; RESISTANT DEPRESSION; CONTROLLED-TRIAL; QUICK INVENTORY; RATING-SCALE; PRIMARY-CARE; ANTIDEPRESSANTS C1 [Leuchter, Andrew F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Lesser, Ira M.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Trivedi, Madhukar H.; Rush, A. John; Morris, David W.; Warden, Diane] Univ Texas SW Med Sch, Dallas, TX USA. [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wisniewski, Stephen R.; Luther, James F.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Perales, Mercedes] Univ Kansas, Lawrence, KS 66045 USA. [Gaynes, Bradley N.] Univ N Carolina, Chapel Hill, NC USA. [Stewart, Jonathan W.] Columbia Univ, Med Ctr, New York, NY 10027 USA. RP Leuchter, AE (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,Rm 37-452, Los Angeles, CA 90024 USA. EM afl@ucla.edu FU NIMH NIH HHS [N01MH90003, N01 MH090003] NR 28 TC 30 Z9 30 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD SEP PY 2008 VL 14 IS 5 BP 271 EP 280 DI 10.1097/01.pra.0000336754.19566.65 PG 10 WC Psychiatry SC Psychiatry GA 356CV UT WOS:000259757200003 PM 18832958 ER PT J AU Morissette, SB Spiegel, DA Barlow, DH AF Morissette, Sandra Baker Spiegel, David A. Barlow, David H. TI Combining exposure and pharmacotherapy in the treatment of social anxiety disorder: A preliminary study of state dependent learning SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE state dependent learning; benzodiazepines; social anxiety disorder; exposure ID COGNITIVE-BEHAVIORAL THERAPY; PANIC DISORDER; ALPRAZOLAM DISCONTINUATION; AGORAPHOBIA; EXTINCTION; DIAZEPAM; ALCOHOL; BENZODIAZEPINES; CONTEXT; RELAPSE AB State dependent learning (SDL) occurs when learning acquired in one context is not retrievable in a different context. Although traditionally SDL is thought of in the context of substance use, the role of SDL should be considered during combined medication and exposure treatment for anxiety disorders. Data are presented from a within-subjects, case-series design of four participants with social anxiety disorder. Participants engaged in a series of situational exposures while taking either alprazolam (0.75 mg), propranolol (40 mg), placebo or no medication. They returned 48 h later and engaged in the same situational exposure in an unmedicated state to determine retention of learning following the shift in drug context. Results suggest that SDL effects are possible when combining pharmacotherapy (alprazolam) with exposure therapy. Future research is needed determine the conditions under which SDL is most likely to occur and ways to facilitate transfer of learning across different contexts. C1 [Morissette, Sandra Baker] VA Boston Healthcare Syst, Psychol Serv 116B, Boston, MA 02130 USA. [Morissette, Sandra Baker; Spiegel, David A.; Barlow, David H.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Morissette, SB (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington St, Boston, MA 02130 USA. EM Sandra.Morissette@va.gov NR 38 TC 7 Z9 7 U1 4 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD SEP PY 2008 VL 30 IS 3 BP 211 EP 219 DI 10.1007/s10862-007-9061-1 PG 9 WC Psychology, Clinical SC Psychology GA 322RO UT WOS:000257393200006 ER PT J AU Kimball, AB AF Kimball, Alexa B. TI Advances in the treatment of acne SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE acne vulgaris; drospirenone; oral contraceptives; combined; YAZ (R) ID HORMONAL CONTRACEPTIVES; SCHOOL-STUDENTS; VULGARIS; PREVALENCE; ADOLESCENTS; MANAGEMENT; SAFETY; HYPERANDROGENEMIA; DROSPIRENONE; PHARMACOLOGY AB Acne vulgaris affects most people at some time in their life. This common condition can have devastating effects on a person's quality of 1 e and may leave permanent scars. Treatment options, which are designed to disrupt one or more of the pathogenic features that characterize acne, include topical therapies (e.g., antibiotics, retinoids, benzoyl peroxide and combination products), systemic treatments (e.g., oral antibiotics, hormonal therapies and oral retinoids, which are indicated for severe recalcitrant nodulocystic acne), and, to a lesser extent, light-based and physical treatments. Combination oral contraceptives (COCs) represent one type of hormonal treatment. Their mode of action is to reduce the availability of free testosterone, which stimulates the sebaceous glands to produce sebum. Most COCs used in the United States contain progestins derived from 19-nortestosterone, giving them at least some degree of androgenic activity. Of the 3 COCs with an FDA indication for the treatment of moderate acne, only YAZ (R) contains drospirenone, a progestin that combines no androgenic activity with antiandrogenic* activity.(1) This drospirenone-containing COC has been shown to be effective in reducing both inflammatory and noninflammatory acne lesions. C1 Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials Skin, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials Skin, 50 Staniford St,246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 53 TC 6 Z9 6 U1 1 U2 3 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD SEP PY 2008 VL 53 IS 9 SU S BP 742 EP 752 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 351VG UT WOS:000259453400004 PM 18980046 ER PT J AU Petri, M Naqibuddin, M Carson, KA Sampedro, M Wallace, DJ Weisman, MH Holliday, SL Padilla, PA Brey, RL AF Petri, Michelle Naqibuddin, Mohammad Carson, Kathryn A. Sampedro, Margaret Wallace, Daniel J. Weisman, Michael H. Holliday, Stephen L. Padilla, Patricia A. Brey, Robin L. TI Cognitive function in a systemic lupus erythematosus inception cohort SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; cognitive function; automated neuropsychological assessment metrics ID OVERT NEUROPSYCHIATRIC MANIFESTATIONS; CA3 PYRAMIDAL NEURONS; NEUROCOGNITIVE DYSFUNCTION; REVISED CRITERIA; APICAL DENDRITES; INDUCED ATROPHY; IMPAIRMENT; PREVALENCE; CLASSIFICATION; DEFINITIONS AB Objective. Measurable cognitive impairment occurs in 30-75% of patients with systemic lupus erythematosus (SLE). We compared cognitive functioning in recently-diagnosed SLE patients and normal controls. Methods. The Automated Neuropsychological Assessment Metrics (ANAM), a repeatable computerized cognitive battery assessing cognitive processing speed and efficiency, was administered to I I I recently diagnosed SLE patients and 79 normal controls. Throughput scores on ANAM subtests were compared using linear regression. Results. After adjusting for age, gender, ethnicity, and education, SLE patients scored significantly lower than controls on throughput measures of 4 ANAM subtests: code substitution immediate recall (p = 0.02), continuous performance (1) = 0.02), matching to sample (p = 0.02), and Sternberg subtest (p = 0.0002). Conclusions. Recently diagnosed SLE patients performed significantly worse than normal controls on 4 of 9 ANAM subtests. ANAM subtests of cognitive efficiency requiring sustained attention/vigilance, visuospatial span of attention/working memory, and simple reaction time showed the greatest impairment. These cognitive deficits were particularly striking, because the SLE patients in this sample were not selected for the presence of neuropsychiatric manifestations, had mild SLE-related disease/damage, and were recently diagnosed with SLE. This suggests that deficits in cognitive efficiency and sustained attention are present early in the course of SLE and in the absence of other significant neuropsychiatric manifestations. C1 [Petri, Michelle; Carson, Kathryn A.] Johns Hopkins Univ, Dept Epidemiol, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Wallace, Daniel J.; Weisman, Michael H.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. [Holliday, Stephen L.] S Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX USA. [Padilla, Patricia A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Neurol, San Antonio, TX 78229 USA. RP Petri, M (reprint author), 1830 E Monument St,Suite 7500, Baltimore, MD 21205 USA. EM mpetri@jhmi.edu FU NIH [RO1 AR049125]; Johns Hopkins University; General Clinical Research Center [M01 RR00052, MO1-RR-01346]; University of Texas Health Science Center at San Antonio FX The Brain CONECTIONS study is supported by NIH RO1 AR049125 and the Johns Hopkins University: General Clinical Research Center (Kathryn Carson is supported by M01 RR00052) and the University of Texas Health Science Center at San Antonio Frederic C. Bartter General Clinical Research Center (MO1-RR-01346). NR 37 TC 30 Z9 31 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 2008 VL 35 IS 9 BP 1776 EP 1781 PG 6 WC Rheumatology SC Rheumatology GA 344CY UT WOS:000258904500015 PM 18634154 ER PT J AU Wang, W Tretriluxana, S Redline, S Surovec, S Gottlieb, DJ Khoo, ACK AF Wang, Wenli Tretriluxana, Suradej Redline, Susan Surovec, Susan Gottlieb, Daniel J. Khoo, Michael C. K. TI Association of cardiac autonomic function measures with severity of sleep-disordered breathing in a community-based sample SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE autonomic function; heart rate variability; obstructive sleep apnea; power spectral analysis ID HEART-RATE-VARIABILITY; RESPIRATORY SINUS ARRHYTHMIA; SPECTRAL-ANALYSIS; CARDIOVASCULAR REGULATION; SYMPATHOVAGAL BALANCE; GENDER-DIFFERENCES; APNEA; AGE; HYPERTENSION; DISEASE AB The goal of this study was to test the hypothesis that spectral indices of heart rate variability, such as high-frequency power (HFP), low-to-high frequency power (LHR), and their respiration-adjusted counterparts (HFPra, LHRra) are correlated with severity of sleep-disordered breathing (SDB), as quantified by the respiratory disturbance index (RDI). A total of 436 subjects, non-smoking, normotensive, and free of cardiovascular disease and diabetes were selected from the Sleep Heart Health Study (SHHS). Of these, 288 records with sufficiently high quality electrocardiogram signals were selected for further analysis [males/females: 221/67; age: 46.1 to 74.9 years; body mass index (BMI): 21.5 to 46.4 kg m(-2); 0.3 < RDI < 85.0(-1)]. From each polysomnogram, the respiration channels (thoracic and abdominal) and R-R interval (RRI) derived from the electrocardiogram were subjected to spectral analysis and autoregressive moving average modeling in consecutive 5-min segments. After adjusting for age and BMI, mean RRI was found to be negatively correlated with RDI in men in all sleep-wake states (all P < 0.001). HFP and HFPra were negatively correlated with RDI in men only during wakefulness (all P < 0.01). In women, LHR and LHRra were not correlated with RDI during wakefulness, but were positively correlated during non-rapid eye movement Stage 1 and 2 sleep (all P < 0.01). These findings suggest that the indices of cardiac autonomic control are correlated with SDB severity, but gender and state affect the nature of these correlations. In both genders, however, vagal modulation of heart rate increases while sympathetic modulation decreases from wakefulness to sleep. C1 [Wang, Wenli; Tretriluxana, Suradej; Khoo, Michael C. K.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Redline, Susan; Surovec, Susan] Case Western Reserve Univ, Dept Pediat, Div Clin Epidemiol, Cleveland, OH 44106 USA. [Gottlieb, Daniel J.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. RP Khoo, ACK (reprint author), Univ So Calif, Dept Biomed Engn, 1042 Downey Way, Los Angeles, CA 90089 USA. EM khoo@bmsr.usc.edu FU NIH [HL-076375, EB-001978, HL-63463, HL53941] FX This study was supported by NIH Grants HL-076375, EB-001978, HL-63463, and HL53941. NR 42 TC 22 Z9 22 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2008 VL 17 IS 3 BP 251 EP 262 DI 10.1111/j.1365-2869.2008.00652.x PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 339VU UT WOS:000258606200003 PM 18547374 ER PT J AU Hawkins, EJ Baer, JS Kivlahan, DR AF Hawkins, Eric J. Baer, John S. Kivlahan, Daniel R. TI Concurrent monitoring of psychological distress and satisfaction measures as predictors of addiction treatment retention SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE concurrent monitoring; feasibility; substance use disorders; retention ID INTERACTIVE VOICE RESPONSE; SUBSTANCE-ABUSE TREATMENT; THERAPEUTIC ALLIANCE; USE DISORDERS; ALCOHOL-CONSUMPTION; OUTCOME PREDICTORS; TREATMENT SERVICES; FOLLOW-UP; CORE-OM; COCAINE AB Dropout from addiction services is common, and strategies to improve retention represent potentially important opportunities for quality improvement and treatment effectiveness. Identification of pretreatment predictors of dropout has not led to advances in treatment delivery. Via telephone monitoring, we examined the feasibility and predictive validity of weekly assessment of psychological distress and treatment satisfaction as factors potentially associated with retention and engagement over the initial 8 weeks of treatment. Participants included 107 addiction treatment patients, of whom 78% met criteria for 4 weeks of engagement and 59%, were retained for 8 weeks. Of 8 weekly assessments, 63% of participants completed six or more calls. Baseline distress, baseline satisfaction, and change in distress over 4 weeks were not related reliably to treatment dropout or engagement. Decrease in satisfaction was significantly but modestly associated with low engagement. Implications for applications of weekly monitoring to improve retention are discussed. Published by Elsevier Inc. C1 [Hawkins, Eric J.] VA Puget Sound Hlth Care Syst, Seattle Div S116ATC, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA 98108 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Baer, John S.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Hawkins, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div S116ATC, Ctr Excellence Substance Abuse Treatment & Educ, 1660 S Columbian Way, Seattle, WA 98108 USA. EM eric.hawkings@va.gov NR 38 TC 21 Z9 21 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP PY 2008 VL 35 IS 2 BP 207 EP 216 DI 10.1016/j.jsat.2007.10.001 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 342QR UT WOS:000258799100012 PM 18082998 ER PT J AU Kozak, KR Moody, JS AF Kozak, Kevin R. Moody, John S. TI The impact of T and N stage on long-term survival of rectal cancer patients in the community SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE prognosis; SEER; TNM staging ID ADJUVANT THERAPY; COLORECTAL-CANCER; POOLED ANALYSIS; BREAST-CANCER; CHEMOTHERAPY; RELAPSE; NUMBER AB Background and Objectives: Use of the TNM staging system has been encouraged for rectal cancer patients. This study examined the impact of T and N stages on long-term Survival as well as the performance of associated risk classification systems. Methods: Patients who underwent surgery for rectal adenocarcinoma from 1988 to 2004 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis was performed for subgroups of patients defined by T and N stage. Results: For the overall Population of 30.826 patients, both T and N stage significantly impacted overall Survival (P < 0.001). N stage variably significantly affected survival regardless of N stage. A previously affected survival for subgroups of patients based on T stage, whereas T developed risk classification system that assigns one of four risk levels outperformed AJCC group Staging ill this Cohort. Based on long-term outcomes, it modified risk classification system was constructed which was highly prognostic for long-term overall survival (P < 0.001). Conclusions: Rectal cancer patients experience widely varying Survival rates based on extent of disease. A new risk classification system is proposed that provides better prognostic information than AJCC group staging, suggesting current rectal cancer staging systems may be improved with appropriate revisions. C1 [Moody, John S.] Univ Alabama, Sch Med, Dept Radiat Oncol, Birmingham, AL 35249 USA. [Kozak, Kevin R.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Moody, JS (reprint author), Univ Alabama, Sch Med, Dept Radiat Oncol, Birmingham, AL 35249 USA. EM jsmoody@uabmc.edu NR 20 TC 10 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD SEP 1 PY 2008 VL 98 IS 3 BP 161 EP 166 DI 10.1002/jso.21107 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 345SE UT WOS:000259016100005 PM 18615481 ER PT J AU Berry, M Mankin, H Gebhardt, M Rosenberg, A Hornicek, F AF Berry, Micah Mankin, Henry Gebhardt, Mark Rosenberg, Andrew Hornicek, Francis TI Osteoblastoma: A 30-year study of 99 cases SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE benign bone tumor; osteoblastoma; orthopedic surgery; osteosarcoma; orthopedic oncology ID OSTEOID OSTEOMA; BENIGN OSTEOBLASTOMA; TUMOR; BONE; SPINE AB Background and Objectives: Osteoblastoma is a rare, bone-forming neoplasm accounting for 1% of primary bone tumors. It arises in young patients and develops in long, bones and posterior elements of the spine. Osteoblastoma is characterized by interconnecting trabeculae of woven bone and rimmed by prominent osteoblasts. In the current study we characterize osteoblastoma by its demographic and anatomic prevalence. We looked Lit rates of recurrence as related to treatment. Methods: We performed a review of our institution's Orthopaedic Oncology tumor registry and identified 99 verified cases of osteoblastoma treated between 1974 and 2006. Data related to demographic, anatomic, Surgical treatment and follow-up information were analyzed. Results: The cohort included 69 males and 30 females with in average age of 24 +/- 14 years. The most common sites of occurrence were the vertebral column (28 patients) and the humerus (21 patients). The tumors were treated with en bloc surgical resection or curettage with allograft or autograft. Local reccurrence rate was 24% and most followed curettage and packing. No patient died of disease. Conclusions: Osteoblastoma frequently affects the long bones and the spine. The recurrence rate following curettage is relatively high and can be minimized by resective surgery, in select cases. C1 [Mankin, Henry; Rosenberg, Andrew; Hornicek, Francis] Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. [Berry, Micah; Mankin, Henry; Gebhardt, Mark; Rosenberg, Andrew; Hornicek, Francis] Harvard Univ, Sch Med, Boston, MA USA. [Gebhardt, Mark] Childrens Hosp, Boston, MA 02115 USA. RP Mankin, H (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol Serv, Jackson Bldg, Boston, MA 02114 USA. EM hmankin@partnerrs.org NR 20 TC 31 Z9 32 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD SEP 1 PY 2008 VL 98 IS 3 BP 179 EP 183 DI 10.1002/jso.21105 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 345SE UT WOS:000259016100008 PM 18561158 ER PT J AU O'Sullivan, JC Fu, D Alam, HB McCabe, JT AF O'Sullivan, Joseph C. Fu, Dadin Alam, Hasan B. McCabe, Joseph T. TI Diazoxide increases liver and kidney HSP25 and HSP70 after shock and stroke SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE brain ischemia; diazoxide; hyperglycaemia; lactate; mitochondria; resuscitation; shock; stroke ID K-ATP CHANNELS; TRAUMATIC BRAIN-INJURY; HEMORRHAGIC-SHOCK; PRECONDITIONING PROTECTS; ISCHEMIA-REPERFUSION; RAT-BRAIN; MECHANISMS; SURVIVAL; LACTATE; GLYCOGEN AB Background. The compound, diazoxide (DZ), is known to induce preconditioning through its effect as a mitochondrial K-ATP channel opener and succinate dehydrogenase inhibitor. Our team tested the hypothesis that pharmacological induction of ischemic preconditioning with DZ can offer cytoprotection and preserve vital tissues after hemorrhagic shock and stroke. Materials and methods. Sprague-Dawley male rats received an intraperitoneal injection of sterile saline or 5 mg/kg DZ in saline 24 h prior to I h of hemorrhagic shock, by similar to 40% total blood loss volume (Shock Study), or a permanent unilateral common carotid ligation just before shock (Stroke + Shock Study). While remaining under isoflurane anesthesia, animals then received 81 mL/kg intravenous sterile saline over the next 45 min for recovery and survived for another 24 h. Results. When DZ was administered 24 h prior to shock, it significantly reduced hyperglycemia, which in vehicle-treated animals persisted after resuscitation. DZ also attenuated hyperlactatemia during the 1-h shock period. With more severe trauma from combined stroke and shock, DZ also decreased hyperlactatemia and hyperglycemia levels but the reduction was only significant for hyperglycemia. The expression levels of heat shock proteins 25 (HSP25) and 70 (HSP70) were used as biomarkers for response of the kidney and liver to DZ and combined stroke and shock. Compared to vehicle-treated animals, DZ-treated rats subjected to shock and stroke exhibited increased HSP25 and HSP70 in kidney and liver tissue. Conclusions. DZ-attenuated physiological indicators of metabolic stress following shock or combined shock and stroke and enhanced the up-regulation of cytoprotective heat shock protein expression. (c) 2008 Elsevier Inc. All rights reserved. C1 [McCabe, Joseph T.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [O'Sullivan, Joseph C.; McCabe, Joseph T.] Uniformed Serv Univ Hlth Sci, Grad Program Neurosci, Bethesda, MD 20814 USA. [Fu, Dadin] Armed Forces Radiobiol Res Inst, Bethesda, MD USA. [Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA USA. RP McCabe, JT (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM JMcCabe@usuhs.mil FU Tri-Service Nursing Research Program [MDA905-04-1-TS06]; USUHS Exploratory [HO70PG] FX The authors hereby state that there is no conflict of interest. The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences. This study was supported by Grant MDA905-04-1-TS06 from the Tri-Service Nursing Research Program to LTC O'Sullivan and USUHS Exploratory Grant HO70PG to Dr. McCabe. NR 44 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2008 VL 149 IS 1 BP 120 EP 130 DI 10.1016/j.jss.2007.12.750 PG 11 WC Surgery SC Surgery GA 340GD UT WOS:000258633200018 PM 18222477 ER PT J AU Faraone, SV Biederman, J Morley, CP Spencer, TJ AF Faraone, Stephen V. Biederman, Joseph Morley, Christopher P. Spencer, Thomas J. TI Effect of stimulants on height and weight: A review of the literature SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE attention-deficit/hyperactivity disorder; growth; stimulants; methylphenidate; amphetamine ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GROWTH-HORMONE; FOLLOW-UP; METHYLPHENIDATE TREATMENT; SHORT STATURE; CHILDREN; ADHD; BOYS; AMPHETAMINE AB Objective: Stimulant medications are effective treatments for attention-deficit/hyperactivity disorder, but concerns remain about their effects on growth. Method: We provide a quantitative analysis of longitudinal studies about deficits in expected growth among children with attention-deficit/hyperactivity disorder treated with stimulant medication. Study selection criteria were use of DSM criteria or clear operational definitions for hyperactivity or minimal brain dysfunction; outcome measures including raw, standardized, or percentile measurement of change in height and/or weight; first assessment of effects on growth occurred during childhood; and follow-up for at least 1 year. For issues not suitable for quantitative analyses, we provide a systematic, qualitative review. Results: The quantitative analyses showed that treatment with stimulant medication led to statistically significant delays in height and weight. This review found statistically significant evidence of attenuation of these deficits over time. The qualitative review suggested that growth deficits may be dose dependent, deficits may not differ between methylphenidate and amphetamine, treatment cessation may lead to normalization of growth, and further research should assess the idea that attention-deficit/hyperactivity disorder itself may be associated with dysregulated growth. Conclusions: Treatment with stimulants in childhood modestly reduced expected height and weight. Although these effects attenuate over time and some data suggest that ultimate adult growth parameters are not affected, more work is needed to clarify the effects of continuous treatment from childhood to adulthood. Although physicians should monitor height, deficits in height and weight do not appear to be a clinical concern for most children treated with stimulants. C1 [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA. [Biederman, Joseph; Spencer, Thomas J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Biederman, Joseph; Spencer, Thomas J.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Morley, Christopher P.] SUNY Upstate Med Univ, Dept Family Med, Syracuse, NY 13210 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu RI Morley, Christopher P/K-1907-2014; OI Morley, Christopher P/0000-0003-0185-7148; Faraone, Stephen/0000-0002-9217-3982 NR 65 TC 116 Z9 118 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2008 VL 47 IS 9 BP 994 EP 1009 DI 10.1097/CHI.0b013e31817e0ea7 PG 16 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 341VE UT WOS:000258742500005 PM 18580502 ER PT J AU Delfino, M Holt, EW Taylor, CR Wittenberg, E Qureshi, AA AF Delfino, Matthew Holt, Elizabeth W. Taylor, Charles R. Wittenberg, Eve Qureshi, Abrar A. TI Willingness-to-pay stated preferences for 8 health-related quality-of-fife domains in psoriasis: A pilot study SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PSYCHOLOGICAL DISTRESS; SKIN-DISEASE; LIFE ISSUES; RELIABILITY; ARTHRITIS; SEVERITY; MELANOMA; INCOME; INDEX AB Background: Psoriasis is a chronic skin condition that has a major impact on health-related quality of life (QOL). We evaluated health-related QOL via willingness to pay and a ranking task for 8 domains of health relevant to psoriasis: intimacy, physical comfort, self-care, ability to work or volunteer, ability to concentrate, emotional health, social comfort, and ability to steep. Objective. The goals of the study were to pilot test a new method to measure QOL impact in psoriasis and identify the areas of life most affected by psoriasis. Methods: Forty participants with a history of psoriasis were interviewed in a face-to-face format. First, participants were asked to rank the 8 domains of health we were investigating. Second, patients were asked how much money they would be willing to pay for a hypothetical cure for each domain of health. Responses in US dollars were interpreted as strength of preference rather than absolute monetary values. Results: About half of the patients in the sample (48%) were female, 60% had a college degree or further education and 38% had an income level over $45,000/y. Physical comfort, social comfort, and emotional health were highly ranked by rnore than 75% of respondents. Ability to concentrate was least likely to be affected by psoriasis with just a quarter (25.7%) of respondents ranking this domain as important. The median amount patients were willing to pay for a hypothetical cure of psoriasis specific to a particular domain was highest for physical cornfort ($2000, 25th quartile = $500, 75th quartile = $5500) and emotional health ($2000, 25th quartile $250, 75th quartile = $5000) and lowest for ability to steep ($625, 25th quartile = $50, 75th quartile $5000). Limitations: The sample size is modest for this pilot study. Willingness to Pay as a method of eliciting stated preferences for qualitative aspects of health may be influenced by individual perception of money. Conclusions: The study successful pilot pilot tested a willingness-to-pay method and a ranking task to measure the relative severity of 8 domains of health-related QOL and found that physical comfort, social comfort, and emotional health were the domains of health most affected by psoriasis. C1 [Delfino, Matthew; Qureshi, Abrar A.] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Holt, Elizabeth W.] Tulane Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Taylor, Charles R.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Taylor, Charles R.] Harvard Univ, Sch Med, Boston, MA USA. [Wittenberg, Eve] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. RP Qureshi, AA (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, 45 Francis St,221L, Boston, MA 02115 USA. EM aqureshi@bics.bwh.harvard.edu FU AHRQ HHS [5 K02 HS014010] NR 27 TC 28 Z9 28 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2008 VL 59 IS 3 BP 439 EP 447 DI 10.1016/j.jaad.2008.05.032 PG 9 WC Dermatology SC Dermatology GA 340TL UT WOS:000258667800008 PM 18639364 ER PT J AU Kimball, AB Gold, MH Zib, B Davis, MW AF Kimball, Alexa Boer Gold, Michael H. Zib, Beth Davis, Mark W. CA Clobetasol Propionate Emulsion For TI Clobetasol propionate emulsion formulation foam 0.05%: Review of phase II open-label and phase III randomized controlled trials in steroid-responsive dermatoses in adults and adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ATOPIC-DERMATITIS; PSORIASIS; VEHICLE AB Background: Clobetasol propionate 0.05% emulsion foam was recently developed for use on multiple body sites. Objective. We sought to evaluate safety and efficacy of clobetasol emulsion foam 0.05% to treat steroid-responsive dermatoses in multiple age groups. Methods: A phase II open-label study evaluated the effect of clobetasol foam on the hypothalamic-pituitary-adrenal axis in 52 participants aged 6 years or older with mild-to-severe atopic dermatitis (AD). Cosyntropin Stimulation test was used to determine the effect of clobetasol foam on hypothalamic-pituitary-adrenal axis, with a normal response considered to be a postinjection serum cortisol level greater than 18 mu g/dL. Another phase II open-label pharmacokinetic safety study was conducted in 32 participants aged 12 years or older with mild-to-moderate plaque-type psoriasis. Pharmacokinetic parameters evaluated included maximal plasma concentration of clobetasol propionate, time to achieve maximum concentration, and area under the curve. Two phase III, randomized controlled studies assessed treatment success in participants aged 12 years or older with moderate-to-severe AD (N = 377) or mild-to-moderate plaque-type psoriasis (N = 497). In all studies, participants received study drug for 2 weeks. In the AD study, treatment success was determined using a composite end point requiring an Investigator's Static Global Assessment (ISGA) score of 0 or 1, erythema score of 0 or 1, induration/papulation score of 0 or 1, and improvement in the ISGA score of at least two grades from baseline. Likewise, the study in plaque-type psoriasis used a composite end point requiring an ISGA score of 0 or 1, erythema score of 0 or 1, scaling score of 0 or 1, plaque thickness score of 0, and improvement in the ISGA score of at least two grades from baseline. Results: Significantly more participants achieved treatment success on clobetasol foam than vehicle foam (P <.0001 and P = .0005 for each study). Reversible hypothalamic-pituitary-adrenal axis suppression was observed in 27% of participants aged 18 years or older and 47% in participants aged between 6 and younger than 12 years but 0% in participants aged between 12 and younger than 18 years. Limitations: The studies evaluated short-term use only. Conclusion: Clobetasol emulsion formulation foam is safe and effective for treatment of moderate-to-severe AD and mild-to-moderate plaque-type psoriasis in patients aged 12 years or older. C1 [Kimball, Alexa Boer] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Unit for Res Trials Skin, Boston, MA 02114 USA. [Kimball, Alexa Boer] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02114 USA. [Gold, Michael H.] Tennessee Clin Res Ctr, Gold Skin Care Ctr, Nashville, TN USA. [Gold, Michael H.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Zib, Beth; Davis, Mark W.] Stiefel Labs Inc, Palo Alto, CA USA. RP Kimball, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Unit for Res Trials Skin, 50 Staniford St 246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU IntraMed Educational Group FX The authors wish to thank Stiefel Laboratories for funding IntraMed Educational Group for editorial support provided in the preparation and styling of this manuscript and facilitating author communication. NR 17 TC 23 Z9 24 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2008 VL 59 IS 3 BP 448 EP 454 DI 10.1016/j.jaad.2008.04.020 PG 7 WC Dermatology SC Dermatology GA 340TL UT WOS:000258667800009 PM 18539358 ER PT J AU Seidler, AM Wasserman, DI Gonzalez-Serva, A Konnikov, N AF Seidler, Anne M. Wasserman, Daniel I. Gonzalez-Serva, Aldo Konnikov, Nellie TI Amyopathic dermatomyositis resembling stasis dermatitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-Academy-of-Dermatology CY FEB 02-06, 2007 CL Washington, DC SP Amer Acad Dermatol ID PENICILLAMINE-INDUCED POLYMYOSITIS; TERM HYDROXYUREA THERAPY; PSEUDO-DERMATOMYOSITIS; ERUPTION; PATIENT; SIMVASTATIN; INHIBITOR; CARCINOMA; MYOPATHY; AGENTS AB This case describes an unusual presentation of dermatomyositis in a patient with ovarian carcinoma. The eruption appeared as a venous stasislike dermatitis. The temporal sequence of onset after chemotherapy administration suggested a possible drug-induced process. However, in the context of underlying ovarian carcinoma, a paraneoplastic process offered an alternative explanation for the dermatomyositis. C1 [Seidler, Anne M.; Wasserman, Daniel I.] Tufts Univ, Dept Dermatol, Sch Med, Medford, MA 02155 USA. [Gonzalez-Serva, Aldo; Konnikov, Nellie] Tufts Univ, Dept Vet Affairs Med Ctr, Sch Med, Medford, MA 02155 USA. RP Konnikov, N (reprint author), Boston Healthcare Syst, Dept Vet Affairs, 150 S Huntington Ave, Boston, MA 02130 USA. EM Nellie.Konnikov@va.gov NR 48 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2008 VL 59 IS 3 BP 515 EP 518 DI 10.1016/j.jaad.2008.02.033 PG 4 WC Dermatology SC Dermatology GA 340TL UT WOS:000258667800019 PM 18571770 ER PT J AU Heiser, A Westhoven, E Hurley, RJ Jarrell, DM AF Heiser, A. Westhoven, E. Hurley, R. J. Jarrell, D. M. TI Refining Rodent Paralysis Models through Animal Care Staff Involvement SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Heiser, A.; Westhoven, E.; Hurley, R. J.; Jarrell, D. M.] Massachusetts Gen Hosp, CCM, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 76 EP 77 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500028 ER PT J AU Gibbons, C Fuller, J Jarrell, DM AF Gibbons, C. Fuller, J. Jarrell, D. M. TI Development of Team Leaders in a Team-oriented Organization SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Gibbons, C.; Fuller, J.; Jarrell, D. M.] Massachusetts Gen Hosp, CCM, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 77 EP 77 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500029 ER PT J AU Hurley, RJ Hurley, JJ AF Hurley, R. J. Hurley, J. J. TI Cesarean-derived SPF Sheep for Biomedical Research SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Hurley, R. J.] Massachusetts Gen Hosp, CCM, Charlestown, MA USA. [Hurley, J. J.] New England Ovis LLC, Rollinsford, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 82 EP 82 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500042 ER PT J AU Blevins, J Overduin, J Fuller, J Cummings, D Matsumoto, K Moralejo, DH AF Blevins, J. Overduin, J. Fuller, J. Cummings, D. Matsumoto, K. Moralejo, D. H. TI Normal Feeding and Body Weight in Fischer 344 Rats Lacking the Cholecystokinin-1 Receptor Gene SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Fuller, J.; Moralejo, D. H.] Univ Washington, Seattle, WA 98195 USA. [Blevins, J.; Overduin, J.; Cummings, D.] VA Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA USA. [Matsumoto, K.] Univ Tokushima, Div Anim Res Resources, Tokushima 770, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 84 EP 84 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500047 ER PT J AU Paster, E Colgin, L Wilk, J Maginnis, G AF Paster, E. Colgin, L. Wilk, J. Maginnis, G. TI Diabetic Ketoacidosis in a Pregnant Rhesus Macaque (Macaca mulatta) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Paster, E.; Colgin, L.; Wilk, J.; Maginnis, G.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 88 EP 88 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500059 ER PT J AU Duran-Struuck, R Cho, PS Moran, SG Teague, A Ferguson, K Lutton, BV Hanekamp, I Wikiel, KJ Horner, B Lo, DP Duggan, M Arn, SJ Billiter, B Houser, S Westmoreland, SV Sachs, DH Huang, CA AF Duran-Struuck, R. Cho, P. S. Moran, S. G. Teague, A. Ferguson, K. Lutton, B. V. Hanekamp, I. Wikiel, K. J. Horner, B. Lo, D. P. Duggan, M. Arn, S. J. Billiter, B. Houser, S. Westmoreland, S. V. Sachs, D. H. Huang, C. A. TI Immunophenotypic Characterization of Spontaneous Myeloid Leukemias in Adult MHC-defined and Histocompatible Miniature Swine: Towards the Development of a Large Animal Transplantable Tumor Model SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Duran-Struuck, R.; Cho, P. S.; Moran, S. G.; Teague, A.; Ferguson, K.; Lutton, B. V.; Hanekamp, I.; Wikiel, K. J.; Horner, B.; Lo, D. P.; Duggan, M.; Arn, S. J.; Billiter, B.; Houser, S.; Sachs, D. H.; Huang, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Westmoreland, S. V.] Harvard Univ, Sch Med, New England Primate Ctr, Southborough, MA 01772 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 89 EP 89 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500061 ER PT J AU Niemi, SM Dempsey, M Sims, N Wollowitz, M AF Niemi, S. M. Dempsey, M. Sims, N. Wollowitz, M. TI Novel Means of Continuously Monitoring Laboratory Rodents SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Dempsey, M.; Sims, N.] Massachusetts Gen Hosp, Ctr Integrat Med, Boston, MA 02114 USA. [Niemi, S. M.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Wollowitz, M.] Tangible Design Inc, Chatham, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 99 EP 100 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500090 ER PT J AU Paster, E Hickman, D Baldwin, R AF Paster, E. Hickman, D. Baldwin, R. TI Dehydration and Excessive Salviation in B6.129-Slc6a4(tm1kpl)N10 Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Paster, E.; Hickman, D.; Baldwin, R.] Portland VA Med Ctr, Portland, OR USA. RI Hickman, Debra/D-3289-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 105 EP 105 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500105 ER PT J AU Koszdin, K Frayo, S Cummings, D AF Koszdin, K. Frayo, S. Cummings, D. TI Method for Repeated Blood Sampling from the Medial Saphenous Vein of Conscious Rats in a Longterm Study SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Koszdin, K.] VA Puget Sound Hlth Care Syst, Anim Res Facil, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 113 EP 113 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500129 ER PT J AU Luboyeski, S AF Luboyeski, S. TI Ensuring Normothermia during General Anesthesia SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Luboyeski, S.] Massachusetts Gen Hosp, CCM, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 113 EP 114 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500130 ER PT J AU Camacho, JN Tsui, J AF Camacho, J. N. Tsui, J. TI Video Enrichment Preferences of Laboratory Macaques (Macaca mulatta) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Camacho, J. N.; Tsui, J.] Massachusetts Gen Hosp, CCM, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 128 EP 129 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500174 ER PT J AU Teixeira, L Graffam, ME Sleboda, S AF Teixeira, L. Graffam, M. E. Sleboda, S. TI Solution to Sipper Tube Removal by Nonhuman Primates SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Teixeira, L.; Graffam, M. E.; Sleboda, S.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 136 EP 136 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500195 ER PT J AU Sun, Y Wang, J Graffam, ME AF Sun, Y. Wang, J. Graffam, M. E. TI Increased Breeding Efficiency in Mice Using Miniature Treats SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Sun, Y.; Wang, J.; Graffam, M. E.] Massachusetts Gen Hosp, CCM, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 137 EP 137 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500197 ER PT J AU Teixeira, L Graffam, ME Sleboda, S AF Teixeira, L. Graffam, M. E. Sleboda, S. TI Refined Method of Cage Changing for Nonhuman Primates SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Teixeira, L.; Graffam, M. E.; Sleboda, S.] Massachusetts Gen Hosp, CCM, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 137 EP 137 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500196 ER PT J AU Sedlacek, RS Jarrell, DM Niemi, SM AF Sedlacek, R. S. Jarrell, D. M. Niemi, S. M. TI Using Gnotobiotic Mice as Technique Sentinels SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Sedlacek, R. S.; Jarrell, D. M.; Niemi, S. M.] Massachusetts Gen Hosp, CCM, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 139 EP 139 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500202 ER PT J AU Sun, Y Moore, M Depathy, M Joncas, J AF Sun, Y. Moore, M. Depathy, M. Joncas, J. TI Maximizing Per Diem Revenues through More Frequent Cage Census SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Sun, Y.; Depathy, M.; Joncas, J.] Massachusetts Gen Hosp, CCM, Charlestown, MA USA. [Moore, M.] Digital Paradigms Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 144 EP 144 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500216 ER PT J AU Huang, P Dawson, M Lanning, R Jain, RK Fukumura, D AF Huang, P. Dawson, M. Lanning, R. Jain, R. K. Fukumura, D. TI Spontaneous Tumors in VEGF(P)-GFP/FVB and Tie2(P)-GFP/FVB Transgenic Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Huang, P.; Dawson, M.; Lanning, R.; Jain, R. K.; Fukumura, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2008 VL 47 IS 5 BP 170 EP 170 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500283 ER PT J AU Goode, PS FitzGerald, MP Richter, HE Whitehead, WE Nygaard, I Wren, PA Zyczynski, HM Cundiff, G Menefee, S Senka, JM Gao, X Weber, AM AF Goode, Patricia S. FitzGerald, Mary P. Richter, Holly E. Whitehead, William E. Nygaard, Ingrid Wren, Patricia A. Zyczynski, Halina M. Cundiff, Geoffrey Menefee, Shawn Senka, Judith M. Gao, Xin Weber, Anne M. CA Pelvic Floor Disorders Network TI Enhancing participation of older women in surgical trials SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PELVIC ORGAN PROLAPSE; RECRUITMENT STRATEGIES; CLINICAL-TRIAL; STRESS-INCONTINENCE; ADULTS; DYSFUNCTION; DEPRESSION; EXCLUSION; PEOPLE AB BACKGROUND: Older participants are often excluded from clinical trials, precluding a representative sample. STUDY DESIGN: Using qualitative and quantitative methods, we examined recruitment and retention of older women with pelvic organ prolapse in two surgical trials: the randomized Colpopexy And Urinary Reduction Efforts (CARE) study and the Longitudinal Pelvic Symptoms and Patient Satisfaction After Colpocleisis cohort study. Using focus groups, we developed a questionnaire addressing factors facilitating and impeding the recruitment and retention of older study participants and administered it to research staff. Enrollment-to-surgery ratios, missed visit rates, and dropout rates for older and younger participants were compared using Fisher's exact test, with cut-points of 70 and 80 years for the CARE and Colpocleisis studies, respectively. RESULTS: Questionnaires were completed by 23 physician investigators and I I nurses or coordinators (92% response rate). Respondents indicated it was more difficult to recruit older research participants (32%), obtain informed con sent (56%), and retain participants to study completion (50%). Challenges to recruitment included caregiver involvement in the decision to participate and participant comorbidities. Perceived barriers to retention were transportation, caregiver availability, and participant fatigue. Data quality was challenged by sensory and cognitive impairment, resulting in a change from telephone inter-views to in-person visits in the Colpocleisis study. Older participants did not have higher dropout rates than younger participants. There were no differences in missed in-person visits or telephone interview rates between age groups. CONCLUSIONS: Strategies, albeit unstudied, could assist investigators in planning surgical trials-that successfully enroll and retain older women. C1 [Goode, Patricia S.] Univ Alabama, Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35233 USA. [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. [Goode, Patricia S.] Vet Affairs Med Ctr, Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [FitzGerald, Mary P.] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. [Whitehead, William E.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Nygaard, Ingrid] Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Wren, Patricia A.] Oakland Univ, Dept Hlth Behav Hlth Educ, Rochester, MI 48063 USA. [Zyczynski, Halina M.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA 15213 USA. [Cundiff, Geoffrey] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada. [Menefee, Shawn] Univ Calif San Diego, Dept Obstet & Gynecol, San Diego, CA 92103 USA. [Senka, Judith M.] Northwestern Univ, Evanston Hosp, Dept Obstet & Gynecol, Evanston, IL 60201 USA. [Gao, Xin] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Weber, Anne M.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Goode, PS (reprint author), Univ Alabama, Birmingham VA Med Ctr, Dept Med, 11G,700 S 19th St, Birmingham, AL 35233 USA. FU National Institute of Child Health and Human Development [U01 HD41249, U10 HD41268, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41269, U10 HD41267] FX Supported by grants from the National Institute of Child Health and Human Development (U01 HD41249, U10 HD41268, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41269, and U10 HD41267). NR 26 TC 10 Z9 11 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 BP 303 EP 311 DI 10.1016/j.jamcollsurg.2008.03.012 PG 9 WC Surgery SC Surgery GA 349FD UT WOS:000259265800001 PM 18722933 ER PT J AU Kirstein, LJ Rafferty, E Specht, MC Moore, RH Taghian, AG Hughes, KS Gadd, MA Smith, BL AF Kirstein, Laurie J. Rafferty, Elizabeth Specht, Michelle C. Moore, Richard H. Taghian, Alphonse G. Hughes, Kevin S. Gadd, Michele A. Smith, Barbara L. TI Outcomes of multiple wire localization for larger breast cancers: When can mastectomy be avoided? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID CARCINOMA IN-SITU; LUMPECTOMY MARGIN ASSESSMENT; RESIDUAL DISEASE; PROGNOSTIC-SIGNIFICANCE; CONSERVING SURGERY; RANDOMIZED TRIAL; RE-EXCISIONS; CONSERVATION; REEXCISION; THERAPY AB BACKGROUND: Mastectomy is often recommended when mammography shows a breast cancer with extensive calcifications. We wished to determine whether the use of multiple localizing wires to guide lumpectomy in this setting was associated with increased rates of breast conservation. We also wanted to identify factors that predicted a poor chance of successful lumpectomy, to avoid multiple lumpectomy attempts in a patient who would ultimately require mastectomy. STUDY DESIGN: Records of 153 women with breast cancer who underwent lumpectomy for larger lesions that required multiple wire localization and 196 controls who required only single wire localization were reviewed retrospectively. The number of localizing wires, specimen. volume, largest specimen dimension, number of surgical procedures, and rates of breast conservation were scored. RESULTS: Seventy-seven percent of patients requiring multiple wire localization had successful breast conservation, compared with 90% of those needing only single wire localization. Only 28% of multiple wire patients required more than I excision to achieve clear margins, compared with 36% of single wire patients (p < 0.01). CONCLUSIONS: Breast conservation is possible in the great majority of breast cancer patients whose mammographic lesions require multiple localizing wires for excision. The use of multiple wires can decrease the number of procedures required to obtain clear lumpectomy margins. C1 [Kirstein, Laurie J.; Specht, Michelle C.; Hughes, Kevin S.; Gadd, Michele A.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02115 USA. [Rafferty, Elizabeth; Moore, Richard H.] Massachusetts Gen Hosp, Div Breast Imaging, Boston, MA 02115 USA. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 9A,55 Fruit St, Boston, MA 02115 USA. OI Hughes, Kevin/0000-0003-4084-6484 NR 22 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 BP 342 EP 346 DI 10.1016/j.jamcollsurg.2008.04.019 PG 5 WC Surgery SC Surgery GA 349FD UT WOS:000259265800006 PM 18722938 ER PT J AU Ahmadiyeh, N Wang, M Yao, J Welch, AA Polyak, K Wang, ZGC Richardson, AL Freedman, ML AF Ahmadiyeh, Nasim Wang, Meng Yao, Jun Welch, Aaron A. Polyak, Kornelia Wang, Zhigang C. Richardson, Andrea L. Freedman, Matthew L. TI Adaptation of the sequenom platform to the targeted determination of amplification and allele-specific imbalance in breast cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 12-16, 2008 CL San Francisco, CA SP Amer Coll Surg C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 SU S BP S44 EP S44 DI 10.1016/j.jamcollsurg.2008.06.089 PG 1 WC Surgery SC Surgery GA 349NV UT WOS:000259288500085 ER PT J AU Hashmi, FF Albadawi, H Kobler, JB Heaton, JT Kang, J Koo, HJ Peck, M Watkins, MT AF Hashmi, Faraz F. Albadawi, Hassan Kobler, James B. Heaton, James T. Kang, Jeanwan Koo, Hyung-Jin Peck, Michael Watkins, Michael T. TI Skeletal muscle functional recovery in the hyperlipidemic murine model of human vascular disease SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 12-16, 2008 CL San Francisco, CA SP Amer Coll Surg C1 [Hashmi, Faraz F.; Albadawi, Hassan; Kobler, James B.; Heaton, James T.; Kang, Jeanwan; Koo, Hyung-Jin; Peck, Michael; Watkins, Michael T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 SU S BP S115 EP S115 DI 10.1016/j.jamcollsurg.2008.06.298 PG 1 WC Surgery SC Surgery GA 349NV UT WOS:000259288500261 ER PT J AU Maduekwe, UN Rothrock, C Ryeom, S Yoon, SS Lee, YJ AF Maduekwe, Ugwuji N. Rothrock, Courtney Ryeom, Sandra Yoon, Sam S. Lee, Yoon-Jin TI Differential effects of VEGF receptor inhibition in the liver and lung SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 12-16, 2008 CL San Francisco, CA SP Amer Coll Surg C1 [Maduekwe, Ugwuji N.; Rothrock, Courtney; Ryeom, Sandra; Yoon, Sam S.; Lee, Yoon-Jin] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 SU S BP S100 EP S100 DI 10.1016/j.jamcollsurg.2008.06.254 PG 1 WC Surgery SC Surgery GA 349NV UT WOS:000259288500221 ER PT J AU Noonan, KM Russell, M VanMarcke, RP Longoni, M Furey, A Jennings, RW Wilson, JM Pober, BR Lee, C Donahoe, PK AF Noonan, Kristin M. Russell, Meaghan VanMarcke, Rafael Piererti Longoni, Mauro Furey, Ann Jennings, Russell W. Wilson, Jay M. Pober, Barbara R. Lee, Charles Donahoe, Patricia K. TI Identification and characterization of genetic hotspots and potential candidate genes for congenital diaphragmatic hernia by high density array comparative genomic hybridization SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 12-16, 2008 CL San Francisco, CA SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RI Longoni, Mauro/I-2526-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 SU S BP S44 EP S45 DI 10.1016/j.jamcollsurg.2008.06.090 PG 2 WC Surgery SC Surgery GA 349NV UT WOS:000259288500086 ER PT J AU Regenbogen, SE Greenberg, CC Resch, SC Kollengode, A Cima, RR Zinner, MJ Gawande, AA AF Regenbogen, Scott E. Greenberg, Caprice C. Resch, Stepben C. Kollengode, Anantha Cima, Robert R. Zinner, Michael J. Gawande, Atul A. TI Novel strategies to prevent retained surgical sponges: A decision-analytic model predicting relative cost-effectiveness SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 12-16, 2008 CL San Francisco, CA SP Amer Coll Surg C1 [Regenbogen, Scott E.; Greenberg, Caprice C.; Resch, Stepben C.; Kollengode, Anantha; Cima, Robert R.; Zinner, Michael J.; Gawande, Atul A.] Mass Gen Hosp, Abt Assoc, Mayo Clin, Harvard Sch PH, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 SU S BP S73 EP S74 DI 10.1016/j.jamcollsurg.2008.06.183 PG 2 WC Surgery SC Surgery GA 349NV UT WOS:000259288500156 ER PT J AU Sailhamer, EA Li, YQ Zhao, H Hales, CA Shuja, F Butt, MU Velmahos, GC de Moya, MA Alam, HB AF Sailhamer, Elizabeth A. Li, Yongqing Zhao, Hang Hales, Charles A. Shuja, Fahad Butt, Muhammad U. Velmahos, George C. de Moya, Marc A. Alam, Hasan B. TI Histone deacetylase inhibition: A novel treatment for lethal septic shock SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 12-16, 2008 CL San Francisco, CA SP Amer Coll Surg C1 [Sailhamer, Elizabeth A.; Li, Yongqing; Zhao, Hang; Hales, Charles A.; Shuja, Fahad; Butt, Muhammad U.; Velmahos, George C.; de Moya, Marc A.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 SU S BP S36 EP S36 DI 10.1016/j.jamcollsurg.2008.06.069 PG 1 WC Surgery SC Surgery GA 349NV UT WOS:000259288500067 ER PT J AU Shuja, F Tabbara, M Li, YQ Liu, BL Butt, MU Sailhamer, EA Velmahos, GC Demoya, MA Alam, HB AF Shuja, Fahad Tabbara, Malek Li, Yongqing Liu, Baoling Butt, Muhammad U. Sailhamer, Elizabeth A. Velmahos, George C. deMoya, Marca A. Alam, Hasan B. TI Profound hypothermia decreases cardiac apoptosis through preservation of Akt survival pathway SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 12-16, 2008 CL San Francisco, CA SP Amer Coll Surg C1 [Shuja, Fahad; Tabbara, Malek; Li, Yongqing; Liu, Baoling; Butt, Muhammad U.; Sailhamer, Elizabeth A.; Velmahos, George C.; deMoya, Marca A.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 SU S BP S27 EP S27 DI 10.1016/j.jamcollsurg.2008.06.045 PG 1 WC Surgery SC Surgery GA 349NV UT WOS:000259288500045 ER PT J AU Veillette, GR Meltzer, AJ Aoyama, A Cochrane, M Houser, S Wain, JC Madsen, JC Sachs, DH Rosengard, BR Allan, JS AF Veillette, Gregory R. Meltzer, Andrew J. Aoyama, Akihiro Cochrane, Meghan Houser, Stuart Wain, John C. Madsen, Joren C. Sachs, David H. Rosengard, Bruce R. Allan, James S. TI Donor brain death inhibits tolerance induction in miniature swine lung transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 12-16, 2008 CL San Francisco, CA SP Amer Coll Surg C1 [Veillette, Gregory R.; Meltzer, Andrew J.; Aoyama, Akihiro; Cochrane, Meghan; Houser, Stuart; Wain, John C.; Madsen, Joren C.; Sachs, David H.; Rosengard, Bruce R.; Allan, James S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2008 VL 207 IS 3 SU S BP S106 EP S106 DI 10.1016/j.jamcollsurg.2008.06.270 PG 1 WC Surgery SC Surgery GA 349NV UT WOS:000259288500236 ER PT J AU Quintiliani, LM Campbell, MK Haines, PS Webber, KH AF Quintiliani, Lisa M. Campbell, Marci K. Haines, Pamela S. Webber, Kelly H. TI The use of the pile sort method in identifying groups of healthful lifestyle behaviors among female community college students SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID FORMATIVE RESEARCH; BODIES AB When encountering new or understudied populations, it is useful to build an understanding of the needs and perceptions of the target audience. This study investigated the application of the qualitative pile sort method for gaining information about nutrition and physical activity behaviors. In a pile sort, individuals make a list of topics relevant to a particular subject, and then they group these topics into related piles. This study investigated whether there was consistency in the ways in which participants grouped behaviors related to having a healthful lifestyle. Pile sorts were conducted during six focus groups among 28 female community college students (46% white; 39% had a 2-year degree or higher). A total of 74 piles of grouped behaviors were coded from the transcripts. Analyses revealed good consistency (identified nine to 12 times) for four groupings: exercise, lifestyle, how you eat, and positive foods. The pile sort method represents an activity that can be incorporated into formative research for interventions focused on complex behaviors with multiple components; in addition, this method may provide structure to counseling sessions and facilitate a better understanding of the perceptions of healthful eating and physical activity from patients' perspectives. C1 [Quintiliani, Lisa M.] Dana Farber Canc Inst, Boston, MA USA. [Quintiliani, Lisa M.] Harvard Univ, Sch Med, Boston, MA USA. [Campbell, Marci K.; Haines, Pamela S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Webber, Kelly H.] Univ Kentucky, Lexington, KY USA. RP Quintiliani, LM (reprint author), 44 Binney St,DFC1,LW 703, Boston, MA 02115 USA. EM lisa_quintiliani@dfci.harvard.edu OI Quintiliani, Lisa/0000-0002-3328-6768 FU University of North Carolina at Chapel Hill; American Dietetic Association Foundation; Smith Graduate Research Grant FX This research was completed while Lisa M. Quintiliani was a doctoral student supported by a predoctoral fellowship from the Lineberger Comprehensive Cancer Center, from the University of North Carolina at Chapel Hill. This research was also supported by a scholarship from the American Dietetic Association Foundation and a Smith Graduate Research Grant.; The authors thank Jennifer Styles, for her help in conducting the focus groups, as well as the student participants. NR 20 TC 8 Z9 8 U1 2 U2 6 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 2008 VL 108 IS 9 BP 1503 EP 1507 DI 10.1016/j.jada.2008.06.428 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 346DR UT WOS:000259049100021 PM 18755323 ER PT J AU Shega, JW Rudy, T Keefe, FJ Perri, LC Mengin, OT Weiner, DK AF Shega, Joseph W. Rudy, Thomas Keefe, Francis J. Perri, Lisa Caitlin Mengin, Olga Telgarska Weiner, Debra K. TI Validity of pain behaviors in persons with mild to moderate cognitive impairment SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognitive impairment; non-cancer pain; pain behaviors ID LOW-BACK-PAIN; NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE; NONMALIGNANT PAIN; SELF-ASSESSMENT; RATING-SCALE; DEMENTIA; INTENSITY; PATTERNS; PATIENT AB OBJECTIVES: To evaluate the validity of traditional pain behaviors (guarding, bracing, rubbing, grimacing, and sighing) in persons with and without cognitive impairment and chronic low back pain (CLBP). DESIGN: Prospective observational study. SETTING: Outpatient clinics. PARTICIPANTS: Thirty-seven cognitively intact and 40 cognitively impaired participants with and without CLBP. MEASUREMENTS: Frequency of traditional pain behaviors. RESULTS: Forty-six of the participants were pain free, and 31 had CLBP. The internal consistency reliability coefficient of the five pain behaviors was 0.32, suggesting that a unidimensional scale did not exist. Multivariate analysis of variance analysis according to the independent variables pain status (pain free vs CLBP) and cognitive status (intact vs impaired) with the dependent variable frequency of pain behaviors found significant differences according to pain status (F[5,61]=3.06, P=.02) and cognitive status (F[5,61]=5.41, P <.001) but without evidence of an interaction (F[5,61]=1.14, P=.35). Participants with CLBP exhibited significantly higher levels of grimacing (P <.001) and guarding (P=.02) than pain-free participants. Intact subjects exhibited fewer guarding (P=.02) and rubbing behaviors (P <.001) but a higher number of bracing behaviors (P=.03) than cognitively impaired participants. CONCLUSION: These results support the utility of facial grimacing in assessing pain in patients with mild to moderate cognitive impairment and call into question the validity of guarding and rubbing in assessing pain in persons with mild to moderate cognitive impairment. C1 [Shega, Joseph W.; Perri, Lisa Caitlin] Northwestern Univ, Div Hematol & Oncol, Dept Med, Chicago, IL 60611 USA. [Rudy, Thomas; Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Rudy, Thomas; Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Rudy, Thomas] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Keefe, Francis J.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Perri, Lisa Caitlin] Duke Univ, Dept Psychol Social & Hlth Sci, Durham, NC USA. [Mengin, Olga Telgarska] Univ Illinois, Coll Med, Chicago, IL USA. [Weiner, Debra K.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Shega, JW (reprint author), Northwestern Univ, Div Hematol & Oncol, Dept Med, 676 N St Clair,Suite 850, Chicago, IL 60611 USA. EM j-shega@northwestern.edu RI Comba, Valentina/G-6210-2014 FU University of Pittsburgh; Alzheimer's Disease Research Center FX The authors would like to thank Dr. Natalia Morone for her thoughtful review of this manuscript.; Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this manuscript. Debra K. Weiner and Francis J. Keefe received federal funding during the study period, but the authors report no known conflicts of interest. The University of Pittsburgh. Alzheimer's Disease Research Center provided funding. NR 32 TC 25 Z9 25 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2008 VL 56 IS 9 BP 1631 EP 1637 DI 10.1111/j.1532-5415.2008.01831.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 347PC UT WOS:000259152500006 PM 18662203 ER PT J AU Barnes, DE Blackwell, T Stone, KL Goldman, SE Hillier, T Yaffe, K AF Barnes, Deborah E. Blackwell, Terri Stone, Katie L. Goldman, Suzanne E. Hillier, Teresa Yaffe, Kristine CA Study Osteoporotic Fractures TI Cognition in older women: The importance of daytime movement SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE movement; exercise; activity; cognition; risk factor ID ALZHEIMERS-DISEASE; LEISURE ACTIVITIES; PHYSICAL-ACTIVITY; OSTEOPOROTIC FRACTURES; RISK; DEMENTIA; ACTIGRAPHY; SLEEP; HEALTH; PARTICIPATION AB OBJECTIVES: To determine whether an objective measure of daytime movement is associated with better cognitive function in women in their 80s. DESIGN: Cross-sectional. SETTING: A study of health and aging. PARTICIPANTS: Two thousand seven hundred thirty-six older women without evidence of dementia. MEASUREMENTS: Daytime movement was assessed using actigraphy, which involved wearing a watch-like device that objectively quantified accelerometer motion over a mean of 3.0 +/- 0.8 days. Cognitive function was measured using the Trail-Making Test, Part B (Trails B) and the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as performing 1.5 standard deviations (SDs) worse than the mean on a given test. RESULTS: Participants had a mean age of 83 +/- 4; 10% were African American. After adjustment for age, race, and education, women in the highest movement quartiles had better mean cognitive test scores (20 +/- 0.3 seconds faster on Trails B and 0.3 +/- 0.2 points higher on MMSE, both P <.001) than those in the lowest quartile and were less likely to be cognitively impaired (odds ratio (OR)=0.61, 95% confidence interval (CI)=0.41-0.92 for Trails B; OR=0.68, 95% CI=0.44-1.07 for MMSE). Associations were similar in different subgroups and were independent of self-reported walking, medical comorbidities, physical function, and other health-related behaviors. CONCLUSION: Daytime movement as measured objectively using actigraphy was associated with better cognitive function and lower odds of cognitive impairment in women in their 80s. Additional studies are needed to clarify the direction of the association and to explore potential mechanisms. C1 [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Blackwell, Terri; Stone, Katie L.; Yaffe, Kristine] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA. [Goldman, Suzanne E.] Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN USA. [Hillier, Teresa] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97201 USA. [Hillier, Teresa] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,151R, San Francisco, CA 94121 USA. EM Deborah.Barnes@ucsf.edu FU National Institutes of Health [AG05407, AR35582, AG05394, AR35584, AR35583, AG08415, K01 AG024069] FX Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this manuscript. The Study of Osteoporotic Fractures was funded through grants from the National Institutes of Health (AG05407, AR35582, AG05394, AR35584, AR35583, AG08415). Dr. Barnes is supported by a Career Development Award from the National Institutes of Health (K01 AG024069). Dr. Yaffe was supported in part by an anonymous foundation for this work. This study was presented at the American Academy of Neurology meeting in Boston, Massachusetts, on May 2, 2007, and at the American Geriatrics Society meeting in San Francisco, California, on November 19, 2007. NR 40 TC 30 Z9 30 U1 1 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2008 VL 56 IS 9 BP 1658 EP 1664 DI 10.1111/j.1532-5415.2008.01841.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 347PC UT WOS:000259152500010 PM 18662201 ER PT J AU Espinoza, SE Hazuda, HP AF Espinoza, Sara E. Hazuda, Helen P. TI Frailty in older Mexican-American and European-American adults: Is there an ethnic disparity? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE frailty; ethnic disparities; screening ID WOMENS HEALTH; ASSOCIATION; OBESITY AB Because conventional frailty screening criteria have been standardized in predominantly European-American (EA) cohorts, applying them to ethnically diverse populations may result in inaccurate estimation of frailty prevalence in ethnic minorities. The objective of this study was to determine whether use of ethnic-specific criteria (EC) to characterize frailty in a bi-ethnic cohort results in significant differences in frailty prevalence when compared with the prevalence obtained using conventional criteria (CC). Data were from a random sample of community-dwelling Mexican Americans (MAs) (n=394) and EAs (n=355) aged 65 to 80 who participated in the baseline examination of the San Antonio Longitudinal Study of Aging. Frailty was defined as three or more of five characteristics: slow walking speed, weak grip strength, low energy expenditure, self-reported exhaustion, and weight loss. For CC, walking speed was standardized to height and sex, grip strength was standardized to body mass index and sex, and energy expenditure was standardized to sex using the pooled sample. For EC, these criteria were applied within each ethnic group. Frailty prevalence in MAs and EAs was compared using chi-square statistic. Using CC, a higher proportion of MAs than EAs were frail (11.3% vs 7.0%, P=.045). Using EC, there was no difference in frailty prevalence between MAs and EAs (9.9% in both ethnic groups). The application of conventional frailty screening criteria in a bi-ethnic cohort results in a higher prevalence of frailty in MAs than in EAs. In determining whether there are ethnic disparities in frailty, future studies should carefully consider whether CC or EC should be applied. C1 [Espinoza, Sara E.; Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Espinoza, Sara E.] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. [Espinoza, Sara E.; Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Espinoza, Sara E.; Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Espinoza, Sara E.] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. [Espinoza, Sara E.] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. RP Espinoza, SE (reprint author), 7703 Floyd Curl Dr,Mail Code 7875, San Antonio, TX 78229 USA. EM espinozas2@uthscsa.edu FU National Institute on Aging [R01AG10444, R01-AG16518]; National Center for Research Resources [M01-RR01346] FX The authors would like to acknowledge Adrienne Boulton for her assistance with data management.; Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this manuscript. This study was supported by National Institute on Aging Grants R01AG10444 and R01-AG16518 and National Center for Research Resources Grant M01-RR01346. NR 16 TC 29 Z9 31 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2008 VL 56 IS 9 BP 1744 EP 1749 DI 10.1111/j.1532-5415.2008.01845.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 347PC UT WOS:000259152500023 PM 18662198 ER PT J AU Ammenwerth, E Schnell-Inderst, P Machan, C Siebert, U AF Ammenwerth, Elske Schnell-Inderst, Petra Machan, Christof Siebert, Uwe TI The effect of electronic prescribing on medication errors and adverse drug events: A systematic review SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review ID PHYSICIAN ORDER ENTRY; CLINICAL DECISION-SUPPORT; INTENSIVE-CARE-UNIT; COMPUTER-ASSISTED MANAGEMENT; RANDOMIZED CONTROLLED TRIALS; PRESCRIPTION ERRORS; HEALTH-CARE; INCREASED MORTALITY; INFORMATION-SYSTEM; IMPACT AB The objective of this systematic review is to analyse the relative risk reduction on medication error and adverse drug events (ADE) by computerized physician order entry systems (CPOE). We included controlled field studies and pretest-posttest studies, evaluating all types of CPOE systems, drugs and clinical settings. We present the results in evidence tables, calculate the risk ratio with 95%, confidence interval and perform subgroup analyses for categorical factors, such as the level of care, patient group, type of drug, type of system, functionality of the system, comparison group type, study design, and the method for detecting errors. Of the 25 studies that analysed the effects on the medication error rate, 23 showed a significant relative risk reduction of 13% to 99%. Six of the nine studies that analysed the effects on potential ADEs showed a significant relative risk reduction of 35% to 98%. Four of the seven studies that analysed the effect on ADEs showed a significant relative risk reduction of 30% to 84%. Reporting quality and Study quality was often insufficient to exclude major Sources of bias. Studies on home-grown systems, studies comparing electronic prescribing to handwriting prescribing, and studies using manual chart review to detect errors seem to show a higher relative risk reduction than other studies. Concluding, it seems that electronic prescribing can reduce the risk for medication errors and ADE. However, studies differ substantially in their setting, design, quality, and results. To further improve the evidence-base of health informatics, more randomized controlled trials (RCTs) are needed, especially to cover a wider range of clinical and geographic settings. In addition, reporting quality of health informatics evaluation studies has to be substantially improved. C1 [Ammenwerth, Elske; Machan, Christof] UMIT Univ Hlth Sci Med Informat & Technol Tyrol, Inst Hlth Informat Syst, Tyrol, Austria. [Schnell-Inderst, Petra; Siebert, Uwe] Med Decis Making & HTA, Dept Publ Hlth, Tyrol, Austria. [Schnell-Inderst, Petra] Univ Duisburg Essen, Chair Med Management, Alfried Krupp von Bohlen & Halbach Fdn, Essen, Germany. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Med, Dept Hlth Policy & Management, Program Hlth Decis Sci, Boston, MA USA. RP Ammenwerth, E (reprint author), UMIT Univ Hlth Sci Med Informat & Technol Tyrol, Inst Hlth Informat Syst, Eduard Wallnofer Zentrum 1, A-6060 Hall In Tyrol, Austria. EM elske.ammenwerth@umit.at RI Ammenwerth, Elske/F-5430-2010 NR 67 TC 277 Z9 280 U1 8 U2 58 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 2008 VL 15 IS 5 BP 585 EP 600 DI 10.1197/jamia.M2667 PG 16 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 352NL UT WOS:000259503800004 PM 18579832 ER PT J AU Jha, AK Laguette, J Seger, A Bates, DW AF Jha, Ashish K. Laguette, Julia Seger, Andrew Bates, David W. TI Can surveillance system identify and avert adverse drug events? A prospective evaluation of a commercial application SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID PHYSICIAN ORDER ENTRY; HOSPITALIZED-PATIENTS; COMPUTERIZED SURVEILLANCE; PREVENTION; ERRORS AB Objective: Computerized monitors can effectively detect and potentially prevent adverse drug events (ADEs). Most monitors have been developed in large academic hospitals and are not readily usable in other settings. We assessed the ability of a commercial program to identify and prevent ADEs in a community hospital. Design and Measurement: We prospectively evaluated the commercial application in a community-based hospital. We examined the frequency and types of alerts produced, how often they were associated with ADEs and potential ADEs, and the potential financial impact of monitoring for ADEs. Results: Among 2,407 patients screened, the application generated 516 high priority alerts. We were able to review 266 alerts at the time they were generated and among these, 30 (11.3%) were considered substantially important to warrant contacting the physician caring for the patient. These 30 alerts were associated with 4 ADEs and 11 potential ADEs. In all 15 cases, the responsible physician was unaware of the event, leading to a change in clinical care in 14 cases. Overall, 23% of high priority alerts were associated with an ADE (95% confidence interval [CI] 12% to 34%) and another 15% were associated with a potential ADE (95% CI 6% to 24%). Active surveillance used approximately 1.5 hours of pharmacist time daily. Conclusions: A commercially available, computer-based ADE detection tool was effective at identifying ADEs. When used as part of an active surveillance program, it can have an impact on preventing or ameliorating ADEs. C1 [Jha, Ashish K.; Bates, David W.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Jha, Ashish K.; Laguette, Julia; Seger, Andrew] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU Robert Wood Johnson Foundation FX Dr. Jha was supported by the Physician Faculty Scholar program of the Robert Wood Johnson Foundation. NR 28 TC 29 Z9 31 U1 7 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 2008 VL 15 IS 5 BP 647 EP 653 DI 10.1197/jamia.M2634 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 352NL UT WOS:000259503800010 PM 18579834 ER PT J AU Phanstiel, D Zhang, Y Marto, JA Coon, JJ AF Phanstiel, Doug Zhang, Yi Marto, Jarrod. A. Coon, Joshua J. TI Peptide and protein quantification using iTRAQ with electron transfer dissociation SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID TANDEM MASS-SPECTROMETRY; QUANTITATIVE PROTEOMIC ANALYSIS; POSTTRANSLATIONAL MODIFICATIONS; SACCHAROMYCES-CEREVISIAE; EXPRESSION; PHOSPHOPEPTIDES; PHOSPHORYLATION; MS/MS AB Electron transfer dissociation (ETD) has become increasingly used in proteomic analyses due to its complementarity to collision-activated dissociation (CAD) and its ability to sequence peptids with post-translation modifications (PTMs). It was previously unknown, however, whether ETD would be compatible with a commonly employed quantification technique, isobaric tags for relative and absolute quantification (iTRAQ), since the fragmentation mechanisms and pathways of ETD differ significantly from CAD. We demonstrate here that ETD of iTRAQ labeled peptides produce c- and Z-type fragment ions as well as reporter ions that are unique from those produced by CAD. Exact molecular formulas, of product ions were determined by ETD fragmentation of iTRAQ-labeled synthetic peptides followed by high mass accuracy orbitrap mass analysis. These experiments revealed that ETD cleavage of the N-C alpha bond of the iTRAQ tag results in fragment ions that could be used for quantification. Synthetic peptide work demonstrates that these fragment ions provide Lip to three charnels of quantification and that the quality is similar to that provided by bearn-type CAD. Protein standards were used to evaluate peptide and protein quantification of iTRAQ labeling in conjunction with ETD, beam-type CAD, and Pulsed Q dissociation (PQD) Oil a hybrid ion trap-orbitrap mass spectrometer. For reporter ion intensities above a certain threshold all three strateaies provided reliable peptide quantification (average error < 10%,). Approximately 36%, 8%, and 16% of scans identified fall below this threshold for ETD, HCD, and PQD, respectively. At the protein level, average errors were 2.3%, 1.7%,, and 3.6% for ETD, HCD, and PQD, respectively. C1 [Phanstiel, Doug; Coon, Joshua J.] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA. [Coon, Joshua J.] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA. [Zhang, Yi; Marto, Jarrod. A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zhang, Yi; Marto, Jarrod. A.] Dana Farber Canc Inst, Blais Proteom Ctr, Boston, MA 02115 USA. [Marto, Jarrod. A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Coon, JJ (reprint author), Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706 USA. EM jcoon@chem.wisc.edu FU Universitv of Wisconsin-Madison; Thermo Scientific; Beckman Foundation; American Society of Mass Spectrometry; Eli Lilly; National Science Foundation [0701846, 0747990]; NIH [1R01GIV1080148, 5T32HGO02760] FX The authors thank Graeme McAlister for instrument Support. They acknowledge financial support for this work by the Universitv of Wisconsin-Madison, Thermo Scientific, the Beckman Foundation, the American Society of Mass Spectrometry, Eli Lilly, the National Science Foundation (0701846; 0747990 both to J.J.C.), and the NIH (1R01GIV1080148 to J.J.C.). D.P. gratefully acknowledges support from NIH predoctoral fellowship (the Genomic Sciences Training Program, NIH 5T32HGO02760). NR 43 TC 41 Z9 42 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD SEP PY 2008 VL 19 IS 9 BP 1255 EP 1262 DI 10.1016/j.jasms.2008.05.023 PG 8 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 354UG UT WOS:000259663900003 PM 18620867 ER PT J AU Chu, JW Levine, RA Chua, S Poh, KK Morris, E Hua, L Ton-Nu, TT Hung, J AF Chu, John W. Levine, Robert A. Chua, Sarah Poh, Kian-Keong Morris, Eleanor Hua, Lanqi Ton-Nu, Thanh-Thao Hung, Judy TI Assessing mitral valve area and orifice geometry in calcific mitral stenosis: A new solution by real-time three-dimensional echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE mitral stenosis; 3D echocardiography; valvular disease ID PRESSURE HALF-TIME; ULTRASOUND; DISEASE; HEART AB Background: Planimetry of mitral valve area (MVA) is difficult in calcific mitral stenosis (CaMS) in which limiting orifice is near the annulus, and unlike rheumatic mitral stenosis (RhMS), does not present an area for planimetry at the leaflet tips. Moreover, pressure half time (PHT)-derived MVA (MVA(PHT)) has limitations in patients with CaMS in whom there are coexisting conditions that affect LV chamber compliance. We tested the hypothesis that real-time 3-dimensional echocardiography (RT3D) can guide measurement at the narrowest orifice in CaMS. Methods: In 34 patients with CaMS, MVA by RT3D (MVA(RT3D)) was obtained using a color-defined planimetry technique performed "en face" at the smallest annular orifice cross-section (diastolic maximum). MVA(RT3D) and MVA(PHT) were compared with an independent standard: MVA by continuity equation (MVA(CEQ)). In a subgroup of 10 patients with CaMS or RhMS, the 3-dimensional shape of the stenotic mitral valve was examined, guided by color flow mapping. Results: MVA(PHT) overestimated the mitral orifice area compared with MVA(CEQ) (2.01 +/- 0.52 cm(2) vs 1.75 +/- 0.46 cm2; P = .037), whereas there was no significant difference in MVA(RT3D) and MVA(CEQ) (1.83 +/- 0.52 cm(2) vs 1.75 +/- 0.46 cm(2), respectively, P = .61). MVA(RT3D) had a greater correlation with MVA(CEQ) than MVA(PHT) (R = 0.86 vs 0.59 MVA(RT3D) vs MVA(PHT), respectively). There was better agreement between MVA by RT3D and MVA by continuity equation than MVA by PHT and MVA by continuity equation (difference in MVA: 0.23 +/- 0.15 cm(2) vs 0.43 +/- 0.29 cm(2); P < .0001, MVA(RT3D) - MVA(CEQ) vs MVA(PHT) - MVA(CEQ), respectively). In CaMS, there was a tubular geometry to the valve shape. In contrast, RhMS had a doming funnel-shaped geometry. Conclusion: RT3D provides an accurate measurement of MVA in CaMS. In contrast with the doming valve shape present in RhMS, the limiting anatomic orifice area occurs at the annulus in CaMS as measured by RT3D and reflects the effective orifice area as present in a tubular valve geometry. C1 [Chu, John W.; Levine, Robert A.; Chua, Sarah; Poh, Kian-Keong; Morris, Eleanor; Hua, Lanqi; Ton-Nu, Thanh-Thao; Hung, Judy] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Hung, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,VBK 508, Boston, MA 02114 USA. EM jhung@partners.org FU National Heart Foundation of New Zealand, Auckland, New Zealand; [K23HL004504]; [R21EB005294]; [R01HL072265] FX Dr John W. Chu was supported in part by a grant from the National Heart Foundation of New Zealand, Auckland, New Zealand. This work was also supported in part by K23HL004504 and R21EB005294 (J. H.) and R01HL072265 (R. A. L.). There are no conflicts to declare. NR 26 TC 35 Z9 37 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2008 VL 21 IS 9 BP 1006 EP 1009 DI 10.1016/j.echo.2008.05.010 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 343DZ UT WOS:000258834200005 PM 18620839 ER PT J AU Choueiri, TK Vaziri, SAJ Jaeger, E Elson, P Wood, L Bhalla, IP Small, EJ Weinberg, V Sein, N Simko, J Golshayan, AR Sercia, L Zhou, M Waldman, FM Rini, BI Bukowski, RM Ganapathi, R AF Choueiri, Toni K. Vaziri, Susan A. J. Jaeger, Erich Elson, Paul Wood, Laura Bhalla, Ish Prasad Small, Eric J. Weinberg, Vivian Sein, Nancy Simko, Jeff Golshayan, Ali-Reza Sercia, Linda Zhou, Ming Waldman, Frederic M. Rini, Brian I. Bukowski, Ronald M. Ganapathi, Ram TI von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma SO JOURNAL OF UROLOGY LA English DT Article DE carcinoma; renal cell; vascular endothelial growth factors; von Hippel-Lindau disease; prognosis ID TUMOR-SUPPRESSOR GENE; EXPRESSION; MUTATIONS; PROGNOSIS; CANCER; SUNITINIB; IMPACT AB Purpose: The von Hippel-Lindau (VHL) gene is often inactivated (by mutation or promoter hypermethylation) in renal cell carcinoma but the relation to therapeutic outcome is unclear. Materials and Methods: Patients with metastatic clear cell renal cell carcinoma with available baseline tumor samples who received vascular endothelial growth factor targeted therapy were included in analysis. Patient characteristics, VHL gene status and clinical outcome were documented. Our primary end point was to test for response rate in relation. to VHL inactivation. Progression-free survival and overall survival in relation to VHL status were investigated as secondary end points. Results: A total of 123 patients were evaluable. Response rate, median progression-free survival and median overall survival were 37% (95% CI 28-46), 10.8 (95% CI 7.7-14.8) and 29.8 (CI not estimable) months, respectively. Patients with VHL inactivation had a response rate of 41% vs 31% for those with wild-type VHL (p = 0.34). Patients with loss of function mutations (frameshift, nonsense, splice and in-frame deletions/insertions) had a 52% response rate vs 31% with wild-type VHL (p = 0.04). On multivariate analysis the presence of a loss of function mutation remained an independent prognostic factor associated with improved response. Progression-free survival and overall survival were not significantly different based on VHL status. Conclusions: To our knowledge this is the largest analysis investigating the impact of VHL inactivation on the outcome of vascular endothelial growth factor targeted agents in metastatic renal cell carcinoma. We did not find a statistically significant increase in response to vascular endothelial growth factor targeted agents in patients with VHL inactivation. Loss of function mutations identified a population of patients with a greater response. Investigation of downstream markers is under way. C1 [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Vaziri, Susan A. J.; Elson, Paul; Wood, Laura; Bhalla, Ish Prasad; Golshayan, Ali-Reza; Sercia, Linda; Zhou, Ming; Rini, Brian I.; Bukowski, Ronald M.; Ganapathi, Ram] Cleveland Clin Taussig Canc Ctr, Cleveland, OH USA. [Jaeger, Erich; Small, Eric J.; Weinberg, Vivian; Sein, Nancy; Simko, Jeff; Waldman, Frederic M.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Choueiri, TK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu NR 20 TC 130 Z9 136 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2008 VL 180 IS 3 BP 860 EP 865 DI 10.1016/j.juro.2008.05.015 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 337TV UT WOS:000258459300017 PM 18635227 ER PT J AU McDougal, WS AF McDougal, W. Scott TI Evaluation of current TNM classification of penile carcinoma - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2008 VL 180 IS 3 BP 938 EP 938 DI 10.1016/j.juro.2008.05.149 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 337TV UT WOS:000258459300042 ER PT J AU Lee, HJ Box, GN Abraham, JBA Deane, LA Elchico, ER Eisner, BH McDougall, EM Clayman, RV AF Lee, Hak J. Box, Geoffrey N. Abraham, Jose Benito A. Deane, Leslie A. Elchico, Erick R. Eisner, Brian H. McDougall, Elspeth M. Clayman, Ralph V. TI In vitro evaluation of nitinol urological retrieval coil and ureteral occlusion device: Retropulsion and holmium laser fragmentation efficiency SO JOURNAL OF UROLOGY LA English DT Article DE ureter; calculi; ureteroscopy; lithotripsy; lasers; solid state ID SHOCK-WAVE LITHOTRIPSY; YAG LASER; STONE CONE; MIGRATION; CALCULI; PREVENTION; EXPERIENCE AB Purpose: Retropulsion of ureteral stones during laser lithotripsy may result in difficult and incomplete stone fragmentation. The Stone Cone (R) nitinol urological retrieval coil and the NTrap (R) nitinol ureteral occlusion device have been introduced into clinical practice to possibly limit stone retropulsion and enhance the efficiency of holmium laser (Convergent Laser Technologies, Alameda, California) stone fragmentation. Materials and Methods: A total of 360 BegoStone Plus phantom stones (Bego USA, Smithfield, Rhode Island) of similar mass and weight were divided into 3 groups, including control, Stone Cone and NTrap. The groups were further subdivided according to fiber size (200 or 400 mu m) and pulse width (350 or 700 mu sec). These stones were placed in a horizontal pipette 12 mm in diameter, submerged in normal saline and disintegrated at laser settings of 1 J and 10 Hz continuously applied for 300 seconds. Retropulsion in cm and fragmentation efficiency with mass loss in mg were measured after treatment. Results: The 2 devices were effective for preventing retropulsion. In the control group the mean +/- SD retropulsion distance using a 350-mu sec pulse width with the 200 and 400 mu m fibers was 18.4 +/- 5.9 and 14.1 +/- 4.6 cm, while it was 6.2 +/- 2.6 and 5.6 +/- 2.4, respectively, using the 700-mu sec pulse width. There was a statistically significant higher loss of stone weight in the Stone Cone and NTrap experimental groups than in the control group (p <0.0001). However, there was no difference between the 2 experimental groups across all groups (p = 0.32). Conclusions: The Stone Cone and NTrap eliminated retropulsion and equally improved fragmentation efficiency. The maximum efficiency of fragmentation was seen using the 200 mu m fiber at a 700-mu sec pulse width. C1 [Clayman, Ralph V.] Univ Calif Irvine, Dept Urol, Orange, CA 92868 USA. [Eisner, Brian H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Clayman, RV (reprint author), Univ Calif Irvine, Dept Urol, 101 City Dr S,Bldg 55,Route 81,Room 304, Orange, CA 92868 USA. EM rclayman@uci.edu NR 20 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2008 VL 180 IS 3 BP 969 EP 973 DI 10.1016/j.juro.2008.05.016 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 337TV UT WOS:000258459300049 PM 18656905 ER PT J AU Fairman, RM Criado, F Farber, M Kwolek, C Mehta, M White, R Lee, A Tuchek, JM AF Fairman, Ronald M. Criado, Frank Farber, Mark Kwolek, Christopher Mehta, Manish White, Rodney Lee, Anthony Tuchek, J. Michael CA VALOR Invest TI Pivotal results of the Medtronic Vascular Talent Thoracic Stent Graft System: The VALOR trial SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the Society-for-Vascular-Surgery CY JUN 06-10, 2007 CL Baltimore, MD SP Soc Vasc Surg ID AORTIC-ANEURYSMS; ENDOVASCULAR REPAIR; 10-YEAR EXPERIENCE; FOLLOW-UP; DISSECTION; PLACEMENT; RISK AB Objective: This report summarizes the 30-day and 12-month results of endovascular treatment using the Medtronic Vascular Talent Thoracic Stent Graft System (Medtronic Vascular, Santa Rosa, Calif) for patients with thoracic aortic aneurysms (TAA) who are considered candidates for open surgical repair. Methods: The study was a prospective, nonrandomized, multicenter, pivotal trial conducted at 38 sites. Enrollment occurred between December 2003 and June 2005. Standard follow-up interval examinations were prescribed at I month, 6 months, 1 year, and annually thereafter. These endovascular results were compared with retrospective open surgical data from three centers of excellence. Results. The Evaluation of the Medtronic Vascular Talent Thoracic Stent Graft System for the Treatment of Thoracic Aortic Aneurysms (VALOR) trial enrolled 195 patients, and 189 were identified as retrospective open surgical subjects. Compared with the open surgery group, the VALOR test group had similar age and sex distributions, but had a smaller TAA size. Patients received a mean number of 2.7 +/- 1.3 stent graft components. The diameters of 25% of the proximal stent graft components implanted were < 26 mm or > 40 mill. Left subclavian artery revascularization was performed before the initial stent graft procedure in 5.2% of patients. Iliac conduits were used in 21.1% of patients. In 33.5% of patients, the bare spring segment of the most proximally implanted device was in zones 1 or 2 of the aortic arch. In 194 patients (99.5%), vessel access and stent graft deployment were successful at the intended site. The 30-day VALOR results included perioperative mortality, 2.1%; major adverse advents, 41%; incidence of paraplegia, 1.5%; paraparesis, 7.2%; and stroke, 3.6%. The 12-month VALOR results included all-cause mortality, 16.1%; aneurysm-related mortality, 3.1%; conversion to open surgery, 0.5%; target aneurysm rupture, 0.5%; stent graft migration > 10 mm, 3.9%; endoleak (12.2%), stent graft patency, 100%; stable or decreasing aneurysm diameter, 91.5%; and loss of stent graft integrity, four patients. No deployment-related events or perforation of the aorta by a graft component occurred. The Talent Thoracic Stent Graft showed statistically superior performance with respect to acute procedural outcomes (P < .001), 30-day major adverse events (41% vs 84.4%, P < .001), perioperative mortality (2% vs 8%, P < .01), and 12-month aneurysm-related mortality (3.1% vs 11.6%, P < .002) vs open surgery. Conclusions: The pivotal VALOR 12-month trial results demonstrate that the Medtronic Talent Thoracic Stent Graft System is a safe and effective endovascular therapy as an alternative to open surgery in patients with TAA who were considered candidates for open surgical repair. C1 [Fairman, Ronald M.] Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Criado, Frank] Union Mem Hosp, Baltimore, MD USA. [Farber, Mark] Univ N Carolina, Chapel Hill, NC USA. [Kwolek, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mehta, Manish] Albany Med Ctr, Albany, NY USA. [White, Rodney] Harbor Univ Calif, Los Angeles Med Ctr, Torrance, CA USA. [Lee, Anthony] Univ Florida, Gainesville, FL USA. [Tuchek, J. Michael] Loyola Univ, Maywood, IL 60153 USA. RP Fairman, RM (reprint author), Hosp Univ Penn, Dept Surg, 3400 Spruce St,4 Silverstein Pavil, Philadelphia, PA 19104 USA. EM ron.fairman@uphs.upenn.edu NR 18 TC 146 Z9 152 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2008 VL 48 IS 3 BP 546 EP 554 DI 10.1016/j.jvs.2008.03.061 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 343FE UT WOS:000258837500005 PM 18572352 ER PT J AU Schanzer, A Ciaranello, AL Schanzer, H AF Schanzer, Andres Ciaranello, Andrea L. Schanzer, Harry TI Brachial artery ligation with total graft excision is a safe and effective approach to prosthetic arteriovenous graft infections SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-for-Clinical-Vascular-Surgery CY MAR 21-24, 2007 CL Orlando, FL SP Soc Clin Vasc Surg ID VASCULAR ACCESS; HEMODIALYSIS ACCESS; MANAGEMENT; FISTULA; EXPERIENCE AB Objective: While autogenous arteriovenous access is preferred, prosthetic arteriovenous grafts (AVG) are still required in a large number of patients. Infection of AVGs occurs frequently and may cause life-threatening bleeding or sepsis. Multiple treatment strategies have been advocated (ranging from graft preservation to excision with complex concomitant reconstructions), indicating a lack of consensus on appropriate management of infected AVGs. We undertook this study to evaluate if, in the setting of anastomotic involvement, brachial artery ligation distal to the origin of the deep brachial artery accompanied by total graft excision (BAL) is safe and effective. Methods: All prosthetic arterioivenous graft infections managed by a single surgeon between 1995 and 2006 were reviewed retrospectively. Patients were identified from a computerized vascular registry, and data were obtained via patient charts and the electronic medical record. Results: We identified 45 AVG infections in 43 patients. Twenty-one patients (49%) demonstrated arterial anastomotic involvement and were treated with BA-L; these form the cohort for this analysis. Mean patient age was 53.2 (SD 9.5) years. The primary etiologies for end stage renal disease (ESRD) were hypertension (29%), HIV (24%), and diabetes (19%). All tipper arm AVG was present in 95% of patients, one (5%) had a forearm AVG. The majority of grafts were polytetrafluoroethylene (PTFE) (90%). Follow-up was 100% at 1 month, 86% at 3 months, and 67% at 6 months. No ischemic or septic complications occurred in the 21 patients who underwent BAL. Conclusion: BNL is all effective and expeditious method to deal with all infected arm AVG in frequently critically ill patients with densely scarred wounds. In the short term, BAL appears to be well tolerated without resulting ischemic complications. Further study with longer duration of follow-up is necessary to ascertain whether BAL results in definitive cure, or whether patients may ultimately manifest ischemic changes and require additional intervention. C1 [Schanzer, Andres] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. [Ciaranello, Andrea L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schanzer, Harry] Mt Sinai Sch Med, New York, NY USA. RP Schanzer, A (reprint author), Univ Massachusetts, Sch Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM schanzeA@ummhc.org RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 FU NIAID NIH HHS [T32 AI007433, T32 AI07433] NR 21 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2008 VL 48 IS 3 BP 655 EP 658 DI 10.1016/j.jvs.2008.04.030 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 343FE UT WOS:000258837500021 PM 18572370 ER PT J AU Kang, J Albadawi, H Patel, VI Abbruzzese, TA Yoo, JH Austen, G Watkins, MT AF Kang, Jeanwan Albadawi, Hassan Patel, Virendra I. Abbruzzese, Thomas A. Yoo, Jin-Hyung Austen, Gerald, Jr. Watkins, Michael T. TI Apolipoprotein E(-/-) mice have delayed skeletal muscle healing after hind limb ischemia-reperfusion SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY OCT 05-06, 2007 CL Ledyard, CT ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; PERIPHERAL ARTERIAL-DISEASE; E-DEFICIENT MICE; VASCULAR-DISEASE; ATHEROSCLEROSIS; INJURY; EXPRESSION; OUTCOMES; MOUSE; ISCHEMIA/REPERFUSION AB Introduction: Classic studies of limb ischemia-reperfusion injury have been performed using young healthy mice. However, patients with peripheral vascular disease are older and often exhibit metabolic derangements that may delay healing after revascularization. Mice with genetic deletion of apolipoprotein E (ApoE(-/-)) have been used as a model ill various experimental scenarios of hypercholesterolemia. These experiments evaluated the inflammatory response and changes in skeletal muscle morphology during the acute and chronic phases of limb ischemia-reperfusion injury ill aged ApoE(-/-) juice. Methods: Age-matched ApoE(-/-) and wild-type (Wt) mice underwent 1.5 hours of unilateral hind limb ischemia, followed by 1, 7, or 14 days of reperfusion (DR). Histologic analysis of skeletal muscle fiber injury was assessed at I DR. Morphologic evidence of muscular fiber maturation was assessed at 14DR. Levels of MyoD and myogenin, markers of skeletal muscle differentiation, were assessed at 7 and 14DR using Western blots. Markers of inflammation, including myeloperoxidase, macrophage inflammatory protein-2 (MIP-2), monocyte chemotactic protein-1 (MCP-1), and osteopontin, were assayed using enzyme-linked immunosorbent assay and chemokine (C-C motif) receptor 2 (CCR-2) using Western blots at 1, 7, and 14DR. After 1DR, tissue adenosine 5'-triphosphate (ATP) levels were measured to assess metabolic activity. Unpaired t test and Mann-Whitney test were used for comparisons. Results: Histologic evaluation of skeletal muscle after 1DR showed no difference in the degree of injury between Wt and ApoE(-/-) mice. However, at 14DR, ApoE(-/-) mice had higher percentage of immature muscle fibers than Wt mice. Myogenin level was lower in the ApoE(-/-) mice at 7DR. Injured skeletal muscle of ApoE-/- mice had lower levels of myeloperoxidase than Wt mice at 7 DR and higher levels of MCP-1 at 14DR. There was no difference in the levels of tissue ATP, MIP-2, osteopontin, or CCK2 at all experimental intervals. Conclusion: Although there was no difference between the injured muscle of Wt and ApoE(-/-) mice during the acute phase of reperfusion, ApoE-/- mice showed delay in skeletal muscle healing during the chronic phase of reperfusion. This lag in muscle regeneration was associated with lower levels of myogenin at 7DR and an increased level of MCP-1 at 14DR in the ApoE(-/-) mice. The delay in skeletal muscle healing in the ApoE(-/-) mice may have broader implications for poor tissue healing and functional recovery in elderly patients who have vascular risk factors such as hypercholesterolemia. C1 [Kang, Jeanwan; Albadawi, Hassan; Patel, Virendra I.; Abbruzzese, Thomas A.; Yoo, Jin-Hyung; Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Kang, Jeanwan; Albadawi, Hassan; Patel, Virendra I.; Abbruzzese, Thomas A.; Yoo, Jin-Hyung; Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. [Austen, Gerald, Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,Ste 440, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 38 TC 15 Z9 16 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2008 VL 48 IS 3 BP 701 EP 708 DI 10.1016/j.jvs.2008.04.006 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 343FE UT WOS:000258837500028 PM 18572367 ER PT J AU Avakian, A Alroy, J Rozanski, E Keating, J Rosenberg, A AF Avakian, Arlen Alroy, Joseph Rozanski, Elizabeth Keating, John Rosenberg, Andrew TI Lipid-rich pleural mesothelioma in a dog SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article DE Lipid-rich; mesothelioma; pericardial ID PERITONEAL MESOTHELIOMA; MALIGNANT MESOTHELIOMA AB An 11-year-old, neutered, male Golden Retriever cross dog was euthanized following a history of recurrent pericardial effusions. At necropsy, blood-tinged pericardial and intrathoracic effusions were seen along with numerous firm to hard plaque-like masses that studded the epicardial, pericardial, mediastinal, and costal pleural surfaces. Within the right thorax, the lesions coalesced into a large mass that Occupied most of the cavity. Histologically, the masses were composed of solid sheets and papillary aggregates of medium-sized polygonal cells that contained abundant vacuolated to clear cytoplasm. Some of the cytoplasmic vacuoles stained positive with oil red O. The stroma contained metaplastic trabeculae of woven and lamellar bone. Immunohistochemically, the neoplastic cells expressed vimentin, pancytokeratin, and S-100 protein. Transmission electron microscopy corroborated the presence of intracytoplasmic vacuoles and demonstrated prominent intercellular junctional complexes and apically located microvilli. These Findings are consistent with a lipid-rich variant of mesothelioma. To the authors' knowledge, this is the First report of a lipid-rich mesothelioma in a dog. C1 [Avakian, Arlen] Charles River Labs, Shrewsbury, MA 01545 USA. [Alroy, Joseph] Tufts Med Ctr, Dept Pathol, Boston, MA USA. [Alroy, Joseph; Keating, John] Tufts Univ, Cummings Sch Vet Med, Dept Biomed Sci, North Grafton, MA USA. [Rozanski, Elizabeth] Tufts Univ, Cummings Sch Vet Med, Dept Clin Sci, North Grafton, MA USA. [Rosenberg, Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Avakian, A (reprint author), Charles River Labs, 334 South St, Shrewsbury, MA 01545 USA. EM arlen.avakian@crl.com NR 14 TC 10 Z9 10 U1 1 U2 2 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD SEP PY 2008 VL 20 IS 5 BP 665 EP 667 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 389ZX UT WOS:000262135200024 PM 18776107 ER PT J AU Miura, T Brockman, MA Brumme, CJ Brumme, ZL Carlson, JM Pereyra, F Trocha, A Addo, MM Block, BL Rothchild, AC Baker, BM Flynn, T Schneidewind, A Li, B Wang, YE Heckerman, D Allen, TM Walker, BD AF Miura, Toshiyuki Brockman, Mark A. Brumme, Chanson J. Brumme, Zabrina L. Carlson, Jonathan M. Pereyra, Florencia Trocha, Alicja Addo, Marylyn M. Block, Brian L. Rothchild, Alissa C. Baker, Brett M. Flynn, Theresa Schneidewind, Arne Li, Bin Wang, Yaoyu E. Heckerman, David Allen, Todd M. Walker, Bruce D. TI Genetic characterization of human immunodeficiency virus type 1 in elite controllers: Lack of gross genetic defects or common amino acid changes SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; ACTIVE ANTIRETROVIRAL THERAPY; T-CELL RESPONSES; HIV-1 INFECTION; DISEASE PROGRESSION; NEUTRALIZING ANTIBODIES; REPLICATION CAPACITY; LOOP SEQUENCES; R77Q MUTATION; NEF SEQUENCES AB Despite reports of viral genetic defects in persons who control human immunodeficiency virus type I (HIV-1) in the absence of antiviral therapy, the extent to which such defects contribute to the long-term containment of viremia is not known. Most previous studies examining for such defects have involved small numbers of subjects, primarily focused on subjects expressing HLA-B57, or have examined single viral genes, and they have focused on cellular proviral DNA rather than plasma viral RNA sequences. Here, we attempted viral sequencing from 95 HIV-1 elite controllers (EC) who maintained plasma viral loads of <50 RNA copies/ml in the absence of therapy, the majority of whom did not express HLA-B57. HIV-1 gene fragments were obtained from 94% (89/95) of the EC, and plasma viral sequences were obtained from 78% (61/78), the latter indicating the presence of replicating virus in the majority of EC. Of 63 persons for whom nef was sequenced, only three cases of nef deletions were identified, and gross genetic defects were rarely observed in other HIV-1 coding genes. In a codon-by-codon comparison between EC and persons with progressive infection, correcting for HLA bias and coevolving secondary mutations, a significant difference was observed at only three codons in Gag, all three of which represented the historic population consensus amino acid at the time of infection. These results indicate that the spontaneous control of HIV replication is not attributable to shared viral genetic defects or shared viral polymorphisms. C1 [Miura, Toshiyuki; Brockman, Mark A.; Brumme, Chanson J.; Brumme, Zabrina L.; Pereyra, Florencia; Trocha, Alicja; Addo, Marylyn M.; Block, Brian L.; Rothchild, Alissa C.; Baker, Brett M.; Flynn, Theresa; Schneidewind, Arne; Li, Bin; Wang, Yaoyu E.; Allen, Todd M.; Walker, Bruce D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Miura, Toshiyuki; Brockman, Mark A.; Brumme, Zabrina L.; Pereyra, Florencia; Addo, Marylyn M.; Schneidewind, Arne; Li, Bin; Wang, Yaoyu E.; Allen, Todd M.; Walker, Bruce D.] Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. [Miura, Toshiyuki; Trocha, Alicja; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Carlson, Jonathan M.; Heckerman, David] Microsoft Res, Redmond, WA 98052 USA. [Carlson, Jonathan M.] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. EM bwalker@partners.org RI Allen, Todd/F-5473-2011; OI Brumme, Chanson/0000-0003-2722-5288; Brockman, Mark/0000-0001-6432-1426 FU NIH [AI28568, AI30914, AI054178] FX We thank the patients, investigators, and clinical staff at MGH and the HIV Controllers Consortium (www.hivcontrollers.org) for their important contributions to this research study.; This work was supported by grants from the NIH to B.D.W. (AI28568 and AI30914) and T.M.A. (AI054178) and a gift from the Mark and Lisa Schwartz Foundation. We have no conflicts of interest to disclose. NR 66 TC 89 Z9 90 U1 3 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2008 VL 82 IS 17 BP 8422 EP 8430 DI 10.1128/JVI.00535-08 PG 9 WC Virology SC Virology GA 339UU UT WOS:000258603600018 PM 18562530 ER PT J AU Matthews, PC Prendergast, A Leslie, A Crawford, H Payne, R Rousseau, C Rolland, M Honeyborne, I Carlson, J Kadie, C Brander, C Bishop, K Mlotshwa, N Mullins, JI Coovadia, H Ndung'u, T Walker, BD Heckerman, D Goulder, PJR AF Matthews, Philippa C. Prendergast, Andrew Leslie, Alasdair Crawford, Hayley Payne, Rebecca Rousseau, Christine Rolland, Morgane Honeyborne, Isobella Carlson, Jonathan Kadie, Carl Brander, Christian Bishop, Karen Mlotshwa, Nonkululeko Mullins, James I. Coovadia, Hoosen Ndung'u, Thumbi Walker, Bruce D. Heckerman, David Goulder, Philip J. R. TI Central role of reverting mutations in HLA associations with human immunodeficiency virus set point SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; LONG-TERM NONPROGRESSORS; HIV-1 INFECTION; VIRAL LOAD; ESCAPE MUTATIONS; TYPE-1 INFECTION; CELL RESPONSES; AIDS VACCINE; FITNESS COST; IN-VIVO AB Much uncertainty still exists over what T-cell responses need to be induced by an effective human immunodeficiency virus (HIV) vaccine. Previous studies have hypothesized that the effective CD8(+) T-cell responses are those driving the selection of escape mutations that reduce viral fitness and therefore revert posttransmission. In this study, we adopted a novel approach to define better the role of reverting escape mutations in immune control of HIV infection. This analysis of sequences from 710 study subjects with chronic C-clade HIV type I infection demonstrates the importance of mutations that impose a fitness cost in the control of viremia. Consistent with previous studies, the viral set points associated with each HILA-B allele are strongly correlated with the number of Gag-specific polymorphisms associated with the relevant HLA-B allele (r = -0.56, P = 0.0034). The viral set points associated with each HLA-C allele were also strongly correlated with the number of Pol-specific polymorphisms associated with the relevant HLA-C allele (r = -0.67, P = 0.0047). However, critically, both these correlations were dependent solely on the polymorphisms identified as reverting. Therefore, despite the inevitable evolution of viral escape, viremia can be controlled through the selection of mutations that are detrimental to viral fitness. The significance of these results is in highlighting the rationale for an HIV vaccine that can induce these broad responses. C1 [Matthews, Philippa C.; Prendergast, Andrew; Leslie, Alasdair; Crawford, Hayley; Payne, Rebecca; Honeyborne, Isobella; Goulder, Philip J. R.] Nuffield Dept Med, Dept Paediat, Oxford OX1 3SY, England. [Rousseau, Christine; Rolland, Morgane; Mullins, James I.] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. [Carlson, Jonathan; Kadie, Carl; Heckerman, David] Microsoft Res, Redmond, WA 98052 USA. [Brander, Christian; Walker, Bruce D.; Goulder, Philip J. R.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Bishop, Karen; Mlotshwa, Nonkululeko; Coovadia, Hoosen; Ndung'u, Thumbi; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Matthews, PC (reprint author), Nuffield Dept Med, Dept Paediat, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. EM p.matthews@doctors.org.uk; philip.goulder@paediatrics.ox.ac.uk OI Brander, Christian/0000-0002-0548-5778; Bishop, Karen/0000-0003-4935-7708; Matthews, Philippa/0000-0002-4036-4269; Ndung'u, Thumbi/0000-0003-2962-3992 FU Medical Research Council [G0501777, , G0500384]; NIAID NIH HHS [2R01AI46995-06, P30 AI027757, R01 AI046995]; PHS HHS [N01-A1-15422, R01A1067073]; Wellcome Trust NR 44 TC 110 Z9 110 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2008 VL 82 IS 17 BP 8548 EP 8559 DI 10.1128/JVI.00580-08 PG 12 WC Virology SC Virology GA 339UU UT WOS:000258603600030 PM 18596105 ER PT J AU Brumme, ZL Brumme, CJ Carlson, J Streeck, H John, M Eichbaum, Q Block, BL Baker, B Kadie, C Markowitz, M Jessen, H Kelleher, AD Rosenberg, E Kaldor, J Yuki, Y Carrington, M Allen, TM Mallal, S Altfeld, M Heckerman, D Walker, BD AF Brumme, Zabrina L. Brumme, Chanson J. Carlson, Jonathan Streeck, Hendrik John, Mina Eichbaum, Quentin Block, Brian L. Baker, Brett Kadie, Carl Markowitz, Martin Jessen, Heiko Kelleher, Anthony D. Rosenberg, Eric Kaldor, John Yuki, Yuko Carrington, Mary Allen, Todd M. Mallal, Simon Altfeld, Marcus Heckerman, David Walker, Bruce D. TI Marked epitope- and allele- specific differences in rates of mutation in human immunodeficiency type 1 (HIV-1) Gag, Pol, and Nef cytotoxic T-lymphocyte epitopes in acute/early HIV-1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; VIRUS TYPE-1; CELL RESPONSES; VIRAL LOAD; VACCINE DESIGN; P24 GAG; DISEASE PROGRESSION; ESCAPE MUTATIONS; IMMUNE-RESPONSES; POPULATION-LEVEL AB During acute human immunodeficiency virus type 1 (HIV-1) infection, early host cellular immune responses drive viral evolution. The rates and extent of these mutations, however, remain incompletely characterized. In a cohort of 98 individuals newly infected with HIV-1 subtype B, we longitudinally characterized the rates and extent of HLA-mediated escape and reversion in Gag, Pol, and Nef using a rational definition of HLA-attributable mutation based on the analysis of a large independent subtype B data set. We demonstrate rapid and dramatic HIV evolution in response to immune pressures that in general reflect established cytotoxic T-lymphocyte (CTL) response hierarchies in early infection. On a population level, HLA-driven evolution was observed in similar to 80% of published CTL epitopes. Five of the 10 most rapidly evolving epitopes were restricted by protective HLA alleles (HLA-B* 13/B* 51/B* 57/B* 5801; P = 0.01), supporting the importance of a strong early CTL response in HIV control. Consistent with known fitness costs of escape, B* 57-associated mutations in Gag were among the most rapidly reverting positions upon transmission to non-B* 57-expressing individuals, whereas many other HLA-associated polymorphisms displayed slow or negligible reversion. Overall, an estimated minimum of 30% of observed substitutions in Gag/Pol and 60% in Nef were attributable to HLA-associated escape and reversion events. Results underscore the dominant role of immune pressures in driving early within-host HIV evolution. Dramatic differences in escape and reversion rates across codons, genes, and HLA restrictions are observed, highlighting the complexity of viral adaptation to the host immune response. C1 [Brumme, Zabrina L.; Brumme, Chanson J.; Streeck, Hendrik; Eichbaum, Quentin; Block, Brian L.; Baker, Brett; Rosenberg, Eric; Allen, Todd M.; Altfeld, Marcus; Walker, Bruce D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Carlson, Jonathan; Kadie, Carl; Heckerman, David] Microsoft Res, Redmond, WA USA. [Carlson, Jonathan] Univ Washington, Dept Comp Sci, Seattle, WA 98195 USA. [John, Mina; Mallal, Simon] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. [John, Mina; Mallal, Simon] Murdoch Univ, Perth, WA, Australia. [Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Jessen, Heiko] Jessen Praxis, Berlin, Germany. [Kelleher, Anthony D.; Kaldor, John] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Yuki, Yuko; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Brumme, ZL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM zbrumme@partners.org RI Allen, Todd/F-5473-2011; Kaldor, John /D-4545-2011; OI Brumme, Chanson/0000-0003-2722-5288 FU Howard Hughes Medical Institute; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [R01AI50429, P30 AI060354, R01 AI050429, U01 AI052403, U01AI052403] NR 78 TC 127 Z9 131 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2008 VL 82 IS 18 BP 9216 EP 9227 DI 10.1128/JVI.01041-08 PG 12 WC Virology SC Virology GA 347OX UT WOS:000259152000026 PM 18614631 ER PT J AU Pittman, J Rawl, SM Schmidt, CM Grant, M Ko, CY Wendel, C Krouse, RS AF Pittman, Joyce Rawl, Susan M. Schmidt, C. Max Grant, Marcia Ko, Clifford Y. Wendel, Christopher Krouse, Robert S. TI Demographic and clinical factors related to ostomy complications and quality of life in veterans with an ostomy SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Article ID PERISTOMAL COMPLICATIONS; STOMA; COLOSTOMY; PATIENT; CARE AB PURPOSE: The purpose of this study is to describe demographic, clinical, and quality-of-life variables related to ostomy complications (skin irritation, leakage, and difficulty adjusting to an ostomy) in a veteran population in the United States. DESIGN: The original study employed a descriptive cross-sectional study using a mixed method design. This secondary analysis used the quantitative data collected. SAMPLE AND SETTING: Two hundred thirty-nine veterans with intestinal ostomies from 3 Veteran's Administration hospitals participated in the study. METHODS: Instruments used for this investigation included the City of Hope Quality of Life: Ostomy Instrument. Demographic and medical history data were collected from the survey, the Veteran's Administration health information system, and the Tumor Registry database. A self-administered survey questionnaire (mCOH-QOL-Ostomy) was mailed to each participant. RESULTS: The severity of skin irritation, problems with leakage, and difficulty adjusting were significantly related to demographic, clinical, and quality-of-life domains. Univariate analyses showed that age, income, employment, preoperative care (stoma site marking and education), having a partner, ostomy type, reason for ostomy, time since surgery, total quality-of-life scores and scores on all 4 domains of quality of life were related to the severity of these ostomy complications. Age was inversely related to severity of all 3 ostomy complications (skin irritation, leakage, and difficulty adjusting). Having an ileostomy, rather than a colostomy, was associated with higher severity of skin irritation. Having had the stoma site marked preoperatively was associated with less difficulty adjusting to an ostomy, and having had preoperative ostomy education was associated with less severe problems with skin irritation and leakage. Severity of each ostomy complication predicted total quality-of-life scores. Difficulty adjusting to the ostomy was related to all 4 quality-of-life domains (physical, psychological, social, and spiritual). CONCLUSIONS: This study found important relationships between demographic and clinical factors and ostomy complications. Skin problems, leakage, and difficulty adjusting predicted total quality of life scores and domains. Establishing relationships among ostomy complications and demographic, clinical factors, and quality of life can enhance identification of patients at risk for the development of complications and is an important first step in identifying the development of effective interventions to reduce the negative impact of complications for people with ostomies. Further study of predictors and outcomes of ostomy complications is needed to improve care. C1 [Pittman, Joyce; Rawl, Susan M.] Indiana Univ Purdue Univ, Sch Nursing, Indianapolis, IN 46202 USA. [Pittman, Joyce] Clarian Hlth Syst Methodist Hosp, Wound Ost Continence Team, Indianapolis, IN USA. [Schmidt, C. Max] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [Schmidt, C. Max] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. [Grant, Marcia] City Hope Natl Med Ctr & Beckman Res, Dept Nursing Res & Educ, Durante, CA USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Wendel, Christopher] So Arizona VA Healthcare Syst, Res Serv Line, Tucson, AZ USA. [Krouse, Robert S.] Univ Arizona, Tucson, AZ USA. RP Pittman, J (reprint author), Clarian Hlth Methodist, 1701 Senate Blvd,B250, Indianapolis, IN 46206 USA. EM jpittma3@clarian.org OI Rawl, Susan/0000-0003-2052-2853 FU Veterans Affairs Health Services Research and Development Service (HSRD) [IIR 02-221-2] FX This research was supported by a grant from the Veterans Affairs Health Services Research and Development Service (HSR&D) IIR 02-221-2: Health-Related Quality of Life in VA Patients with Intestinal Stomas. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 22 TC 75 Z9 80 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD SEP-OCT PY 2008 VL 35 IS 5 BP 493 EP 503 PG 11 WC Nursing SC Nursing GA 357FC UT WOS:000259830700006 PM 18794701 ER EF