FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Smumyy, Y Toms, AV Hickson, GR Eck, MJ Eggert, US AF Smumyy, Yegor Toms, Angela V. Hickson, Gilles R. Eck, Michael J. Eggert, Ulrike S. TI Binucleine 2, an lsoform-Specific Inhibitor of Drosophila Aurora B Kinase, Provides Insights into the Mechanism of Cytokinesis SO ACS CHEMICAL BIOLOGY LA English DT Article ID SMALL-MOLECULE INHIBITOR; CHEMICAL BIOLOGY; PHOSPHORYLATION; ACTIVATION; RESISTANCE; MUTATIONS; DISCOVERY; GROWTH; INCENP; POLES AB Aurora kinases are key regulators of cell division and important targets for cancer therapy. We report that Binuclelne 2 Is a highly isoform-specific Inhibitor of Drosophila Aurora B kinase, and we identify a single residue within the kinase active site that confers specificify for Aurora B. Using Binucleine 2, we show that Aurora B kinase activity is not required during. contractile ring Ingression, providing insight into the mechanism of cytokinesis. C1 [Smumyy, Yegor; Toms, Angela V.; Eck, Michael J.; Eggert, Ulrike S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Smumyy, Yegor; Toms, Angela V.; Eck, Michael J.; Eggert, Ulrike S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hickson, Gilles R.] Univ Montreal, St Justine Hosp Res Ctr, Montreal, PQ H3T 1C5, Canada. [Hickson, Gilles R.] Univ Montreal, Fac Med, Dept Pathol & Cell Biol, Montreal, PQ H3T 1J4, Canada. RP Eggert, US (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ulrike_eggert@dfci.harvard.edu FU National Institutes of Health [R01 CA080942, R0I GM082834]; Canadian Institutes of Health Research; Canadian Foundation for Innovation; Dana-Farber Cancer Institute. FX We thank the staff at the Nikon Imaging Center at Harvard Medical School for their assistance and Nathanael Gray, Ryoma Ohi, and Piotr Sliz for helpful discussions. We also thank Ryoma Ohi for the gift of Xenopus Aurora B kinase. A.V.T. and M.J.E. were supported by National Institutes of Health grant R01 CA080942. G.R.H. is a Leukemia & Lymphoma Society special fellow and a Fonds de la Recherche en Sante du Quebec junior I investigator and is supported by grants from the Canadian Institutes of Health Research and the Canadian Foundation for Innovation. Y.S. and U.E. were supported by NIH grant R01 GM082834 and the Dana-Farber Cancer Institute. NR 24 TC 1 Z9 1 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD NOV PY 2010 VL 5 IS 11 BP 1015 EP 1020 DI 10.1021/cb1001685 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 682YB UT WOS:000284437800003 ER PT J AU Hynes, BG Margey, R Moran, D Ruggiero, NJ Kiernan, TJ Jaff, MR AF Hynes, B. G. Margey, R. Moran, D. Ruggiero, N. J. Kiernan, T. J. Jaff, M. R. TI "The Challenge Facing Renal Artery Revascularization: What Have we Not Proven and Why we Must?" SO ACTA CHIRURGICA BELGICA LA English DT Review DE Renal artery; revascularization; stenting ID ATHEROSCLEROTIC RENOVASCULAR DISEASE; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; FRACTIONAL FLOW RESERVE; BLOOD-PRESSURE CONTROL; STENT PLACEMENT; HYPERTENSIVE PATIENTS; FOLLOW-UP; ISCHEMIC NEPHROPATHY; BALLOON ANGIOPLASTY; RANDOMIZED-TRIAL AB Endovascular renal artery stent therapy for atherosclerotic renal artery stenosis (RAS) is associated with excellent acute technical success, low complication rates and acceptable long-term patency. However, the clinical benefits to patients of renal artery stenting remain uncertain. To facilitate debate regarding the treatment of RAS, we need to understand the epidemiology, basic physiology and clinical consequences of renal artery stenosis. We must attempt to determine which patients are likely to benefit from renal artery stenting, assess the nuances of the percutaneous procedure and review the current literature pertaining to renal artery stenting. C1 [Jaff, M. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr,Div Cardiol,Sect Vasc Med, Boston, MA 02115 USA. [Moran, D.; Kiernan, T. J.] Univ Coll Cork Sch Med, Cork Univ Hosp, Dept Cardiol, Cork, Ireland. [Ruggiero, N. J.] Thomas Jefferson Hosp, Sect Intervent Cardiol, Philadelphia, PA USA. RP Jaff, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr,Div Cardiol,Sect Vasc Med, Boston, MA 02115 USA. EM mjaff@partners.org NR 102 TC 0 Z9 0 U1 0 U2 0 PU ACTA MEDICAL BELGICA PI BRUSSELS PA AVENUE CIRCULAIRE 138 A, B-1180 BRUSSELS, BELGIUM SN 0001-5458 J9 ACTA CHIR BELG JI Acta Chir. Belg. PD NOV-DEC PY 2010 VL 110 IS 6 BP 575 EP 583 PG 9 WC Surgery SC Surgery GA 719ER UT WOS:000287184100002 PM 21337836 ER PT J AU Lain, AH Lieberman, AP Pfannl, R Hedley-Whyte, ET AF Lain, Aurelio Hernandez Lieberman, Andrew P. Pfannl, Rolf Hedley-Whyte, E. Tessa TI Nodular bilateral amygdala degeneration in demented individuals SO ACTA NEUROPATHOLOGICA LA English DT Article DE Amygdala; Alzheimer disease; Neurodegeneration ID ALZHEIMERS-DISEASE; HIPPOCAMPAL-FORMATION; LIPOID PROTEINOSIS; RHESUS-MONKEY; EFFERENTS; ISCHEMIA; LESIONS; DAMAGE AB Among more than 2,050 brains in our Alzheimer disease brain banks, we came across three brains with well-demarcated indurated white-yellow nodules in the amygdalas. Microscopically, these nodules were composed of numerous lipid-laden macrophages located in the central region surrounded by an eosinophilic hyaline-like material with minimal reactive gliosis in the periphery. Neurons within these lesions had a normal appearance but were moderately decreased in number. Beta-amyloid, tau and alpha-synuclein immunostaining revealed no abnormal deposits within the nodules. The three patients had long histories of dementia (one linked to a presenilin-1 mutation). The neuropathological diagnoses were Alzheimer disease in two of them and an unclassified tauopathy with argyrophilic grains in the third. In conclusion, the pathogenesis of these lesions is uncertain. We favor that the degeneration has some relationship to the underlying dementing disease, either secondary to deafferentation or an alteration in metabolic demand, perhaps related to the bi-directional anatomical and functional connections that exist between the amygdala and the hippocampus or less likely as a primary event. C1 [Lain, Aurelio Hernandez; Hedley-Whyte, E. Tessa] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Lain, Aurelio Hernandez] Hosp Univ 12 Octubre, Dept Pathol Neuropathol, Madrid, Spain. [Lieberman, Andrew P.] Univ Michigan, Dept Pathol Neuropathol, Ann Arbor, MI 48109 USA. [Pfannl, Rolf] Tufts Univ, Sch Med, Dept Pathol, Tufts Med Ctr, Boston, MA 02111 USA. RP Hedley-Whyte, ET (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, WRN 325,55 Fruit St, Boston, MA 02114 USA. EM ehedleywhyte@partners.org FU National Institutes of Health [P50 AG005134, P50 AG08671]; Contrato Rio Hortega del Instituo Salud Carlos III FX This study was supported by Grant Nos. P50 AG005134 and P50 AG08671 from the National Institutes of Health and the Contrato Rio Hortega del Instituo Salud Carlos III. Case 2 was discussed at the Annual Diagnostic Slide Session of the Annual Meeting of the American Association of Neuropathologists in 2003. The authors declare that they have no conflicts of interest. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD NOV PY 2010 VL 120 IS 5 BP 683 EP 688 DI 10.1007/s00401-010-0745-3 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 665XU UT WOS:000283071800013 ER PT J AU Quintiliani, L Yang, M Sorensen, G AF Quintiliani, Lisa Yang, May Sorensen, Glorian TI A process evaluation of tobacco-related outcomes from a telephone and print-delivered intervention for motor freight workers SO ADDICTIVE BEHAVIORS LA English DT Article DE Smoking; Tobacco; Truck drivers; Blue-collar workers; Process evaluation ID SMOKING-CESSATION; HEALTH AB Interventions are needed to address the high prevalence of tobacco use among blue-collar, motor freight workers in the United States. In the present study, we conducted an evaluation of the Gear Up for Health study to evaluate which intervention components associated with this print- and telephone counseling-based tobacco intervention were associated with affecting psychosocial indicators of future quitting, number of quit attempts, and quitting tobacco. The sample is comprised of 64 baseline tobacco users. The intervention components evaluated were receipt of nicotine replacement therapy (NRT), aspects of the counseling calls, the targeted and tailored print materials, and goal setting. The results indicated that several intervention components were related to tobacco cessation, and less frequently related to psychosocial indicators (i.e. intention and self-efficacy) and quit attempts. A higher percentage of those who quit using tobacco, versus not quitting, thought the number of calls were just right (100% vs. 75%), received NRT (87% vs. 56%), read most or all of the materials (100% vs. 70%), found the materials to be very helpful (87% vs. 30%), set tobacco goals (93% vs. 58%) and met these goals (100% vs. 44%) (p <= 0.05 for all). These results may be used in planning future interventions and indicated that perceptions of materials, call number, and call content may be more important than absolute call number or duration. Thus, the number and duration of counseling calls may be flexible and determined in response to the needs of participants. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Quintiliani, Lisa; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02116 USA. [Quintiliani, Lisa; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Yang, May] New England Res Inst, St Watertown, MA 02472 USA. RP Quintiliani, L (reprint author), 801 Massachusetts Ave,2nd Floor,MISU, Boston, MA 02118 USA. EM lmquinti@bu.edu; MYang@neriscience.com; Glorian_sorensen@dfci.harvard.edu OI Quintiliani, Lisa/0000-0002-3328-6768 FU Centers for Disease Control and Prevention [5 R01 DP000099-01] FX Funding for this study was provided by grant 5 R01 DP000099-01 to Dr. Sorensen from the Centers for Disease Control and Prevention. The funding source had no additional role in the study. NR 14 TC 6 Z9 6 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD NOV PY 2010 VL 35 IS 11 BP 1036 EP 1039 DI 10.1016/j.addbeh.2010.06.003 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 646YN UT WOS:000281581700017 PM 20605073 ER PT J AU Henderson, C Jackson, C Slade, M Young, AS Strauss, JL AF Henderson, Claire Jackson, Carlos Slade, Mike Young, Alexander S. Strauss, Jennifer L. TI How Should we Implement Psychiatric Advance Directives? Views of Consumers, Caregivers, Mental Health Providers and Researchers SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Psychiatric advance directives; Consensus study; Implementation ID RANDOMIZED CONTROLLED-TRIAL; SERVICES; ILLNESS; CARE AB The aim of this study was to measure expert consensus on the implementation of Psychiatric Advance Directives (PADs) within the Veterans Health Administration. We conducted a two-round Delphi study with 55 panelists including consumers, caregivers, mental health providers and researchers. For a number of items where no positive or negative consensus was reached we found differences between the views of consumers and non-consumers, reflecting consumer's preferences for nonmedical settings for completion and assistance with completion independent of the treatment team. Thus, the principle of consumer choice that applies to MHAD content should also be applied to the process of completion offered. C1 [Henderson, Claire; Slade, Mike] Kings Coll London, Inst Psychiat, Hlth Serv, London SE5 8AF, England. [Henderson, Claire; Jackson, Carlos] James J Peters VA Med Ctr, Bronx, NY USA. [Young, Alexander S.] Greater Los Angeles VA, Los Angeles, CA USA. [Young, Alexander S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Strauss, Jennifer L.] Durham VA Med Ctr, Durham, NC USA. [Strauss, Jennifer L.] Duke Univ, Med Ctr, Durham, NC USA. [Henderson, Claire; Slade, Mike] Kings Coll London, Inst Psychiat, Populat Res Dept, London SE5 8AF, England. RP Henderson, C (reprint author), Kings Coll London, Inst Psychiat, Hlth Serv, P029,Crespigny Pk, London SE5 8AF, England. EM Claire.Henderson@iop.kcl.ac.uk RI Henderson, Claire/E-4664-2010; Slade, Mike/C-1641-2010; Young, Alexander/A-1523-2009 OI Henderson, Claire/0000-0002-6998-5659; Slade, Mike/0000-0001-7020-3434; Young, Alexander/0000-0002-9367-9213 NR 30 TC 14 Z9 14 U1 3 U2 7 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD NOV PY 2010 VL 37 IS 6 BP 447 EP 458 DI 10.1007/s10488-010-0264-5 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 711RW UT WOS:000286610100001 PM 20099077 ER PT J AU Fife, CE Yankowsky, KW Ayello, EA Capitulo, KL Fowler, E Krasner, DL Mulder, G Sibbald, RG AF Fife, Caroline E. Yankowsky, Kevin W. Ayello, Elizabeth A. Capitulo, Kathleen Leask Fowler, Evonne Krasner, Diane L. Mulder, Gerit Sibbald, R. Gary TI Legal Issues in the Care of Pressure Ulcer Patients: Key Concepts for Healthcare Providers-A Consensus Paper from the International Expert Wound Care Advisory Panel (c) SO ADVANCES IN SKIN & WOUND CARE LA English DT Article ID ELECTRONIC MEDICAL-RECORD; M SKIN CONDITIONS; LONG-TERM-CARE; BRADEN SCALE; RELIABILITY C1 [Fife, Caroline E.] Univ Texas Hlth Sci Ctr, Div Cardiol, Houston, TX USA. [Fife, Caroline E.] Mem Hermann Ctr Wound Healing, Houston, TX USA. [Yankowsky, Kevin W.] Fulbright & Jaworski LLP, Houston, TX USA. [Ayello, Elizabeth A.] John A Hartford Inst Geriatr Nursing, New York, NY USA. [Capitulo, Kathleen Leask] James J Peters VA Med Ctr, Bronx, NY USA. [Capitulo, Kathleen Leask] Case Western Univ, Cleveland, OH USA. [Capitulo, Kathleen Leask] Wenzhou Med Coll, Wenzhou, Peoples R China. [Fowler, Evonne] San Gorgonio Mem Hosp, Banning, CA USA. [Krasner, Diane L.] Rest Haven York, York, PA USA. [Mulder, Gerit] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Sibbald, R. Gary] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. RP Fife, CE (reprint author), Univ Texas Hlth Sci Ctr, Div Cardiol, Houston, TX USA. NR 35 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-7941 J9 ADV SKIN WOUND CARE JI Adv. Skin Wound Care PD NOV PY 2010 VL 23 IS 11 BP 493 EP + DI 10.1097/01.ASW.0000390494.20964.a5 PG 14 WC Dermatology; Nursing; Surgery SC Dermatology; Nursing; Surgery GA 832ZF UT WOS:000295849100003 PM 20975333 ER PT J AU Ho, CH Powell, HL Collins, JF Bauman, WA Spungen, AM AF Ho, Chester H. Powell, Heather L. Collins, Joseph F. Bauman, William A. Spungen, Ann M. TI Poor Nutrition Is a Relative Contraindication to Negative Pressure Wound Therapy for Pressure Ulcers: Preliminary Observations in Patients with Spinal Cord Injury SO ADVANCES IN SKIN & WOUND CARE LA English DT Article ID VACUUM-ASSISTED CLOSURE; PREVALENCE AB OBJECTIVE: To assess the efficacy of negative-pressure wound therapy (NPWT) for healing of pressure ulcers (PrUs) in individuals with spinal-cord injury (SCI). DESIGN: Multicenter, 28-day observational study. SETTING: Ten Veterans Affairs Medical Center SCI centers. PATIENTS: Eighty-six SCI inpatients with Stage III/IV pelvic PrUs. INTERVENTIONS: Standard wound care with NPWT versus standard wound care alone (NoNPWT). MAIN OUTCOME MEASURES: Change in wound surface area (WSA) using the Verg Videometer Measurement Documentation software. MAIN RESULTS: The proportion of patients demonstrating a decrease in WSA (healing subgroup) was not significantly different between the NPWT (n = 33) and NoNPWT (n = 53) groups (67% vs 70%, respectively). In the healing subgroup, there was no significant difference between the NPWT versus NoNPWT groups in WSA decrease (-43 +/- 22% vs -50% +/- 26%, not statistically significant). Similarly, in the nonhealing subgroup, there was no significant difference between NPWT and NoNPWT groups (31% +/- 26% vs 32% +/- 34%). In the NPWT group, the nonhealing subgroup (11/33) had significantly lower serum albumin levels than the healing subgroup (22/33) (2.9 +/- 0.4 vs 3.3 +/- 0.5 mg/dL, P < .05). In the NoNPWT group, there was no significant difference in serum albumin levels between the healing versus nonhealing subgroups (3.2 +/- 0.3 vs 3.2 +/- 0.3 mg/dL). CONCLUSION: In SCI patients with Stage III/IV pelvic PrUs, NPWT did not significantly influence the rate of healing. Additionally, in malnourished individuals (albumin <3.0 mg/dL), NPWT was not efficacious. Healing outcomes in the NPWT group were significantly influenced by albumin levels, whereas no such disparity was noted between the healing and nonhealing PrUs for the NoNPWT group. Nutritional status appears to be important in the effectiveness of NPWT. C1 [Ho, Chester H.; Powell, Heather L.] Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Cleveland, OH USA. [Ho, Chester H.; Powell, Heather L.] Case Western Reserve Univ, Dept Phys Med & Rehabil, Cleveland, OH 44106 USA. [Collins, Joseph F.] VA Med Ctr, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. [Bauman, William A.; Spungen, Ann M.] James J Peters VA Med Ctr, RR&D Ctr Excellence Med Consequences Spinal Cord, Bronx, NY USA. [Bauman, William A.; Spungen, Ann M.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, William A.; Spungen, Ann M.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. FU Department of Veterans Affairs, VA Office of Research and Development, Clinical Sciences Service [535]; SCI Service and Rehabilitation Research and Development Center of Excellence for the Medical Consequences of SCI, VA Medical Center, Bronx, New York [B4162C] FX Funding for this study was provided by the Department of Veterans Affairs, VA Office of Research and Development, Clinical Sciences Service, Cooperative Studies Program, CS #535; SCI Service and Rehabilitation Research and Development Center of Excellence for the Medical Consequences of SCI #B4162C, James J. Peters VA Medical Center, Bronx, New York. The authors acknowledge Dr William Krol, as well as the following participating sites and site investigators for their effort and participation in this project: Charlie Norwood VA Medical Center (Augusta, Georgia)-Rose C. Trincher, MD; James J. Peters VA Medical Center (Bronx, New York)-George A. Deitrick, MD; Louis Stokes VA Medical Center (Cleveland, Ohio)-Chester H. Ho, MD; VA North Texas Healthcare System: Dallas VA Medical Center-Lance L. Goetz, MD; Edward Hines Jr VA Hospital (Hines, Illinois)-Bernard A. Nemchausky, MD; Michael E. Debakey VA Medical Center (Houston, Texas)-Sally A. Holmes, MD; VA Palo Alto Health Care System (Palo Alto, California)-Roy Sasaki, MD; Hunter Holmes McGuire VA Medical Center (Richmond, Virginia)-Meena Midha, MD; James A. Haley Veterans' Hospital (Tampa, Florida)-John L. Merritt, MD; and VA Boston Healthcare System, West Roxbury Campus (Boston, Massachusetts)-Sunil Sabharwal, MD. NR 21 TC 11 Z9 13 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-7941 J9 ADV SKIN WOUND CARE JI Adv. Skin Wound Care PD NOV PY 2010 VL 23 IS 11 BP 508 EP 516 DI 10.1097/01.ASW.0000390493.43835.ec PG 9 WC Dermatology; Nursing; Surgery SC Dermatology; Nursing; Surgery GA 832ZF UT WOS:000295849100004 PM 20975334 ER PT J AU Crankshaw, T Corless, IB Giddy, J Nicholas, PK Eichbaum, Q Butler, LM AF Crankshaw, Tamaryn Corless, Inge B. Giddy, Janet Nicholas, Patrice K. Eichbaum, Quentin Butler, Lisa M. TI Exploring the Patterns of Use and the Feasibility of Using Cellular Phones for Clinic Appointment Reminders and Adherence Messages in an Antiretroviral Treatment Clinic, Durban, South Africa SO AIDS PATIENT CARE AND STDS LA English DT Article ID HIV; INTERNET; THERAPY AB In preparation for a proposed intervention at an antiretroviral therapy (ART) clinic in Durban, South Africa, we explored the dynamics and patterns of cellular phone use among this population, in order to ascertain whether clinic contact via patients' cellular phones was a feasible and acceptable modality for appointment reminders and adherence messages. Adults, who were more than 18 years old, ambulatory, and who presented for treatment at the clinic between October-December 2007, were consecutively recruited until the sample size was reached (n=300). A structured questionnaire was administered, including questions surrounding socio-demographics, cellular phone availability, patterns of use, and acceptability of clinic contact for the purpose of clinic appointment reminders and adherence support. Most respondents (n=242; 81%) reported current ownership of a cellular phone with 95% utilizing a prepaid airtime service. Those participants who currently owned a cellular phone reported high cellular phone turnover due to theft or loss (n=94, 39%) and/or damage (n=68, 28%). More females than men switched their cell phones off during the day (p-0.002) and were more likely to not take calls in certain social milieus (p <= 0.0001). Females were more likely to share their cell phone with others (p-0.002) or leave it in a place where someone could access it (p-0.005). Most respondents were willing to have clinic contact via their cellular phones, either verbally (99%) or via text messages (96%). The use of cellular phones for intervention purposes is feasible and should be further investigated. The findings highlight the value of gender-based analyses in informing interventions. C1 [Crankshaw, Tamaryn; Giddy, Janet] McCord Hosp, Durban, South Africa. [Corless, Inge B.; Nicholas, Patrice K.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Eichbaum, Quentin] Texas Tech Univ, Paul L Foster Sch Med, Hlth Sci Ctr, El Paso, TX USA. [Butler, Lisa M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Crankshaw, T (reprint author), McCord Hosp, POB 37587, ZA-4067 Overport, South Africa. EM tamaryn@mccord.co.za OI Corless, Inge/0000-0003-0438-2037 FU Maurice Webb Trust FX This study was carried out with financial support from the Maurice Webb Trust Fund. NR 13 TC 39 Z9 39 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD NOV PY 2010 VL 24 IS 11 BP 729 EP 734 DI 10.1089/apc.2010.0146 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 678RP UT WOS:000284098200007 PM 21039181 ER PT J AU Spiegel, BMR Bolus, R Harris, LA Lucak, S Chey, WD Sayuk, G Esrailian, E Lembo, A Karsan, H Tillisch, K Talley, J Chang, L AF Spiegel, B. M. R. Bolus, R. Harris, L. A. Lucak, S. Chey, W. D. Sayuk, G. Esrailian, E. Lembo, A. Karsan, H. Tillisch, K. Talley, J. Chang, L. TI Characterizing abdominal pain in IBS: guidance for study inclusion criteria, outcome measurement and clinical practice SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; QUALITY-OF-LIFE; VISCERAL SENSITIVITY INDEX; ILLNESS SEVERITY; END-POINTS; VALIDATION; TRIALS; QUESTIONNAIRE; DISORDERS; SYMPTOMS AB P>Background Although irritable bowel syndrome (IBS) is a multisymptom disorder, abdominal pain drives illness severity more than other symptoms. Despite consensus that IBS trials should measure pain to define study entry and determine efficacy, the optimal method of measuring pain remains uncertain. Aim To determine whether combining information from multiple pain dimensions may capture the IBS illness experience more effectively than the approach of measuring 'pain predominance' or pain intensity alone. Methods Irritable bowel syndrome patients rated dimensions of pain, including intensity, frequency, constancy, predominance, predictability, duration, speed of onset and relationship to bowel movements. We evaluated the impact of each dimension on illness severity using multivariable regression techniques. Results Among the pain dimensions, intensity, frequency, constancy and predictability were strongly and independently associated with illness severity; the other dimensions had weaker associations. The clinical definition of 'pain predominance', in which patients define pain as their most bothersome symptom, was insufficient to categorize patients by illness severity. Conclusions Irritable bowel disease pain is multifaceted; some pain dimensions drive illness more than others. IBS trials should measure various pain dimensions, including intensity, constancy, frequency and predictability; this may improve upon the customary use of measuring pain as a unidimensional symptom in IBS. C1 [Spiegel, B. M. R.; Talley, J.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Spiegel, B. M. R.; Bolus, R.; Esrailian, E.; Tillisch, K.; Chang, L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Spiegel, B. M. R.; Bolus, R.; Tillisch, K.; Chang, L.] Univ Calif Los Angeles, Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Spiegel, B. M. R.; Bolus, R.; Esrailian, E.; Talley, J.; Chang, L.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ CORE, Los Angeles, CA 90095 USA. [Harris, L. A.] Mayo Clin, Div Gastroenterol & Hepatol, Scottsdale, AZ USA. [Lucak, S.] Columbia Univ, Dept Gastroenterol, New York, NY USA. [Chey, W. D.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Sayuk, G.] Washington Univ, Dept Gastroenterol, St Louis, MO USA. [Lembo, A.] Harvard Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA USA. [Karsan, H.] Atlanta Gastroenterol Associates, Atlanta, GA USA. RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Prometheus; Rose Pharma A/G; Takeda; Shire Pharmaceuticals; U01 NIH/NIAMS [AR057936A]; NIH [P50 DK64539] FX Declaration of personal interests: The opinions and assertions contained herein are the sole views of the authors and are not to be construed as official or as reflecting the views of the Department of Veteran Affairs. The Principal Investigator, Dr Spiegel, maintained full control over all aspects of the study design, implementation, data collection, data analysis, data interpretation and manuscript preparation. Dr Spiegel had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Spiegel has served as a consultant and advisory board member for AstraZeneca, Ironwood, Prometheus, Takeda and Procter & Gamble, and has received research funding from Prometheus, Rose Pharma A/G, Takeda and Shire Pharmaceuticals. Declaration of funding interests: Drs Spiegel, Chang and Bolus are supported by U01 NIH/NIAMS AR057936A. Dr Chang is supported by NIH Grant No. P50 DK64539. This study was supported by an investigator-initiated research grant by Rose Pharma A/S. NR 34 TC 13 Z9 13 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD NOV 1 PY 2010 VL 32 IS 9 BP 1192 EP 1202 DI 10.1111/j.1365-2036.2010.04443.x PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 659MO UT WOS:000282570800016 PM 20807217 ER PT J AU Cernadas, JR Brockow, K Romano, A Aberer, W Torres, MJ Bircher, A Campi, P Sanz, ML Castells, M Demoly, P Pichler, WJ AF Cernadas, J. R. Brockow, K. Romano, A. Aberer, W. Torres, M. J. Bircher, A. Campi, P. Sanz, M. L. Castells, M. Demoly, P. Pichler, W. J. CA European Network Drug Allergy EAACI Interest Grp Drug TI General considerations on rapid desensitization for drug hypersensitivity - a consensus statement SO ALLERGY LA English DT Article DE desensitization; drug hypersensitivity; graded challenge; tolerance induction ID EXACERBATED RESPIRATORY-DISEASE; BETA-LACTAM ANTIBIOTICS; SUBCUTANEOUS INSULIN INFUSION; ASPIRIN DESENSITIZATION; ORAL DESENSITIZATION; CYSTIC-FIBROSIS; MAST-CELLS; TRIMETHOPRIM-SULFAMETHOXAZOLE; CARBOPLATIN HYPERSENSITIVITY; INTRAVENOUS DESENSITIZATION AB P>Drug hypersensitivity reactions can occur with most drugs, are unpredictable, may affect any organ or system, and range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. However, for certain patients, the particular drug may be essential for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance of a compound responsible for a hypersensitivity reaction. It is performed by administering increasing doses of the medication concerned over a short period of time (from several hours to a few days) until the total cumulative therapeutic dose is achieved and tolerated. It is a high-risk procedure used only in patients in whom alternatives are less effective or not available after a positive risk/benefit analysis. Desensitization protocols have been developed and are used in patients with allergic reactions to antibiotics (mainly penicillin), insulins, sulfonamides, chemotherapeutic and biologic agents, and many other drugs. Desensitization is mainly performed in IgE-mediated reactions, but also in reactions where drug-specific IgE have not been demonstrated. Desensitization induces a temporary tolerant state, which can only be maintained by continuous administration of the medication. Thus, for treatments like chemotherapy, which have an average interval of 4 weeks between cycles, the procedure must be repeated for every new course. In this paper, some background information on rapid desensitization procedures is provided. We define the drugs and drug reactions indicated for such procedures, describe the possible mechanism of action, and discuss the indications and contraindications. The data should serve as background information for a database (accessible via the EAACI-homepage) with standardized protocols for rapid desensitization for antibiotics, chemotherapeutic agents, monoclonal antibodies/fusion proteins, and other drugs. C1 [Cernadas, J. R.] Med Univ, Dept Allergy & Clin Immunol, Oporto, Portugal. [Brockow, K.] Tech Univ Munich, Div Environm Dermatol & Allergol, Helmholtz Zentrum Munchen TUM, Dept Dermatol & Allergol Biederstein, Munich, Germany. [Romano, A.] CI Columbus, Allergy Unit, Rome, Italy. [Romano, A.] IRCCS Oasi Maria SS, Troina, Italy. [Aberer, W.] Med Univ Graz, Dept Dermatol, Graz, Austria. [Torres, M. J.] Carlos Haya Hosp, Allergy Serv, Res Unit Allerg Dis, Malaga, Spain. [Bircher, A.] Univ Basel Hosp, Dept Dermatol, Allergy Unit, CH-4031 Basel, Switzerland. [Campi, P.] Azienda Sanit Firenze, Allergy Clin, Florence, Italy. [Sanz, M. L.] Univ Navarra, Univ Clin, Dept Allergol & Clin Immunol, E-31080 Pamplona, Spain. [Castells, M.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Castells, M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Demoly, P.] Univ Hosp Montpellier, Hop Arnaud Villeneuve, INSERM, U657, Montpellier, France. [Pichler, W. J.] Univ Bern, Inselspital, Clin Rheumatol & Clin Immunol Allergol, CH-3010 Bern, Switzerland. RP Cernadas, JR (reprint author), Med Univ HS Joao, Dept Allergy & Clin Immunol, Alameda Hernani Monteiro, P-4000 Oporto, Portugal. EM josefinacernadas@gmail.com OI Romano, Antonino/0000-0001-9742-9898 FU EAACI FX There is no conflict of interest for any member of the consensus group. The desensitization task force was financially supported by EAACI. NR 99 TC 88 Z9 90 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD NOV PY 2010 VL 65 IS 11 BP 1357 EP 1366 DI 10.1111/j.1398-9995.2010.02441.x PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 661AJ UT WOS:000282693900002 PM 20716314 ER PT J AU Vassallo, MF Banerji, A Rudders, SA Clark, S Camargo, CA AF Vassallo, M. F. Banerji, A. Rudders, S. A. Clark, S. Camargo, C. A., Jr. TI Season of birth and food-induced anaphylaxis in Boston SO ALLERGY LA English DT Editorial Material DE food-induced anaphylaxis; season of birth; ultraviolet light B; vitamin D C1 [Camargo, C. A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ccamargo@partners.org FU NIAID NIH HHS [T32 AI060548, T32 AI007512] NR 0 TC 20 Z9 20 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2010 VL 65 IS 11 BP 1492 EP 1493 DI 10.1111/j.1398-9995.2010.02384.x PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 661AJ UT WOS:000282693900025 PM 20456318 ER PT J AU Kim, MS Wang, TY Ou, FS Klein, AJ Hudson, PA Messenger, JC Masoudi, FA Rumsfeld, JS Ho, PM AF Kim, Michael S. Wang, Tracy Y. Ou, Fang-Shu Klein, Andrew J. Hudson, Paul A. Messenger, John C. Masoudi, Frederick A. Rumsfeld, John S. Ho, P. Michael TI Association of prior coronary artery bypass graft surgery with quality of care of patients with non-ST-segment elevation myocardial infarction: A report from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines SO AMERICAN HEART JOURNAL LA English DT Article ID RITA-3 RANDOMIZED-TRIAL; UNSTABLE ANGINA; FOLLOW-UP; GLYCOPROTEIN IIB/IIIA; NONINVASIVE STRATEGY; SURVIVAL; DISEASE; IMPROVEMENT AB Background The American College of Cardiology/American Health Association guidelines recommend both an early invasive strategy and administration of antiplatelet/anticoagulant therapy for high-risk patients in the absence of contraindications. Little is known about adherence to guideline recommendations in patients with prior coronary artery bypass graft (CABG) surgery presenting with non-ST-segment elevation myocardial infarction (NSTEMI). Methods We analyzed 47,557 patients with NSTEMI in the 2007-2008 National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines. Treatment patterns were compared between patients with and without prior CABG surgery. Multivariable regression with generalized estimating equations evaluated the association between prior CABG and in-hospital outcomes. Results In this study, 8,790 NSTEMI patients (18.5%) had a history of CABG surgery. Prior CABG surgery was associated with a significantly lower adjusted likelihood of early cardiac catheterization (adjusted odds ratio [OR] 0.88, 95% CI 0.83-0.92), higher rates of short-term clopidogrel use (adjusted OR 1.08, 95% CI 1.02-1.14), and comparable use of anticoagulant therapy (adjusted OR 0.96, 95% CI 0.88-1.04). Adjusted risks of bleeding and in-hospital mortality did not differ significantly between the 2 groups (adjusted ORs 1.00, 95% CI 0.92-1.11 and 0.99, 95% CI 0.87-1.11, respectively). Conclusions Patients with prior CABG surgery presenting with NSTEMI are often felt to be at high risk for adverse outcomes and therefore require aggressive treatment. Our study indicates that they are less likely to undergo guideline-recommended early cardiac catheterization but equally or more likely to receive guideline-recommended antiplatelet and anticoagulant therapy. This risk-treatment paradox, however, does not appear to negatively influence short-term clinical outcomes. (Am Heart J 2010;160:951-7.) C1 [Kim, Michael S.] Univ Washington, Med Ctr, Sch Med, Seattle, WA 98195 USA. [Wang, Tracy Y.; Ou, Fang-Shu] Duke Clin Res Inst, Durham, NC USA. [Klein, Andrew J.] John Cochran VA Med Ctr, St Louis, MO USA. [Hudson, Paul A.; Messenger, John C.] Univ Colorado Denver, Aurora, CO USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. [Rumsfeld, John S.; Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. RP Kim, MS (reprint author), Univ Washington, Med Ctr, Sch Med, 1959 NE Pacific St,Box 356116, Seattle, WA 98195 USA. EM mshkim@u.washington.edu NR 25 TC 9 Z9 10 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2010 VL 160 IS 5 BP 951 EP 957 DI 10.1016/j.ahj.2010.07.025 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 683FX UT WOS:000284458700025 PM 21095285 ER PT J AU McKeown, NM Troy, LM Jacques, PF Hoffmann, U O'Donnell, CJ Fox, CS AF McKeown, Nicola M. Troy, Lisa M. Jacques, Paul F. Hoffmann, Udo O'Donnell, Christopher J. Fox, Caroline S. TI Whole- and refined-grain intakes are differentially associated with abdominal visceral and subcutaneous adiposity in healthy adults the Framingham Heart Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID OVERWEIGHT LATINO ADOLESCENTS; FOOD FREQUENCY QUESTIONNAIRE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; METABOLIC SYNDROME; HYPOCALORIC DIET; OBESITY; FIBER; CONSUMPTION AB Background Observational studies have linked higher intakes of whole grains to lower abdominal adiposity however the association between whole and refined-grain intake and body fat compartments has yet to be reported Objective Different aspects of diet may be differentially related to body fat distribution The purpose of this study was to assess associations between whole- and refined grain intake and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) Design Cross sectional associations between whole and refined-grain intakes waist circumference measures and abdominal SAT and VAT volumes were examined in 2834 Framingham Heart Study participants (49 4% women age range 32-83 y) Dietary information was assessed with the use of a semiquantitative food frequency questionnaire Results Whole grain intake was inversely associated with SAT (2895 compared with 2552 cm(3) in the lowest compared with the highest quintile category P for trend < 0 001) and VAT (1883 compared with 1563 cm(3) P for trend < 0 001) after adjustment for age sex current smoking status total energy and alcohol intake In contrast, refined-grain intake was positively associated with SAT (2748 compared with 2934 cm(3) P for trend = 0 01) and VAT (1727 compared with 19'8 cm(3), P for trend < 0 001) in multivanable models When SAT and VAT were evaluated jointly the P value for SAT was attenuated (P = 0 28 for whole grains P = 0 60 for refined grams) whereas VAT remained associated with both whole grains (P < 0 001) and refined grains (P < 0 001) Conclusions Increasing whole grain Intake is associated with lower VAT in adults whereas higher intakes of refined grains are associated with higher VAT Further research is required to elicit the potential mechanisms whereby whole- and refined grain foods may influence body fat distribution Am J Clin Altar 2010 92 1165-71 C1 [McKeown, Nicola M.; Troy, Lisa M.; Jacques, Paul F.] Tufts Univ, Nutr Epidemiol Program, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Hoffmann, Udo; O'Donnell, Christopher J.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. RP McKeown, NM (reprint author), Tufts Univ, Nutr Epidemiol Program, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. FU USDA [58 1950 7 707]; Framingham Heart Study of the National Heart Lung and Blood Institute of the NIH [NO1 HC 25195]; General Mills Bell Institute of Health and Nutrition Minneapolis MN FX Supported by the USDA (agreement 58 1950 7 707) the Framingham Heart Study of the National Heart Lung and Blood Institute of the NIH (contract NO1 HC 25195) and by a research grant from General Mills Bell Institute of Health and Nutrition Minneapolis MN NR 28 TC 58 Z9 58 U1 2 U2 11 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2010 VL 92 IS 5 BP 1165 EP 1171 DI 10.3945/ajcn.2009.29106 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 677DJ UT WOS:000283969000021 PM 20881074 ER PT J AU Kang, JX AF Kang, Jing X. TI Differential effects of omega-6 and omega-3 fatty acids on telomere length SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter C1 [Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Charlestown, MA 02129 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, 149 13th St,Room 4433, Charlestown, MA 02129 USA. NR 9 TC 2 Z9 3 U1 1 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2010 VL 92 IS 5 BP 1276 EP 1277 DI 10.3945/ajcn.110.000463 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 677DJ UT WOS:000283969000038 PM 20844067 ER PT J AU Lawson, N Thompson, K Saunders, G Saiz, J Richardson, J Brown, D Ince, N Caldwell, M Pope, D AF Lawson, Nancy Thompson, Kim Saunders, Gabrielle Saiz, Jaya Richardson, Jeannette Brown, Deborah Ince, Naomi Caldwell, Marc Pope, Diana TI SOUND INTENSITY AND NOISE EVALUATION IN A CRITICAL CARE UNIT SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID ENVIRONMENTAL NOISE; SLEEP DISRUPTION; HOSPITAL WARDS; ICU; INTERVENTION; SETTINGS; NIGHT AB Background Sound levels in intensive care units can be high. Unfortunately, high levels of sound tend to result in poor sleep quality, which leads to slower healing, poorer immune response, and decreased cognitive function. Objectives To measure sound levels to which patients in intensive care units are typically exposed. Methods Peak sound pressure levels of alarms on medical devices set at different output levels were measured. Additionally, ambient sound pressure levels for durations of 10 to 24 hours were measured on 12 occasions in patients' rooms in the intensive care unit. Results Peak levels of equipment alarms measured inside a patient's room were high, and increased as the setting of the alarm level increased. The levels of these alarms when measured in an adjacent room did not increase with alarm output level. Mean sound levels inside the patient's room were generally less than 45 dB(A), but peak levels were often greater than 85 dB(C). Closing the door of the adjacent room did not decrease these peak levels. Peak and mean levels did not differ systematically during 24 hours of measurement. Conclusions High-intensity equipment alarms disturb patients' sleep but are critical in a medical emergency. However, nurses should not assume that raising the alarm output level will ensure that the alarm is audible from an adjacent room. Ambient noise measurements indicate high peak levels during both day and night. (American Journal of Critical Care. 2010; 19:e88-e99) C1 [Lawson, Nancy; Thompson, Kim; Saunders, Gabrielle; Brown, Deborah; Ince, Naomi] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. [Caldwell, Marc] Seattle VA Med Ctr, Seattle, WA USA. RP Saunders, G (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Gabrielle.saunders@va.gov FU Department of Veterans Affairs, Veterans Health Administration Rehabilitation Research and Development [4844C] FX This study was supported in part by grant 4844C from the Department of Veterans Affairs, Veterans Health Administration Rehabilitation Research and Development. NR 40 TC 25 Z9 26 U1 1 U2 9 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 NOV 1 PY 2010 VL 19 IS 6 BP E88 EP E99 DI 10.4037/ajcc2010180 PG 12 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 673LB UT WOS:000283662100003 PM 21041190 ER PT J AU Spiegel, BMR AF Spiegel, Brennan M. R. TI Treatment Strategies for Acid Reflux: EncomPASSing Practical Solutions for Primary Care SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID DISEASE; TRIALS AB Despite a steady diet of randomized controlled trials (RCTs) for over three decades, nearly all of our routine clinical decisions remain incompletely supported, or even totally unaddressed, by the burgeoning pile of RCT data. The biomedical literature tends to focus on explanatory RCTs that compare new agents with placebo; it is less common to find pragmatic clinical trials (PCTs) that test the risks, benefits, and costs of competing active therapies within the context of usual practice settings. In this issue of the American Journal of Gastroenterology, Moayeddi and colleagues report the results of the EncomPASS study-a novel PCT for the primary care management of reflux disease. In this editorial, the results of EncomPASS are discussed, and the study is highlighted as a model for investigators to follow as we continue to emphasize pragmatic trials that address everyday challenges in clinical care. C1 [Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu NR 9 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 NOV PY 2010 VL 105 IS 11 BP 2347 EP 2349 DI 10.1038/ajg.2010.378 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 674UM UT WOS:000283775600003 PM 21048680 ER PT J AU Kaplan, GG Hubbard, J Korzenik, J Sands, BE Panaccione, R Ghosh, S Wheeler, AJ Villeneuve, PJ AF Kaplan, Gilaad G. Hubbard, James Korzenik, Joshua Sands, Bruce E. Panaccione, Remo Ghosh, Subrata Wheeler, Amanda J. Villeneuve, Paul J. TI The Inflammatory Bowel Diseases and Ambient Air Pollution: A Novel Association SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CROHNS-DISEASE; DIESEL EXHAUST; PARTICLES; EXPOSURE; CHILDREN; HEALTH; RISK; MICE AB OBJECTIVES: The inflammatory bowel diseases (IBDs) emerged after industrialization. We studied whether ambient air pollution levels were associated with the incidence of IBD. METHODS: The health improvement network (THIN) database in the United Kingdom was used to identify incident cases of Crohn's disease (n=367) or ulcerative colitis (n=591), and age- and sex-matched controls. Conditional logistic regression analyses assessed whether IBD patients were more likely to live in areas of higher ambient concentrations of nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), and particulate matter <10 mu m (PM(10)), as determined by using quintiles of concentrations, after adjusting for smoking, socioeconomic status, non-steroidal anti-inflammatory drugs (NSAIDs), and appendectomy. Stratified analyses investigated effects by age. RESULTS: Overall, NO(2), SO(2), and PM(10) were not associated with the risk of IBD. However, individuals <= 23 years were more likely to be diagnosed with Crohn's disease if they lived in regions with NO(2) concentrations within the upper three quintiles (odds ratio (OR)=2.31; 95% confidence interval (CI)=1.25-4.28), after adjusting for confounders. Among these Crohn's disease patients, the adjusted OR increased linearly across quintile levels for NO(2) (P=0.02). Crohn's disease patients aged 44-57 years were less likely to live in regions of higher NO(2) (OR=0.56; 95% CI=0.33-0.95) and PM(10) (OR=0.48; 95% CI=0.29-0.80). Ulcerative colitis patients <= 25 years (OR=2.00; 95% CI=1.08-3.72) were more likely to live in regions of higher SO(2); however, a dose-response effect was not observed. CONCLUSIONS: On the whole, air pollution exposure was not associated with the incidence of IBD. However, residential exposures to SO(2) and NO(2) may increase the risk of early-onset ulcerative colitis and Crohn's disease, respectively. Future studies are needed to explore the age-specific effects of air pollution exposure on IBD risk. C1 [Kaplan, Gilaad G.] Univ Calgary, Teaching Res & Wellness Ctr, Div Gastroenterol, Dept Med, Calgary, AB T2N 4N1, Canada. [Kaplan, Gilaad G.] Univ Calgary, Teaching Res & Wellness Ctr, Div Gastroenterol, Dept Community Hlth Sci, Calgary, AB T2N 4N1, Canada. [Korzenik, Joshua; Sands, Bruce E.] Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Korzenik, Joshua; Sands, Bruce E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Korzenik, Joshua; Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Wheeler, Amanda J.] Air Hlth Sci Div, Ottawa, ON, Canada. [Villeneuve, Paul J.] Hlth Canada, Populat Studies Div, Ottawa, ON K1A 0L2, Canada. [Villeneuve, Paul J.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. RP Kaplan, GG (reprint author), Univ Calgary, Teaching Res & Wellness Ctr, Div Gastroenterol, Dept Med, 3280 Hosp Dr NW,6th Floor,Room 6D17, Calgary, AB T2N 4N1, Canada. EM ggkaplan@ucalgary.ca OI Wheeler, Amanda/0000-0001-9288-8163; Kaplan, Gilaad/0000-0003-2719-0556 FU Broad Foundation; CCFC Chair in IBD Research; Canadian Institute of Health Research; Alberta Heritage Foundation for Medical Research FX This work was supported by an operating grant from the Broad Medical Research Program of the Broad Foundation and from the CCFC Chair in IBD Research. G.G.K. is supported through a New Investigator Award from the Canadian Institute of Health Research and a Population Health Investigator Award from the Alberta Heritage Foundation for Medical Research. NR 32 TC 45 Z9 46 U1 2 U2 9 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 NOV PY 2010 VL 105 IS 11 BP 2412 EP 2419 DI 10.1038/ajg.2010.252 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 674UM UT WOS:000283775600012 PM 20588264 ER PT J AU Blacker, D AF Blacker, Deborah TI Beyond the Dawning of the Age of Biomarkers SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material ID PITTSBURGH COMPOUND-B; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; ASSOCIATION; PREDICTION; DIAGNOSIS; BETA; NUN C1 [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Blacker, D (reprint author), Mass Gen Hosp E, 149 13th St,149-2691, Charlestown, MA 02129 USA. EM blacker@psych.mgh.harvard.edu NR 31 TC 2 Z9 2 U1 0 U2 3 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 NOV PY 2010 VL 18 IS 11 BP 955 EP 958 DI 10.1097/JGP.0b013e3181f52877 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 669DM UT WOS:000283326600001 PM 20808152 ER PT J AU Kvale, EA Woodby, L Williams, BR AF Kvale, Elizabeth A. Woodby, Lesa Williams, Beverly Rosa TI The Experience of Older Patients With Cancer in Phase 1 Clinical Trials: A Qualitative Case Series SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE aging; cancer psychosocial aspects; hope; illness and disease experiences; older people; pain; research participation; social support; symptom management ID RANDOMIZED CONTROLLED-TRIAL; OF-LIFE; I TRIALS; BODY-IMAGE; HOPE; PARTICIPATION; PERCEPTIONS; CHEMOTHERAPY; EXPECTATIONS; PERSPECTIVE AB This article explores the experiences of older patients with cancer in phase 1 clinical trials. Conducting a case series of face-to-face, in-depth, open-ended interviews and using qualitative methods of analysis, we find that the psychosocial process of social comparison is relevant for understanding older adults' phase 1 clinical trial participation. Social comparison influences decisions to enroll in a phase 1 clinical trial, shapes perceptions of supportive care needs, and encourages the utilization of hope. Additional research should develop strategies for addressing supportive care needs among this patient cohort whose use of social comparison can inhibit articulation of pain, suffering, and symptom burden as well as use of informal support systems. C1 [Kvale, Elizabeth A.; Woodby, Lesa; Williams, Beverly Rosa] Birmingham Atlanta Geriatr Res Educ & Clin Ctr GR, Birmingham, AL USA. [Kvale, Elizabeth A.; Woodby, Lesa; Williams, Beverly Rosa] Birmingham VA Med Ctr, Birmingham, AL USA. [Kvale, Elizabeth A.; Woodby, Lesa; Williams, Beverly Rosa] Univ Alabama, Ctr Aging, Birmingham, AL USA. [Kvale, Elizabeth A.; Woodby, Lesa; Williams, Beverly Rosa] Univ Alabama, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. RP Kvale, EA (reprint author), CH19 Room 219R, Birmingham, AL 35205 USA. EM ekvale@aging.uab.edu NR 61 TC 1 Z9 1 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD NOV PY 2010 VL 27 IS 7 BP 474 EP 481 DI 10.1177/1049909110365072 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 669BV UT WOS:000283322300007 PM 20388935 ER PT J AU O'Seaghdha, CM Hwang, SJ Upadhyay, A Meigs, JB Fox, CS AF O'Seaghdha, Conall M. Hwang, Shih-Jen Upadhyay, Ashish Meigs, James B. Fox, Caroline S. TI Predictors of Incident Albuminuria in the Framingham Offspring Cohort SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Microalbuminuria; albuminuria; proteinuria ID CARDIOVASCULAR RISK-FACTORS; GLYCOSYLATION END-PRODUCTS; TYPE-2 DIABETIC-PATIENTS; CHRONIC KIDNEY-DISEASE; URINARY ALBUMIN; GENERAL-POPULATION; NONDIABETIC POPULATION; INSULIN-RESISTANCE; METABOLIC SYNDROME; CIGARETTE-SMOKING AB Background: Predictors for incident albuminuria are not well known in population-based cohorts. The purpose of this study is to identify predictors of incident albuminuria in an unselected middle-aged population. Study Design: Observational cohort study. Setting & Participants: Framingham Offspring Study participants who attended both the sixth (baseline; 1995-1998) and eighth (2005-2008) examination cycles. Predictors: Standard clinical predictors were used. Predictors of incident albuminuria were identified using stepwise logistic regression analysis with age and sex forced into the model. Outcomes & Measurements: Albuminuria was defined as urine albumin-creatinine ratio (UACR) >= 17 mg/g (men) or >= 25 mg/g (women). Individuals with albuminuria at baseline were excluded. Results: 1,916 participants were available for analysis (mean age, 56 years; 54% women). Albuminuria developed in 10.0% of participants (n = 192) during 9.5 years. Age (OR, 2.09; P < 0.001), baseline diabetes (OR, 1.93; P = 0.01), smoking (OR, 2.09; P < 0.001), and baseline log UACR (OR per 1-SD increase in log UACR, 1.56; P < 0.001) were associated with incident albuminuria in a stepwise model. An inverse relationship with female sex (OR, 0.53; P < 0.001) and high-density lipoprotein (HDL) cholesterol level (OR, 0.80; P = 0.007) also was observed. Results were similar when participants with baseline chronic kidney disease (n = 102), defined as estimated glomerular filtration rate < 60 mL/min/1.73m(2), were excluded from the model. Age, male sex, low HDL cholesterol level, smoking, and log UACR continued to be associated with incident albuminuria when baseline diabetes (n = 107) was excluded. Age, male sex, and log UACR correlated with incident albuminuria after participants with baseline hypertension were excluded (n = 651). Limitations: Causality may not be inferred because of the observational nature of the study. One-third of participants did not return for follow-up, potentially attenuating the observed risks of albuminuria. Conclusions: The known cardiovascular risk factors of increasing age, male sex, diabetes, smoking, low HDL cholesterol level, and albuminuria within the reference range are correlates of incident albuminuria in the general population. Am J Kidney Dis 56: 852-860. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Upadhyay, Ashish] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Upadhyay, Ashish] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Upadhyay, Ashish/0000-0002-0536-5776 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; American Diabetes Association FX Support: The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). Dr Meigs is supported by Career Development Awards from the American Diabetes Association Research Grant and the American Diabetes Association. Urinary albumin excretion assay reagents were donated by Roche Diagnostics Inc. NR 56 TC 30 Z9 31 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 NOV PY 2010 VL 56 IS 5 BP 852 EP 860 DI 10.1053/j.ajkd.2010.04.013 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 668IL UT WOS:000283261700012 PM 20599306 ER PT J AU Choi, A Scherzer, R Bacchetti, P Tien, PC Saag, MS Gibert, CL Szczech, LA Grunfeld, C Shlipak, MG AF Choi, Andy Scherzer, Rebecca Bacchetti, Peter Tien, Phyllis C. Saag, Michael S. Gibert, Cynthia L. Szczech, Lynda A. Grunfeld, Carl Shlipak, Michael G. TI Cystatin C, Albuminuria, and 5-Year All-Cause Mortality in HIV-Infected Persons SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Kidney disease; mortality; human immunodeficiency virus (HIV) infection ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR EVENTS; SERUM CREATININE; ELDERLY PERSONS; RISK; OUTCOMES; DEATH AB Background: Compared with controls, human immunodeficiency virus (HIV)-infected persons have a greater prevalence of kidney disease, assessed according to high cystatin C level and albuminuria, but not according to creatinine level. However, the clinical importance of increased cystatin C level and albuminuria in the HIV-infected population has not been studied. Study Design: We conducted an observational cohort study to determine the association of kidney disease (measured according to albuminuria, cystatin C, and serum creatinine) with mortality. Setting & Participants: 922 HIV-infected persons enrolled in the FRAM (Fat Redistribution and Metabolic Change in HIV Infection) Study. Predictor: Serum cystatin C and serum creatinine levels were used to estimate glomerular filtration rates (eGFR(SCysC) and eGFR(SCr), respectively). Albuminuria was defined as a positive urine dipstick result (>= 1+) or urine albumin-creatinine ratio >30 mg/g. Outcome: 5-Year mortality. Results: At baseline, decreased kidney function (eGFR(SCysC) <60 mL/min/1.73 m(2)) or albuminuria was present in 28% of participants. After 5 years of follow-up, mortality was 48% in those with both eGFR(SCysC) <60 mL/min/1.73 m(2) and albuminuria, 23% in those with eGFR(SCysC) <60 mL/min/1.73 m(2) alone, 20% in those with albuminuria alone, and 9% in those with neither condition. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, and inflammatory marker levels, eGFR(SCysC) <60 mL/min/1.73 m(2) and albuminuria were associated with a nearly 2-fold increase in mortality, whereas eGFR(SCr) <60 mL/min/1.73 m(2) did not appear to have a substantial association with mortality. Together, eGFR(SCysC) <60 mL/min/1.73 m(2) and albuminuria accounted for 17% of the population-level attributable risk of mortality. Limitations: Vital status was unknown in 261 participants from the original cohort. Conclusions: Kidney disease marked by albuminuria or increased cystatin C level appears to be an important risk factor for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on serum creatinine to estimate kidney function in clinical practice. Am J Kidney Dis 56: 872-882. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Grunfeld, Carl] Univ Calif San Francisco, FRAM Study, Off Principal Investigator, Vet Affairs Med Ctr,Metab Sect 111F, San Francisco, CA 94121 USA. [Choi, Andy; Scherzer, Rebecca; Tien, Phyllis C.; Grunfeld, Carl; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Saag, Michael S.] Univ Alabama, Birmingham, AL USA. [Gibert, Cynthia L.] DC VA Med Ctr, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Washington, DC USA. [Szczech, Lynda A.] Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA. RP Grunfeld, C (reprint author), Univ Calif San Francisco, FRAM Study, Off Principal Investigator, Vet Affairs Med Ctr,Metab Sect 111F, 4150 Clement St, San Francisco, CA 94121 USA. EM carl.grunfeld@ucsf.edu FU National Institutes of Health (NIH) [R01 DK57508, R01 HL74814, R01 HL53359, K23 AI66943, K23 DK080645-01A1]; NIH center [P30 AI027767, M01 RR00036, M01 RR00051, M01 RR00052, M01 RR00054, M01 RR00083, M01 RR0636, M01 RR00865, KL2 RR024130, UL1 RR024131] FX Support: This study was supported by National Institutes of Health (NIH) grants R01 DK57508, R01 HL74814, R01 HL53359, K23 AI66943, and K23 DK080645-01A1 and NIH center grants P30 AI027767, M01 RR00036, M01 RR00051, M01 RR00052, M01 RR00054, M01 RR00083, M01 RR0636, M01 RR00865, KL2 RR024130, and UL1 RR024131. The funding agency had no role in the conduct of the study, collection of the data, management of the study, analysis of data, interpretation of the data, or preparation of the manuscript. A representative of the funding agent participated in planning the protocol. NR 45 TC 57 Z9 58 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2010 VL 56 IS 5 BP 872 EP 882 DI 10.1053/j.ajkd.2010.05.019 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 668IL UT WOS:000283261700014 PM 20709438 ER PT J AU Fortney, JC Pyne, JM Steven, CA Williams, JS Hedrick, RG Lunsford, AK Raney, WN Ackerman, BA Ducker, LO Bonner, LM Smith, JL AF Fortney, John C. Pyne, Jeffrey M. Steven, Christopher A. Williams, J. Silas Hedrick, Richard G. Lunsford, Amanda K. Raney, William N. Ackerman, Betty A. Ducker, Loretta O. Bonner, Laura M. Smith, Jeffrey L. TI A Web-Based Clinical Decision Support System for Depression Care Management SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL AB Objective: To inform the design of future informatics systems that support the chronic care model. Study Design: We describe the development and functionality of a decision support system for the chronic care model of depression treatment, known as collaborative care. Dissemination of evidence-based collaborative care models has been slow, and fidelity to the evidence base has been poor during implementation initiatives. Implementation could be facilitated by a decision support system for depression care managers, the cornerstone of the collaborative care model. The Net Decision Support System (https://www.netdss.net/) is a free Web-based system that was developed to support depression care manager activities and to facilitate the dissemination of collaborative care models that maintain high fidelity to the evidence base. Methods: The NetDSS was based on intervention materials used for a randomized trial of depression care management that improved clinical outcomes compared with usual care. The NetDSS was developed jointly by a cross-functional design team of psychiatrists, depression care managers, information technology specialists, technical writers, and researchers. Results: The NetDSS has the following functional capabilities: patient registry, patient encounter scheduler, trial management, clinical decision support, progress note generator, and workload and outcomes report generator. The NetDSS guides the care manager through a self-documenting patient encounter using evidence-based scripts and self-scoring instruments. The NetDSS has been used to provide evidence-based depression care management to more than 1700 primary care patients. Conclusion: Intervention protocols can be successfully converted to Web-based decision support systems that facilitate the implementation of evidence-based chronic care models into routine care with high fidelity. (Am J Manag Care. 2070;76(17):849-854) C1 [Fortney, John C.; Pyne, Jeffrey M.; Steven, Christopher A.; Hedrick, Richard G.; Ducker, Loretta O.; Smith, Jeffrey L.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Fortney, John C.; Pyne, Jeffrey M.; Williams, J. Silas; Lunsford, Amanda K.; Raney, William N.; Ackerman, Betty A.; Smith, Jeffrey L.] Cent Arkansas Vet Healthcare Syst, HSR&D Ctr Mental Hlth & Outcomes Res, N Little Rock, AR USA. [Bonner, Laura M.] VA Puget Sound Healthcare Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA USA. RP Fortney, JC (reprint author), Univ Arkansas Med Sci, Dept Psychiat, 4301 W Markham St, Little Rock, AR 72205 USA. EM fortneyjohnc@uams.edu FU Department of Veterans Affairs [IMV 04-360, IIR 00-078-3, MNT 05-152, MHS-03-218, MNH 98-000]; National Institute of Mental Health [R01 MH076908-01]; Department of Psychiatry, University of Arkansas for Medical Sciences FX This study was funded by grants IMV 04-360, IIR 00-078-3, MNT 05-152, MHS-03-218, and MNH 98-000 from the Department of Veterans Affairs; by grant R01 MH076908-01 from the National Institute of Mental Health; and by a pilot grant from the Department of Psychiatry, University of Arkansas for Medical Sciences. NR 18 TC 10 Z9 11 U1 2 U2 7 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2010 VL 16 IS 11 BP 849 EP 854 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 689GL UT WOS:000284915400005 PM 21348556 ER PT J AU Lin, HW Lister, MT Deschler, DG AF Lin, Harrison W. Lister, Matthew T. Deschler, Daniel G. TI Cystic masses of the supraclavicular fossa: clinical features and diagnostic strategies SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID LATERAL CERVICAL CYSTS; NEEDLE-ASPIRATION; NECK; CARCINOMA; HEAD; LYMPHADENITIS; METASTASES AB Purpose: Cystic masses of the supraclavicular fossa (SCF) are uncommon. The diverse anatomical structures within the SCF create an extended differential diagnosis for any mass arising in the SCF. This study describes the presenting symptoms, radiologic findings, medical and surgical management, and posttreatment outcomes of various cystic mass presenting in the SCF. A review of the literature and diagnostic and therapeutic algorithms are also provided. Methods: A retrospective study of an academic tertiary care head and neck cancer center was done. Seven cases of treated cystic masses of the SCF were identified. Diagnostic and therapeutic interventions are described. Results: Cross-sectional imaging and needle aspiration or biopsy were obtained in all 7 cases. Aspirates accurately differentiated benign from malignant lesions in 6 cases, identified the offending pathology in 3 cases, and provided inoculum for culture-directed antibiotic therapy in 1 case. Surgical intervention was used for definitive therapy in 6 cases. All patients achieved complete resolution of signs and symptoms of the mass. Conclusions: Effective evaluation of a cystic lesion within the SCF mandates a thorough understanding of the anatomy and differential diagnosis. A well-defined algorithm allows successful management of benign and malignant lesions in the SCF. (C) 2010 Elsevier Inc. All rights reserved. C1 [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. EM harrison_lin@meei.harvard.edu NR 23 TC 1 Z9 1 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 2010 VL 31 IS 6 BP 435 EP 441 DI 10.1016/j.amjoto.2009.08.008 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 677GS UT WOS:000283977700007 PM 20015800 ER PT J AU Otsuka, H Arimura, N Sonoda, S Nakamura, M Hashiguchi, T Maruyama, I Nakao, S Hafezi-Moghadam, A Sakamoto, T AF Otsuka, Hiroki Arimura, Noboru Sonoda, Shozo Nakamura, Makoto Hashiguchi, Teruto Maruyama, Ikuro Nakao, Shintaro Hafezi-Moghadam, Ali Sakamoto, Taiji TI Stromal Cell-Derived Factor-1 Is Essential for Photoreceptor Cell Protection in Retinal Detachment SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; FIBRILLARY ACIDIC PROTEIN; ENDOTHELIAL GROWTH-FACTOR; UP-REGULATION; EXPERIMENTAL-MODEL; CYTOKINE FAMILY; VITREOUS LEVELS; CROSS-TALK; EXPRESSION; DEGENERATION AB Stromal cell-derived factor-1 (SDF-1) causes chemotaxis of CXCR4-expressing bone marrow-derived cells. SDF-1 is involved in the pathogenesis of various vascular diseases, including those of the eye. However, the role of SDF-1 in neuronal diseases is not completely understood. Here, we show higher SDF-1 levels in the vitreous humor of patients with retinal detachment (RD) compared with normal patients. SDF-1 correlated positively with the duration as well as the extent of RD. Furthermore, SDF-1 correlated significantly with levels of interleukin-6 and interleukin-8, but not with vascular endothelial growth factor. Western blot analysis results showed significant SDF-1 up-regulation in detached rat retinas compared with normal animals Immunohistochemistry data showed that SDF-1 was co-localized with the glial cells of the detached retina. SDF-1 blockade with a neutralizing antibody increased photoreceptor cell loss and macrophage accumulation in the subretinal space. The retinal precursor cell line R28 expressed CXCR4. SDF-1 rescued serum starvation-induced apoptosis in R28 cells and enhanced their ability to participate in wound closure in a scratch assay. Our results indicate a surprising, protective role for SDF-1 in RD. This effect may be mediated directly or indirectly through other cell types. (Am J Pathol 2010, 177:2268-2277 DOI: 10.2353/ajpath.2010.100134) C1 [Otsuka, Hiroki; Arimura, Noboru; Sonoda, Shozo; Sakamoto, Taiji] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Ophthalmol, Kagoshima 8908520, Japan. [Hashiguchi, Teruto; Maruyama, Ikuro] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Lab & Vasc Med, Kagoshima 8908520, Japan. [Nakamura, Makoto] Kobe Univ, Div Ophthalmol, Dept Surg, Grad Sch Med, Kobe, Hyogo 657, Japan. [Nakao, Shintaro; Hafezi-Moghadam, Ali] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab,Dept Ophthalmol, Boston, MA USA. RP Sakamoto, T (reprint author), Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Ophthalmol, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan. EM tsakamot@m3.kufm.kagoshirna-u.ac.jp OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU Ministry of Education, Science, and Culture of the Japanese Government [20390450] FX Supported in part by a grant from the Research Committee on Chorioretinal Degeneration and Optic Atrophy, Ministry of Health, Labor, and Welfare (T.S.), and by a Grant-in-Aid for Scientific Research (number 20390450) from the Ministry of Education, Science, and Culture of the Japanese Government. NR 42 TC 23 Z9 24 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2010 VL 177 IS 5 BP 2268 EP 2277 DI 10.2353/ajpath.2010.100134 PG 10 WC Pathology SC Pathology GA 679TE UT WOS:000284182900015 PM 20889568 ER PT J AU Jurkunas, UV Bitar, MS Funaki, T Azizi, B AF Jurkunas, Ula V. Bitar, Maya S. Funaki, Toshinari Azizi, Behrooz TI Evidence of Oxidative Stress in the Pathogenesis of Fuchs Endothelial Corneal Dystrophy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ANTIOXIDANT RESPONSIVE ELEMENT; MITOCHONDRIAL-DNA DAMAGE; PARKINSONS-DISEASE; EPITHELIAL-CELLS; NEURODEGENERATIVE DISEASES; TRANSCRIPTION FACTOR; HUMAN BRAIN; NRF2; EXPRESSION; ACTIVATION AB Fuchs endothelial corneal dystrophy (FECD) is a progressive, blinding disease characterized by corneal endothelial (CE) cell apoptosis. Corneal transplantation is the only measure currently available to restore vision in these patients. Despite the identification of some genetic factors, the pathophysiology of FECD remains unclear. In this study, we observed a decrease in the antioxidant response element-driven antioxidants in FECD corneal endothelium. We further demonstrated that nuclear factor erythroid 2-related factor 2, a transcription factor known to bind the antioxidant response element and activate antioxidant defense, is down-regulated in FECD endothelium. Importantly, we detected significantly higher levels of oxidative DNA damage and apoptosis in FECD endothelium compared with normal controls and pseudophakic bullous keratopathy (iatrogenic CE cell loss) specimens. A marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, colocalized to mitochondria, indicating that the mitochondrial genome is the specific target of oxidative stress in FECD. Oxidative DNA damage was not detected in pseudophakic bullous keratopathy corneas, whereas it colocalized with terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling-positive cells in FECD samples. Ex vivo, oxidative stress caused characteristic morphological changes and apoptosis of CE, suggestive of findings that characterize FECD in vivo. Together, these data suggest that suboptimal nuclear factor erythroid 2-related factor 2-regulated defenses may account for oxidant-antioxidant imbalance in FECD, which in turn leads to oxidative DNA damage and apoptosis. This study provides evidence that oxidative stress plays a key role in FECD pathogenesis. (Ant J Pathol 2010, 177:2278-2289; DOI: 10.2353/ajpath.2010.100279) C1 [Jurkunas, Ula V.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Jurkunas, Ula V.; Bitar, Maya S.; Funaki, Toshinari; Azizi, Behrooz] Schepens Eye Res Inst, Boston, MA USA. [Jurkunas, Ula V.; Bitar, Maya S.; Funaki, Toshinari; Azizi, Behrooz] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Jurkunas, UV (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM ula_jurkunas@meei.harvard.edu FU NEI [K12 EY016335]; National Institute of Health [RO1 EY020581] FX Supported by NEI K12 EY016335 (U.V.J.) and RO1 EY020581 from National Institute of Health. NR 55 TC 77 Z9 77 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2010 VL 177 IS 5 BP 2278 EP 2289 DI 10.2353/ajpath.2010.100279 PG 12 WC Pathology SC Pathology GA 679TE UT WOS:000284182900016 PM 20847286 ER PT J AU Tantiwong, P Shanmugasundaram, K Monroy, A Ghosh, S Li, MY DeFronzo, RA Cersosimo, E Sriwijitkamol, A Mohan, S Musi, N AF Tantiwong, Puntip Shanmugasundaram, Karthigayan Monroy, Adriana Ghosh, Sangeeta Li, Mengyao DeFronzo, Ralph A. Cersosimo, Eugenio Sriwijitkamol, Apiradee Mohan, Sumathy Musi, Nicolas TI NF-kappa B activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE nuclear factor-kappa B; skeletal muscle; monocyte chemotactic protein-1; interleukin-6 ID INDUCED INSULIN-RESISTANCE; SKELETAL-MUSCLE; GLUCOSE; PATHWAY AB Tantiwong P, Shanmugasundaram K, Monroy A, Ghosh S, Li M, DeFronzo RA, Cersosimo E, Sriwijitkamol A, Mohan S, Musi N. NF-kappa B activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions. Am J Physiol Endocrinol Metab 299: E794-E801, 2010. First published August 24, 2010; doi: 10.1152/ajpendo.00776.2009.-NF-kappa B is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-kappa B activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-kappa B activity in muscle. The effect that exercise has on NF-kappa B activity/signaling also is not clear. We measured NF-kappa B DNA-binding activity and the mRNA level of putative NF-kappa B-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-kappa B activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-kappa B activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-kappa B activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-kappa B activity in muscle. Acute exercise stimulates NF-kappa B in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-kappa B activity, which could be explained by the already elevated NF-kappa B activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-kappa B activity, suggesting that other factors promote gene expression of these cytokines during exercise. C1 [Musi, Nicolas] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. [Tantiwong, Puntip; Monroy, Adriana; Ghosh, Sangeeta; Li, Mengyao; DeFronzo, Ralph A.; Cersosimo, Eugenio; Sriwijitkamol, Apiradee; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Texas Diabet Inst, San Antonio, TX 78229 USA. [Shanmugasundaram, Karthigayan; Mohan, Sumathy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Ctr Healthy Aging, San Antonio, TX 78229 USA. RP Musi, N (reprint author), S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. FU American Diabetes Association; National Institutes of Health [AG-030979, DK-80157, DK-24092, CA-112175]; San Antonio Nathan Shock Center; UTHSCSA Executive Research Committee; South Texas Health Research Center; US Department of Veterans Affairs; Faculty of Medicine Siriraj Hospital Mahidol University of Thailand; Endocrine Fellows Foundation; Thai Ministry of Public Health and Maharat Nakhon Ratchasima Hospital; [T32-HL-04776] FX This study was supported by grants from the American Diabetes Association (N. Musi, E. Cersosimo, and R. A. DeFronzo), the National Institutes of Health (AG-030979 and DK-80157 to N. Musi, DK-24092 to R. A. DeFronzo, and CA-112175 to S. Mohan), the San Antonio Nathan Shock Center (N. Musi), the UTHSCSA Executive Research Committee (N. Musi), the South Texas Health Research Center (N. Musi), the US Department of Veterans Affairs (R. A. DeFronzo), the Faculty of Medicine Siriraj Hospital Mahidol University of Thailand (A. Sriwijitkamol), the Endocrine Fellows Foundation (A. Sriwijitkamol), and the Thai Ministry of Public Health and Maharat Nakhon Ratchasima Hospital (P. Tantiwong). S. Ghosh was funded by T32-HL-04776. NR 14 TC 39 Z9 42 U1 0 U2 3 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 NOV PY 2010 VL 299 IS 5 BP E794 EP E801 DI 10.1152/ajpendo.00776.2009 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 673LX UT WOS:000283665600012 PM 20739506 ER PT J AU Kurz, FT Aon, MA O'Rourke, B Armoundas, AA AF Kurz, Felix T. Aon, Miguel A. O'Rourke, Brian Armoundas, Antonis A. TI Wavelet analysis reveals heterogeneous time-dependent oscillations of individual mitochondria SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE mitochondrial cluster; frequency; amplitude; mitochondrial oscillator ID COUPLED OSCILLATORS; HEART-CELLS; ORGANIZATION; POPULATIONS; CRITICALITY; DYNAMICS; NETWORK; RHYTHMS AB Kurz FT, Aon MA, O'Rourke B, Armoundas AA. Wavelet analysis reveals heterogeneous time-dependent oscillations of individual mitochondria. Am J Physiol Heart Circ Physiol 299: H1736-H1740, 2010. First published September 10, 2010; doi:10.1152/ajpheart.00640.2010.-Mitochondrial inner membrane potential oscillations in cardiac myocytes synchronize under oxidative or metabolic stress, leading to synchronized whole cell oscillations. Gaining information about the temporal properties of individual mitochondrial oscillators is essential to comprehend the network's intrinsic spatiotemporal organization. We have developed methods to detect individual mitochondrial tetramethylrhodamine ethyl ester fluorescence oscillations and assess their dynamical properties using wavelet analysis. We demonstrate that these advanced signal processing tools can provide quantitative spatiotemporal information about intermitochondrial coupling. We have found that the mean frequency of selected groups of continuously oscillating mitochondria was 16.49 +/- 1.04 mHz, whereas the mean frequency in the normalized mean global wavelet spectrum was 22.84 +/- 1.80 mHz (n = 9 myocytes). In conclusion, this novel methodology will help shed new light on the dynamical properties of the mitochondrial network on the verge of synchronization. C1 [Kurz, Felix T.; Armoundas, Antonis A.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Kurz, Felix T.] Charite, Klin mS Kardiol, D-13353 Berlin, Germany. [Aon, Miguel A.; O'Rourke, Brian] Johns Hopkins Univ, Inst Mol Cardiobiol, Dept Med, Baltimore, MD USA. RP Armoundas, AA (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM aarmoundas@partners.org RI Aon, Miguel/A-6564-2008 OI Aon, Miguel/0000-0002-4355-5431 FU American Heart Association [0635127N]; National Institutes of Health [R37-HL-54598, 1R21-AG-035128, 1RO1-HL-103961]; Cardiovascular Research Society; Boehringer Ingelheim Fonds FX The work was supported by an American Heart Association Scientist Development Grant 0635127N; by National Institutes of Health Grants R37-HL-54598, 1R21-AG-035128, and 1RO1-HL-103961; by the Cardiovascular Research Society; and by a fellowship from the Boehringer Ingelheim Fonds. NR 27 TC 16 Z9 16 U1 0 U2 14 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 NOV PY 2010 VL 299 IS 5 BP H1736 EP H1740 DI 10.1152/ajpheart.00640.2010 PG 5 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 673HB UT WOS:000283649000052 PM 20833956 ER PT J AU Chen, LM Zhao, JH Musa-Aziz, R Pelletier, MF Drummond, IA Boron, WF AF Chen, Li-Ming Zhao, Jinhua Musa-Aziz, Raif Pelletier, Marc F. Drummond, Iain A. Boron, Walter F. TI Cloning and characterization of a zebrafish homologue of human AQP1: a bifunctional water and gas channel SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE Xenopus oocyte; gas permeability; surface pH; intracellular pH ID HUMAN ERYTHROCYTE-MEMBRANE; EEL ANGUILLA-ANGUILLA; XENOPUS OOCYTES; CO2 PERMEABILITY; FUNCTIONAL-CHARACTERIZATION; SEAWATER ACCLIMATION; STRUCTURAL BASIS; CELL MEMBRANE; AQUAPORIN 1; TRANSPORT AB Chen LM, Zhao J, Musa-Aziz R, Pelletier MF, Drummond IA, Boron WF. Cloning and characterization of a zebrafish homologue of human AQP1: a bifunctional water and gas channel. Am J Physiol Regul Integr Comp Physiol 299: R1163-R1174, 2010. First published August 25, 2010; doi:10.1152/ajpregu.00319.2010.-The mammalian aquaporins AQP1, AQP4, and AQP5 have been shown to function not only as water channels but also as gas channels. Zebrafish have two genes encoding an AQP1 homologue, aqp1a and aqp1b. In the present study, we cloned the cDNA that encodes the zebrafish protein Aqp1a from the 72-h postfertilization (hpf) embryo of Danio rerio, as well as from the swim bladder of the adult. The deduced amino-acid sequence of aqp1a consists of 260 amino acids and is 59% identical to human AQP1. By analyzing the genomic DNA sequence, we identified four exons in the aqp1a gene. By in situ hybridization, aqp1a is expressed transiently in the developing vasculature and in erythrocytes from 16 to 48 h of development. Later, at 72 hpf, aqp1a is expressed in dermal ionocytes and in the swim bladder. Western blot analysis of adult tissues reveals that Aqp1a is most highly expressed in the eye and swim bladder. Xenopus oocytes expressing aqp1a have a channel-dependent (*) osmotic water permeability (P-f*) that is indistinguishable from that of human AQP1. On the basis of the magnitude of the transient change in surface pH (Delta pHS) that were recorded as the oocytes were exposed to either CO2 or NH3, we conclude that zebrafish Aqp1a is permeable to both CO2 and NH3. The ratio (Delta pHS*)CO2/P-f* is about half that of human AQP1, and the ratio (Delta pHS*)NH3/P-f* is about one-quarter that of human AQP1. Thus, compared with human AQP1, zebrafish Aqp1a has about twice the selectivity for CO2 over NH3. C1 [Chen, Li-Ming; Musa-Aziz, Raif; Boron, Walter F.] Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. [Chen, Li-Ming] Huazhong Univ Sci & Technol, Sch Life Sci & Technol, Key Lab Mol Biophys, Dept Biol Sci,Minist Educ, Wuhan 430074, Hubei Province, Peoples R China. [Chen, Li-Ming; Musa-Aziz, Raif; Boron, Walter F.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Zhao, Jinhua; Drummond, Iain A.] Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. [Zhao, Jinhua] Med Ctr, Dept Vet Affairs, Div Nephrol, Cleveland, OH USA. [Musa-Aziz, Raif] Univ Sao Paulo, Dept Physiol & Biophys, Sao Paulo, Brazil. [Pelletier, Marc F.] Aeromics LLC, Cleveland, OH USA. RP Boron, WF (reprint author), Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. EM walter.boron@case.edu RI Musa-Aziz, Raif/F-3434-2013; OI Chen, Li-Ming/0000-0002-8129-9563; Boron, Walter/0000-0003-4741-7287 FU Office of Naval Research [1N00014-05-0345]; National Institutes of Health [R01 DK52093]; Polycystic Kidney Disease Foundation [38a2f] FX This work was supported by Grant 1N00014-05-0345 from the Office of Naval Research to W. F. Boron and National Institutes of Health Grant R01 DK52093 to I. A. Drummond. J. Zhao was supported by fellowship # 38a2f from the Polycystic Kidney Disease Foundation. NR 60 TC 16 Z9 16 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD NOV PY 2010 VL 299 IS 5 BP R1163 EP R1174 DI 10.1152/ajpregu.00319.2010 PG 12 WC Physiology SC Physiology GA 674NP UT WOS:000283753900005 PM 20739606 ER PT J AU Kerfoot, BP Lawler, EV Sokolovskaya, G Gagnon, D Conlin, PR AF Kerfoot, B. Price Lawler, Elizabeth V. Sokolovskaya, Galina Gagnon, David Conlin, Paul R. TI Durable Improvements in Prostate Cancer Screening from Online Spaced Education A Randomized Controlled Trial SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID CONTINUING MEDICAL-EDUCATION; RETENTION; MEMORY; GUIDELINES; RETRIEVAL; MORTALITY; KNOWLEDGE; STUDENTS; OUTCOMES; TEACH AB Context: Prostate cancer screening with prostate-specific antigen (PSA) is frequently performed, counter to clinical practice guidelines. Background: It was hypothesized that an e-mail-based intervention termed "spaced education" could reduce clinicians' inappropriate screening for prostate cancer. Design: The study was conducted as an RCT. Setting/participants: The study involved 95 primary care clinicians in eight Veterans Affairs medical centers from January 2007 to February 2009. Intervention: Participants were randomized into two cohorts: spaced education clinicians received four isomorphic cycles of nine e-mails over 36 weeks (zero to two e-mails per week), whereas control clinicians received no intervention. Each e-mail presented a clinical scenario and asked whether it was appropriate to obtain a PSA test. Participants received immediate feedback after submitting their answers. Main outcome measures: The primary outcome was the number and percentage of inappropriate PSA screening tests ordered. Inappropriate testing was defined as use of PSA for prostate cancer screening in patients aged >76 or <40 years. Appropriateness of screening was dichotomized based on patient age at time of screening. Patients with PSA testing for non-screening reasons were excluded using a validated protocol. Logistic regression with adjustment for patient clustering by clinician was performed. Analyses were conducted in 2009. Results: During the intervention period (Weeks 1-36), clinicians receiving spaced education e-mails ordered significantly fewer inappropriate PSA screening tests than control clinicians (10.5% vs 14.2%, p=0.041). Over the 72-week period following the intervention (Weeks 37-108), spaced education clinicians continued to order fewer inappropriate tests compared to controls (7.8% vs 13.1%, respectively, p=0.011), representing a 40% relative reduction in inappropriate screening. Conclusions: Spaced education durably improves the prostate cancer screening behaviors of clinicians and represents a promising new methodology to improve patient care across healthcare systems. (Am J Prev Med 2010;39(5):472-478) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Kerfoot, B. Price; Lawler, Elizabeth V.; Sokolovskaya, Galina; Gagnon, David; Conlin, Paul R.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Lawler, Elizabeth V.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kerfoot, B. Price; Conlin, Paul R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lawler, Elizabeth V.; Sokolovskaya, Galina; Gagnon, David] Massachusetts Vet Epidemiol Res & Informat Ctr MA, Pharmacoepidemiol Res Grp, Boston, MA USA. [Gagnon, David] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Lawler, Elizabeth V.; Conlin, Paul R.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kerfoot, BP (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,151DIA, Jamaica Plain, MA 02130 USA. EM price.kerfoot@gmail.com OI Gagnon, David/0000-0002-6367-3179 FU Veterans Affairs Health Services Research & Development Service [TEL-02-100, IIR-04-045]; U.S. Agency for Healthcare Research and Quality; American Urological Association Foundation; Astellas Pharma U.S., Inc.; Wyeth, Inc.; NIH [K24 DK63214, R01 HL77234] FX This study was supported by the Research Career Development Award Program and research grants TEL-02-100 and IIR-04-045 from the Veterans Affairs Health Services Research & Development Service, the U.S. Agency for Healthcare Research and Quality, the American Urological Association Foundation (Linthicum MD), Astellas Pharma U.S., Inc., Wyeth, Inc., and the NIH (K24 DK63214 and R01 HL77234). NR 39 TC 23 Z9 24 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2010 VL 39 IS 5 BP 472 EP 478 DI 10.1016/j.amepre.2010.07.016 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 665TQ UT WOS:000283058800013 PM 20965387 ER PT J AU Scherz, N Labarere, J Mean, M Ibrahim, SA Fine, MJ Aujesky, D AF Scherz, Nathalie Labarere, Jose Mean, Marie Ibrahim, Said A. Fine, Michael J. Aujesky, Drahomir TI Prognostic Importance of Hyponatremia in Patients with Acute Pulmonary Embolism SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE hyponatremia; prognosis; pulmonary embolism ID ELEVATION MYOCARDIAL-INFARCTION; COMMUNITY-ACQUIRED PNEUMONIA; HEART-FAILURE; TOTAL HIP; OUTCOMES; HYPERTENSION; ADMISSION; HOSPITALIZATION; ARTHROPLASTY; MORTALITY AB Rationale: Although associated with adverse outcomes in other cardiopulmonary conditions, the prognostic value of hyponatremia, a marker of neurohormonal activation, in patients with acute pulmonary embolism (PE) is unknown. Objectives: To examine the associations between hyponatremia and mortality and hospital readmission rates for patients hospitalized with PE. Methods: We evaluated 13,728 patient discharges with a primary diagnosis of PE from 185 hospitals in Pennsylvania (January 2000 to November 2002). We used random-intercept logistic regression to assess the independent association between serum sodium levels at the time of presentation and mortality and hospital readmission within 30 days, adjusting for patient (race, insurance, severity of illness, use of thrombolytic therapy) and hospital factors (region, size, teaching status). Measurements and Main Results. Hyponatremia (sodium <= 135 mmol/L) was present in 2,907 patients (21.1%). Patients with a sodium level greater than 135, 130-135, and less than 130 mmol/L had a cumulative 30-day mortality of 8.0, 13.6, and 28.5% (P < 0.001), and a readmission rate of 11.8, 15.6, and 19.3% (P < 0.001), respectively. Compared with patients with a sodium greater than 135 mmol/L, the adjusted odds of dying were significantly greater for patients with a sodium 130-135 mmol/L (odds ratio [OR], 1.53; 95% confidence interval [Cl], 1.33-1.76) and a sodium less than 130 mmol/L (OR, 3.26; 95% Cl, 2.48-4.29). The adjusted odds of readmission were also increased for patients with a sodium of 130-135 mmol/L (OR, 1.28; 95% Cl, 1.12-1.46) and a sodium less than 130 mmol/L (OR, 1.44; 95% Cl, 1.02-2.02). Conclusions: Hyponatremia is common in patients presenting with PE, and is an independent predictor of short-term mortality and hospital readmission. C1 [Scherz, Nathalie; Mean, Marie] Univ Lausanne, Div Gen Internal Med, Lausanne, Switzerland. [Labarere, Jose] Univ Grenoble 1, CNRS, UMR 5525, TIMC, Grenoble, France. [Ibrahim, Said A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Philadelphia Vet Affairs VA Med Ctr, Philadelphia, PA USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Aujesky, Drahomir] Univ Bern, Div Gen Internal Med, Bern, Switzerland. RP Aujesky, D (reprint author), Univ Hosp Bern, Klin Allgemeine Innere Med, CH-3010 Bern, Switzerland. EM drahomir.aujesky@insel.ch RI Labarere, Jose/N-1688-2014; OI Labarere, Jose/0000-0001-7621-6586 FU National Heart, Lung, and Blood Institute [1 R21 HL075521-01A1]; Swiss National Science Foundation [33CSCO-122659]; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Zynx Health, Inc.; McQuaide Blasko; Up-To-Date; National Institutes of Health FX Supported in part by grant 1 R21 HL075521-01A1 from the National Heart, Lung, and Blood Institute, by grant 33CSCO-122659 from the Swiss National Science Foundation, and by a K24 career development award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (S.A.I.).; D.A. serves on the advisory board for Sanofi Aventis and Bayer for $1,001-$5,000 each; M.J.F. received consultancy fees from Zynx Health, Inc. for less than $1,000 and expert witness fees from McQuaide Blasko for $5,001-$10,000, and also receives royalties from Up-To-Date for less than $1,000; S.A.I. received a sponsored grant from the National Institutes of Health for more than $100,001; J.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; M.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; N.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. NR 27 TC 35 Z9 37 U1 1 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2010 VL 182 IS 9 BP 1178 EP 1183 DI 10.1164/rccm.201003-0481OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 677DQ UT WOS:000283969700014 PM 20595225 ER PT J AU Hall, MN Jagannathan, JP Ramaiya, NH Shinagare, AB Van den Abbeele, AD AF Hall, Matthew N. Jagannathan, Jyothi P. Ramaiya, Nikhil H. Shinagare, Atul B. Van den Abbeele, Annick D. TI Imaging of Extraosseous Myeloma: CT, PET/CT, and MRI Features SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; extraosseous multiple myeloma; lymphatic system; MRI; PET/CT ID MULTIPLE-MYELOMA; EXTRAMEDULLARY DISEASE AB OBJECTIVE. A minority of patients with multiple myeloma have imaging findings of extraosseous involvement. Extraosseous myeloma may affect any organ and can mimic other malignancies. The objective of this article is to describe the clinical relevance of extraosseous myeloma and to present the diverse imaging findings of extraosseous myeloma. CONCLUSION. The presence of radiologically detectable extraosseous myeloma is associated with a poor prognosis and thus is an important factor in the initial workup and follow-up evaluation. C1 [Hall, Matthew N.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Shinagare, Atul B.; Van den Abbeele, Annick D.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Hall, Matthew N.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Shinagare, Atul B.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Hall, MN (reprint author), Brigham & Womens Hosp, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. EM mhall7777@gmail.com NR 13 TC 23 Z9 24 U1 1 U2 3 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 NOV PY 2010 VL 195 IS 5 BP 1057 EP 1065 DI 10.2214/AJR.10.4384 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 668TY UT WOS:000283295300015 PM 20966307 ER PT J AU Rojas, CA El-Sherief, A Medina, HM Chung, JH Choy, G Ghoshhajra, BB Abbara, S AF Rojas, Carlos A. El-Sherief, Ahmed Medina, Hector M. Chung, Jonathan H. Choy, Garry Ghoshhajra, Brian B. Abbara, Suhny TI Embryology and Developmental Defects of the Interatrial Septum SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE atrial septal defects; cardiac CT; CT angiography; interatrial septum; MRI; patent foramen ovale; patent fossa ovale ID PATENT FORAMEN OVALE; SURGICAL-TREATMENT; SINUS AB OBJECTIVE. The various types of atrial septal defects (ASDs) can be differentiated on the basis of their imaging appearance on MDCT. CONCLUSION. It is fundamental for the cardiac imager to understand the embryologic development of the interatrial septum and the morphogenic differences of ASDs. C1 [Rojas, Carlos A.; El-Sherief, Ahmed; Medina, Hector M.; Chung, Jonathan H.; Choy, Garry; Ghoshhajra, Brian B.; Abbara, Suhny] Harvard Univ, Sch Med, Dept Cardiac Imaging, Boston, MA 02114 USA. [Rojas, Carlos A.; El-Sherief, Ahmed; Medina, Hector M.; Chung, Jonathan H.; Choy, Garry; Ghoshhajra, Brian B.; Abbara, Suhny] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rojas, CA (reprint author), Harvard Univ, Sch Med, Dept Cardiac Imaging, 165 Cambridge St,CPZ-4-400, Boston, MA 02114 USA. EM caranrojas@gmail.com RI Ghoshhajra, Brian/J-2114-2016 OI Ghoshhajra, Brian/0000-0002-3865-3432 NR 11 TC 5 Z9 6 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 NOV PY 2010 VL 195 IS 5 BP 1100 EP 1104 DI 10.2214/AJR.10.4277 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 668TY UT WOS:000283295300021 PM 20966313 ER PT J AU Pulli, B Fintelmann, F Liu, B Rosenthal, DI AF Pulli, Benjamin Fintelmann, Florian Liu, Bob Rosenthal, Daniel I. TI Semiautomated Fluoroscopy Radiation Dose Capture and Reporting SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE dose; fluoroscopy; medical radiation; quality assurance; radiology report ID INTERVENTIONAL RADIOLOGY PROCEDURES; RAD-IR AB OBJECTIVE. This article describes a semiautomated system for the capture and reporting of fluoroscopic dose data in a large radiology department. By use of a novel Web-based interface, dose data are entered by technologists at the time of examination, and radiology reports are populated automatically. CONCLUSION. Dose data were successfully captured in 94% of 5,914 reports generated over the course of 6 months. Missing data were attributed to system malfunction (9.5%) and human error (90.5%) and could be reconstructed by quality control measurements in most instances. C1 [Pulli, Benjamin; Fintelmann, Florian; Liu, Bob; Rosenthal, Daniel I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Pulli, B (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM bpulli@partners.org NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2010 VL 195 IS 5 BP 1180 EP 1182 DI 10.2214/AJR.09.4162 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 668TY UT WOS:000283295300033 PM 20966325 ER PT J AU Zukotynski, K Grant, FD Curtis, C Micheli, L Treves, ST AF Zukotynski, Katherine Grant, Frederick D. Curtis, Christine Micheli, Lyle Treves, S. Ted TI Skeletal Scintigraphy in Pediatric Sports Medicine SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE musculoskeletal; pediatric; skeletal scintigraphy; sports medicine ID LOW-BACK-PAIN; PET; SPONDYLOLYSIS; RADIOGRAPHY; SPECT AB OBJECTIVE. Athletes can have pain derived from fractures or alternate pathology. Skeletal scintigraphy may detect abnormalities before anatomic imaging and provides a practical tool for whole-body imaging. However, study interpretation in children can be challenging. This pictorial essay describes a technique for pediatric skeletal scintigraphy and reviews findings commonly encountered in athletes. CONCLUSION. Skeletal scintigraphy complements anatomic findings in pediatric athletes. Familiarity with imaging technique and study interpretation can improve diagnosis. C1 [Grant, Frederick D.; Treves, S. Ted] Childrens Hosp Boston, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02115 USA. [Zukotynski, Katherine] Dana Farber Canc Inst, Div Nucl Med, Dept Imaging, Boston, MA 02115 USA. [Zukotynski, Katherine; Grant, Frederick D.; Curtis, Christine; Micheli, Lyle; Treves, S. Ted] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Curtis, Christine; Micheli, Lyle] Childrens Hosp Boston, Div Sports Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Treves, ST (reprint author), Childrens Hosp Boston, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02115 USA. EM treves@childrens.harvard.edu NR 15 TC 0 Z9 0 U1 0 U2 4 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 NOV PY 2010 VL 195 IS 5 BP 1212 EP 1219 DI 10.2214/AJR.10.4562 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 668TY UT WOS:000283295300038 PM 20966330 ER PT J AU Alpert, JM Wuerz, TH O'Donnell, TFX Carroll, KM Brucker, NN Gill, TJ AF Alpert, Joshua M. Wuerz, Thomas H. O'Donnell, Thomas F. X. Carroll, Kaitlin M. Brucker, Nathan N. Gill, Thomas J. TI The Effect of Age on the Outcomes of Arthroscopic Repair of Type II Superior Labral Anterior and Posterior Lesions SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT Interim Meeting of the American-Orthopaedic-Society-for-Sports-Medicine CY MAR, 2010 CL New Orleans, LA SP Amer Orthopaed Soc Sports Med DE superior labral anterior and posterior lesion (SLAP); shoulder; arthroscopy; age ID IISLAP LESIONS; SLAP LESIONS; FIXATION; SHOULDER; TEARS; DEBRIDEMENT; TACK AB Background: The majority of clinical outcome studies of type II superior labral anterior and posterior (SLAP) repair assess patients younger than age 40. Biceps tenotomy or tenodesis is often recommended for patients older than age 40 with superior labrum-biceps complex injury. Hypothesis: There is no difference in patient clinical outcomes comparing arthroscopic type II SLAP repair in patients younger or older than age 40. Study Design: Cohort study; Level of evidence, 3. Methods: Fifty-two patients stratified to groups younger than age 40 (21 patients; average age, 32.9 years) and older than age 40 (31 patients; average age, 55.1 years) were identified at a minimum 2-year follow-up (average, 28 months) after type II SLAP repair by a single surgeon using suture anchors. Outcome scores included American Shoulder and Elbow Society scores (ASES), Short Form-12 scores, Simple Shoulder Test scores, and visual analog pain scale. Results: At follow-up, there was no statistical difference in visual analog pain scale (P = .16), ASES scores (P = .07), Simple Shoulder Test scores (P =. 41), Short Form-12 testing, or range of motion testing. Patients older than age 40 noted their shoulder to be 87% of normal; 26 of 31 (84%) were satisfied to completely satisfied, and 28 of 31 (90%) would have the surgery again. Patients younger than 40 noted their shoulder to be approximately 89% of normal; 20 of 21 (95%) were satisfied to completely satisfied, and 18 of 21 (86%) would have the same procedure performed again. Conclusion: Our findings support that arthroscopic treatment of isolated type II SLAP repair using suture anchors can yield good to excellent results in patients older and younger than age 40. We found no statistically significant difference in patient outcome scores, satisfaction levels, or willingness to have the same procedure again when comparing arthroscopic SLAP repair in patients younger or older than age 40. C1 [Alpert, Joshua M.; Wuerz, Thomas H.; O'Donnell, Thomas F. X.; Carroll, Kaitlin M.; Brucker, Nathan N.; Gill, Thomas J.] Massachusetts Gen Hosp, Sports Med Serv, Boston, MA 02114 USA. RP Alpert, JM (reprint author), Midwest Bone & Joint Inst, 420 W NW Highway, Barrington, IL 60010 USA. EM joshalpert@gmail.com NR 27 TC 25 Z9 25 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD NOV PY 2010 VL 38 IS 11 BP 2299 EP 2303 DI 10.1177/0363546510377741 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 669KT UT WOS:000283348600025 PM 20739578 ER PT J AU Russell, JS Sawhney, R Monto, A Nanavati, S Ben Davoren, J Aslam, R Corvera, CU AF Russell, Jeffery S. Sawhney, Rajiv Monto, Alexander Nanavati, Sujal Ben Davoren, J. Aslam, Rizwan Corvera, Carlos U. TI Periprocedural complications by Child-Pugh class in patients undergoing transcatheter arterial embolization or chemoembolization to treat unresectable hepatocellular carcinoma at a VA medical center SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Hepatitis C; Hepatocellular carcinoma; Transcatheter arterial embolization; Chemoembolization; Surgical complications AB BACKGROUND For patients with compensated cirrhosis transcatheter arterial embolization with and without additive chemotherapy has been shown to improve survival The aim of this study was to compare periprocedural complications in a population with hepatitis C virus related hepatocellular carcinoma to evaluate for differences in complications by severity of liver disease METHODS Patients with unresectable hepatocellular carcinoma treated by transcatheter arterial embolization with or without additive chemotherapy procedures from 2003 to 2006 were retrospectively reviewed and compared by Child Pugh (CP) class A total of 141 embolizations were done in 76 patients RESULTS Complication rates were seen in 27% of CP class A and 17% of CP class B patients There was no significant difference in the grade of complications between the 2 groups or between procedure types Survival rate was dependent on the degree of liver dysfunction (3-year CP class A, 49%, CP class B, 13%, P = 0048) CONCLUSION Embolization procedures to treat hepatitis C virus related hepatocellular carcinoma can be performed safely with low morbidity and mortality rates even in patients with a compromised hepatic reserve Published by Elsevier Inc C1 [Corvera, Carlos U.] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA. [Russell, Jeffery S.] Univ Calif San Francisco, Med Ctr, Dept Med, San Francisco, CA 94143 USA. [Sawhney, Rajiv; Nanavati, Sujal; Aslam, Rizwan] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA USA. [Monto, Alexander] San Francisco VA Med Ctr, Dept Gastroenterol, San Francisco, CA USA. [Ben Davoren, J.] San Francisco VA Med Ctr, Dept Hematol Oncol, San Francisco, CA USA. RP Corvera, CU (reprint author), San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA. FU Veteran Health Administration; Northern California Institute for Research and Education FX Supported by a grant from the Veteran Health Administration and from the Northern California Institute for Research and Education (CUC) This manuscript was presented at the 2010 Association of VA Surgeons Conference on May 10 2010 NR 12 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2010 VL 200 IS 5 BP 659 EP 664 DI 10.1016/j.amjsurg.2010.07.021 PG 6 WC Surgery SC Surgery GA 691LS UT WOS:000285081900021 PM 21056149 ER PT J AU Thirunavukarasu, P Brewster, LP Pecora, SM Hall, DE AF Thirunavukarasu, Pragatheeshwar Brewster, Luke P. Pecora, Stephanie M. Hall, Daniel E. TI Educational intervention is effective in improving knowledge and confidence in surgical ethics-a prospective study SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Surgical ethics; Ethics education; ACGME; Core competency; Professionalism; Resident ethics education ID RESIDENCY PROGRAMS; RANDOMIZED-TRIAL; CLINICAL ETHICS; SURGERY; OUTCOMES AB BACKGROUND Professionalism and ethics are Accreditation Council for Graduate Medical Education (ACGME) core competencies but there is little evidence regarding the effectiveness of ethics education METHODS General surgery residents at the University of Pittsburgh completed questionnaires measuring attitudes and knowledge about surgical ethics before and after four 60-minute faculty-facilitated seminars implementing the American College of Surgeons ethics curriculum RESULTS Most residents experienced ethical challenges at least once every rotation competition of Interests (75%) professional obligations (75%) confidentiality (83%) truth telling (88%), surrogate decision making (91%) and end-of life issues (100%) The educational intervention increased both knowledge about surgical ethics (P = 013) and confidence in dealing with competition of interests (P = 001) professional obligations (P = 011), truth telling (P = 013) confidentiality (P = 011), end of-life issues (P = 007) and surrogate decision making (P = 052) Most residents recommended the American College of Surgeons text for future use (84%) considering ethics education a standard part of residency training (70%) CONCLUSIONS Focused instruction using the American College of Surgeons ethics curriculum can effectively Improve both knowledge and confidence about surgical ethics Published by Elsevier Inc C1 [Thirunavukarasu, Pragatheeshwar; Hall, Daniel E.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15260 USA. [Brewster, Luke P.] Emory Clin, Atlanta, GA 30322 USA. [Pecora, Stephanie M.; Hall, Daniel E.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Hall, DE (reprint author), Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15260 USA. RI Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 FU Kamangar Foundation; Center for Study of Ethics and Human Values University of Washington St Louis FX This study was supported by funding through the Kamangar Foundation and Award Center for Study of Ethics and Human Values University of Washington St Louis NR 22 TC 4 Z9 4 U1 0 U2 4 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 NOV PY 2010 VL 200 IS 5 BP 665 EP 669 DI 10.1016/j.amjsurg.2010.08.002 PG 5 WC Surgery SC Surgery GA 691LS UT WOS:000285081900022 PM 21056150 ER PT J AU Le Huu, AR Jokinen, CH Ruben, BP Mihm, MC Weiss, SW North, PE Dadras, SS AF Le Huu, Aude Rimella Jokinen, Chris H. Ruben, Brian P. Mihm, Martin C. Weiss, Sharon W. North, Paula E. Dadras, Soheil S. TI Expression of Prox1, Lymphatic Endothelial Nuclear Transcription Factor, in Kaposiform Hemangioendothelioma and Tufted Angioma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Prox1; LYVE-1; podoplanin (D2-40); CD31; CD34; infantile hemangioma; kaposiform hemangioendothelioma; tufted angioma ID KASABACH-MERRITT-SYNDROME; PEDIATRIC VASCULAR TUMORS; MARKER; HEMANGIOMAS; DIFFERENTIATION; MALFORMATIONS; SARCOMA; LESIONS; D2-40; CELLS AB Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare tumors mainly occurring in early childhood. Our recent results showed that ectopic overexpression of human Prox1 gene, a lymphatic endothelial nuclear transcription factor, promoted an aggressive behavior in 2 murine models of KHE. This dramatic Prox1-induced phenotype prompted us to investigate immunohistochemical staining pattern of Prox1, podoplanin (D2-40), LYVE-1, and Prox1/CD34 as well as double immunofluorescent staining pattern of LYVE-1/CD31 in KHE and TA, compared with other pediatric vascular tumors. For this purpose, we examined 75 vascular lesions: KHE (n = 18), TA (n = 13), infantile hemangioma (n = 13), pyogenic granuloma (n = 18), and granulation tissue (n = 13). Overall, KHE and TA shared an identical endothelial immunophenotype: the neoplastic spindle cells were Prox1(+), podoplanin(+), LYVE-1(+), CD31(+), and CD34(+), whereas endothelial cells within glomeruloid foci were Prox1(-), podoplanin(-), LYVE-1(-), CD31(+), and CD34(+). The lesional cells of all infantile hemangiomas and pyogenic granulomas were negative for Prox1 in the presence of positive internal control. These findings provide immunophenotypic evidence to support a preexisting notion that KHE and TA are closely related, if not identical. Overall, our results show, for the first time, that Prox1 is an immunohistochemical biomarker helpful in confirming the diagnosis of KHE/TA and in distinguishing it from infantile hemangioma and pyogenic granuloma. C1 [Le Huu, Aude Rimella; Dadras, Soheil S.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Le Huu, Aude Rimella; Dadras, Soheil S.] Stanford Univ, Dept Dermatol, Sch Med, Stanford, CA 94305 USA. [Jokinen, Chris H.; Ruben, Brian P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Mihm, Martin C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Weiss, Sharon W.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. [North, Paula E.] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. [Le Huu, Aude Rimella] Univ Lausanne Hosp, Dept Dermatol DHURDV, Lausanne, Switzerland. RP Dadras, SS (reprint author), Univ Connecticut, Ctr Hlth, Dept Dermatol, 21 South Rd, Farmington, CT 06032 USA. EM dadras@uchc.edu FU Departments of Pathology and Dermatology from Stanford University Medical Center FX This work was supported in part by the Departments of Pathology and Dermatology research funds from Stanford University Medical Center. NR 44 TC 35 Z9 36 U1 1 U2 1 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 NOV PY 2010 VL 34 IS 11 BP 1563 EP 1573 DI 10.1097/PAS.0b013e3181f6076f PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 671IG UT WOS:000283493800001 PM 20975337 ER PT J AU Woodford, RL Nikiforov, YE Hunt, JL Bellizzi, AM Zhang, XT Mills, SE Stelow, EB AF Woodford, Randall Lyndon Nikiforov, Yuri E. Hunt, Jennifer L. Bellizzi, Andrew M. Zhang, Xiaotang Mills, Stacey E. Stelow, Edward B. TI Encapsulated Papillary Oncocytic Neoplasms of the Thyroid: Morphologic, Immunohistochemical, and Molecular Analysis of 18 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE papillary; oncocytic; Hurthle cell; BRAF mutation; thyroid; immunohistochemistry; CD56; HBME1; CK19 ID BRAF MUTATIONS; HIGH PREVALENCE; RET/PTC REARRANGEMENTS; CARCINOMA; RET; EXPRESSION; CHILDREN; DIAGNOSIS; CK19; CD56 AB Encapsulated papillary oncocytic neoplasms (EPONs) of the thyroid are rare tumors, whose relationship to other thyroid tumors has not been thoroughly elucidated. Earlier, they have been regarded as variants of papillary thyroid carcinoma (PTC), hyperplastic lesions, and follicular neoplasms. Eighteen EPONs were retrieved from our surgical pathology files and reviewed for defining morphologic features. Cases having the typical nuclear features of PTC were excluded. Immunohistochemistry (IHC) for CK19, HBME1, and CD56 was carried out. Microdissection, polymerase chain reaction, and sequencing of exon 15 of the BRAF gene were completed. Cases were evaluated for rearranged in transformation/papillary thyroid carcinoma RET/PTC rearrangement by fluorescent in situ hybridization (FISH). The majority of the tumors exhibited a distinctive histologic appearance. They were composed of true papillae lined by a single layer of predominantly cuboidal cells with oncocytic cytoplasm; hobnailing was typically prominent. Three tumors showed taller cells with uniformly apical nuclei and no hobnailing. Ten of 18 cases showed vascular and/or capsular invasion; hence, if the diagnostic criteria used to evaluate follicular neoplasms are applied, more than half of the tumors would be considered minimally invasive carcinomas. No cases were immunoreactive with antibodies to HBME1, whereas only 1 of 13 was immunoreactive for CK19. Six of 7 interpretable cases were immunoreactive for CD56. No BRAF point mutations or RET/PTC rearrangements were identified in the examined cases. All patients were alive at the time of last follow-up and no locally recurrent disease had been reported; however, 1 case was remarkable for a lymph node metastasis. Our results confirm that EPONs are histologically, immunohistochemically, and molecularly distinct from papillary thyroid carcinoma and seem to be most related to follicular neoplasms. C1 [Woodford, Randall Lyndon; Mills, Stacey E.; Stelow, Edward B.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA 22908 USA. [Nikiforov, Yuri E.] Univ Pittsburgh, Dept Pathol, Med Ctr, Pittsburgh, PA USA. [Hunt, Jennifer L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bellizzi, Andrew M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Zhang, Xiaotang] Cleveland Clin, Dept Pathol, Cleveland, OH 44106 USA. RP Stelow, EB (reprint author), Univ Virginia Hlth Syst, Dept Pathol, Box 800214, Charlottesville, VA 22908 USA. EM es7yj@virginia.edu NR 51 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2010 VL 34 IS 11 BP 1582 EP 1590 DI 10.1097/PAS.0b013e3181f2d820 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 671IG UT WOS:000283493800003 PM 20924280 ER PT J AU Demicco, EG Deshpande, V Nielsen, GP Kattapuram, SV Rosenberg, AE AF Demicco, Elizabeth G. Deshpande, Vikram Nielsen, G. Petur Kattapuram, Susan V. Rosenberg, Andrew E. TI Well-differentiated Osteosarcoma of the Jaw Bones A Clinicopathologic Study of 15 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE well-differentiated osteosarcoma; jaw bones; maxilla; mandible; low grade ID GRADE INTRAOSSEOUS OSTEOSARCOMA; PAROSTEAL OSTEOGENIC SARCOMA; FOLLOW-UP; FIBROUS DYSPLASIA; EXPERIENCE; MAXILLA; HEAD; NECK; OUTCOMES; REGION AB Well-differentiated osteosarcoma of the jaw bones is rare, and is often confused with a variety of benign fibroosseous lesions. To better understand its clinicopathologic features, we reviewed our experience with 15 cases. The patients included 7 males and 8 females (age range 14 to 66y; mean 42.8y). Six of the tumors arose in the mandible, and 9 in the maxilla. Microscopically, the tumors were infiltrative, relatively hypocellular, and consisted of monomorphic, minimally atypical spindle cells that were usually arranged in fascicles. The tumor cells were intimately related to the surfaces of elongated trabeculae of neoplastic woven bone that lacked osteoblastic rimming. Nine patients were treated with wide excision, 2 patients with marginal excision, and 2 patients with excision and radiation therapy. After definitive therapy, there were no reports of recurrence or metastasis over an average follow-up of 34 months (range 1 to 80 mo). Well-differentiated gnathic osteosarcoma is a low-grade malignancy that may be successfully treated with wide local excision. The prognosis in our series was excellent. C1 [Demicco, Elizabeth G.; Deshpande, Vikram; Nielsen, G. Petur; Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kattapuram, Susan V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rosenberg, AE (reprint author), Massachusetts Gen Hosp, Dept Pathol WRN 2, 55 Fruit St, Boston, MA 02114 USA. EM arosenberg@partners.org NR 46 TC 6 Z9 8 U1 0 U2 1 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 NOV PY 2010 VL 34 IS 11 BP 1647 EP 1655 DI 10.1097/PAS.0b013e3181f7dac6 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 671IG UT WOS:000283493800010 PM 20975343 ER PT J AU Elco, CP Marino-Enriquez, A Abraham, JA Dal Cin, P Hornick, JL AF Elco, Christopher P. Marino-Enriquez, Adrian Abraham, John A. Dal Cin, Paola Hornick, Jason L. TI Hybrid Myxoinflammatory Fibroblastic Sarcoma/Hemosiderotic Fibrolipomatous Tumor: Report of a Case Providing Further Evidence for a Pathogenetic Link SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE myxoinflammatory fibroblastic sarcoma; hemosiderotic fibrolipomatous tumor; t(1;10); cytogenetics; low-grade sarcoma; soft tissue tumor ID FIBROHISTIOCYTIC LIPOMATOUS LESION; HYALINIZING ANGIECTATIC TUMOR; MYXOHYALINE TUMOR; SARCOMA; CELLS AB Myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor are rare, slow-growing soft tissue tumors of the distal extremities with recurrent potential. Recent cytogenetic studies have shown a t(1;10)(p22;q24) or der(10) t(1;10) in combination with aberrations of chromosome 3 in a limited number of cases of both entities. Here we report a case of a 42-year-old female with a soft tissue tumor of the ankle showing hybrid morphologic features of myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor, a der(10) t(1;10), and abnormalities of chromosome 3. This hybrid lesion provides further evidence for a close relationship between these 2 tumor types. C1 [Elco, Christopher P.; Marino-Enriquez, Adrian; Dal Cin, Paola; Hornick, Jason L.] Harvard Univ, Dept Pathol, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Abraham, John A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Bone & Sarcoma Oncol, Boston, MA 02115 USA. [Marino-Enriquez, Adrian] Univ Autonoma Madrid, Hosp Univ La Paz, Dept Anat Patol, Madrid, Spain. RP Hornick, JL (reprint author), Harvard Univ, Dept Pathol, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jhornick@partners.org FU Fundacion Alfonso Martin Escudero, Madrid, Spain FX Adrian Marino-Enriquez is supported by a research grant from Fundacion Alfonso Martin Escudero, Madrid, Spain. NR 16 TC 22 Z9 27 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 NOV PY 2010 VL 34 IS 11 BP 1723 EP 1727 DI 10.1097/PAS.0b013e3181f17d51 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 685DK UT WOS:000284607300001 PM 20871391 ER PT J AU Hanto, DW Maki, T Yoon, MH Csizmadia, E Chin, BY Gallo, D Konduru, B Kuramitsu, K Smith, NR Berssenbrugge, A Attanasio, C Thomas, M Wegiel, B Otterbein, LE AF Hanto, D. W. Maki, T. Yoon, M. H. Csizmadia, E. Chin, B. Y. Gallo, D. Konduru, B. Kuramitsu, K. Smith, N. R. Berssenbrugge, A. Attanasio, C. Thomas, M. Wegiel, B. Otterbein, L. E. TI Intraoperative Administration of Inhaled Carbon Monoxide Reduces Delayed Graft Function in Kidney Allografts in Swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Carbon monoxide; delayed graft function; ischemia reperfusion injury; kidney transplantation ID ACUTE-RENAL-FAILURE; ISCHEMIA/REPERFUSION INJURY; HEME OXYGENASE-1; EPITHELIAL-CELLS; PROVIDES PROTECTION; REPERFUSION INJURY; KINASE PATHWAY; GENE-TRANSFER; RISK-FACTORS; LUNG INJURY AB Ischemia/reperfusion injury and delayed graft function (DGF) following organ transplantation adversely affect graft function and survival. A large animal model has not been characterized. We developed a pig kidney allograft model of DGF and evaluated the cytoprotective effects of inhaled carbon monoxide (CO). We demonstrate that donor warm ischemia time is a critical determinant of DGF as evidenced by a transient (4-6 days) increase in serum creatinine and blood urea nitrogen following transplantation before returning to baseline. CO administered to recipients intraoperatively for 1 h restored kidney function more rapidly versus air-treated controls. CO reduced acute tubular necrosis, apoptosis, tissue factor expression and P-selectin expression and enhanced proliferative repair as measured by phosphorylation of retinol binding protein and histone H3. Gene microarray analyses with confirmatory PCR of biopsy specimens showed that CO blocked proinflammatory gene expression of MCP-1 and heat shock proteins. In vitro in pig renal epithelial cells, CO blocks anoxia-reoxygenation-induced cell death while promoting proliferation. This large animal model of DGF can be utilized for testing therapeutic strategies to reduce or prevent DGF in humans. The efficacy of CO on improving graft function posttransplant validates the model and offers a potentially important therapeutic strategy to improve transplant outcomes. C1 [Hanto, D. W.; Maki, T.; Yoon, M. H.; Csizmadia, E.; Chin, B. Y.; Gallo, D.; Konduru, B.; Kuramitsu, K.; Thomas, M.; Wegiel, B.; Otterbein, L. E.] Harvard Univ, Sch Med, Transplant Inst, Cambridge, MA 02138 USA. [Hanto, D. W.; Maki, T.; Yoon, M. H.; Csizmadia, E.; Chin, B. Y.; Gallo, D.; Konduru, B.; Kuramitsu, K.; Thomas, M.; Wegiel, B.; Otterbein, L. E.] Beth Israel Deaconess Med Ctr, Div Transplantat, Dept Surg, Boston, MA USA. [Smith, N. R.] Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. [Berssenbrugge, A.] Ikaria Inc, Clinton, NJ USA. [Attanasio, C.] Osped Cardarelli Hosp, Ctr Biotechnol, Naples, Italy. RP Hanto, DW (reprint author), Harvard Univ, Sch Med, Transplant Inst, Cambridge, MA 02138 USA. EM dhanto@bidmc.harvard.edu; lotterbe@bidmc.harvard.edu FU Ikaria; Transplant Institute of BIDMC FX We would like to acknowledge Fredy Rocuts and members of the Animal Research Facility, Sandy Vertentes and Laurie Skowronski for their help with the animal experiments. We would like to thank Drs. Martin Bilban and Florian Klinglmueller from the Medical University of Vienna, Department of Laboratory of Medicine for their help with the gene array analyses. This work was supported by Ikaria and the Julie Henry Research Fund in the Transplant Institute of BIDMC. NR 47 TC 30 Z9 32 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2010 VL 10 IS 11 BP 2421 EP 2430 DI 10.1111/j.1600-6143.2010.03289.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 672OM UT WOS:000283595700007 PM 20977633 ER PT J AU Wong, W DeVito, J Nguyen, H Sarracino, D Porcheray, F Dargon, I Pelle, PD Collins, AB Tolkoff-Rubin, N Smith, RN Colvin, R Zorn, E AF Wong, W. DeVito, J. Nguyen, H. Sarracino, D. Porcheray, F. Dargon, I. Pelle, P. D. Collins, A. B. Tolkoff-Rubin, N. Smith, R. N. Colvin, R. Zorn, E. TI Chronic Humoral Rejection of Human Kidney Allografts Is Associated with MMP-2 Accumulation in Podocytes and its Release in the Urine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Chronic humoral rejection; kidney transplantation; MMP-2 ID MATRIX METALLOPROTEINASES; PROSPECTIVE TRIAL; HLA ANTIBODIES; GLOMERULONEPHRITIS; CLASSIFICATION; EXPRESSION; SURVIVAL; DAMAGE AB Chronic humoral rejection (CHR) is an important cause of late graft failures following kidney transplantation. Overall, the pathophysiology of CHR is poorly understood. Matrix metalloproteinase-2 (MMP-2), a type IV collagenase, has been implicated in chronic kidney disease and allograft rejection in previous studies. We examined the presence of MMP-2 in allograft biopsies and in the urine of kidney transplant recipients with CHR. MMP-2 staining was detected by immunohistochemistry in podocytes for all CHR patients but less frequently in patients with other renal complications. Urinary MMP-2 levels were also significantly higher in CHR patients (median 4942 pg/mL, N = 27) compared to non-CHR patients (median 598 pg/mL, N = 65; p < 0.001). Elevated urinary MMP-2 correlated with higher levels of proteinuria in both CHR and non-CHR patients. Longitudinal analysis indicated that increase in urine MMP-2 coincided with initial diagnosis of CHR as documented by the biopsies. Using an enzymatic assay, we demonstrated that MMP-2 was present in its active form in the urine of patients with CHR. Overall, our findings associate MMP-2 with glomerular injury as well as interstitial fibrosis and tubular atrophy observed in patients with CHR. C1 [DeVito, J.; Porcheray, F.; Dargon, I.; Zorn, E.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Boston, MA 02115 USA. [Wong, W.; Nguyen, H.; Tolkoff-Rubin, N.] Harvard Univ, Sch Med, Dept Med, Renal Unit, Boston, MA USA. [Sarracino, D.] Harvard Univ, Sch Med, Ctr Genet & Genom, Cambridge, MA 02138 USA. [Pelle, P. D.; Collins, A. B.; Smith, R. N.; Colvin, R.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Zorn, E (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Boston, MA 02115 USA. EM ezorn@partners.org RI porcheray, fabrice/B-9505-2012 FU Fahd and Nadia Alireza's Research Fund; Milton Fund, Boston, MA FX We are indebted to Drs Yongguang Yang and Robert Hawley for their thoughtful review of our manuscript. This work was supported by the Fahd and Nadia Alireza's Research Fund as well as the Milton Fund, Boston, MA. NR 20 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2010 VL 10 IS 11 BP 2463 EP 2471 DI 10.1111/j.1600-6143.2010.03290.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 672OM UT WOS:000283595700011 PM 20977637 ER PT J AU Saidi, RF Bradley, J Greer, D Luskin, R O'Connor, K Delmonico, F Kennealey, P Pathan, F Schuetz, C Elias, N Ko, DSC Kawai, T Hertl, M Cosimi, AB Markmann, JF AF Saidi, R. F. Bradley, J. Greer, D. Luskin, R. O'Connor, K. Delmonico, F. Kennealey, P. Pathan, F. Schuetz, C. Elias, N. Ko, D. S. C. Kawai, T. Hertl, M. Cosimi, A. B. Markmann, J. F. TI Changing Pattern of Organ Donation at a Single Center: Are Potential Brain Dead Donors Being Lost to Donation After Cardiac Death? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Donation; donor pool; transplantation; transplantation policy ID UNITED-STATES 1998-2007; PANCREAS TRANSPLANTATION; KIDNEY-TRANSPLANTATION; LIVER AB We detected significant changes in the make-up of the donor pool over the past decade. That the changes in diagnosis over time did not differ between DCD and DBD groups suggests this difference is not responsible for the increase in DCD rates. Instead, we suggest that changes in clinical practice, especially in management of patients with severe brain injury may account for the increased proportion of DCD. C1 [Saidi, R. F.; Greer, D.; Kennealey, P.; Pathan, F.; Schuetz, C.; Elias, N.; Ko, D. S. C.; Kawai, T.; Hertl, M.; Cosimi, A. B.; Markmann, J. F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Saidi, R. F.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Bradley, J.; Luskin, R.; Delmonico, F.] New England Organ Bank Inc, Newton, MA USA. [O'Connor, K.] Life Ctr, Seattle, WA USA. RP Markmann, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM jmarkmann@partners.org RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 18 TC 37 Z9 38 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2010 VL 10 IS 11 BP 2536 EP 2540 DI 10.1111/j.1600-6143.2010.03215.x PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA 672OM UT WOS:000283595700020 PM 21043059 ER PT J AU Finney, CA Musoke, C Dhabangi, A Oravecz, T Dzik, W Cserti-Gazdewich, C Liles, C Kain, K AF Finney, Constance A. Musoke, Charles Dhabangi, Aggrey Oravecz, Tamas Dzik, Walter Cserti-Gazdewich, Christine Liles, Conrad Kain, Kevin TI IMPLICATING THE S1P PATHWAY IN CEREBRAL MALARIA PATHOLOGY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Finney, Constance A.; Liles, Conrad; Kain, Kevin] Univ Toronto, Toronto, ON, Canada. [Musoke, Charles; Dhabangi, Aggrey] Mulago Hosp, Kampala, Uganda. [Oravecz, Tamas] Lexicon Pharmaceut, The Woodlands, TX USA. [Dzik, Walter] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cserti-Gazdewich, Christine] Toronto Gen Hosp, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 117 BP 35 EP 36 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819700118 ER PT J AU Krezanoski, PJ AF Krezanoski, Paul J. TI EFFECT OF INCENTIVES ON INSECTICIDE-TREATED BED NET USE IN SUB-SAHARAN AFRICA: A CLUSTER RANDOMIZED TRIAL IN MADAGASCAR SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Krezanoski, Paul J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 299 BP 90 EP 90 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819700299 ER PT J AU Kuchta, AL Rahman, T Bhuiyan, TR Arifuzzaman, M Rashu, R Khan, AI Chowdhury, F Saha, A Ryan, ET Calderwood, SB Qadri, F Harris, JB AF Kuchta, Alison L. Rahman, Taibur Bhuiyan, Taufiiqur R. Arifuzzaman, Mohammad Rashu, Rasheduzzaman Khan, Ashraful I. Chowdhury, Fahima Saha, Amit Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi Harris, Jason B. TI PROLIFERATION OF CYTOKINE PRODUCING T CELLS IN RESPONSE TO VIBRIO CHOLERAE O1 INFECTION OR VACCINATION IN BANGLADESHI ADULTS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Kuchta, Alison L.; Rahman, Taibur; Bhuiyan, Taufiiqur R.; Arifuzzaman, Mohammad; Rashu, Rasheduzzaman; Khan, Ashraful I.; Chowdhury, Fahima; Saha, Amit; Qadri, Firdausi] ICDDR B, Dhaka, Bangladesh. [Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 483 BP 144 EP 145 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819700484 ER PT J AU Uddin, T Harris, JB Bhuiyan, T Shirin, T Uddin, MI Kahn, AI Chowdhury, F Alam, NH Ryan, ET Calderwood, SB Qadri, F AF Uddin, Taher Harris, Jason B. Bhuiyan, Taufiqur Shirin, Tahmina Uddin, M. Ikhtear Kahn, Ashraful I. Chowdhury, Fahima Alam, Nur Haq Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi TI MUCOSAL IMMUNOLOGIC RESPONSES IN CHOLERA PATIENTS IN BANGLADESH SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Uddin, Taher; Bhuiyan, Taufiqur; Shirin, Tahmina; Uddin, M. Ikhtear; Kahn, Ashraful I.; Chowdhury, Fahima; Alam, Nur Haq; Qadri, Firdausi] ICDDR B, Dhaka, Bangladesh. [Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 484 BP 145 EP 145 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819700485 ER PT J AU Alam, MM Riyadh, MA Fatema, K Rahman, MA Akhtar, N Ahmed, T Chowdhury, MI Chowdhury, F Calderwood, SB Harris, JB Ryan, ET Qadri, F AF Alam, Mohammad Murshid Riyadh, Md Asrafuzzaman Fatema, Kaniz Rahman, Mohammad Arif Akhtar, Nayeema Ahmed, Tanvir Chowdhury, Mohiul Islam Chowdhury, Fahima Calderwood, Stephen B. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi TI ANTIGEN SPECIFIC MEMORY B-CELL RESPONSES IN BANGLADESHI ADULTS AFTER ONE OR TWO DOSE OF ORAL CHOLERA VACCINATION, AND COMPARISON WITH NATURAL INFECTION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Alam, Mohammad Murshid; Riyadh, Md Asrafuzzaman; Fatema, Kaniz; Rahman, Mohammad Arif; Akhtar, Nayeema; Ahmed, Tanvir; Chowdhury, Mohiul Islam; Chowdhury, Fahima; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Calderwood, Stephen B.; Harris, Jason B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 638 BP 190 EP 191 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819701007 ER PT J AU Peniche, AG Osorio, EY Melby, PC Travi, BL AF Peniche, Alex G. Osorio, Elvia Y. Melby, Peter C. Travi, Bruno L. TI DEVELOPMENT OF A MEDIUM THROUGHPUT SYSTEM THAT USES LYMPH NODE EX VIVO EXPLANT CULTURES TO IDENTIFY COMPOUNDS AGAINST CUTANEOUS LEISHMANIASIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 687 BP 205 EP 205 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819701056 ER PT J AU Kelly, JX Li, YX Forquer, I Melendez, V Hickman, M O'Neil, M Cooper, R Harris, E Pybus, B Sousa, J Li, QG Smilkstein, M Winter, R Hinrichs, D Riscoe, M AF Kelly, Jane X. Li, Yuexin Forquer, Isaac Melendez, Victor Hickman, Mark O'Neil, Michael Cooper, Roland Harris, Erin Pybus, Brandon Sousa, Jason Li, Qigui Smilkstein, Martin Winter, Rolf Hinrichs, Dave Riscoe, Mike TI NOVEL ACRIDONES AS BROAD-SPECTRUM ANTIMALARIALS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Kelly, Jane X.] Portland State Univ, Portland, OR 97207 USA. [Li, Yuexin; Forquer, Isaac; Winter, Rolf; Hinrichs, Dave; Riscoe, Mike] Portland VA Med Ctr, Portland, OR USA. [Melendez, Victor; Hickman, Mark; O'Neil, Michael; Harris, Erin; Pybus, Brandon; Sousa, Jason; Li, Qigui] Walter Reed Army Inst Res, Silver Spring, MD USA. [Cooper, Roland] Old Dominion Univ, Norfolk, VA USA. [Smilkstein, Martin] Oregon Translat Res & Drug Dev Inst, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 716 BP 213 EP 213 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819701084 ER PT J AU Charles, RC Sheikh, A Krastins, B Harris, JB Bhuiyan, MS LaRocque, RC Logvinenko, T Sarracino, DA Kudva, IT Eisenstein, J Podolsky, M Kalsy, A Ludwig, A John, M Calderwood, SB Qadri, F Ryan, ET AF Charles, Richelle C. Sheikh, Alaullah Krastins, Bryan Harris, Jason B. Bhuiyan, Md Saruar LaRocque, Regina C. Logvinenko, Tanya Sarracino, David A. Kudva, Indira T. Eisenstein, Jana Podolsky, Michael Kalsy, Anuj Ludwig, Albrecht John, Manohar Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. TI CHARACTERIZATION OF ANTI-SALMONELLA ENTERICA SEROTYPE TYPHI ANTIBODY RESPONSES IN BACTEREMIC BANGLADESHI PATIENTS USING IMMUNO-AFFINITY PROTEOMIC-BASED TECHNOLOGY (IPT) SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Charles, Richelle C.; Harris, Jason B.; LaRocque, Regina C.; Eisenstein, Jana; Podolsky, Michael; Kalsy, Anuj; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sheikh, Alaullah; Bhuiyan, Md Saruar; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Krastins, Bryan; Sarracino, David A.] Thermo Fisher Sci, Cambridge, MA USA. [Logvinenko, Tanya] Tufts Univ, Med Ctr, Boston, MA 02111 USA. [Kudva, Indira T.] USDA, Ames, IA USA. [Ludwig, Albrecht] Klinikum Johann Wolfgang Goethe Univ, Frankfurt, Germany. [John, Manohar] Pathovacs Inc, Ames, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 855 BP 255 EP 255 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819701223 ER PT J AU Kendall, EA Chowdhury, F Begum, Y Kahn, AI Li, S Thierir, JH Bailey, J Tacket, CO LaRocque, RC Harris, JB Ryan, ET Qadri, F Calderwood, SB Stine, OC AF Kendall, Emily A. Chowdhury, Fahima Begum, Yasmin Kahn, Ashraful I. Li, Shan Thierir, James H. Bailey, Jason Tacket, Carol O. LaRocque, Regina C. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi Calderwood, Stephen B. Stine, O. C. TI RELATEDNESS OF VIBRIO CHOLERAE O1/O139 FROM PATIENTS AND THEIR HOUSEHOLD CONTACTS, DETERMINED BY MULTILOCUS VARIABLE NUMBER TANDEM REPEAT ANALYSIS (MLVA) SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Kendall, Emily A.] Vanderbilt Univ, Nashville, TN USA. [Chowdhury, Fahima; Begum, Yasmin; Kahn, Ashraful I.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Li, Shan; Thierir, James H.; Bailey, Jason; Tacket, Carol O.; Stine, O. C.] Univ Maryland, Baltimore, MD 21201 USA. [LaRocque, Regina C.; Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 896 BP 268 EP 268 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819701264 ER PT J AU Wylie, B Mawindo, P Nyirenda, O Kalilani-Phiri, L Madanitsa, M Kuyenda, R Malenga, A Membe, G Makanani, B Thesing, P Laufer, M AF Wylie, Blair Mawindo, Patricia Nyirenda, Osward Kalilani-Phiri, Linda Madanitsa, Mwayi Kuyenda, Redson Malenga, Albert Membe, Gladys Makanani, Bonus Thesing, Philip Laufer, Miriam TI ACCURACY OF GESTATIONAL DATING IN AN OBSERVATIONAL PREGNANCY MALARIA COHORT IN MALAWI: AN ULTRASOUND DEMONSTRATION PROJECT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Wylie, Blair] Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. [Mawindo, Patricia; Nyirenda, Osward; Kuyenda, Redson; Malenga, Albert] Univ Malawi, Coll Med, Blantyre Malaria Project, Blantyre, Malawi. [Thesing, Philip] Univ Maryland, Blantyre Malaria Project, Blantyre, Malawi. [Thesing, Philip] Univ Maryland, Ctr Vaccine Dev, Sch Med, Blantyre, Malawi. [Laufer, Miriam] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 961 BP 287 EP 287 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819701329 ER PT J AU Lorberg, B Wilens, TE Martelon, M Wong, P Parcell, T AF Lorberg, Boris Wilens, Timothy E. Martelon, MaryKate Wong, Patricia Parcell, Tiffany TI Reasons for Substance Use among Adolescents with Bipolar Disorder SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; SELF-MEDICATION HYPOTHESIS; USE SCREENING INVENTORY; CONDUCT DISORDER; SPECTRUM DISORDERS; MANIA; CHILDREN; ABUSE; PHENOMENOLOGY; ALCOHOL AB We examined whether children and adolescents with bipolar disorder (BPD) "self-medicate" with cigarettes, alcohol, or other substances of abuse. One hundred and five adolescents with BPD and 98 controls were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and the Drug Use Screening Inventory (DUSI) for self-medication. Thirteen control (mean +/- standard deviation [SD] = 15.31 +/- 1.18 years) and 27 BPD (15.30 +/- 2.09 years) subjects endorsed use of one of the listed drugs in the DUSI Section A within the past year and were included in all analyses. BPD adolescents were more likely than nonmood disordered, substance-using controls to report starting to use their preferred drug for mood-altering effects. There were no differences between groups in motivation for use with respect to starting substances to sleep better or get high, or in continuing substances to change mood, sleep better, or get high. These data may contribute to increased prevention of substance use disorders and to the treatment of adolescent BPD. Further studies clarifying the characteristics of self-medication are necessary. (Am J Addict 2010;00:1-7). C1 [Lorberg, Boris; Wilens, Timothy E.; Martelon, MaryKate; Wong, Patricia; Parcell, Tiffany] Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Lorberg, Boris; Wilens, Timothy E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, YAW 6A,55 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org FU NIDA NIH HHS [R01 DA012945] NR 45 TC 11 Z9 12 U1 4 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD NOV-DEC PY 2010 VL 19 IS 6 BP 474 EP 480 DI 10.1111/j.1521-0391.2010.00077.x PG 7 WC Substance Abuse SC Substance Abuse GA 666YE UT WOS:000283158100002 PM 20958841 ER PT J AU Wu, J Campuzano, S Halford, C Haake, DA Wang, J AF Wu, Jie Campuzano, Susana Halford, Colin Haake, David A. Wang, Joseph TI Ternary Surface Mono layers for Ultrasensitive (Zeptomole) Amperometric Detection of Nucleic Acid Hybridization without Signal Amplification SO ANALYTICAL CHEMISTRY LA English DT Article ID SELF-ASSEMBLED MONOLAYERS; ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY; ESCHERICHIA-COLI O157-H7; DNA HYBRIDIZATION; GOLD ELECTRODES; CHARGE-TRANSFER; IMMOBILIZATION; BIOSENSORS; SENSOR; DITHIOTHREITOL AB A ternary surface monolayer, consisting of coassembled thiolated capture probe, mercaptohexanol and dithiothreitol, is shown to offer dramatic improvements in the signal-to-noise characteristics of electrochemical DNA hybridization biosensors based on common self-assembled monolayers. Remarkably low detection limits down to 40 zmol (in 4 mu L samples) as well as only 1 CFU Escherichia coli per sensor are thus obtained without any additional amplification step in connection to the commonly used horseradish peroxidase/3,3',5,5'-tetramethylbenzidine system. Such dramatic improvements in the detection limits (compared to those of common binary alkanethiol interfaces and to those of most electrochemical DNA sensing strategies without target or signal amplification) are attributed primarily to the remarkably higher resistance to nonspecific adsorption. This reflects the highly compact layer (with lower pinhole density) produced by the coupling of the cyclic- and linear-configuration "backfillers" that leads to a remarkably low background noise even in the presence of complex sample matrixes. A wide range of surface compositions have been investigated, and the ternary mixed monolayer has been systematically optimized. Detailed impedance spectroscopy and cyclic voltammetric studies shed useful insights into the surface coverage. The impressive sensitivity and high specificity of the simple developed methodology indicate great promise for a wide range of nucleic acid testing, including clinical diagnostics, biothreat detection, food safety, and forensic analysis. C1 [Wu, Jie; Campuzano, Susana; Wang, Joseph] Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA. [Halford, Colin; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Halford, Colin; Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Wang, J (reprint author), Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA. EM josephwang@ucsd.edu RI Campuzano Ruiz, Susana/C-6448-2011; Wang, Joseph/C-6175-2011 FU National Institutes of Health [U01 AI075565]; National Science Foundation [CHE 0506529]; University Complutense of Madrid; Programa Becas Complutense del Amo FX Financial support from the National Institutes of Health (Award U01 AI075565) and National Science Foundation (Award CHE 0506529) is gratefully acknowledged. S.C. thanks the University Complutense of Madrid and Programa Becas Complutense del Amo (2010-2011). NR 39 TC 64 Z9 66 U1 1 U2 36 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 2010 VL 82 IS 21 BP 8830 EP 8837 DI 10.1021/ac101474k PG 8 WC Chemistry, Analytical SC Chemistry GA 671SS UT WOS:000283531200014 PM 20883023 ER PT J AU Rafalko, A Iliopoulos, O Fusaro, VA Hancock, W Hincapie, M AF Rafalko, Agnes Iliopoulos, Othon Fusaro, Vincent A. Hancock, William Hincapie, Marina TI Immunoaffinity Enrichment and Liquid Chromatography-Selected Reaction Monitoring Mass Spectrometry for Quantitation of Carbonic Anhydrase 12 in Cultured Renal Carcinoma Cells SO ANALYTICAL CHEMISTRY LA English DT Article ID BREAST-CANCER; MAGNETIC BEADS; PROTEOMICS; PROTEIN; EXPRESSION; GENE; DISCOVERY; ABUNDANCE; PEPTIDES; ASSAYS AB Liquid chromatography-selected reaction monitoring (LC-SRM) is a highly specific and sensitive mass spectrometry (MS) technique that is widely being applied to selectively qualify and validate candidate markers within complex biological samples. However, in order for LC-SRM methods to take on these attributes, target-specific optimization of sample processing is required, in order to reduce analyte complexity, prior to LC-SRM. In this study, we have developed a targeted platform consisting of protein immunoaffinity enrichment on magnetic beads and LC-SRM for measuring carbonic anhydrase 12 (CA12) protein in a renal cell carcinoma (RCC) cell line (PRC3), a candidate biomarker for RCC whose expression at the protein level has not been previously reported. Sample processing and LC-SRM assay were optimized for signature peptides selected as surrogate markers of CA12 protein. Using LC-SRM coupled with stable isotope dilution, we achieved limits of quantitation in the low fmol range sufficient for measuring clinically relevant biomarkers with good intra- and interassay accuracy and precision (<= 17%). Our results show that using a quantitative immunoaffinity capture approach provides specific, accurate, and robust assays amenable to high-throughput verification of potential biomarkers. C1 [Rafalko, Agnes; Hancock, William; Hincapie, Marina] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA. [Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Fusaro, Vincent A.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Fusaro, Vincent A.] Harvard Univ, Cambridge, MA 02138 USA. RP Hincapie, M (reprint author), Northeastern Univ, Barnett Inst Chem & Biol Anal, 360 Huntington Ave,341 Mugar Hall, Boston, MA 02115 USA. EM m.hincapie@neu.edu FU National Institutes of Health/National Cancer Institute (NIH/NCI) [1RO1 CA122591]; Korean Research WCU [R31-2008-000-10086-0] FX This work was supported by National Institutes of Health/National Cancer Institute (NIH/NCI) Grant 1RO1 CA122591 and by Korean Research WCU Grant R31-2008-000-10086-0. We also thank Dr. Tomas Rejtar from the Barnett Institute for helpful discussions. Contribution Number 952 from the Barnett Institute. NR 32 TC 9 Z9 9 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 2010 VL 82 IS 21 BP 8998 EP 9005 DI 10.1021/ac101981t PG 8 WC Chemistry, Analytical SC Chemistry GA 671SS UT WOS:000283531200037 PM 20936840 ER PT J AU Reinhold, B Keskin, DB Reinherz, EL AF Reinhold, Bruce Keskin, Derin B. Reinherz, Ellis L. TI Molecular Detection of Targeted Major Histocompatibility Complex I-Bound Peptides Using a Probabilistic Measure and Nanospray MS3 on a Hybrid Quadrupole-Linear Ion Trap SO ANALYTICAL CHEMISTRY LA English DT Article ID IONIZATION MASS-SPECTROMETRY; ANTIGEN PRESENTATION; STRUCTURAL BASIS; MHC AB A nanospray MS3 method deployed on a quadrupole linear ion trap hybrid can detect targeted peptides with high dynamic range and high sensitivity from complex mixtures without separations. The method uses a recognition algorithm that is a modification of the relative (Kullback-Leibler, KO entropy characterization of probabilistic distance to detect if reference MS3 fragmentation patterns are components of acquired MS3 spectra. The recognition reflects the probabilistic structure of physical MS measurements unlike the Euclidean or inner product metrics widely used for comparing spectra. It capably handles spectra with a significant chemical ion background in contrast to the Euclidean metric or the direct relative entropy. The full nanospray MS3 method allows both the detection and quantitation of targets without the need to obtain isotopically labeled standards. By avoiding chromatographic separations and its associated surface losses, the detection can be applied to complex samples on a very limited material scale. The methodology is illustrated by applications to the medically important problem of detecting targeted major histocompatibility complex (MHC) I associated peptides extracted from limited cell numbers. C1 [Reinhold, Bruce; Reinherz, Ellis L.] Harvard Univ, Sch Med, Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Reinhold, Bruce; Keskin, Derin B.; Reinherz, Ellis L.] Harvard Univ, Sch Med, Immunobiol Lab, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Reinhold, B (reprint author), Harvard Univ, Sch Med, Canc Vaccine Ctr, Dana Farber Canc Inst, HIM 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM bruce_reinhold@dfci.harvard.edu FU NIAID [U19 AI57330]; DFCI Cancer Vaccine Center FX This work was supported in part by U19 AI57330 from NIAID and DFCI Cancer Vaccine Center funding. NR 18 TC 13 Z9 13 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 2010 VL 82 IS 21 BP 9090 EP 9099 DI 10.1021/ac102387t PG 10 WC Chemistry, Analytical SC Chemistry GA 671SS UT WOS:000283531200049 PM 20932029 ER PT J AU Chamberlin, NL Eikermann, M AF Chamberlin, Nancy L. Eikermann, Matthias TI This Is No Humbug Anesthetic Agent-induced Unconsciousness and Sleep Are Visibly Different SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Chamberlin, Nancy L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Chamberlin, Nancy L.; Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Chamberlin, NL (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM meikermann@partners.org NR 10 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2010 VL 113 IS 5 BP 1007 EP 1009 PG 3 WC Anesthesiology SC Anesthesiology GA 673NX UT WOS:000283671300003 PM 20881591 ER PT J AU Brookman, JC Sair, HI Benkwitz, C Gulur, P AF Brookman, Jason C. Sair, Haris I. Benkwitz, Claudia Gulur, Padma TI Wandering Epidural Catheter SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Brookman, Jason C.; Sair, Haris I.; Benkwitz, Claudia; Gulur, Padma] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brookman, JC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jc.brookman.md@gmail.com NR 3 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2010 VL 113 IS 5 BP 1198 EP 1198 PG 1 WC Anesthesiology SC Anesthesiology GA 673NX UT WOS:000283671300026 PM 20938338 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI Switch or augment? Lessons from STAR*D SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; CLINICAL-PRACTICE; DOUBLE-BLIND; DEPRESSION; MEDICATION; OUTPATIENTS; RATIONALE; BUSPIRONE; OUTCOMES; TRIALS C1 [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Boston, MA USA. FU Bristol Myers Squibb Company; Cederroth; AB Cyberonics Inc; Eli Lilly and Company; Forest Laboratories Inc; GlaxoSmithKline; Janssen Pharmaceutica; Lichtwer Pharma; NARSAD; NIMH; Pfizer Inc FX Dr Nierenberg has disclosed that he has received grants or research support from Bristol Myers Squibb Company Cederroth AB Cyberonics Inc Eli Lilly and Company, Forest Laboratories Inc GlaxoSmithKline Janssen Pharmaceutica Lichtwer Pharma NARSAD NIMH Pfizer Inc Shire The Stanley Foundation and Wyeth Ayerst Laboratories and honoraria from Bristol Myers Squibb Company Cyberonics Inc Eli Lilly and Company Forest Laboratories Inc GlaxoSmithKline MGH Psychiatry Academy Physicians Postgraduate Press Inc Shire and Wyeth Ayerst Laboratories He is a retained consultant for Abbott Laboratories AstraZeneca Basilea Pharmaceutica Ltd BrainCells Inc Bristol Myers Squibb Company Eli Lilly and Company EPI Q Inc Genaissance Pharmaceuticals Inc GlaxoSmithKline Innapharma Inc Janssen Pharmaceutica Jazz Pharmaceuticals Merck & Co Inc Novartis Pfizer Inc PGxHealth Schering Plough Sepracor Inc Shire Somerset Pharmaceuticals Inc Takeda Pharmaceuticals North America Inc and Targacept Inc and a stock shareholder of Appliance Computing II Inc (Mindsite) and BrainCells Inc NR 21 TC 0 Z9 0 U1 0 U2 0 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD NOV PY 2010 VL 22 IS 4 SU S BP S4 EP S8 PG 5 WC Psychiatry SC Psychiatry GA 697PY UT WOS:000285528600001 PM 21180665 ER PT J AU Papakostas, GI AF Papakostas, George I. TI Switching, combination, and augmentation strategies for major depressive disorder SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; TREATMENT-RESISTANT-DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; TREATMENT-REFRACTORY DEPRESSION; STAR-ASTERISK-D; EXTENDED-RELEASE QUETIAPINE; PRELIMINARY DOUBLE-BLIND; LITHIUM AUGMENTATION; ADJUNCTIVE THERAPY; TRIIODOTHYRONINE AUGMENTATION C1 [Papakostas, George I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Papakostas, George I.] Harvard Univ, Sch Med, Boston, MA USA. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Bristol Myers Squibb Company; Forest Laboratories Inc; Pamlab LLC; Pfizer Inc; Precision Human Biosystems FX Dr Papakostas has disclosed that he has received grants or research support from Bristol Myers Squibb Company Forest Laboratories Inc Pamlab LLC Pfizer Inc and Precision Human Biosystems He is a retained consultant for AstraZeneca Bristol Myers Squibb Company Eli Lilly and Company Pamlab LLC and Wyeth Pharmaceuticals and has received honoraria for non-speakers bureau presentations from AstraZeneca Bristol Myers Squibb Company GlaxoSmithKline Lundbeck Inc and Otsuka America Pharmaceutical Inc NR 62 TC 2 Z9 2 U1 1 U2 2 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD NOV PY 2010 VL 22 IS 4 SU S BP S9 EP S14 PG 6 WC Psychiatry SC Psychiatry GA 697PY UT WOS:000285528600002 PM 21180666 ER PT J AU Kaji, AH Lewis, RJ Beavers-May, T Berg, R Bulger, E Cairns, C Callaway, C Camargo, CA Carcillo, J DeBiasi, R Diaz, T Ducharme, F Glickman, S Heilpern, K Hickey, R Vanden Hoek, T Hollander, J Janson, S Jurkovich, G Kellermann, A Kingsmore, S Kline, J Kuppermann, N Lowe, R McLario, D Nathanson, L Nichol, G Peitzman, A Richardson, L Sanders, A Shah, M Shapiro, N Silverman, R Than, M Wilber, S Yealy, DM AF Kaji, Amy H. Lewis, Roger J. Beavers-May, Tony Berg, Robert Bulger, Eileen Cairns, Charles Callaway, Clifton Camargo, Carlos A., Jr. Carcillo, Joseph DeBiasi, Roberta Diaz, Tania Ducharme, Francine Glickman, Seth Heilpern, Katherine Hickey, Robert Vanden Hoek, Terry Hollander, Judd Janson, Susan Jurkovich, Gregory Kellermann, Arthur Kingsmore, Stephen Kline, Jeffrey Kuppermann, Nathan Lowe, Robert McLario, David Nathanson, Larry Nichol, Graham Peitzman, Andrew Richardson, Lynne Sanders, Arthur Shah, Manish Shapiro, Nathan Silverman, Robert Than, Martin Wilber, Scott Yealy, Donald M. CA Roundtable External Participants Roundtable Steering Comm Fed Participants TI Summary of NIH Medical-Surgical Emergency Research Roundtable Held on April 30 to May 1, 2009 SO ANNALS OF EMERGENCY MEDICINE LA English DT Article AB Study objective: In 2003, the Institute of Medicine Committee on the Future of Emergency Care in the United States Health System convened and identified a crisis in emergency care in the United States, including a need to enhance the research base for emergency care. As a result, the National Institutes of Health (NIH) formed an NIH Task Force on Research in Emergency Medicine to enhance NIH support for emergency care research. Members of the NIH Task Force and academic leaders in emergency care participated in 3 roundtable discussions to prioritize current opportunities for enhancing and conducting emergency care research. The objectives of these discussions were to identify key research questions essential to advancing the scientific underpinnings of emergency care and to discuss the barriers and best means to advance research by exploring the role of research networks and collaboration between the NIH and the emergency care community. Methods: The Medical-Surgical Research Roundtable was convened on April 30 to May 1, 2009. Before the roundtable, the emergency care domains to be discussed were selected and experts in each of the fields were invited to participate in the roundtable. Domain experts were asked to identify research priorities and challenges and separate them into mechanistic, translational, and clinical categories. After the conference, the lists were circulated among the participants and revised to reach a consensus. Results: Emergency care research is characterized by focus on the timing, sequence, and time sensitivity of disease processes and treatment effects. Rapidly identifying the phenotype and genotype of patients manifesting a specific disease process and the mechanistic reasons for heterogeneity in outcome are important challenges in emergency care research. Other research priorities include the need to elucidate the timing, sequence, and duration of causal molecular and cellular events involved in time-critical illnesses and injuries, and the development of treatments capable of halting or reversing them; the need for novel animal models; and the need to understand why there are regional differences in outcome for the same disease processes. Important barriers to emergency care research include a limited number of trained investigators and experienced mentors, limited research infrastructure and support, and regulatory hurdles. The science of emergency care may be advanced by facilitating the following: (1) training emergency care investigators with research training programs; (2) developing emergency care clinical research networks; (3) integrating emergency care research into Clinical and Translational Science Awards; (4) developing emergency-care specific initiatives within the existing structure of NIH institutes and centers; (5) involving emergency specialists in grant review and research advisory processes; (6) supporting learn-phase or small, clinical trials; and (7) performing research to address ethical and regulatory issues. Conclusion: Enhancing the research base supporting the care of medical and surgical emergencies will require progress in specific mechanistic, translational, and clinical domains; effective collaboration of academic investigators across traditional clinical and scientific boundaries; federal support of research in high-priority areas; and overcoming limitations in available infrastructure, research training, and access to patient populations. [Ann Emerg Med. 2010;56:522-537.] C1 [Kaji, Amy H.; Lewis, Roger J.] Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA. [Beavers-May, Tony] Arkansas Childrens Hosp, Microbiol Lab, Little Rock, AR 72202 USA. [Berg, Robert] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, Div Crit Care Med, Philadelphia, PA 19104 USA. [Bulger, Eileen; Jurkovich, Gregory] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Cairns, Charles; Glickman, Seth] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC 27599 USA. [Callaway, Clifton] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA 15261 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Carcillo, Joseph] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15261 USA. [DeBiasi, Roberta] Childrens Natl Med Ctr, Pediat Infect Dis Training Program, Washington, DC 20010 USA. [Ducharme, Francine] Univ Montreal, CHU St Justine Res Ctr, Dept Pediat, Montreal, PQ H3T 1C5, Canada. [Kellermann, Arthur] Emory Univ, Dept Emergency Med, Sch Med, Atlanta, GA 30322 USA. [Hickey, Robert] Childrens Hosp Pittsburgh, Div Pediat Emergency Med, Pittsburgh, PA 15201 USA. [Vanden Hoek, Terry] Univ Chicago, Dept Med, Sect Emergency Med, Chicago, IL 60637 USA. [Hollander, Judd] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Janson, Susan] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kingsmore, Stephen] Natl Ctr Genome Resources, Santa Fe, NM 87505 USA. [Kline, Jeffrey] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. [Kuppermann, Nathan] Univ Calif Davis, Sch Med, Dept Emergency Med, Sacramento, CA 95817 USA. [Lowe, Robert] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97239 USA. [McLario, David] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Emergency Dept Qual Improvement, Sect Emergency Med,Dept Pediat, Little Rock, AR 72202 USA. [Nathanson, Larry; Shapiro, Nathan] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Nichol, Graham] Univ Washington, Harborview Med Ctr, Dept Med, Ctr Prehosp Emergency Care, Seattle, WA 98104 USA. [Peitzman, Andrew] Univ Pittsburgh, Sch Med, Dept Surg, Presbyterian Univ Hosp F1281, Pittsburgh, PA 15213 USA. [Richardson, Lynne] Mt Sinai Sch Med, Dept Emergency Med, Acad Program, New York, NY 10029 USA. [Richardson, Lynne] Mt Sinai Sch Med, Dept Emergency Med, Res Program, New York, NY 10029 USA. [Richardson, Lynne] Mt Sinai Sch Med, Dept Emergency Med, Community Program, New York, NY 10029 USA. [Sanders, Arthur] Univ Arizona, Dept Emergency Med, Tucson, AZ 85724 USA. [Shah, Manish] Univ Rochester, Med Ctr, Dept Emergency Med, Rochester, NY 14642 USA. [Silverman, Robert] N Shore Long Isl Jewish Hlth Syst, Long Isl Jewish Med Ctr, Dept Emergency Med, Queens, NY 11040 USA. [Than, Martin] Christchurch Publ Hosp, Emergency Dept, Christchurch 4710, New Zealand. [Wilber, Scott] Northeastern Ohio Univ Coll Med & Pharm, Dept Emergency Med, Coll Med, Akron, OH 44309 USA. [Wilber, Scott] Northeastern Ohio Univ Coll Med & Pharm, Dept Emergency Med, Coll Pharm, Akron, OH 44309 USA. [Yealy, Donald M.] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA 15241 USA. RP Kaji, AH (reprint author), Harbor UCLA Med Ctr, Dept Emergency Med, 1000 W Carson St,Box 21, Torrance, CA 90509 USA. EM akaji@emedharbor.edu; roger@emedharbor.edu; maytk@archildrens.org; bergra@email.chop.edu; ebulger@u.washington.edu; ccairns@med.unc.edu; callawaycw@upmc.edu; ccamargo@partners.org; carcilloja@ccm.upmc.edu; rdebiasi@cnmc.org; tanimita@hotmail.com; francine.m.ducharme@umontreal.ca; swglick@med.unc.edu; kheilpe@emory.edu; robert.hickey@chp.edu; thoek@medicine.bsd.uchicago.edu; judd.hollander@uphs.upenn.edu; susan.janson@nursing.ucsf.edu; jerryj@u.washington.edu; akell01@emory.edu; sfk@ncgr.org; jkline@carolinas.org; nkuppermann@ucdavis.edu; ralowe@usa.net; mclariodavidj@uams.edu; lnathans@bidmc.harvard.edu; nichol@u.washington.edu; peitzmanab@upmc.edu; lynne.richardson@mssm.edu; art@aemrc.arizona.edu; manish.shah@rochester.edu; nshapiro@bidmc.harvard.edu; aresilv@aol.com; martinthan@xtra.co.nz; wilbers@summa-health.org; yealydm@upmc.edu RI Shapiro, Nathan/F-1718-2016; OI kingsmore, stephen/0000-0002-3758-4631; Hollander, Judd/0000-0002-1318-2785; Callaway, Clifton/0000-0002-3309-1573; Guerrero, Giovanna/0000-0003-4931-8530; Kopp, Jeffrey/0000-0001-9052-186X FU NIH; Clinical and Translational Science; NIH Institutes and Centers; [K02/K08/K23] FX We believe that the science of emergency care may thus be advanced by facilitating the following: (1) training new investigators with dedicated emergency care research training programs (eg, national K12, T32 programs within the existing NIH structure, and enhanced K02/K08/K23 support); (2) developing new emergency care clinical research networks; (3) integrating emergency care research into existing Clinical and Translational Science Award programs; (4) developing emergency care-specific initiatives within the existing structure of NIH Institutes and Centers; (5) involving emergency specialists in grant review and research advisory processes; (6) supporting learn-phase or small clinical trials; and (7) performing research to address ethical and regulatory issues (emergency consent, use of central institutional review boards, and data linkages and privacy). NR 7 TC 14 Z9 14 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2010 VL 56 IS 5 BP 522 EP 537 DI 10.1016/j.annemergmed.2010.03.014 PG 16 WC Emergency Medicine SC Emergency Medicine GA 681DY UT WOS:000284292800018 PM 21036293 ER PT J AU Wen, LS AF Wen, Leana S. TI Phantom Leg Edema SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency Brigha, Boston, MA 02115 USA. RP Wen, LS (reprint author), Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency Brigha, 75 Francis St,Neville House 236-A, Boston, MA 02115 USA. EM wen.leana@gmail.com OI Wen, Leana/0000-0003-0259-0537 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2010 VL 56 IS 5 BP 580 EP 581 DI 10.1016/j.annemergmed.2010.02.001 PG 2 WC Emergency Medicine SC Emergency Medicine GA 681DY UT WOS:000284292800025 PM 21036298 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI CURRENT THERAPY GUIDELINES FOR MULTIPLE MYELOMA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th Annual Meeting of the Japanese-Society-of-Medical-Oncology CY MAR 18-19, 2010 CL Tokyo, JAPAN SP Japanese Soc Med Oncol C1 [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 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 NOV PY 2010 VL 21 SU 9 BP 3 EP 3 PG 1 WC Oncology SC Oncology GA 673LL UT WOS:000283663700007 ER PT J AU Mabrouk, D Gurcan, HM Keskin, DB Christen, WG Ahmed, AR AF Mabrouk, Dalia Guercan, Hakan M. Keskin, Derin B. Christen, William G. Ahmed, A. Razzaque TI Association Between Cancer and Immunosuppressive Therapy-Analysis of Selected Studies in Pemphigus and Pemphigoid SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE cancer; immunosuppressive agents; pemphigoid; pemphigus ID LONG-TERM CYCLOSPORINE; RHEUMATOID-ARTHRITIS; FOLLOW-UP; AZATHIOPRINE THERAPY; BLISTERING DISEASES; MULTIPLE-SCLEROSIS; MYASTHENIA-GRAVIS; MYCOPHENOLIC-ACID; RELATIVE RISK; CELL LYMPHOMA AB OBJECTIVE: To determine whether there is an association between the use of immunosuppressive agents (ISAs) and cancer in patients with pemphigus and pemphigoid-rare, potentially fatal diseases of the skin and mucous membranes, often requiring long-term use of ISAs. DATA SOURCE: Literature was accessed through PubMed (all years available), using the search terms cancer, immunosuppressive agents, pemphigoid, and pemphigus. STUDY SELECTION AND DATA EXTRACTION: A retrospective review of the literature was conducted. Inclusion criteria for studies were: (1) English language, (2) diagnosis of pemphigus and/or pemphigoid based on histology and immunopathology, (3) more than 10 patients evaluated, (4) investigators had a high index of suspicion of cancer and patients were monitored for it, (5) follow-up information was provided for at least 1 year after initiation of therapy, and (6) absence of diagnosis of cancer before initiation of an ISA. Case reports were not included in the analysis. DATA SYNTHESIS: A total of 929 patients diagnosed with either pemphigus or pemphigoid in 17 studies were identified. Patients were divided into 2 groups. Group A comprised patients treated with azathioprine, cyclophosphamide, cyclosporine, or mycophenolate mofetil in combination with prednisone. In Group A, 22 cases of cancer were reported in 21 of the 218 patients (9.6%). Group B comprised patients treated with systemic corticosteroids only. In this group, cancer was reported in 11 of the 711 patients (1.5%). In this study there was no control group (untreated patients) and the sample sizes were small. CONCLUSIONS: Preliminary data suggest a possible association between the use of azathioprine, cyclophosphamide, and cyclosporine and increased susceptibility to cancer in patients with pemphigus and pemphigoid. C1 [Mabrouk, Dalia; Guercan, Hakan M.; Ahmed, A. Razzaque] New England Baptist Hosp, Ctr Blistering Dis, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Christen, William G.] Harvard Univ, Sch Med, Div Prevent Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ahmed, AR (reprint author), New England Baptist Hosp, Ctr Blistering Dis, Boston, MA USA. EM aramanuscript@msn.com NR 54 TC 7 Z9 7 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 2010 VL 44 IS 11 BP 1770 EP 1776 DI 10.1345/aph.1P309 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 679XX UT WOS:000284195200010 PM 20923942 ER PT J AU Gaffo, AL Roseman, JM Jacobs, DR Lewis, CE Shikany, JM Mikuls, TR Jolly, PE Saag, KG AF Gaffo, Angelo L. Roseman, Jeffrey M. Jacobs, David R., Jr. Lewis, Cora E. Shikany, James M. Mikuls, Ted R. Jolly, Pauline E. Saag, Kenneth G. TI Serum urate and its relationship with alcoholic beverage intake in men and women: findings from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; URIC-ACID; PURINE-BASES; CARDIOVASCULAR MORTALITY; PLASMA-CONCENTRATIONS; METABOLIC SYNDROME; LONG-TERM; CONSUMPTION; BEER AB Objective To investigate if beer, liquor (spirits), wine and total alcohol intakes have different associations with serum urate (SU) concentrations at different ages in a cohort of young men and women. Methods Data from 3123 participants at baseline and follow-up at 20 years were used, with balanced proportions of Caucasians and African Americans. The relationships of SU with categories of beer, liquor, wine and total alcohol intake referent to no intake were examined in sex-specific, cross-sectional analyses. Results Mean age (SD) at the beginning of follow-up was 25.1 (3.6) years. Compared with non-drinkers, significant associations between higher SU concentrations and greater beer intake were observed among men and women, with more pronounced and consistent associations for women. An association between greater liquor intake and higher SU concentrations was only seen for men at the year 20 evaluation. Wine intake was not associated with SU in either sex and total alcohol was associated with higher SU concentrations in both men and women. The magnitude of the associations between alcoholic beverages intake and SU was modest (<= 0.03 mg/dl/alcoholic beverage serving). Conclusion An association between higher SU concentrations and greater beer intake was consistent and pronounced among women, but also present in men. Despite the small magnitude of the increases in SU associated with alcohol intake, clinical implications in conditions such as cardiovascular disease and gout in young adults who are moderate and heavy drinkers cannot be ruled out. C1 [Gaffo, Angelo L.] Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Gaffo, Angelo L.; Saag, Kenneth G.] Univ Alabama, Div Rheumatol, Birmingham, AL USA. [Roseman, Jeffrey M.; Jolly, Pauline E.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway. [Lewis, Cora E.; Shikany, James M.] Univ Alabama, Div Prevent Med, Birmingham, AL USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Sect Rheumatol & Clin Immunol, Omaha, NE USA. [Mikuls, Ted R.] Omaha Vet Affairs Med Ctr, Omaha, NE USA. RP Saag, KG (reprint author), FOT 820,1530 3rd Ave S, Birmingham, AL 35294 USA. EM ksaag@uab.edu FU NHLBI NIH HHS [N01 HC048047] NR 34 TC 23 Z9 24 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2010 VL 69 IS 11 BP 1965 EP 1970 DI 10.1136/ard.2010.129429 PG 6 WC Rheumatology SC Rheumatology GA 665UI UT WOS:000283060600013 PM 20525839 ER PT J AU Carroll, DL Dykes, PC Hurley, AC AF Carroll, Diane L. Dykes, Patricia C. Hurley, Ann C. TI Patients' perspectives of falling while in an acute care hospital and suggestions for prevention SO APPLIED NURSING RESEARCH LA English DT Article ID INJURIES; VIEWS AB Patient falls and falls with injury are the largest category of reportable incidents and a significant problem in hospitals. Patients are an important part of fall prevention; therefore, we asked patients who have fallen about reason for fall and how falls could be prevented. There were two categories for falls: the need to toilet coupled with loss of balance and unexpected weakness. Patients asked to be included in fall risk communication and asked to be part of the team to prevent them from falling. Nurses need to share a consistent and clear message that they are there for patient safety. (C) 2010 Elsevier Inc. All rights reserved. C1 [Carroll, Diane L.] Massachusetts Gen Hosp, Inst Patient Care, Boston, MA 02114 USA. [Dykes, Patricia C.] Partners HlthCare, Wellesley, MA 02481 USA. [Hurley, Ann C.] Brigham & Womens Hosp, Ctr Nursing Excellence, Chestnut Hill, MA 02467 USA. RP Carroll, DL (reprint author), Massachusetts Gen Hosp, Inst Patient Care, POB 429, Boston, MA 02114 USA. EM dcarroll3@partners.org; pdykes@partners.org; ahurley@partners.org FU Interdisciplinary Nursing Quality Initiative, Robert Wood Johnson Foundation FX Funded by the Interdisciplinary Nursing Quality Initiative, Robert Wood Johnson Foundation. NR 10 TC 16 Z9 16 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD NOV PY 2010 VL 23 IS 4 BP 238 EP 241 DI 10.1016/j.apnr.2008.10.003 PG 4 WC Nursing SC Nursing GA 677AP UT WOS:000283961800009 PM 21035035 ER PT J AU Mata, IF Shi, M Agarwal, P Chung, KA Edwards, KL Factor, SA Galasko, DR Ginghina, C Griffith, A Higgins, DS Kay, DM Kim, H Leverenz, JB Quinn, JF Roberts, JW Samii, A Snapinn, KW Tsuang, DW Yearout, D Zhang, J Payami, H Zabetian, CP AF Mata, Ignacio F. Shi, Min Agarwal, Pinky Chung, Kathryn A. Edwards, Karen L. Factor, Stewart A. Galasko, Douglas R. Ginghina, Carmen Griffith, Alida Higgins, Donald S. Kay, Denise M. Kim, Hojoong Leverenz, James B. Quinn, Joseph F. Roberts, John W. Samii, Ali Snapinn, Katherine W. Tsuang, Debby W. Yearout, Dora Zhang, Jing Payami, Haydeh Zabetian, Cyrus P. TI SNCA Variant Associated With Parkinson Disease and Plasma alpha-Synuclein Level SO ARCHIVES OF NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; LOCUS TRIPLICATION; RISK-FACTORS; GENE; SUSCEPTIBILITY; BLOOD; TRANSCRIPTION; VARIABILITY; EXPRESSION; BIOMARKERS AB Background: A functional repeat polymorphism in the SNCA promoter (REP1) conveys susceptibility for Parkinson disease (PD). There is also increasing evidence that single-nucleotide polymorphisms (SNPs) elsewhere in the gene are associated with PD risk. Objectives: To further explore the association of common SNCA SNPs with PD susceptibility, to determine whether evidence of allelic heterogeneity exists, and to examine the correlation between PD-associated variants and plasma alpha-synuclein levels. Design: Two-tiered analysis. Setting: Academic research. Patients: Patients and control subjects from the NeuroGenetics Research Consortium. Main Outcome Measures: We performed a 2-tiered analysis of 1956 patients with PD and 2112 controls from the NeuroGenetics Research Consortium using a comprehensive tag SNP approach. Previously published REP1 genotypes were also included. Plasma alpha-synuclein was assayed in 86 patients with PD and 78 controls using a highly sensitive Luminex assay. Results: Five of 15 SNPs genotyped were associated with PD under an additive model in tier 1 (alpha=.05). Of these, 4 were successfully replicated in tier 2. In the combined sample, the most significant marker was rs356219 (odds ratio, 1.41; 95% confidence interval, 1.28-1.55; P=1.6 x 10-12), located approximately 9 kilobases downstream from the gene. A regression model containing rs356219 alone best fit the data. The linkage disequilibrium correlation coefficient between this SNP and REP1 was low (r(2)=0.09). The risk-associated Callele of rs356219 was also correlated with higher transformed plasma alpha-synuclein levels in patients under an adjusted additive model (P=.005). Conclusions: Our data suggest that 1 or more unidentified functional SNCA variants modify risk for PD and that the effect is larger than and independent of REP1. This variant(s), tagged by rs356219, might act by upregulating SNCA expression in a dose-dependent manner. C1 [Mata, Ignacio F.; Yearout, Dora; Zabetian, Cyrus P.] Univ Washington, Geriatr Res Educ & Clin Ctr, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Leverenz, James B.; Tsuang, Debby W.] Univ Washington, Mental Illness Res Educ & Clin Ctr, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Leverenz, James B.; Samii, Ali; Zabetian, Cyrus P.] Univ Washington, Parkinsons Dis Res Educ & Clin Ctr, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Kim, Hojoong; Samii, Ali] Univ Washington, Neurol Sect, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Mata, Ignacio F.; Kim, Hojoong; Leverenz, James B.; Samii, Ali; Yearout, Dora; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Sch Med, Seattle, WA 98108 USA. [Shi, Min; Ginghina, Carmen; Zhang, Jing] Univ Washington, Dept Pathol, Sch Med, Seattle, WA 98108 USA. [Edwards, Karen L.; Snapinn, Katherine W.] Univ Washington, Dept Epidemiol, Sch Med, Seattle, WA 98108 USA. [Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98108 USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Agarwal, Pinky; Griffith, Alida] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Chung, Kathryn A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Chung, Kathryn A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Higgins, Donald S.] Neurol Serv, Samuel Stratton Vet Affairs Med Ctr, Albany, NY USA. [Kay, Denise M.; Payami, Haydeh] New York State Dept Hlth, Genom Inst, Wadsworth Ctr, Albany, NY 12237 USA. RP Zabetian, CP (reprint author), Univ Washington, Geriatr Res Educ & Clin Ctr, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Mailstop S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Shi, Min/G-6165-2012; Tsuang, Debby/L-7234-2016 OI Shi, Min/0000-0002-6901-2558; Tsuang, Debby/0000-0002-4716-1894 FU Ipsen; Schering Plough; Teva Neuroscience; Michael J. Fox Foundation; Parkinson's Disease Foundation; American Parkinson Disease Association; Department of Veterans Affairs [1101BX000531]; National Institutes of Health [P30 AG008017, P42 ES004696, P50 NS062684, R01 AG033398, R01 NS065070, R01 NS036960, R01 NS057567] FX Dr Agarwal serves on advisory boards for Ipsen and Merz Pharmaceuticals and has received compensation as a speaker for Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Teva Neuroscience. Dr Factor has received research grants from Ipsen, Schering Plough, and Teva Neuroscience and is a consultant for Allergan, Boehringer Ingelheim, Lundbeck, and UCB. Dr Samii has received compensation as a speaker for Boehringer Ingelheim, Ipsen, and Teva Neuroscience.; This work was supported by the Michael J. Fox Foundation, by the Parkinson's Disease Foundation, by the American Parkinson Disease Association, by grant 1101BX000531 from the Department of Veterans Affairs, and by grants P30 AG008017, P42 ES004696, P50 NS062684, R01 AG033398, R01 NS065070, R01 NS036960, and R01 NS057567 from the National Institutes of Health. NR 30 TC 69 Z9 73 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2010 VL 67 IS 11 BP 1350 EP 1356 DI 10.1001/archneurol.2010.279 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 676RQ UT WOS:000283935300013 PM 21060011 ER PT J AU Klawiter, EC Benzinger, T Roy, A Naismith, RT Parks, BJ Cross, AH AF Klawiter, Eric C. Benzinger, Tammie Roy, Abhik Naismith, Robert T. Parks, Becky Jo Cross, Anne H. TI Spinal Cord Ring Enhancement in Multiple Sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID IMAGING SIGN; DISABILITY; DISEASE AB Objective: To describe the clinical and imaging characteristics of spinal cord ring enhancement in multiple sclerosis (MS). Design: Clinical case series. Setting: Academic referral center. Patients: Twenty patients with MS who had spinal cord ring enhancement were retrospectively identified from 322 cervical and thoracic spinal cord magnetic resonance imaging studies during a 3-year period. Main Outcome Measures: Demographics, disability, and pattern of enhancement on spinal cord and concomitant brain magnetic resonance imaging results. Results: Ring enhancement was seen in 20 patients with spinal cord enhancement, most commonly in the cervical cord. Incomplete or "open" ring enhancement was the dominant pattern in 19 of the 20 patients (95%). Concurrent enhancing brain lesions were present in 14 patients, 8 of which (57%) exhibited a ring pattern of enhancement. At the time of imaging, the Expanded Disability Status Scale scores ranged from 1.0 to 7.0 (median score, 3.0). Conclusions: Ring enhancement is not an uncommon pattern for spinal cord lesions in MS, occurring with a prevalence of 6.2% (20 of 322 imaging studies). The most common pattern is incomplete ring enhancement in the cervical spinal cord. Recognition of this pattern may improve and expedite the diagnosis of MS and preclude the need for invasive diagnostic interventions. C1 [Benzinger, Tammie; Roy, Abhik] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Klawiter, Eric C.] Massachusetts Gen Hosp, Dept Neurol, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. RP Klawiter, EC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang Ambulatory Care Ctr, 15 Parkman St,Ste 835, Boston, MA 02114 USA. EM eklawiter@partners.org FU Biomedical Systems; Bayer HealthCare; Biogen Idec; EMD Serono Inc; Pfizer Incorporated; Teva Neuroscience Inc.; Acorda Therapeutics; Elan Pharmaceuticals; Teva Neuroscience Inc; Acorda Therapeutics Inc; BioMS Medical Corp; Consortium of Multiple Sclerosis Centers; Eli Lilly and Company; Genentech Inc; Hoffman-La Roche Ltd; National MS Society USA [CA-1012]; NIH [UL1RR024992, K23NS052430-01A1]; American Academy of Neurology Foundation; Bracco/American Roentgen Ray Society FX Dr Klawiter has received speaking honoraria from Bayer HealthCare and Teva Neuroscience Inc. Dr Benzinger reports receiving travel expenses from Siemens AG and consulting fees from Biomedical Systems. Dr Parks reports being an investigator in clinical trials for Biogen Idec, BioMS Medical Corp, Genzyme Corporation, the National Institutes of Health (NIH), Novartis AG, and Teva Neuroscience Inc. She also reports receiving consulting fees or speaking honoraria from Bayer HealthCare, Biogen Idec, EMD Serono Inc, Pfizer Incorporated, and Teva Neuroscience Inc. Dr Naismith reports being an investigator in clinical trials sponsored by Acorda Therapeutics. He also reports receiving consulting fees and speaking honoraria from Bayer HealthCare, Biogen Idec, Elan Pharmaceuticals, and Teva Neuroscience Inc and research funding from the National Multiple Sclerosis (MS) Society USA and the NIH. Dr Cross reports receiving research funding, clinical trial funding, honoraria, or consulting fees from Acorda Therapeutics Inc, Bayer HealthCare, Biogen Idec, BioMS Medical Corp, the Consortium of Multiple Sclerosis Centers, Eli Lilly and Company, EMD Serono Inc, Genentech Inc, Hoffman-La Roche Ltd, the National MS Society USA, the NIH, and Teva Neuroscience Inc. This study was supported in part by grants UL1RR024992 (Dr Klawiter) and K23NS052430-01A1 (Dr Naismith) from the NIH and grant CA-1012 from the National MS Society USA (Dr Cross). Dr Klawiter was supported by an American Academy of Neurology Foundation Clinical Research Training Fellowship; Dr Benzinger, by a Bracco/American Roentgen Ray Society Scholar Award; and Dr Cross, by the Manny and Rosalyn Rosenthal-Dr John L. Trotter Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. NR 11 TC 6 Z9 6 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2010 VL 67 IS 11 BP 1395 EP 1398 DI 10.1001/archneurol.2010.271 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 676RQ UT WOS:000283935300020 PM 21060017 ER PT J AU Christen, WG Glynn, RJ Sesso, HD Kurth, T MacFadyen, J Bubes, V Buring, JE Manson, JE Gaziano, JM AF Christen, William G. Glynn, Robert J. Sesso, Howard D. Kurth, Tobias MacFadyen, Jean Bubes, Vadim Buring, Julie E. Manson, JoAnn E. Gaziano, J. Michael TI Age-Related Cataract in a Randomized Trial of Vitamins E and C in Men SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; BETA-CAROTENE; PHYSICIANS HEALTH; CIGARETTE-SMOKING; LENS OPACITIES; CARDIOVASCULAR-DISEASE; ANTIOXIDANT VITAMINS; LIPID-PEROXIDATION; NUCLEAR CATARACTS; NUTRIENT INTAKE AB Objective: To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of age-related cataract in a large cohort of men. Methods: In a randomized, double-masked, placebo-controlled trial, 11 545 apparently healthy US male physicians 50 years or older without a diagnosis of cataract at baseline were randomly assigned to receive 400 IU of vitamin E or placebo on alternate days and 500 mg of vitamin C or placebo daily. Main Outcome Measure: Incident cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review. Application to Clinical Practice: Long-term use of vitamin E and C supplements has no appreciable effect on cataract. Results: After 8 years of treatment and follow-up, 1174 incident cataracts were confirmed. There were 579 cataracts in the vitamin E-treated group and 595 in the vitamin E placebo group (hazard ratio, 0.99; 95% confidence interval, 0.88-1.11). For vitamin C, there were 593 cataracts in the treated group and 581 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14). Conclusion: Long-term alternate-day use of 400 IU of vitamin E and daily use of 500 mg of vitamin C had no notable beneficial or harmful effect on the risk of cataract. C1 [Christen, William G.; Glynn, Robert J.; Sesso, Howard D.; Kurth, Tobias; MacFadyen, Jean; Bubes, Vadim; Buring, Julie E.; Manson, JoAnn E.; Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02215 USA. [Sesso, Howard D.; Kurth, Tobias; Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02215 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Cardiovasc Dis, Dept Med, Boston, MA 02215 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Sesso, Howard D.; Kurth, Tobias; Buring, Julie E.; Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Christen, WG (reprint author), Brigham & Womens Hosp, Div Prevent Med, Dept Med, 900 Commonwealth Ave, Boston, MA 02215 USA. EM wchristen@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU National Institutes of Health [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; BASF Corp.; National Eye Institute; National Institute on Aging FX This work was supported by grants CA 97193 (which included funding from the National Eye Institute and the National Institute on Aging), CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health and by an investigator-initiated grant from BASF Corp. NR 52 TC 36 Z9 36 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 EI 1538-3601 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2010 VL 128 IS 11 BP 1397 EP 1405 DI 10.1001/archophthalmol.2010.266 PG 9 WC Ophthalmology SC Ophthalmology GA 676RD UT WOS:000283932600002 PM 21060040 ER PT J AU Schaumberg, DA Chasman, D Morrison, MA Adams, SM Guo, Q Hunter, DJ Hankinson, SE DeAngelis, MM AF Schaumberg, Debra A. Chasman, Daniel Morrison, Margaux A. Adams, Scott M. Guo, Qun Hunter, David J. Hankinson, Susan E. DeAngelis, Margaret M. TI Prospective Study of Common Variants in the Retinoic Acid Receptor-Related Orphan Receptor alpha Gene and Risk of Neovascular Age-Related Macular Degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID C-REACTIVE PROTEIN; BEAVER DAM EYE; CIGARETTE-SMOKING; NUCLEAR RECEPTOR; ROR-ALPHA; ATTRIBUTABLE RISK; STAGGERER MOUSE; DIETARY-FAT; FACTOR-H; SUSCEPTIBILITY AB Objectives: The retinoic acid receptor (RAR)-related orphan receptor alpha gene (RORA) is implicated as a candidate for age-related macular degeneration (AMD) through a previous microarray expression study, linkage data, biological plausibility, and 2 clinic-based cross-sectional studies. We aimed to determine if common variants in RORA predict future risk of neovascular AMD. Methods: We measured genotypes for 18 variants in intron 1 of the RORA gene among 164 cases who developed neovascular AMD and 485 age-and sex-matched controls in a prospective, nested, case-control study within the Nurses' Health Study and the Health Professionals Follow-up Study. We determined the incidence rate ratios and 95% confidence intervals (CI) for neovascular AMD for each variant and examined interactions with other AMD associated variants and modifiable risk factors. Results: We identified one single-nucleotide polymorphism (rs12900948) that was significantly associated with increased incidence of neovascular AMD. Participants with 1 and 2 copies of the G allele were 1.73 (CI, 1.32-2.27) and 2.99 (CI, 1.74-5.14) times more likely to develop neovascular AMD. Individuals homozygous for both the G allele of rs12900948 and ARMS2 A69S had a 40.8-fold increased risk of neovascularAMD(CI, 10.1-164; P=.017). Cigarette smokers who carried 2 copies of the G allele had a 9.89-fold risk of neovascular AMD but the interaction was not significant (P=.08). We identified a significant AMD-associated haplotype block containing the single-nucleotide polymorphisms rs730754, rs8034864, and rs12900948, with P values for ACA=1.16 X 10(-9), ACG=5.85 X 10(-12), and GAA=.0001 when compared with all other haplotypes. Conclusions: Common variants and haplotypes within the RORA gene appear to act synergistically with the ARMS2 A69S polymorphism to increase risk of neovascular AMD. These data add further evidence of a high level of complexity linking genetic and modifiable risk factors to AMD development and should help efforts at risk prediction. C1 [Schaumberg, Debra A.; Chasman, Daniel] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02215 USA. [Guo, Qun; Hunter, David J.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. [Schaumberg, Debra A.; Morrison, Margaux A.; Adams, Scott M.; DeAngelis, Margaret M.] Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. [Schaumberg, Debra A.; Morrison, Margaux A.; Adams, Scott M.; DeAngelis, Margaret M.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Schaumberg, Debra A.; Hunter, David J.; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Schaumberg, DA (reprint author), Brigham & Womens Hosp, Div Prevent Med, Dept Med, 900 Commonwealth Ave E,3rd Floor, Boston, MA 02215 USA. EM dschaumberg@rics.bwh.harvard.edu RI DeAngelis, e/J-7863-2015 FU National Institutes of Health [EY017362, EY013834, EY009611, EY014458, CA87969, CA49449, HL35464]; Lincy Fund FX This work was supported by National Institutes of Health grants EY017362, EY013834, EY009611, EY014458, CA87969, CA49449, and HL35464, and the Lincy Fund. NR 49 TC 13 Z9 15 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2010 VL 128 IS 11 BP 1462 EP 1471 DI 10.1001/archophthalmol.2010.261 PG 10 WC Ophthalmology SC Ophthalmology GA 676RD UT WOS:000283932600012 PM 21060049 ER PT J AU Goguen, LA Chapuy, CI Li, Y Zhao, SD Annino, DJ AF Goguen, Laura A. Chapuy, Claudia I. Li, Yi Zhao, Sihai D. Annino, Donald J. TI Neck Dissection After Chemoradiotherapy Timing and Complications SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; SQUAMOUS-CELL CARCINOMA; ADVANCED HEAD; CONCURRENT CHEMORADIATION; COMPUTED TOMOGRAPHY; CANCER; UTILITY; RADIOCHEMOTHERAPY; SURVEILLANCE; THERAPY AB Objectives: To determine the incidence of postchemo-radiotherapy (post-CRT) neck dissection (ND) complications; to ascertain whether timing (< 12 vs >= 12 weeks) from CRT to ND or other factors are associated with increased complications; and to determine whether ND timing influences disease control or survival. Design: Ten-year retrospective analysis. Setting: Tertiary care center. Patients: One hundred five patients with head and neck cancer undergoing ND after CRT. Main Outcome Measures: Complications and survival variables compared between groups undergoing ND less than 12 weeks (less-than-12-weeks ND group) and 12 weeks or more (12-weeks-or-more ND group) after CRT. Results: Sixty-seven NDs were performed less than 12 weeks and 38 were performed 12 weeks or more after CRT. Patient characteristics, treatment, and ND pathology results were comparable between the 2 ND groups. The incidence of complications between the less-than-12-weeks and the 12-weeks-or-more ND groups included major wound complications in 8 of 67 (11.9%) vs 1 of 38 (2.6%; P = .15), minor wound complications in 11 of 67 (16.4%) vs 4 of 38 (10.5%; P = .56), airway complications in 7 of 67 (10.4%) vs 2 of 38 (5.3%; P = .48), and systemic complications in 9 of 67 (13.4%) vs 2 of 38 (5.3%; P = .32). The number of patients with at least 1 complication was significantly smaller in the 12-weeks-or-more ND group (P = .04). Multivariate analysis showed that radical ND was significantly associated with an increased number of complications, and higher radiation doses approached significance (P = .05). Induction chemotherapy was associated with fewer wound complications (P = .01). There were no significant differences in overall survival (P = .82), progression-free survival (P = .77), or regional relapse (P = .54) between groups. Positive ND findings were associated with diminished progression-free and overall survival. Conclusion: These findings indicate that ND can be safely performed 12 weeks or more after CRT without adversely affecting surgical complications or survival variables. C1 [Goguen, Laura A.; Annino, Donald J.] Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, Boston, MA 02115 USA. [Chapuy, Claudia I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Li, Yi; Zhao, Sihai D.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Goguen, LA (reprint author), Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, 45 Francis St, Boston, MA 02115 USA. EM lgoguen@partners.org NR 25 TC 18 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2010 VL 136 IS 11 BP 1071 EP 1077 DI 10.1001/archoto.2010.188 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 680KO UT WOS:000284231000004 PM 21079159 ER PT J AU Wilde, EA Whiteneck, GG Bogner, J Bushnik, T Cifu, DX Dikmen, S French, L Giacino, JT Hart, T Malec, JF Millis, SR Novack, TA Sherer, M Tulsky, DS Vanderploeg, RD von Steinbuechel, N AF Wilde, Elisabeth A. Whiteneck, Gale G. Bogner, Jennifer Bushnik, Tamara Cifu, David X. Dikmen, Sureyya French, Louis Giacino, Joseph T. Hart, Tessa Malec, James F. Millis, Scott R. Novack, Thomas A. Sherer, Mark Tulsky, David S. Vanderploeg, Rodney D. von Steinbuechel, Nicole TI Recommendations for the Use of Common Outcome Measures in Traumatic Brain Injury Research SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Outcome assessment; health care; Brain injuries; Neurobehavioral manifestations; Research; Rehabilitation ID QUALITY-OF-LIFE; PORTLAND ADAPTABILITY INVENTORY; POST-CONCUSSION SYMPTOMS; FAMILY ASSESSMENT DEVICE; BEHAVIOR SCALE FRSBE; MINOR HEAD-INJURY; NOS-TBI; POSTCONCUSSION SYNDROME; ALCOHOL-CONSUMPTION; SIGNIFICANT OTHERS AB This article summarizes the selection of outcome measures by the interagency Traumatic Brain Injury (TBI) Outcomes Workgroup to address primary clinical research objectives, including documentation of the natural course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements Workgroups, the TBI Outcomes Workgroup adopted the standard 3-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in TBI from each identified domain, including global level of function, neuropsychological impairment, psychological status, TBI-related symptoms, executive functions, cognitive and physical activity limitations, social role participation, and perceived health-related quality of life. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to some older ("legacy") measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges. C1 [Wilde, Elisabeth A.; Sherer, Mark] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Wilde, Elisabeth A.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Wilde, Elisabeth A.] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. [Sherer, Mark] TIRR Mem Hermann, Houston, TX USA. [Wilde, Elisabeth A.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. [Sherer, Mark] Univ Texas Med Sch Houston, Houston, TX USA. [Whiteneck, Gale G.] Craig Hosp, Englewood, CO USA. [Bogner, Jennifer] Ohio State Univ, Dept Phys Med & Rehabil, Columbus, OH 43210 USA. [Bushnik, Tamara] Rusk Inst Rehabil, Dept Rehabil Med, New York, NY USA. [Cifu, David X.] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, PM&R Serv, Hunter Holmes McGuire Vet Adm Med Ctr, Richmond, VA USA. [Dikmen, Sureyya] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [French, Louis] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA. [Giacino, Joseph T.] JFK Johnson Rehabil Inst, Edison, NJ USA. [Giacino, Joseph T.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. [Hart, Tessa] Moss Rehabil Res Inst, Elkins Pk, PA USA. [Malec, James F.] Indiana Univ Sch Med, Dept Phys Med & Rehabil, Indianapolis, IN USA. [Malec, James F.] Rehabil Hosp Indiana, Indianapolis, IN USA. [Millis, Scott R.] Wayne State Univ, Sch Med, Dept Phys Med & Rehabil, Detroit, MI USA. [Millis, Scott R.] Wayne State Univ, Sch Med, Dept Emergency Med, Detroit, MI USA. [Novack, Thomas A.] Univ Alabama Birmingham, Dept Phys Med & Rehabil, Birmingham, AL USA. [Tulsky, David S.] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. [Vanderploeg, Rodney D.] James A Haley Vet Hosp, Psychol Serv, Tampa, FL 33612 USA. [Vanderploeg, Rodney D.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [Vanderploeg, Rodney D.] Univ S Florida, Dept Psychiat, Tampa, FL USA. [von Steinbuechel, Nicole] Univ Gottingen, Dept Med Psychol & Med Sociol, Univ Med Ctr, Gottingen, Germany. RP Wilde, EA (reprint author), Baylor Coll Med, Dept Phys Med & Rehabil, 1709 Dryden Rd,Ste 1200, Houston, TX 77030 USA. EM ewilde@bcm.edu OI Bushnik, Tamara/0000-0003-3328-257X FU National Institutes of Health (NIH: National Institute of Neurological Disorders and Stroke); U.S. Department of Veterans Affairs (VA); U.S. Department of Defense (DoD); U.S. Department of Education/National Institute on Disability and Rehabilitation Research FX Supported by the National Institutes of Health (NIH: National Institute of Neurological Disorders and Stroke), U.S. Department of Veterans Affairs (VA), U.S. Department of Defense (DoD), and U.S. Department of Education/National Institute on Disability and Rehabilitation Research. NR 101 TC 123 Z9 125 U1 8 U2 29 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 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2010 VL 91 IS 11 BP 1650 EP 1660 DI 10.1016/j.apmr.2010.06.033 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 681UQ UT WOS:000284346400004 PM 21044708 ER PT J AU Duhaime, AC Gean, AD Haacke, EM Hicks, R Wintermark, M Mukherjee, P Brody, D Latour, L Riedy, G AF Duhaime, Ann-Christine Gean, Alisa D. Haacke, E. Mark Hicks, Ramona Wintermark, Max Mukherjee, Pratik Brody, David Latour, Lawrence Riedy, Gerard CA Common Data Elements Neuroimaging Pediat Working Grp Members TI Common Data Elements in Radiologic Imaging of Traumatic Brain Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Clinical research; Clinical trials; Database; Head injury; Magnetic resonance imaging; Radiology; Rehabilitation; Traumatic brain injury ID DIFFUSE AXONAL INJURY; HEAD-INJURY; CLASSIFICATION; MICROBLEEDS; CHILDREN; VOLUME; MILD AB Radio logic brain imaging is the most useful means of visualizing and categorizing the location, nature, and degree of damage to the central nervous system sustained by patients with traumatic brain injury (TBI). In addition to determining acute patient management and prognosis, imaging is crucial for the characterization and classification of injuries for natural history studies and clinical trials. This article is the initial result of a workshop convened by multiple national health care agencies in March 2009 to begin to make recommendations for potential data elements dealing with specific radiologic features and definitions needed to characterize injuries, as well as specific techniques and parameters needed to optimize radiologic data acquisition. The neuroimaging work group included professionals with expertise in basic imaging research and physics, clinical neuroradiology, neurosurgery, neurology, physiatry, psychiatry, TBI research, and research database formation. This article outlines the rationale and overview of their specific recommendations. In addition, we review the contributions of various imaging modalities to the understanding of TBI and the general principles needed for database flexibility and evolution over time to accommodate technical advances. C1 [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gean, Alisa D.] San Francisco Gen Hosp, Dept Radiol, Brain & Spinal Cord Injury Ctr, San Francisco, CA 94110 USA. [Haacke, E. Mark] Wayne State Univ, Dept Biomed Engn, Detroit, MI USA. [Hicks, Ramona] NIH, Repair & Plast Program, Bethesda, MD 20892 USA. [Wintermark, Max; Mukherjee, Pratik] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Mukherjee, Pratik] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. [Brody, David] Washington Univ, Dept Neurol, St Louis, MO USA. [Latour, Lawrence] Natl Inst Neurol Disorders & Stroke, Stroke Diagnost & Therapeut Sect, Stroke Branch, Bethesda, MD USA. [Riedy, Gerard] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. RP Duhaime, AC (reprint author), Massachusetts Gen Hosp, Wang 331,115 Parkman St, Boston, MA 02114 USA. EM aduhaime@partners.org RI Mukherjee, Pratik/A-5446-2008; OI Mukherjee, Pratik/0000-0001-7473-7409; Wintermark, Max/0000-0002-6726-3951 NR 18 TC 43 Z9 43 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2010 VL 91 IS 11 BP 1661 EP 1666 DI 10.1016/j.apmr.2010.07.238 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 681UQ UT WOS:000284346400005 PM 21044709 ER PT J AU Nash, WP Vasterling, J Ewing-Cobbs, L Horn, S Gaskin, T Golden, J Riley, WT Bowles, SV Favret, J Lester, P Koffman, R Farnsworth, LC Baker, DG AF Nash, William P. Vasterling, Jennifer Ewing-Cobbs, Linda Horn, Sarah Gaskin, Thomas Golden, John Riley, William T. Bowles, Stephen V. Favret, James Lester, Patricia Koffman, Robert Farnsworth, Laura C. Baker, Dewleen G. TI Consensus Recommendations for Common Data Elements for Operational Stress Research and Surveillance: Report of a Federal Interagency Working Group SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Combat disorders; Military personnel; Preventive psychiatry; Rehabilitation; Research design; Stress; psychological ID MENTAL-HEALTH; POSTTRAUMATIC GROWTH; MILITARY PERSONNEL; COMBAT DEPLOYMENT; IRAQ-WAR; AFGHANISTAN; DISORDERS; INVENTORY; RESILIENCE; PREVENTION AB Empirical studies and surveillance projects increasingly assess and address potentially adverse psychological health outcomes from the stress of military operations, but no standards yet exist for common concept definitions, variable categories, and measures. This article reports the consensus recommendations of the federal interagency Operational Stress Working Group for common data elements to be used in future operational stress research and surveillance with the goal of improving comparability across studies. Operational stress encompasses more than just combat; it occurs everywhere service members and their families live and work. Posttraumatic stress is not the only adverse mental or behavioral health outcome of importance. The Operational Stress Working Group contends that a primary goal of operational stress research and surveillance is to promote prevention of adverse mental and behavioral outcomes, especially by recognizing the preclinical and subclinical states of distress and dysfunction that portend a risk for failure of role performance or future mental disorders. Recommendations for data elements are divided into 3 tiers: core, supplemental, and emerging, including variable domains and specific measures for assessing operational stressor exposures, stress outcomes, moderating factors, and mediating processes. Attention is drawn to the emerging construct of stress injury as a generic term for subclinical operational stress, and to emerging data elements addressing biological, psychological, and spiritual mediators of risk. Methodologies are needed for identifying preclinical and subclinical states of distress or dysfunction that are markers of risk for failure of role performance and future clinical mental disorders, so that targeted prevention interventions can be developed and evaluated. C1 [Nash, William P.; Horn, Sarah; Golden, John] Def Ctr Excellence Psychol Hlth & Traumat Brain I, Vet Adm, Arlington, VA USA. [Nash, William P.; Baker, Dewleen G.] Vet Adm San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Vasterling, Jennifer] VA Boston Healthcare Syst, Boston, MA USA. [Vasterling, Jennifer] Natl Ctr PTSD, Boston, MA USA. [Ewing-Cobbs, Linda] Univ Texas Houston, Houston, TX USA. [Ewing-Cobbs, Linda] Childrens Learning Inst, Dan L Duncan Neurodev Clin, Houston, TX USA. [Nash, William P.; Baker, Dewleen G.] Univ Calif San Diego, San Diego, CA 92103 USA. [Gaskin, Thomas] Marine Corps, Headquarters, Combat & Operat Stress Control, Quantico, VA USA. [Riley, William T.] NIMH, Bethesda, MD 20892 USA. [Bowles, Stephen V.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Favret, James] USAF, Washington, DC 20330 USA. [Lester, Patricia] Univ Calif Los Angeles, Semel Inst Neurosc & Human Behav, Los Angeles, CA USA. [Koffman, Robert] USN, Bur Med & Surg, Washington, DC USA. [Farnsworth, Laura C.] San Jose State Univ, San Jose, CA 95192 USA. RP Nash, WP (reprint author), POB 10920, Burke, VA 22015 USA. EM william.nash@opstress.net NR 69 TC 20 Z9 20 U1 3 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2010 VL 91 IS 11 BP 1673 EP 1683 DI 10.1016/j.apmr.2010.06.035 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 681UQ UT WOS:000284346400007 PM 21044711 ER PT J AU Kaloupek, DG Chard, KM Freed, MC Peterson, AL Riggs, DS Stein, MB Tuma, F AF Kaloupek, Danny G. Chard, Kathleen M. Freed, Michael C. Peterson, Alan L. Riggs, David S. Stein, Murray B. Tuma, Farris TI Common Data Elements for Posttraumatic Stress Disorder Research SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Diagnostic techniques and procedures; Outcome assessment; Rehabilitation; Stress disorders, post-traumatic ID TRAUMATIC BRAIN-INJURY; LIFE EVENTS QUESTIONNAIRE; INTERAGENCY WORKING GROUP; PREFERENCE-BASED MEASURE; ADMINISTERED PTSD SCALE; MENTAL-HEALTH PROBLEMS; PSYCHOMETRIC PROPERTIES; MILITARY SERVICE; RISK-FACTORS; DSM-IV AB An expert work group with 7 members was formed under the cosponsorship of 5 U.S. federal agencies to identify common data elements for research related to posttraumatic stress disorder (PTSD). The work group reviewed both previous and contemporary measurement standardization efforts for PTSD research and engaged in a series of electronic and live discussions to address a set of predefined aims. Eight construct domains relevant to PTSD were identified: (1) traditional demographics, (2) exposure to stressors and trauma, (3) potential stress moderators, (4) trauma assessment, (5) PTSD screening, (6) PTSD symptoms and diagnosis, (7) PTSD-related functioning and disability, and (8) mental health history. Measures assigned to the core data elements category have relatively low time-and-effort costs in order to make them potentially applicable across a wide range of studies for which PTSD is a relevant condition. Measures assigned to the supplemental data elements category have greater costs but generally demonstrate stronger psychometric performance and provide more extensive information. Accordingly, measures designated as supplemental are recommended instead of or in addition to corresponding core measures whenever resources and study design allow. The work group offered 4 caveats that highlight potential limitations and emphasize the voluntary nature of standardization for PTSD-related measurement. C1 [Kaloupek, Danny G.] Boston Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Vet Affairs Natl Ctr Posttraumat Stress Disorder, Boston, MA 02118 USA. [Kaloupek, Danny G.] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. [Chard, Kathleen M.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. [Chard, Kathleen M.] Univ Cincinnati, Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. [Freed, Michael C.] Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Washington, DC 20307 USA. [Freed, Michael C.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Freed, Michael C.] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Riggs, David S.] Uniformed Serv Univ Hlth Sci, Ctr Deployment Psychol, Bethesda, MD 20814 USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Tuma, Farris] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Kaloupek, DG (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM danny.kaloupek@va.gov OI Kaloupek, Danny/0000-0002-0795-593X NR 69 TC 18 Z9 18 U1 4 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2010 VL 91 IS 11 BP 1684 EP 1691 DI 10.1016/j.apmr.2010.06.032 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 681UQ UT WOS:000284346400008 PM 21044712 ER PT J AU Chan, MC Hilyard, AC Wu, C Davis, BN Hill, NS Lal, A Lieberman, J Lagna, G Hata, A AF Chan, Mun Chun Hilyard, Aaron C. Wu, Connie Davis, Brandi N. Hill, Nicholas S. Lal, Ashish Lieberman, Judy Lagna, Giorgio Hata, Akiko TI Antagonism Between Platelet-Derived Growth Factor and Transforming Growth Factor beta Through Modulation of microRNA-24 in Control of Phenotype Switching in Vascular Smooth Muscle Cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Chan, Mun Chun; Hilyard, Aaron C.; Hill, Nicholas S.; Lagna, Giorgio; Hata, Akiko] Tufts Med Cntr, Boston, MA USA. [Wu, Connie; Davis, Brandi N.] Sackler Sch BioMed Sci, Boston, MA USA. [Lal, Ashish; Lieberman, Judy] Harvard Univ, Sch Med, Boston, MA USA. [Lal, Ashish; Lieberman, Judy] Program Cellular & Mol Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E307 EP E307 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800561 ER PT J AU Choi, TY Nasir, K Zeb, I Mao, SS Flores, F Budoff, M AF Choi, Tae-young Nasir, Khurram Zeb, Irfan Mao, Song S. Flores, Fred Budoff, Matthew TI Relationship of Coronary Calcium Score with Coronary Plaque Burden and Morphology with Aging SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Choi, Tae-young; Zeb, Irfan; Mao, Song S.; Flores, Fred; Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles BioMed Rsch Inst, Torrance, CA 90509 USA. [Nasir, Khurram] Harvard Univ, Sch Med, Boston, MA USA. [Nasir, Khurram] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E235 EP E235 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800238 ER PT J AU Houbballah, R Robaldo, A Albadawi, H Titus, J LaMuraglia, G AF Houbballah, Rabih Robaldo, Alessandro Albadawi, Hassan Titus, James LaMuraglia, Glenn TI A Novel Model of Accelerated Intimal Hyperplasia in the Pig Iliac Artery SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Houbballah, Rabih; Robaldo, Alessandro; Albadawi, Hassan; Titus, James; LaMuraglia, Glenn] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E314 EP E314 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800597 ER PT J AU Ignjatovic, T Yamamoto, Y Lee, HJ Romeo, G Lee, J Libby, P Sukhova, GK Shoelson, SE AF Ignjatovic, Tatjana Yamamoto, Yasuhiko Lee, Hyuek Jong Romeo, Giulio Lee, Jongsoon Libby, Peter Sukhova, Galina K. Shoelson, Steven E. TI Salicylate Protects Against Atherosclerosis by Reducing Vascular Leukocyte Recruitment SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Ignjatovic, Tatjana; Yamamoto, Yasuhiko; Lee, Hyuek Jong; Romeo, Giulio; Lee, Jongsoon; Shoelson, Steven E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Libby, Peter; Sukhova, Galina K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E230 EP E230 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800218 ER PT J AU Isaacs, A Fouchier, SW Hofman, A Uitterlinden, AG Defesche, JC Witteman, JC Kathiresan, S Kastelein, JJ van Duijn, CM AF Isaacs, Aaron Fouchier, Sigrid W. Hofman, Albert Uitterlinden, Andre G. Defesche, Joep C. Witteman, Jacqueline C. Kathiresan, Sekar Kastelein, John J. van Duijn, Cornelia M. TI Risk Score Derived from GWAS LDL-C SNPs Predicts Atherosclerosis and Incidence of Coronary Heart Disease SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Isaacs, Aaron; Hofman, Albert; Uitterlinden, Andre G.; Witteman, Jacqueline C.; van Duijn, Cornelia M.] Erasmus Med Cntr, Rotterdam, Netherlands. [Fouchier, Sigrid W.; Defesche, Joep C.; Kastelein, John J.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Fouchier, Sigrid/A-8310-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E242 EP E242 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800273 ER PT J AU Jethwani, K Janket, SJ Jones, J Baird, A Meurman, J Van Dyke, T AF Jethwani, Kamal Janket, Sok-Ja Jones, Judith Baird, Alison Meurman, Jukka Van Dyke, Thomas TI Salivary Lysozyme as a Predictor of Cardiovascular Mortality SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Jethwani, Kamal] Massachusetts Gen Hosp, Cambridge, MA USA. [Jones, Judith] Boston Univ, Sch Dent Med, Boston, MA 02215 USA. [Baird, Alison] SUNY Downstate Med Cntr, New York, NY USA. [Meurman, Jukka] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Van Dyke, Thomas] Boston Univ, Henry M Goldman Sch Dent Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E234 EP E234 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800235 ER PT J AU McKittrick, IB Romeo, GR Moulton, KS AF McKittrick, Ian B. Romeo, Giulio R. Moulton, Karen S. TI Plaque Angiogenesis Is Induced by Diabetes and Accelerates Atherosclerosis Beyond Metabolic Factors SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [McKittrick, Ian B.; Moulton, Karen S.] Univ Colorado Denver, Aurora, CO USA. [Romeo, Giulio R.] Joslin Diabet Cntr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E200 EP E200 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800080 ER PT J AU Oklu, R Hesketh, R Wicky, S AF Oklu, Rahmi Hesketh, Robin Wicky, Stephan TI Activation of the Transforming Growth Factor-beta/Activin Signaling Pathway in Human Atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Oklu, Rahmi; Wicky, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hesketh, Robin] Univ Cambridge, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E293 EP E293 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800496 ER PT J AU Oklu, R Hesketh, R Wicky, S AF Oklu, Rahmi Hesketh, Robin Wicky, Stephan TI Localization of Latent Transforming Growth Factor-beta Binding Protein-1 (LTBP1) in Human Coronary Atherosclerotic Plaques SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Oklu, Rahmi; Wicky, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hesketh, Robin] Univ Cambridge, Cambridge, England. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E253 EP E253 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800324 ER PT J AU Oklu, R Hesketh, R Wicky, S AF Oklu, Rahmi Hesketh, Robin Wicky, Stephan TI Expression of Latent Transforming Growth Factor-beta Binding Protein-1 (LTBP1) Isoforms in Coronary Atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Oklu, Rahmi; Wicky, Stephan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hesketh, Robin] Univ Cambridge, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E216 EP E216 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800153 ER PT J AU Rayner, KJ Suarez, Y Davalos, A Parathath, S Fitzgerald, ML Tamehiro, N Fisher, EA Moore, KJ Fernandez-Hernando, C AF Rayner, Katey J. Suarez, Yajaira Davalos, Alberto Parathath, Saj Fitzgerald, Michael L. Tamehiro, Norimasa Fisher, Edward A. Moore, Kathryn J. Fernandez-Hernando, Carlos TI Mir-33 Coordinates Genes Regulating Cholesterol Homeostasis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Rayner, Katey J.; Suarez, Yajaira; Davalos, Alberto; Parathath, Saj; Fisher, Edward A.; Moore, Kathryn J.; Fernandez-Hernando, Carlos] NYU, Sch Med, New York, NY USA. [Fitzgerald, Michael L.; Tamehiro, Norimasa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E191 EP E191 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800041 ER PT J AU Rayner, KJ Rodrigues-Fernandes, L Martin-Fuentes, P Wilkinson, K Stewart, C van Gils, JM Stuart, L Moore, KJ AF Rayner, Katey J. Rodrigues-Fernandes, Luciana Martin-Fuentes, Paula Wilkinson, Kim Stewart, Cameron van Gils, Janine M. Stuart, Lynda Moore, Kathryn J. TI CD36 Partners with a Novel TLR Heterodimer TLR4/TLR6 to Promote Atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Rayner, Katey J.; van Gils, Janine M.; Moore, Kathryn J.] NYU, Langone Med Cntr, New York, NY USA. [Rodrigues-Fernandes, Luciana; Martin-Fuentes, Paula; Wilkinson, Kim; Stewart, Cameron; Stuart, Lynda] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E186 EP E186 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800018 ER PT J AU Ripplinger, CM Li, CQ Kim, J McCarthy, JR Lin, CP Jaffer, FA AF Ripplinger, Crystal M. Li, Chunqiang Kim, JinWon McCarthy, Jason R. Lin, Charles P. Jaffer, Farouc A. TI Multispectral in Vivo Molecular, Functional, and Anatomical Imaging of Venous Thrombosis Resolution SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Ripplinger, Crystal M.; Li, Chunqiang; Kim, JinWon; McCarthy, Jason R.; Lin, Charles P.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E185 EP E185 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800013 ER PT J AU Strong, A Musunuru, K Frank-Kamenetsky, M Sachs, KV Li, XY Li, H Lund-Katz, S Phillips, M Wong, J Cantley, W Koteliansky, V Fitzgerald, K Krauss, RM Kathiresan, S Rader, DJ AF Strong, Alanna Musunuru, Kiran Frank-Kamenetsky, Maria Sachs, Katherine V. Li, Xiaoyu Li, Hui Lund-Katz, Sissel Phillips, Michael Wong, Jamie Cantley, Will Koteliansky, Victor Fitzgerald, Kevin Krauss, Ronald M. Kathiresan, Sekar Rader, Daniel J. TI Sortilin Is a Novel Modulator of Low-Density Lipoprotein Cholesterol SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Strong, Alanna; Sachs, Katherine V.; Li, Xiaoyu; Li, Hui; Rader, Daniel J.] Univ Penn, Philadelphia, PA 19104 USA. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Musunuru, Kiran] Harvard Univ, Sch Med, Boston, MA USA. [Frank-Kamenetsky, Maria; Wong, Jamie; Cantley, Will; Koteliansky, Victor; Fitzgerald, Kevin] Alnylam Pharmaceut, Cambridge, MA USA. [Lund-Katz, Sissel; Phillips, Michael] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Krauss, Ronald M.] Childrens Hosp, Oakland Rsch Inst, Oakland, CA 94609 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E188 EP E188 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800025 ER PT J AU Taylor, CM Ramanathan, K Banerji, D Heydari, B Hoffmann, U Leipsic, J Heilbron, B AF Taylor, Carolyn M. Ramanathan, Krishnan Banerji, Dahlia Heydari, Bobby Hoffmann, Udo Leipsic, Jonathon Heilbron, Brett TI Coronary Artery Plaque Morphology and Distribution Differs by Age but Not by Conventional Risk Factor Burden SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Taylor, Carolyn M.; Ramanathan, Krishnan; Heydari, Bobby] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Banerji, Dahlia; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leipsic, Jonathon; Heilbron, Brett] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E254 EP E254 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800326 ER PT J AU van Gils, JM Stewart, MC Rayner, KJ Fernandes, LR McDonald, TO OBrien, KD Moore, KJ AF van Gils, Janine M. Stewart, Merran C. Rayner, Katey J. Fernandes, Luciana R. McDonald, Thomas O. OBrien, Kevin D. Moore, Kathryn J. TI Netrin-1: A Multifunctional Guidance Cue that Promotes Atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [van Gils, Janine M.; Rayner, Katey J.; Moore, Kathryn J.] NYU Langone Med Cntr, New York, NY USA. [Stewart, Merran C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fernandes, Luciana R.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [McDonald, Thomas O.; OBrien, Kevin D.] Univ Washington, Seattle, WA 98195 USA. RI Rayner, Katey/K-8914-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E292 EP E292 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800492 ER PT J AU Yang, C Yuan, C Canton, G Hatsukami, T Tang, D AF Yang, Chun Yuan, Chun Canton, Gador Hatsukami, Thomas Tang, Dalin TI Advanced Human Carotid Plaque Progression Correlates Positively with Flow Shear Stress: An in Vivo MRI Multipatient 3D FSI Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 08-10, 2010 CL San Francisco, CA C1 [Yang, Chun] Beijing Normal Univ, Beijing 100875, Peoples R China. [Yuan, Chun; Canton, Gador; Hatsukami, Thomas] Univ Washington, Seattle, WA 98195 USA. [Hatsukami, Thomas] VA Puget Sound HCS, Seattle, WA USA. [Tang, Dalin] Worcester Polytech Inst, Worcester, MA 01609 USA. RI Canton, Gador/H-4227-2016 OI Canton, Gador/0000-0002-0594-2764 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2010 VL 30 IS 11 BP E315 EP E315 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 667YS UT WOS:000283234800600 ER PT J AU Deane, KD O'Donnell, CI Hueber, W Majka, DS Lazar, AA Derber, LA Gilliland, WR Edison, JD Norris, JM Robinson, WH Holers, VM AF Deane, Kevin D. O'Donnell, Colin I. Hueber, Wolfgang Majka, Darcy S. Lazar, Ann A. Derber, Lezlie A. Gilliland, William R. Edison, Jess D. Norris, Jill M. Robinson, William H. Holers, V. Michael TI The Number of Elevated Cytokines and Chemokines in Preclinical Seropositive Rheumatoid Arthritis Predicts Time to Diagnosis in an Age-Dependent Manner SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CYCLIC CITRULLINATED PEPTIDE; C-REACTIVE PROTEIN; UP-REGULATION; BLOOD-DONORS; 1ST-DEGREE RELATIVES; PROSPECTIVE COHORT; EFFECTS MODELS; ANTIBODIES; ONSET; AUTOANTIBODIES AB Objective. To evaluate levels of biomarkers in preclinical rheumatoid arthritis (RA) and to use elevated biomarkers to develop a model for the prediction of time to future diagnosis of seropositive RA. Methods. Stored samples obtained from 73 military cases with seropositive RA prior to RA diagnosis and from controls (mean 2.9 samples per case; samples collected a mean of 6.6 years prior to diagnosis) were tested for rheumatoid factor (RF) isotypes, anti-cyclic citrullinated peptide (anti-CCP) antibodies, 14 cytokines and chemokines (by bead-based assay), and C-reactive protein (CRP). Results. Preclinical positivity for anti-CCP and/or >= 2 RF isotypes was >96% specific for future RA. In preclinical RA, levels of the following were positive in a significantly greater proportion of RA cases versus controls: interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, fibroblast growth factor 2, flt-3 ligand, tumor necrosis factor alpha, interferon-gamma-inducible 10-kd protein, granulocyte-macrophage colony-stimulating factor, and CRP. Also, increasing numbers of elevated cytokines/chemokines were present in cases nearer to the time of diagnosis. RA patients who were >= 40 years old at diagnosis had a higher proportion of samples positive for cytokines/chemokines 5-10 years prior to diagnosis than did patients who were <40 years old at diagnosis (P < 0.01). In regression modeling using only case samples positive for autoantibodies highly specific for future RA, increasing numbers of cytokines/chemokines were predictive of decreased time to diagnosis, and the predicted time to diagnosis based on cytokines/chemokines was longer in older compared with younger cases. Conclusion. Levels of autoantibodies, cytokines/chemokines, and CRP are elevated in the preclinical period of RA development. In preclinical autoantibody-positive cases, the number of elevated cytokines/chemokines is predictive of the time of diagnosis of future RA in an age-dependent manner. C1 [Deane, Kevin D.] Univ Colorado, Sch Med, Div Rheumatol, Aurora, CO 80045 USA. [O'Donnell, Colin I.; Norris, Jill M.] Colorado Sch Publ Hlth, Aurora, CO USA. [Hueber, Wolfgang; Robinson, William H.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Hueber, Wolfgang; Robinson, William H.] Stanford Univ, Stanford, CA 94305 USA. [Hueber, Wolfgang] Novartis Inst BioMed Res, Basel, Switzerland. [Majka, Darcy S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Lazar, Ann A.] Harvard Univ, Boston, MA 02115 USA. [Lazar, Ann A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gilliland, William R.; Edison, Jess D.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Deane, KD (reprint author), Univ Colorado, Sch Med, Div Rheumatol, 1775 Aurora Court,Mail Stop B-115, Aurora, CO 80045 USA. EM Kevin.Deane@UCDenver.edu FU NIH [AR-51394, AI-50864, AR-051461, T32-CA-09337, P30-DE-020752, AR-058713, AR-054822]; American College of Rheumatology Research and Education Foundation FX Drs. Deane, Norris, and Holers, Mr. O'Donnell, and Ms Derber's work was supported by NIH grants AR-51394, AI-50864, and AR-051461. Dr. Lazar's work was supported by NIH grants T32-CA-09337 and P30-DE-020752. Dr. Robinson's work was supported by NIH grants AR-058713 and AR-054822 and by the American College of Rheumatology Research and Education Foundation. NR 37 TC 82 Z9 86 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-US JI Arthritis Rheum. PD NOV PY 2010 VL 62 IS 11 BP 3161 EP 3172 DI 10.1002/art.27638 PG 12 WC Rheumatology SC Rheumatology GA 674UU UT WOS:000283776400005 PM 20597112 ER PT J AU Clancy, RM Marion, MC Kaufman, KM Ramos, PS Adler, A Harley, JB Langefeld, CD Buyon, JP AF Clancy, Robert M. Marion, Miranda C. Kaufman, Kenneth M. Ramos, Paula S. Adler, Adam Harley, John B. Langefeld, Carl D. Buyon, Jill P. CA Int Consortium Syst Lupus TI Identification of Candidate Loci at 6p21 and 21q22 in a Genome-Wide Association Study of Cardiac Manifestations of Neonatal Lupus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CONGENITAL HEART-BLOCK; PRIMARY SJOGRENS-SYNDROME; ANTI-SSA/RO; TNF-ALPHA; ATRIOVENTRICULAR-BLOCK; ENDOTHELIAL-CELLS; SSB/LA ANTIBODIES; RECURRENCE RATES; SS-A/RO; ERYTHEMATOSUS AB Objective. Cardiac manifestations of neonatal lupus, comprising atrioventricular conduction defects and cardiomyopathy, occur in fetuses exposed to anti-Ro/SSA antibodies, and carry substantial mortality. There is strong evidence of a genetic contribution to the risk. This study was undertaken to evaluate single-nucleotide polymorphisms (SNPs) for associations with cardiac neonatal lupus. Methods. Children of European ancestry with cardiac neonatal lupus (n = 116) were genotyped using the Illumina 370K SNP platform and merged with 3,351 controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for association with cardiac neonatal lupus were determined. Results. The 17 most significant associations with cardiac neonatal lupus were found in the HLA region. The region near the MICB gene showed the strongest variant (rs3099844; P(dom) = 4.52 x 10(-10), OR 3.34 [95% CI 2.29-4.89]), followed by a missense variant within C6orf10 (rs7775397; P(dom) = 1.35 x 10(-9), OR 3.30), which lies between NOTCH4 and BTNL2, and several SNPs near the tumor necrosis factor alpha gene, including rs2857595 (P(add) = 1.96 x 10(-9), OR 2.37), rs2230365 (P(add) = 1.00 x 10(-3), OR 0.46), and rs3128982 (P(add) = 6.40 x 10(-6), OR 1.86). Outside the HLA region, an association was detected at 21q22, upstream of the transcription regulator ets-related isoform 1 (rs743446; P = 5.45 x 10(-6), OR 2.40). HLA notwithstanding, no individual locus previously implicated in autoimmune diseases achieved genome-wide significance. Conclusion. These results suggest that variation near genes related to inflammatory and apoptotic responses may promote cardiac injury initiated by passively acquired autoantibodies. C1 [Clancy, Robert M.] NYU, Langone Sch Med, New York, NY 10003 USA. [Marion, Miranda C.; Ramos, Paula S.; Langefeld, Carl D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Harley, John B.] Univ Oklahoma, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Clancy, RM (reprint author), NYU, Langone Sch Med, 301 E 17th St, New York, NY 10003 USA. EM bobdclancy@aol.com FU NIH [AR-42455, N01-AR-42271, P01-AI-083194-01, P20-RR-020143-06, U19-AI-082714-01, P01-AR-049084-07, N01-AR-62277, R01-DE-018209-01A1, R37-AI-024717-21, R01-AR-042460-15]; American Heart Association [0655938T]; Wake Forest University Health Sciences Center for Public Health Genomics; Alliance for Lupus Research FX Supported by NIH grants AR-42455 and N01-AR-42271 and by American Heart Association grant-in-aid 0655938T. Ms Marion and Drs. Ramos and Langefeld's work was supported by the Wake Forest University Health Sciences Center for Public Health Genomics. Drs. Kaufman and Harley are recipients of US Department of Veterans Affairs Merit Awards. Dr. Harley's work was also supported by NIH grants P01-AI-083194-01, P20-RR-020143-06, U19-AI-082714-01, P01-AR-049084-07, N01-AR-62277, R01-DE-018209-01A1, R37-AI-024717-21, and R01-AR-042460-15. The International Consortium on Systemic Lupus Erythematosus Genetics was funded by the Alliance for Lupus Research. NR 50 TC 33 Z9 36 U1 0 U2 2 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 NOV PY 2010 VL 62 IS 11 BP 3415 EP 3424 DI 10.1002/art.27658 PG 10 WC Rheumatology SC Rheumatology GA 674UU UT WOS:000283776400033 PM 20662065 ER PT J AU Jensen, KB Petzke, F Carville, S Fransson, P Marcus, H Williams, SCR Choy, E Mainguy, Y Gracely, R Ingvar, M Kosek, E AF Jensen, Karin B. Petzke, Frank Carville, Serena Fransson, Peter Marcus, Hanke Williams, Steven C. R. Choy, Ernest Mainguy, Yves Gracely, Richard Ingvar, Martin Kosek, Eva TI Anxiety and Depressive Symptoms in Fibromyalgia Are Related to Poor Perception of Health but Not to Pain Sensitivity or Cerebral Processing of Pain SO ARTHRITIS AND RHEUMATISM LA English DT Article ID BACK-PAIN; SOMATOSENSORY PERCEPTION; CLINICAL PAIN; DOUBLE-BLIND; MODULATION; DISORDER; BRAIN; DULOXETINE; ARTHRITIS; TRIAL AB Objective. Mood disturbance is common among patients with fibromyalgia (FM), but the influence of psychological symptoms on pain processing in this disorder is unknown. We undertook the present study to investigate the differential effect of depressive symptoms, anxiety, and catastrophizing on 1) pain symptoms and subjective ratings of general health status and 2) sensitivity to pain and cerebral processing of pressure pain. Methods. Eighty-three women (mean +/- SD age 43.8 +/- 8.1 years) who fulfilled the American College of Rheumatology 1990 criteria for the classification of FM participated in the study. Patients rated pain intensity (100-mm visual analog scale [VAS]), severity of FM (Fibromyalgia Impact Questionnaire), general health status (Short Form 36), depressive symptoms (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), and catastrophizing (Coping Strategies Questionnaire). Experimental pain in the thumb was induced using a computer-controlled pressure stimulator. Event-related functional magnetic resonance imaging was performed during administration of painful stimuli representing 50 mm on a pain VAS, as well as nonpainful pressures. Results. A correlation analysis including all self-ratings showed that depressive symptoms, anxiety, and catastrophizing scores were correlated with one another (P < 0.001), but did not correlate with ratings of clinical pain or with sensitivity to pressure pain. However, the subjective rating of general health was correlated with depressive symptoms and anxiety (P < 0.001). Analyses of imaging results using self-rated psychological measures as covariates showed that brain activity during experimental pain was not modulated by depressive symptoms, anxiety, or catastrophizing. Conclusion. Negative mood in FM patients can lead to a poor perception of one's physical health (and vice versa) but does not influence performance on assessments of clinical and experimental pain. Our data provide evidence that 2 partially segregated mechanisms are involved in the neural processing of experimental pain and negative affect. C1 [Jensen, Karin B.; Fransson, Peter; Ingvar, Martin; Kosek, Eva] Karolinska Inst, Osher Ctr Integrat Med, Stockholm Brain Inst, Stockholm, Sweden. [Petzke, Frank; Marcus, Hanke] Univ Hosp Cologne, Dept Anesthesiol & Postoperat Intens Care Med, Cologne, Germany. [Carville, Serena; Choy, Ernest] Kings Coll London, Acad Dept Rheumatol, Kings Musculoskeletal Clin Trials Unit, London WC2R 2LS, England. [Williams, Steven C. R.] Kings Coll London, Inst Psychiat, Ctr Neuroimaging Sci, London WC2R 2LS, England. [Mainguy, Yves] Pierre Fabre Medicament, Labege, France. [Gracely, Richard] Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC USA. RP Jensen, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. EM karinj@nmr.mgh.harvard.edu RI Jensen, Karin/G-6360-2012; Williams, Steve/D-6979-2011; Fransson, Peter/M-5679-2014; OI Williams, Steve/0000-0003-4299-1941; Fransson, Peter/0000-0002-1305-9875; Ingvar, Martin/0000-0002-9041-5714; Jensen, Karin/0000-0003-2521-3160 FU Pierre Fabre Medicament [2004-004249-16] FX This study was performed in collaboration with Pierre Fabre Medicament, Labege, France. The results in this study are derived in part from a placebo-controlled drug intervention study (EudraCT # 2004-004249-16) financed by Pierre Fabre Medicament. NR 45 TC 38 Z9 41 U1 0 U2 6 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 NOV PY 2010 VL 62 IS 11 BP 3488 EP 3495 DI 10.1002/art.27649 PG 8 WC Rheumatology SC Rheumatology GA 674UU UT WOS:000283776400041 PM 20617526 ER PT J AU Grossman, JM Gordon, R Ranganath, VK Deal, C Caplan, L Chen, WL Curtis, JR Furst, DE McMahon, M Patkar, NM Volkmann, E Saag, KG AF Grossman, Jennifer M. Gordon, Rebecca Ranganath, Veena K. Deal, Chad Caplan, Liron Chen, Weiling Curtis, Jeffrey R. Furst, Daniel E. McMahon, Maureen Patkar, Nivedita M. Volkmann, Elizabeth Saag, Kenneth G. TI American College of Rheumatology 2010 Recommendations for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID CORTICOSTEROID-INDUCED OSTEOPOROSIS; INDUCED BONE LOSS; INTERMITTENT CYCLICAL ETIDRONATE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; VERTEBRAL FRACTURE ASSESSMENT; INTRANASAL SALMON-CALCITONIN; CONNECTIVE-TISSUE DISEASE; HIGH-DOSE GLUCOCORTICOIDS AB Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. C1 [Grossman, Jennifer M.; Gordon, Rebecca; Ranganath, Veena K.; Chen, Weiling; Furst, Daniel E.; McMahon, Maureen; Volkmann, Elizabeth] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Gordon, Rebecca] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Deal, Chad] Cleveland Clin, Cleveland, OH 44106 USA. [Caplan, Liron] Univ Colorado, Denver, CO 80202 USA. [Curtis, Jeffrey R.; Patkar, Nivedita M.; Saag, Kenneth G.] Univ Alabama, Birmingham, AL USA. RP Grossman, JM (reprint author), Univ Calif Los Angeles, 1000 Vet Ave,Room 32-59,Rehabil Bldg, Los Angeles, CA 90095 USA. EM jgrossman@mednet.ucla.edu FU Lilly; Amgen; Genentech; Eli Lilly; Procter Gamble; Novartis; Roche/Genentech; Merck; Aventis; AstraZeneca; Pfizer; Horizon FX Dr. Deal has received consultant fees, speaking fees, and/or honoraria (more than $10,000 each) from Lilly, Amgen, and Genentech. Dr. Curtis has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Eli Lilly and Procter & Gamble, and (more than $10,000 each) from Novartis, Amgen, Roche/Genentech, and Merck. Dr. Saag has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Merck, Lilly, Novartis, Aventis, Genentech, AstraZeneca, Pfizer, and Horizon. NR 104 TC 316 Z9 341 U1 3 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD NOV PY 2010 VL 62 IS 11 BP 1515 EP 1526 DI 10.1002/acr.20295 PG 12 WC Rheumatology SC Rheumatology GA 678BA UT WOS:000284041200001 PM 20662044 ER PT J AU Davis, LA Larson, MM Caplan, L AF Davis, Lisa A. Larson, Molly M. Caplan, Liron TI Observational Study to Determine Predictors of Rheumatology Clinic Visit Provider Contact Time SO ARTHRITIS CARE & RESEARCH LA English DT Article ID LENGTH AB Objective. To address perceived inefficiencies in an academic rheumatology practice, a timing/work-flow evaluation was initiated to determine the factors that predict the provider contact time (PCT), i.e., the amount of time that attending physicians spend with patients during an outpatient encounter. Methods. This prospective observational study was conducted at the University of Colorado Hospital Rheumatology Clinic for return patient visits in early 2008. Each patient encounter was subdivided into components, and the time for each component was recorded. Up to 20 return-visit encounters per provider were randomly selected for inclusion. Multivariate linear regression was used to predict the time, in minutes, that providers spent with patients, and logistic regression was used to determine the time intervals associated with the patient's perception that the visit ran on time. Results. Variables associated with increased PCT were whether a procedure was performed in the clinic (P = 0.037) and whether the visit occurred in the afternoon (P < 0.025). For every minute a provider was late in beginning to see a patient, the PCT decreased by 0.32 minutes (95% confidence interval [ 95% CI] 0.15, 0.49). Variables associated with the patient's perception that the visit ran on time included the check-in to vitals delay (odds ratio [ OR] 0.95; 95% CI 0.92, 0.99) and the provider delay (OR 0.92; 95% CI 0.86, 0.99). Conclusion. The patient's punctuality and the presence of a resident are not significantly associated with the time that a provider spends with a patient. However, the degree to which the provider runs late was associated with decreased PCT and diminishes the patient's perception that the visit is running on time. C1 [Davis, Lisa A.; Larson, Molly M.; Caplan, Liron] Univ Colorado, Sch Med, Denver, CO 80045 USA. [Caplan, Liron] Denver VAMC, Denver, CO USA. RP Caplan, L (reprint author), Univ Colorado, Sch Med, POB 6511,B115, Denver, CO 80045 USA. EM liron.caplan@ucdenver.edu FU NIH, National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32-AR007534-24]; VA Health Services [CDP 09-388] FX Dr. Davis's work was supported by the NIH (grant T32-AR007534-24 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases). Dr. Caplan's work was supported by a VA Health Services Research and Development Award (CDP 09-388). NR 12 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD NOV PY 2010 VL 62 IS 11 BP 1650 EP 1654 DI 10.1002/acr.20281 PG 5 WC Rheumatology SC Rheumatology GA 678BA UT WOS:000284041200017 PM 20583104 ER PT J AU Chou, RC Mihm, MC Stone, JH AF Chou, Richard C. Mihm, Martin C. Stone, John H. TI A 44-Year-Old Woman With Right Ankle Pain SO ARTHRITIS CARE & RESEARCH LA English DT Editorial Material ID RHEUMATOLOGY 1990 CRITERIA; C VIRUS-INFECTION; HEPATITIS-C; MICROSCOPIC POLYANGIITIS; WEGENERS-GRANULOMATOSIS; POLYARTERITIS-NODOSA; ANTIPHOSPHOLIPID SYNDROME; LIVEDOID VASCULOPATHY; VASCULITIS; ARTHRITIS C1 [Stone, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02114 USA. RP Stone, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Yawkey 2-55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org NR 38 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 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD NOV PY 2010 VL 62 IS 11 BP 1665 EP 1672 DI 10.1002/acr.20242 PG 8 WC Rheumatology SC Rheumatology GA 678BA UT WOS:000284041200020 PM 20506413 ER PT J AU Lee, DBN Roberts, M Bluchel, CG Odell, RA AF Lee, David B. N. Roberts, Martin Bluchel, Christian G. Odell, Ross A. TI Zirconium: Biomedical and Nephrological Applications SO ASAIO JOURNAL LA English DT Article ID OSTEOBLAST-LIKE CELLS; STAGE RENAL-FAILURE; IN-VITRO; TRACE-ELEMENT; HEAVY-METALS; DIALYSIS OSTEOMALACIA; ORGANIC-SUBSTANCES; ENDOTHELIAL-CELLS; URINARY-EXCRETION; CLINICAL REPORT AB Recent years have witnessed a rapid increase in the use of zirconium (Zr)-containing compounds in artificial internal organs. Examples include dental implants and other restorative practices, total knee and hip replacement, and middle-ear ossicular chain reconstruction. In nephrological practice, Zr-containing sorbents have been used in hemofiltration, hemodialysis, peritoneal dialysis, and in the design and construction of wearable artificial kidneys. Zr compounds continue to be widely and extensively used in deodorant and antiperspirant preparations. In the public health arena, Zr compounds have been studied or used in controlling phosphorus pollution and in the reclamation of poison and bacteria-contaminated water. Experimental and clinical studies support the general consensus that Zr compounds are biocompatible and exhibit low toxicity. Reports on possible Zr-associated adverse reactions are rare and, in general, have not rigorously established a cause-and-effect relationship. Although publications on the use of Zr compounds have continued to increase in recent years, reports on Zr toxicity have virtually disappeared from the medical literature. Nevertheless, familiarity with, and continued vigilant monitoring of, the use of these compounds are warranted. This article provides an updated review on the biomedical use of Zr compounds. ASAIO Journal 2010; 56:550-556. C1 [Lee, David B. N.; Roberts, Martin] VA Greater Healthcare Syst, Nephrol Sect, Sepulveda Ambulatory Care Ctr & Nursing Home, North Hills, CA 91343 USA. [Lee, David B. N.; Roberts, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lee, David B. N.; Roberts, Martin; Bluchel, Christian G.] AWAK Technol Inc, Burbank, CA USA. [Lee, David B. N.; Roberts, Martin; Bluchel, Christian G.] AWAK Technol Inc, Singapore, Singapore. [Bluchel, Christian G.] Temasek Polytechn, Temasek Engn Sch, Singapore, Singapore. [Odell, Ross A.] Univ New S Wales, Grad Sch Biomed Engn, Sydney, NSW, Australia. RP Lee, DBN (reprint author), VA Greater Healthcare Syst, Nephrol Sect, Sepulveda Ambulatory Care Ctr & Nursing Home, Room 3526,Bldg 200,16111 Plummer St, North Hills, CA 91343 USA. EM dbnlee@ucla.edu NR 86 TC 25 Z9 25 U1 1 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD NOV-DEC PY 2010 VL 56 IS 6 BP 550 EP 556 DI 10.1097/MAT.0b013e3181e73f20 PG 7 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 674FH UT WOS:000283719600012 PM 21245802 ER PT J AU Neale, B AF Neale, Benjamin TI Genome-wide association analysis of attention deficit hyperactivity disorder SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 40th Annual Meeting of Behavior-Genetics-Association CY MAY, 2009 CL State Coll, Pennsylvania, PA SP Behavior Genet Assoc HO State Coll C1 [Neale, Benjamin] Broad Inst Harvard & MIT, Cambridge, MA USA. [Neale, Benjamin] Massachusetts Gen Hosp, 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 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2010 VL 40 IS 6 SI SI BP 807 EP 807 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 686KW UT WOS:000284696200085 ER PT J AU Neale, BM Rivas, MA Voight, BF Altshuler, D Devlin, B Orho-Melander, M Katherisan, S Roeder, K Daly, MJ AF Neale, Benjamin M. Rivas, Manuel A. Voight, Benjamin F. Altshuler, David Devlin, Bernie Orho-Melander, Marju Katherisan, Sekar Roeder, Kathryn Daly, Mark J. TI Testing for an unusual distribution of rare variation SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 40th Annual Meeting of Behavior-Genetics-Association CY MAY, 2009 CL State Coll, Pennsylvania, PA SP Behavior Genet Assoc HO State Coll C1 [Neale, Benjamin M.; Rivas, Manuel A.; Voight, Benjamin F.; Altshuler, David; Katherisan, Sekar; Daly, Mark J.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Neale, Benjamin M.; Rivas, Manuel A.; Voight, Benjamin F.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Devlin, Bernie] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Orho-Melander, Marju] Malmo Univ Hosp, Dept Clin Res, Malmo, Sweden. [Katherisan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Roeder, Kathryn] Carnie Mellon Univ, Dept Stat, Pittsburgh, PA USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 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 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2010 VL 40 IS 6 SI SI BP 807 EP 807 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 686KW UT WOS:000284696200086 ER PT J AU Fertig, EJ Ding, J Favorov, AV Parmigiani, G Ochs, MF AF Fertig, Elana J. Ding, Jie Favorov, Alexander V. Parmigiani, Giovanni Ochs, Michael F. TI CoGAPS: an R/C++ package to identify patterns and biological process activity in transcriptomic data SO BIOINFORMATICS LA English DT Article ID MATRIX FACTORIZATION; MICROARRAY DATA AB Coordinated Gene Activity in Pattern Sets (CoGAPS) provides an integrated package for isolating gene expression driven by a biological process, enhancing inference of biological processes from transcriptomic data. CoGAPS improves on other enrichment measurement methods by combining a Markov chain Monte Carlo (MCMC) matrix factorization algorithm (GAPS) with a threshold-independent statistic inferring activity on gene sets. The software is provided as open source C++ code built on top of JAGS software with an R interface. C1 [Fertig, Elana J.; Favorov, Alexander V.; Ochs, Michael F.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Fertig, Elana J.; Favorov, Alexander V.; Ochs, Michael F.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Oncol Biostat & Bioinformat, Baltimore, MD 21205 USA. [Ding, Jie; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Favorov, Alexander V.] Res Inst Genet & Select Ind Microorganisms, Moscow 117545, Russia. RP Fertig, EJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. EM ejfertig@jhmi.edu; mfo@jhu.edu FU National Library of Medicine [LM009382]; National Science Foundation [0342111] FX National Library of Medicine (Grant LM009382); National Science Foundation (Grant 0342111). NR 12 TC 14 Z9 14 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV PY 2010 VL 26 IS 21 BP 2792 EP 2793 DI 10.1093/bioinformatics/btq503 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 673LT UT WOS:000283665000026 PM 20810601 ER PT J AU Perlis, RH AF Perlis, Roy H. TI Can Single Genes Matter in a Polygenic World? SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID BIPOLAR DISORDER; ASSOCIATION C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Lab Psychiat Pharmacogenom, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Lab Psychiat Pharmacogenom, Boston, MA 02114 USA. EM rperlis@partners.org NR 12 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2010 VL 68 IS 9 BP 783 EP 784 DI 10.1016/j.biopsych.2010.09.010 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 672TA UT WOS:000283608600002 PM 20946974 ER PT J AU Porter, DL Alyea, EP Antin, JH DeLima, M Estey, E Falkenburg, JHF Hardy, N Kroeger, N Leis, J Levine, J Maloney, DG Peggs, K Rowe, JM Wayne, AS Giralt, S Bishop, MR van Besien, K AF Porter, David L. Alyea, Edwin P. Antin, Joseph H. DeLima, Marcos Estey, Eli Falkenburg, J. H. Frederik Hardy, Nancy Kroeger, Nicolaus Leis, Jose Levine, John Maloney, David G. Peggs, Karl Rowe, Jacob M. Wayne, Alan S. Giralt, Sergio Bishop, Michael R. van Besien, Koen TI NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic stem cell transplantation; Treatment; Donor lymphocyte infusion ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; DONOR LEUKOCYTE INFUSIONS; CHRONIC MYELOGENOUS LEUKEMIA; NON-HODGKIN-LYMPHOMA; MINIMAL RESIDUAL DISEASE; MINOR HISTOCOMPATIBILITY ANTIGENS AB Relapse is a major cause of treatment failure after allogeneic hematopoietic stern cell transplantation (alloHSCT). Treatment options for relapse have been inadequate, and the majority of patients ultimately die of their disease. There is no standard approach to treating relapse after alloHSCT. Withdrawal of immune suppression and donor lymphocyte infusions are commonly used for all diseases; although these interventions are remarkably effective for relapsed chronic myelogenous leukemia, they have limited efficacy in other hematologic malignancies. Conventional and novel chemotherapy, monoclonal antibody therapy, targeted therapies, and second transplants have been utilized in a variety of relapsed diseases, but reports on these therapies are generally anecdotal and retrospective. As such, there is an immediate need for well-designed, disease-specific trials for treatment of relapse after alloHSCT. This report summarizes current treatment options under investigation for relapse after alloHSCT in a disease-specific manner. In addition, recommendations are provided for specific areas of research necessary in the treatment of relapse after alloHSCT. C1 [Porter, David L.] Univ Penn, Div Hematol Oncol, Med Ctr, Philadelphia, PA 19104 USA. [Alyea, Edwin P.; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [DeLima, Marcos; Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Estey, Eli; Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Falkenburg, J. H. Frederik] Leiden Univ, Med Ctr, Leiden, Netherlands. [Kroeger, Nicolaus] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Leis, Jose] Mayo Clin, Scottsdale, AZ USA. [Levine, John] Univ Michigan, Ann Arbor, MI 48109 USA. [Peggs, Karl] UCL, London, England. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. [Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [van Besien, Koen] Univ Chicago, Chicago, IL 60637 USA. RP Porter, DL (reprint author), Univ Penn, Div Hematol Oncol, Med Ctr, PCAM 2 W Pavil,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM david.porter@uphs.upenn.edu RI PEGGS, Karl/B-3869-2009; van Besien, Koen/G-4221-2012 OI van Besien, Koen/0000-0002-8164-6211 FU NCI NIH HHS [K24 CA117879] NR 321 TC 62 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2010 VL 16 IS 11 BP 1467 EP 1503 DI 10.1016/j.bbmt.2010.08.001 PG 37 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 675KY UT WOS:000283830800001 PM 20699125 ER PT J AU Baldessarini, RJ AF Baldessarini, Ross J. TI Commentary: The Bipolar Affective Disorder: Lithium/Anticonvulsant Evaluation (BALANCE) Study SO BIPOLAR DISORDERS LA English DT Editorial Material DE BALANCE trial; bipolar disorder; lithium; long-term treatment; valproate ID I DISORDER; LITHIUM; MAINTENANCE; RELAPSE C1 [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Psychopharmacol Program, Belmont, MA USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org NR 12 TC 3 Z9 3 U1 0 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 NOV PY 2010 VL 12 IS 7 BP 669 EP 672 DI 10.1111/j.1399-5618.2010.00860.x PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 673VA UT WOS:000283690700002 PM 21066906 ER PT J AU Katz, L Choueiri, TK Bellmunt, J AF Katz, Leah Choueiri, Toni K. Bellmunt, Joaquim TI 11C-METHIONINE POSITRON-EMISSION TOMOGRAPHY AND COMPUTED TOMOGRAPHY (PET-CT) IN EVALUATING METASTATIC TRANSITIONAL CELL CARCINOMA RESPONSE TO SUNITINIB THERAPY SO BJU INTERNATIONAL LA English DT Editorial Material DE angiogenesis; sunitinib; transitional cell carcinoma; Carbon 11-methionine; PET CT C1 [Katz, Leah] Tulane Univ, Sch Med, New Orleans, LA 70130 USA. [Choueiri, Toni K.; Bellmunt, Joaquim] Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Bellmunt, Joaquim] RETICC Htal Mar, Barcelona, Spain. RP Katz, L (reprint author), Tulane Univ, Sch Med, 801 Race St Apt 7408, New Orleans, LA 70130 USA. EM leahkatz85@gmail.com NR 3 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD NOV PY 2010 VL 106 IS 9 BP 1249 EP 1250 DI 10.1111/j.1464-410X.2010.09732.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 665XL UT WOS:000283070700002 PM 20963928 ER PT J AU Mahindra, A Hideshima, T Anderson, KC AF Mahindra, Anuj Hideshima, Teru Anderson, Kenneth C. TI Multiple myeloma: biology of the disease SO BLOOD REVIEWS LA English DT Review DE Adhesion molecules; Cytokines; Multiple myeloma; Pathophysiology; Stromal cells; Biology; Molecular biology; Lenalidomide; Thalidomide; Bortezomib ID ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR-3; B-CELL DIFFERENTIATION; IN-SITU HYBRIDIZATION; MARROW STROMAL CELLS; NORMAL PLASMA-CELLS; NF-KAPPA-B; BONE-MARROW; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY AB Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the aberrant expansion of plasma cells within the bone marrow, as well as at extramedullary sites. Decades of scientific research are now beginning to unravel the intricate biology that underlies the pathophysiology of MM. In particular, the roles of cellular differentiation, molecular pathogenesis, and oncogenes involved in the natural history of MM are becoming clearer. This has enabled the identification of specific cytokines, adhesion molecules, and stromal cells that affect MM cell development, disease progression, and treatment responses. This review describes our current understanding regarding the biology of MM, and how this has led to a robust pipeline of novel therapeutic agents with the potential to overcome resistance to existing MM therapies and, therefore, further improve outcomes in patients with MM. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Mahindra, Anuj] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hideshima, Teru; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mahindra, A (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM amahindra@partners.org FU Celgene Corporation FX The authors received editorial support from Excerpta Medica in the preparation of this manuscript, funded by Celgene Corporation. The authors were fully responsible for content and editorial decisions for this manuscript. NR 98 TC 56 Z9 62 U1 4 U2 18 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0268-960X J9 BLOOD REV JI Blood Rev. PD NOV PY 2010 VL 24 SU 1 BP S5 EP S11 DI 10.1016/S0268-960X(10)70003-5 PG 7 WC Hematology SC Hematology GA 710UQ UT WOS:000286542900002 PM 21126636 ER PT J AU Janeway, KA Walkley, CR AF Janeway, Katherine A. Walkley, Carl R. TI Modeling human osteosarcoma in the mouse: From bedside to bench SO BONE LA English DT Review DE Osteosarcoma; Mouse model; Bone biology; Cancer ID ROTHMUND-THOMSON-SYNDROME; TUMOR-SUPPRESSOR GENE; RADIATION-INDUCED SARCOMAS; SOFT-TISSUE SARCOMAS; LI-FRAUMENI-SYNDROME; P53 MUTATIONS; METASTATIC OSTEOSARCOMA; TRANSGENIC MICE; BREAST-CANCER; OSTEOBLAST DIFFERENTIATION AB Osteosarcoma (OS) is the most common primary tumour of bone, occurring predominantly in the second decade of life. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for patients with localized (non-metastatic) disease approaching 70%. At presentation approximately 20% of patients have metastases and almost all patients with recurrent OS have metastatic disease and cure rates for patients with metastatic or recurrent disease remain poor (<20% survival). Over the past 20 years, considerable progress has been made in the understanding of OS pathogenesis, yet these insights have not translated into substantial therapeutic advances and clinical outcomes. Further progress is essential in order to develop molecularly based therapies that target both primary lesions as well as metastatic disease. The increasing sophistication with which gene expression can be modulated in the mouse, both positively and negatively in addition to temporally, has allowed for the recent generation of more faithful OS models than have previously been available. These murine OS models can recapitulate all aspects of the disease process, from initiation and establishment to invasion and dissemination to distant sites. The development and utilisation of murine models that faithfully recapitulate human osteosarcoma, complementing existing approaches using human and canine disease, holds significant promise in furthering our understanding of the genetic basis of the disease and, more critically, in advancing pre-clinical studies aimed at the rational development and trialing of new therapeutic approaches. (C) 2010 Elsevier Inc. All rights reserved. C1 [Janeway, Katherine A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pediat Oncol,Dana Farber Canc Inst,Div Hemat, Boston, MA 02115 USA. [Walkley, Carl R.] Univ Melbourne, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. [Walkley, Carl R.] Univ Melbourne, Dept Med, Fitzroy, Vic 3065, Australia. RP Janeway, KA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pediat Oncol,Dana Farber Canc Inst,Div Hemat, 44 Binney St, Boston, MA 02115 USA. EM Katherine_Janeway@dfci.harvard.edu; cwalkley@svi.edu.au OI Walkley, Carl/0000-0002-4784-9031 FU NHMRC of Australia; NHMRC FX We thank Dr Tony Mutsaers for critical reading and comment Work in C.R.W's laboratory is supported by grants from the NHMRC of Australia. C.R.W. was a Special Fellow of the Leukemia & Lymphoma Society, an NHMRC Career Development Award holder and is the Leukaemia Foundation Phillip Desbrow Senior Research Fellow. NR 92 TC 13 Z9 14 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD NOV PY 2010 VL 47 IS 5 BP 859 EP 865 DI 10.1016/j.bone.2010.07.028 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 668PM UT WOS:000283282000003 PM 20696288 ER PT J AU Armand, P Kim, HT Mayer, E Cutler, CS Ho, VT Koreth, J Alyea, EP Antin, JH Soiffer, RJ AF Armand, P. Kim, H. T. Mayer, E. Cutler, C. S. Ho, V. T. Koreth, J. Alyea, E. P. Antin, J. H. Soiffer, R. J. TI Outcome of allo-SCT for women with MDS or AML occurring after breast cancer therapy SO BONE MARROW TRANSPLANTATION LA English DT Article DE therapy-related disease; myelodysplastic syndromes; acute myelogenous leukemia; SCT ID ACUTE MYELOID-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; MYELODYSPLASTIC SYNDROME; DE-NOVO; ADJUVANT CHEMOTHERAPY; HODGKINS-DISEASE; COMBINATION CHEMOTHERAPY; RANDOMIZED-TRIAL; FOLLOW-UP; CYCLOPHOSPHAMIDE AB Women with breast cancer who receive adjuvant therapy are at risk for developing therapy-related myelodysplastic syndrome (MDS) or AML (tMDS/AML). Patients with tMDS/AML are often referred for consideration of allogeneic hematopoietic SCT (HSCT). However, the outcomes of HSCT in such patients have not been well described. We report a retrospective study of all women who were treated with HSCT for MDS or AML at our institution between 1991 and 2008. We compared the transplantation outcomes for 24 women with a history of breast cancer with those for 271 women with de novo disease. Three-year OS and disease-free survival (DFS) for patients with a history of breast cancer were 41 and 45%, respectively. The cumulative incidences of tMDS/AML relapse and non-relapse mortality (NRM) were 38 and 17%, respectively. Those outcomes were very similar to those of patients with de novo disease. In multivariable analyses, a history of breast cancer had no impact on OS, DFS, relapse or NRM. A significant proportion of women with tAML/MDS after breast cancer treatment experience DFS after HSCT, similar to that of patients with de novo MDS or AML. This justifies consideration of HSCT for selected patients in this setting. Bone Marrow Transplantation (2010) 45, 1611-1617; doi:10.1038/bmt.2010.20; published online 15 February 2010 C1 [Armand, P.; Mayer, E.; Cutler, C. S.; Ho, V. T.; Koreth, J.; Alyea, E. P.; Antin, J. H.; Soiffer, R. J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, H. T.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM parmand@partners.org FU National Institute of Allergy and Infectious Diseases [P01 AI 29350]; Leukemia and Lymphoma Society FX This work was funded in part by P01 AI 29350 from the National Institute of Allergy and Infectious Diseases. PA is the recipient of a career development award from the Leukemia and Lymphoma Society. NR 33 TC 5 Z9 5 U1 0 U2 0 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 NOV PY 2010 VL 45 IS 11 BP 1611 EP 1617 DI 10.1038/bmt.2010.20 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 678HA UT WOS:000284063500006 PM 20154738 ER PT J AU Domchek, SM Friebel, TM Garber, JE Isaacs, C Matloff, E Eeles, R Evans, DG Rubinstein, W Singer, CF Rubin, S Lynch, HT Daly, MB Weitzel, J Ganz, PA Pichert, G Olopade, OI Tomlinson, G Tung, N Blum, JL Couch, F Rebbeck, TR AF Domchek, Susan M. Friebel, Tara M. Garber, Judy E. Isaacs, Claudine Matloff, Ellen Eeles, Rosalind Evans, D. Gareth Rubinstein, Wendy Singer, Christian F. Rubin, Stephen Lynch, Henry T. Daly, Mary B. Weitzel, Jeffrey Ganz, Patricia A. Pichert, Gabriella Olopade, Olufunmilayo I. Tomlinson, Gail Tung, Nadine Blum, Joanne L. Couch, Fergus Rebbeck, Timothy R. TI Occult ovarian cancers identified at risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Hereditary ovarian cancer; Prophylactic Surgery; BRCA1; BRCA2 ID PROPHYLACTIC OOPHORECTOMY; FALLOPIAN-TUBE; BREAST-CANCER; PATHOLOGICAL FINDINGS; SURGICAL PROPHYLAXIS; WOMEN; SURGERY; HYSTERECTOMY; REDUCTION; SPECIMENS AB Risk-reducing salpingo-oophorectomy (RRSO) is widely used for cancer risk reduction in BRCA1 or BRCA2 (BRCA1/2) mutation carriers. Occult ovarian/fallopian tube cancers (OOC) detected at the time of RRSO have been reported in several studies with wide variability in reported prevalence. We estimated the prevalence of OOC in a prospective cohort of 647 BRCA1/2 mutation carriers from 18 centers (PROSE consortium) who underwent RRSO between 2001 and 2008. OOC was detected in 16 of 647 women (2.5%). The mean age at RRSO was 51.7 in those with OOC versus 46.6 in those without OOC (P = 0.017). Twelve of the 16 OOCs (75%) were diagnosed in women with BRCA1 mutations. Thirty-eight percent of women with OOC had stage 1 cancer versus none of the women in the PROSE database diagnosed with ovarian cancer outside of screening. Among 385 women (60%) in whom pathology reports were available for central review, 246 (64%) RRSOs were performed at participating PROSE centers while 139 (36%) were performed at local sites. Ovarian and fallopian tube tissues removed at major genetics referral centers were significantly more likely to have been examined in toto compared to specimens obtained at non-referral centers (75% vs. 30%, P < 0.001). Our results confirm that OOC may be found at the time of RRSO in BRCA1/2 mutation carriers and suggest that OOC are of a more favorable stage than cancers found outside RRSO. An unacceptably high proportion of pathologic examinations did not adequately examine ovaries and fallopian tubes obtained at RRSO. C1 [Domchek, Susan M.; Rubin, Stephen; Rebbeck, Timothy R.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Friebel, Tara M.; Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Isaacs, Claudine] Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. [Matloff, Ellen] Yale Univ, New Haven, CT USA. [Eeles, Rosalind] Inst Canc Res, Sutton, Surrey, England. [Eeles, Rosalind] Royal Marsden NHS Trust Fdn, Sutton, Surrey, England. [Evans, D. Gareth] St Marys Hosp, Manchester M13 0JH, Lancs, England. [Rubinstein, Wendy] Northshore Univ Hlth Syst, Evanston, IL USA. [Singer, Christian F.] Univ Vienna, Vienna, Austria. [Lynch, Henry T.] Creighton Univ, Omaha, NE 68178 USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Weitzel, Jeffrey] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Pichert, Gabriella] Guys Hosp, London SE1 9RT, England. [Olopade, Olufunmilayo I.] Univ Chicago, Chicago, IL 60637 USA. [Tomlinson, Gail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Couch, Fergus] Mayo Clin, Coll Med, Rochester, MN USA. RP Domchek, SM (reprint author), Univ Penn, Sch Med, Abramson Canc Ctr, 3W Perelman Ctr,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM Susan.domchek@uphs.upenn.edu OI Eeles, Rosalind/0000-0002-3698-6241; Evans, Gareth/0000-0002-8482-5784 FU Public Health Service [R01-CA83855, R01-CA102776, CA74415, NO1-CN-6700]; University of Pennsylvania Cancer Center; Cancer Genetics Network; Department of Defense [DAMD-17-96-I- 6088, DAMD-17-94-J-4340, DAMD-17-97-I-7112, DAMD-17-03-1-0619]; Utah State Department of Health; National Cancer Institute [2 P30 CA51008-15]; Nebraska State Cancer and Smoking-Related Diseases Research Program [LB595]; NIHR Biomedical Research centre at Central Manchester Foundation Trust FX All participants provided written informed consent for participation in this study using protocols approved by the Institutional Review Boards of each contributing institution. In addition, the University of Pennsylvania Institutional Review Board approved the overall data collection and analysis protocol for the collaborative data. This study was supported by grants from the Public Health Service (R01-CA83855 and R01-CA102776 to TRR; CA74415 to SLN), the University of Pennsylvania Cancer Center (to TRR), the Cancer Genetics Network (to SMD and CI) the Dana-Farber Women's Cancers Program (to JEG), the Department of Defense (DAMD-17-96-I- 6088 to AKG; DAMD-17-94-J-4340 and DAMD-17-97-I-7112 to HTL; DAMD-17-03-1-0619 to SMD), The Utah Cancer registry (funded by Public Health Service Grant NO1-CN-6700), the Utah State Department of Health,), the National Cancer Institute (2 P30 CA51008-15 to CI) and the Nebraska State Cancer and Smoking-Related Diseases Research Program (LB595 to HTL). DGE is supported by the NIHR Biomedical Research centre at Central Manchester Foundation Trust. OIO is Doris Duke Distinguished Clinical Scientist. None of these funding agencies had involvement in the study design; collection, analysis, or interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. NR 34 TC 24 Z9 24 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2010 VL 124 IS 1 BP 195 EP 203 DI 10.1007/s10549-010-0799-x PG 9 WC Oncology SC Oncology GA 657QM UT WOS:000282427400018 PM 20180014 ER PT J AU Moorman, PG Iversen, ES Marcom, PK Marks, JR Wang, F Cuningham, K Lee, E Ursin, G Rebbeck, TR Domchek, SM Arun, B Susswein, L Isaacs, C Garber, JE Visvanathan, K Griffin, CA Sutphen, R Brzosowicz, J Gruber, S Finkelstein, DM Schildkraut, JM AF Moorman, Patricia G. Iversen, Edwin S. Marcom, P. Kelly Marks, Jeffrey R. Wang, Frances Cuningham, Kathleen Lee, Eunjung Ursin, Giske Rebbeck, Timothy R. Domchek, Susan M. Arun, Banu Susswein, Lisa Isaacs, Claudine Garber, Judy E. Visvanathan, Kala Griffin, Constance A. Sutphen, Rebecca Brzosowicz, Jennifer Gruber, Stephen Finkelstein, Dianne M. Schildkraut, Joellen M. CA Consortium Res Familial Breast TI Evaluation of established breast cancer risk factors as modifiers of BRCA1 or BRCA2: a multi-center case-only analysis SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; BRCA1; BRCA2; Mutations; Modifiers ID ORAL-CONTRACEPTIVE USE; MUTATION CARRIERS; REPRODUCTIVE FACTORS; COHORT; AGE; NONCARRIERS; PREGNANCY; MENARCHE; IBCCS AB The incomplete penetrance of mutations in BRCA1 and BRCA2 suggests that some combination of environmental and genetic factors modifies the risk of breast cancer in mutation carriers. This study sought to identify possible interactions between established breast cancer risk factors and BRCA1 or BRCA2 mutations using a case-only study design. Breast cancer cases that had been tested for BRCA1 and BRCA2 mutations were identified from 11 collaborating centers. Comparisons of reproductive and lifestyle risk factors were made between women with breast cancer who were positive for BRCA1 mutations (n = 283), BRCA2 mutations (n = 204), or negative for both BRCA1 and BRCA2 mutations (n = 894). Interaction risk ratios (IRRs) were calculated using multinominal logistic regression models. Compared with non-carriers, statistically significant IRRs were observed for later age at menarche among BRCA2 mutation carriers, for a greater number of pregnancies among both BRCA1 and BRCA2 mutation carriers, and for alcohol use among BRCA1 mutation carriers. Our data suggest that the risk for breast cancer among BRCA1 or BRCA2 carriers may be modified by reproductive characteristics and alcohol use. However, our results should be interpreted cautiously given the overall inconsistency in the epidemiologic literature on modifiers of BRCA1 and BRCA2. C1 [Moorman, Patricia G.; Wang, Frances; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Dept Community & Family Med, Durham, NC 27705 USA. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC 27705 USA. [Marcom, P. Kelly] Duke Univ, Med Ctr, Div Oncol, Dept Med, Durham, NC 27705 USA. [Marks, Jeffrey R.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27705 USA. [Marks, Jeffrey R.] Kathleen Cuningham Consortium Res Familial Breast, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Lee, Eunjung; Ursin, Giske] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ursin, Giske] Univ Oslo, Dept Nutr, Oslo, Norway. [Rebbeck, Timothy R.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.; Domchek, Susan M.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Domchek, Susan M.] Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Arun, Banu] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Susswein, Lisa] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Garber, Judy E.] Dana Farber Canc Inst, Dept Med Oncol & Populat Sci, Boston, MA 02115 USA. [Visvanathan, Kala] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Visvanathan, Kala; Griffin, Constance A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sutphen, Rebecca] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA. [Brzosowicz, Jennifer] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Gruber, Stephen] Univ Michigan, Div Mol Med & Genet, Ann Arbor, MI 48109 USA. [Finkelstein, Dianne M.] Harvard Sch Publ Hlth, Boston, MA USA. [Finkelstein, Dianne M.] Harvard Univ, Sch Med, Boston, MA USA. RP Moorman, PG (reprint author), Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Dept Community & Family Med, Durham, NC 27705 USA. EM patricia.moorman@duke.edu FU National Cancer Institute, National Institutes of Health [P50-CA068438]; Duke University Medical Center; Cancer Genetics Network, Massachusetts General Hospital [U01 CA78284, HHSN 261200744000C] FX This study was funded by the following grants and contracts from the National Cancer Institute, National Institutes of Health: P50-CA068438 Specialized Program of Research Excellence (SPORE) in breast cancer, Duke University Medical Center; Cancer Genetics Network (U01 CA78284 and HHSN 261200744000C), Massachusetts General Hospital. NR 30 TC 15 Z9 15 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2010 VL 124 IS 2 BP 441 EP 451 DI 10.1007/s10549-010-0842-y PG 11 WC Oncology SC Oncology GA 666QQ UT WOS:000283132800016 PM 20309627 ER PT J AU Anderson, KS Petersson, S Wong, J Shubbar, E Lokko, NN Carlstrom, M Enerback, C AF Anderson, K. S. Petersson, S. Wong, J. Shubbar, E. Lokko, N. N. Carlstrom, M. Enerback, C. TI Elevation of serum epidermal growth factor and interleukin 1 receptor antagonist in active psoriasis vulgaris SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE chemokines; cytokines; psoriasis ID CYTOKINES; ARTHRITIS; OBESITY; SYSTEM; IMPACT AB Background Psoriatic plaques present a complex expression profile, including high levels of cytokines, chemokines and growth factors. Circulating cytokines have been suggested to reflect the activation status of the inflammatory process. Objectives To analyse 20 cytokines, chemokines and growth factors in 14 patients with psoriasis vulgaris at the start and during the course of ultraviolet B treatment. Methods A multiplex cytokine assay was used. Results We identified increased serum levels of epidermal growth factor (EGF) (mean 323 vs. 36 6 pg mL(-1), P = 0 0001), interleukin (IL)-1 receptor antagonist (mean 39 1 vs. 14 6 pg mL(-1), P = 0 02) and tumour necrosis factor-alpha (mean 7 5 vs. 4 5 pg mL(-1), P = 0 04) at baseline in patients with psoriasis compared with matched controls. None of these cytokines was correlated to the severity of the disease (Psoriasis Area and Severity Index) or decreased with phototherapy, suggesting that sources other than lesional skin contribute to the production of these cytokines. Using cluster analysis, we observed coordinate upregulation of EGF, IL-6, macrophage inflammatory protein-1 beta and vascular endothelial growth factor. Conclusions The sustained high expression of inflammatory circulating cytokines is a potential mechanism linking psoriasis with its extracutaneous comorbidities. C1 [Carlstrom, M.; Enerback, C.] Linkoping Univ, Div Cell Biol & Dermatol, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden. [Anderson, K. S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Anderson, K. S.] Harvard Univ, Sch Med, Canc Vaccine Ctr, Boston, MA USA. [Petersson, S.; Shubbar, E.] Sahlgrens Univ Hosp, Dept Clin Genet, SE-41345 Gothenburg, Sweden. RP Enerback, C (reprint author), Linkoping Univ, Div Cell Biol & Dermatol, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden. EM charlotta.enerback@liu.se FU Swedish Psoriasis Association; Welander Foundation; Swedish Society of Medicine; Cancer Vaccine Center, Dana Farber Cancer Institute FX The authors thank Dr Lin Li Lu for assistance in data analysis, and Dr James Lederer for advice on cytokine pathway evaluation. These studies were supported by the Swedish Psoriasis Association, the Welander Foundation, the Swedish Society of Medicine and the Cancer Vaccine Center, Dana Farber Cancer Institute. NR 19 TC 27 Z9 30 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 2010 VL 163 IS 5 BP 1085 EP 1089 DI 10.1111/j.1365-2133.2010.09990.x PG 5 WC Dermatology SC Dermatology GA 672PC UT WOS:000283597500028 PM 20716221 ER PT J AU Setlur, SR Ihm, C Tchinda, J Shams, S Werner, L Cho, EK Thompson, C Phillips, K Rassenti, LZ Kipps, TJ Neuberg, D Freedman, AS Lee, C Brown, JR AF Setlur, Sunita R. Ihm, Chunhwa Tchinda, Joelle Shams, Soheil Werner, Lillian Cho, Eun Kyung Thompson, Christina Phillips, Kimberly Rassenti, Laura Z. Kipps, Thomas J. Neuberg, Donna Freedman, Arnold S. Lee, Charles Brown, Jennifer R. TI Comparison of familial and sporadic chronic lymphocytic leukaemia using high resolution array comparative genomic hybridization SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; familial; deletion 11q ID NEWLY-DIAGNOSED PATIENTS; COPY-NUMBER ALTERATIONS; CYTOGENETIC ABNORMALITIES; DISEASE PROGRESSION; CLL; ABERRATIONS; MICROARRAY; DELETIONS; SURVIVAL; MALIGNANCIES AB P>Approximately 10% of patients with chronic lymphocytic leukaemia (CLL) have a family history of the disease or a related lymphoproliferative disorder, yet the relationship of familial CLL to genomic abnormalities has not been characterized in detail. We therefore studied 75 CLL patients, half familial and half sporadic, using high-resolution array comparative genomic hybridization (CGH), in order to better define the relationship of genomic abnormalities to familial disease and other biological prognostic factors. Our results showed that the most common high-risk deletion in CLL, deletion 11q, was significantly associated with sporadic disease. Comparison of familial to sporadic disease additionally identified a copy number variant region near the centromere on 14q, proximal to IGH@, in which gains were associated both with familial CLL, and with mutated IGHV and homozygous deletion of 13q. Homozygous deletion of 13q was also found to be associated with mutated IGHV and low expression of ZAP-70, and a significantly longer time to first treatment compared to heterozygous deletion or lack of alteration. This study is the first high resolution effort to investigate and report somatic genetic differences between familial and sporadic CLL. C1 [Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Setlur, Sunita R.; Ihm, Chunhwa; Tchinda, Joelle; Cho, Eun Kyung; Lee, Charles] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Shams, Soheil] BioDiscovery Inc, El Segundo, CA USA. [Rassenti, Laura Z.; Kipps, Thomas J.] Moores UCSD Canc Ctr, La Jolla, CA USA. [Lee, Charles] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Brown, JR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jbrown2@partners.org FU NIH [K23 CA115682, CA111560, PO1-CA081534, 2P01CA092625, CA-103244]; Leukaemia and lymphoma translational grant [6161-05]; Okonow-Lipton Fund FX We are indebted to the patients who participated in this study and the clinic staff who support our research sample collection. This work was supported in part by NIH grant K23 CA115682 to JRB, a leukaemia and lymphoma translational grant (6161-05) and NIH grant CA111560 to CL, and by the Okonow-Lipton Fund. The work of LZR, TJK, DN and JRB in sample collection, analysis and determination of IGHV and ZAP70 status was supported by NIH grant PO1-CA081534 for the CLL Research Consortium (CRC). ASF is supported in part by NIH grants 2P01CA092625 and CA-103244. NR 33 TC 6 Z9 6 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 NOV PY 2010 VL 151 IS 4 BP 336 EP 345 DI 10.1111/j.1365-2141.2010.08341.x PG 10 WC Hematology SC Hematology GA 672PD UT WOS:000283597600004 PM 20812997 ER PT J AU Merry, AF Cooper, JB Soyannwo, O Wilson, IH Eichhorn, JH AF Merry, Alan F. Cooper, Jeffrey B. Soyannwo, Olaitan Wilson, Iain H. Eichhorn, John H. TI An iterative process of global quality improvement: the International Standards for a Safe Practice of Anesthesia 2010 SO CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article ID DEVELOPING-COUNTRIES; MORTALITY; OXIMETRY; SURGERY; PROJECT; DEATHS AB To enhance patient safety through contemporaneous and comprehensive standards for a safe practice of anesthesia that augment, enhance, and support similar standards already published by various countries and that provide a resource for countries that have yet to formulate such standards. The Safe Anesthesia Working Group of the World Health Organization's "Safe Surgery Saves Lives" global initiative updated the 1992 International Standards for the Safe Practice of Anaesthesia (Standards) through an iterative process of literature review, consultation, debate, drafting, and refinement. These Standards address, in detail, the organization, support, practices, and infrastructure for anesthesia care. The Standards are grounded in the fundamental principle of safety in anesthesia, i.e., the continuous presence of an appropriately trained, vigilant anesthesia professional. In effect, the use of pulse oximetry during anesthesia is now considered mandatory, with acknowledgement that compromise may be unavoidable in emergencies. At the World Congress of Anaesthesiologists in 2008, drafts were presented for comment, further refinements were made, and the Revised Standards were adopted by the World Federation of Societies of Anaesthesiologists (WFSA). These Revised Standards were posted on the WFSA website for further feedback, and minor revisions followed. The International Standards for a Safe Practice of Anesthesia 2010 were endorsed by the Executive Committee of the WFSA in March 2010. Ongoing periodic revision is planned. While they are universally applicable, the 2010 Standards primarily target lesser-resourced areas. They are designed particularly for regions that have yet to formulate or adopt their own standards so as to promote optimum patient outcomes in every anesthetizing location in the world. C1 [Merry, Alan F.] Univ Auckland, Dept Anaesthesiol, Auckland 1142, New Zealand. [Merry, Alan F.] Auckland City Hosp, Dept Anaesthesia, Auckland 1142, New Zealand. [Cooper, Jeffrey B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Soyannwo, Olaitan] Univ Ibadan, Coll Med, Univ Coll Hosp, Dept Anaesthesia, Ibadan, Nigeria. [Wilson, Iain H.] Royal Devon & Exeter NHS Fdn Trust, Exeter, Devon, England. [Eichhorn, John H.] Univ Kentucky, Coll Med, Dept Anesthesiol, Lexington, KY USA. [Eichhorn, John H.] Univ Kentucky, Med Ctr, Lexington, KY USA. [Merry, Alan F.; Cooper, Jeffrey B.; Soyannwo, Olaitan; Wilson, Iain H.; Eichhorn, John H.] World Hlth Org Safe Surg Saves Lives Global Chall, Safe Anesthesia Working Grp, Exeter, Devon, England. RP Merry, AF (reprint author), Univ Auckland, Dept Anaesthesiol, Private Bag 92019, Auckland 1142, New Zealand. EM a.merry@auckland.ac.nz OI Merry, Alan/0000-0001-7100-009X NR 22 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0832-610X EI 1496-8975 J9 CAN J ANESTH JI Can. J. Anesth. PD NOV PY 2010 VL 57 IS 11 BP 1021 EP 1026 DI 10.1007/s12630-010-9380-7 PG 6 WC Anesthesiology SC Anesthesiology GA 668CX UT WOS:000283247300009 PM 20857255 ER PT J AU Merry, AF Cooper, JB Soyannwo, O Wilson, IH Eichhorn, JH AF Merry, Alan F. Cooper, Jeffrey B. Soyannwo, Olaitan Wilson, Iain H. Eichhorn, John H. TI International Standards for a Safe Practice of Anesthesia 2010 SO CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article C1 [Merry, Alan F.] Univ Auckland, Dept Anaesthesiol, Auckland 1142, New Zealand. [Merry, Alan F.] Auckland City Hosp, Dept Anaesthesia, Auckland 1142, New Zealand. [Cooper, Jeffrey B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Soyannwo, Olaitan] Univ Ibadan, Coll Med, Univ Coll Hosp, Dept Anaesthesia, Ibadan, Nigeria. [Wilson, Iain H.] Royal Devon & Exeter NHS Fdn Trust, Exeter, Devon, England. [Eichhorn, John H.] Univ Kentucky, Coll Med, Dept Anesthesiol, Lexington, KY USA. [Eichhorn, John H.] Univ Kentucky, Med Ctr, Lexington, KY USA. RP Merry, AF (reprint author), Univ Auckland, Dept Anaesthesiol, Private Bag 92019, Auckland 1142, New Zealand. EM a.merry@auckland.ac.nz OI Merry, Alan/0000-0001-7100-009X NR 0 TC 46 Z9 49 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0832-610X J9 CAN J ANESTH JI Can. J. Anesth. PD NOV PY 2010 VL 57 IS 11 BP 1027 EP 1034 DI 10.1007/s12630-010-9381-6 PG 8 WC Anesthesiology SC Anesthesiology GA 668CX UT WOS:000283247300010 PM 20857254 ER PT J AU Hartzell, TL Gardiner, S Skavdahl, M AF Hartzell, Tristan L. Gardiner, Sonya Skavdahl, Maryanne TI Portal venous gas in a patient with abdominal pain SO CANADIAN JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material DE abdominal pain; portal venous gas; appendicitis ID CLINICAL-SIGNIFICANCE; COMPUTED-TOMOGRAPHY; VEIN GAS; TRAUMA; EMBOLIZATION; PNEUMATOSIS C1 [Hartzell, Tristan L.] Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Gardiner, Sonya] Univ Cambridge, Sch Clin Med, Cambridge, England. [Skavdahl, Maryanne] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Hartzell, TL (reprint author), Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM tristanhartzell@gmail.com NR 14 TC 1 Z9 1 U1 0 U2 0 PU DECKER PUBL INC PI HAMILTON PA 69 JOHN ST S, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1481-8035 J9 CAN J EMERG MED JI Can. J. Emerg. Med. PD NOV PY 2010 VL 12 IS 6 BP 525 EP + PG 4 WC Emergency Medicine SC Emergency Medicine GA 677JX UT WOS:000283989200008 PM 21073780 ER PT J AU Flaherty, KT McArthur, G AF Flaherty, Keith T. McArthur, Grant TI BRAF, a Target in Melanoma Implications for Solid Tumor Drug Development SO CANCER LA English DT Review DE BRAF; melanoma; oncogene; kinase inhibitor; mutation ID GASTROINTESTINAL STROMAL TUMORS; MALIGNANT MELANOCYTIC LESIONS; PAPILLARY THYROID-CARCINOMA; MISMATCH REPAIR DEFICIENCY; B-RAF; ANTITUMOR-ACTIVITY; SIGNALING PATHWAY; PHASE-I; ACQUIRED-RESISTANCE; AZD6244 ARRY-142886 AB The successful translation of therapies targeting signal-transduction pathways that are activated by oncogenes has provided a model for molecularly targeted therapy, and the identification of mutations in v-raf murine sarcoma viral oncogene homolog B1 (BRAF), a serine/threonine kinase, has turned the attention of the melanoma field toward this concept. The current review indicated that BRAF represents an important target in cancer, in part because it is present in 7% of all cancers and also because it represents the first intracellular signaling molecule that is activated by point mutations for which single-agent therapy appears to have efficacy. Therapy for advanced melanoma has progressed slowly over the past 3 decades, although significant advances have been made in other cancers with the application of cytotoxic chemotherapy and targeted therapies. However, in melanoma, cytotoxic chemotherapies have severe limits, chemotherapy does not convincingly improve on the natural history of metastatic disease and has no role in the adjuvant setting, and cytokine therapy may have a niche in both the adjuvant and metastatic settings but confers only a modest benefit to a small proportion of patients at the cost of severe toxicity. Thus, there are few other cancers in which completely novel therapies are so highly prioritized in clinical research. Understanding network of signal-transduction pathways and how that network may adapt to BRAF inhibition or mitogen-activated protein kinase kinase inhibition will point to the next generation of clinical trials investigating rational combination regimens. The current investigations in melanoma will create a set of hypotheses to be tested in each cancer that harbors BRAF mutations. Cancer 2010;116:4902-13. (C) 2010 American Cancer Society. C1 [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA. [McArthur, Grant] Peter MacCallum Canc Ctr, Translat Res Grp, Melbourne, Vic, Australia. RP Flaherty, KT (reprint author), 51 N 39th St,Suite 103,Med Art Bldg, Philadelphia, PA 19104 USA. EM ktflaherty@aol.com NR 89 TC 51 Z9 54 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 1 PY 2010 VL 116 IS 21 BP 4902 EP 4913 DI 10.1002/cncr.25261 PG 12 WC Oncology SC Oncology GA 670CE UT WOS:000283397700006 PM 20629085 ER PT J AU Rowe, JM Kim, HT Cassileth, PA Lazarus, HM Litzow, MR Wiernik, PH Tallman, MS AF Rowe, Jacob M. Kim, Haesook T. Cassileth, Peter A. Lazarus, Hillard M. Litzow, Mark R. Wiernik, Peter H. Tallman, Martin S. TI Adult Patients With Acute Myeloid Leukemia Who Achieve Complete Remission After 1 or 2 Cycles of Induction Have a Similar Prognosis A Report on 1980 Patients Registered to 6 Studies Conducted by the Eastern Cooperative Oncology Group SO CANCER LA English DT Article DE acute myeloid leukemia; induction therapy; prognostic factors; residual disease; complete remission ID BONE-MARROW BIOPSY; MINIMAL RESIDUAL DISEASE; 1ST REMISSION; POSTREMISSION THERAPY; NORMAL CYTOGENETICS; PERIPHERAL-BLOOD; CEBPA MUTATIONS; BLAST CLEARANCE; FREE SURVIVAL; OLDER-ADULTS AB BACKGROUND: Patients with newly diagnosed acute myeloid leukemia (AML) often have residual leukemia in the bone marrow 10 to 14 days after the start of induction therapy. Some cooperative groups administer a second cycle of similar induction therapy on Day 14 if there is residual leukemia. It is a common perception that the presence of residual leukemia at that point predicts a worse prognosis irrespective of the therapy received. The objective of this study was to determine whether patients who required a second cycle of induction (given on or about Day 14) to achieve complete remission (CR) had a worse prognosis than patients who achieved CR after only 1 cycle, because a worse prognosis may alter postremission therapy. METHODS: Patients who were enrolled on 6 consecutive studies for AML that were conducted by the Eastern Cooperative Oncology Group (ECOG) between 1983 to 1993 received induction therapy. If residual leukemia was present in the bone marrow on the Day 14 after the start of induction, then patients were to receive a second cycle of identical induction therapy. All patients who achieved CR after 1 or 2 cycles received the identical postremission therapy. RESULTS: In each of the 6 ECOG studies, the long-term outcome was similar for patients who required 1 or 2 cycles of induction therapy to achieve CR, and their outcome was independent of other prognostic variables, such as age or karyotype. CONCLUSIONS: The presence of residual leukemia in bone marrow 10 to 14 days after induction therapy did not predict a worse prognosis if patients received second, similar cycle of induction therapy and achieved CR. Cancer 2010;116:5012-21. (C) 2010 American Cancer Society. C1 [Rowe, Jacob M.] Rambam Med Ctr, Dept Hematol & Bone Marrow Transplantat, IL-31096 Haifa, Israel. [Rowe, Jacob M.] Technion Israel Inst Technol, IL-31096 Haifa, Israel. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Cassileth, Peter A.] Univ Miami, Sylvester Canc Ctr, Div Hematol Oncol, Miami, FL USA. [Lazarus, Hillard M.] Univ Hosp Cleveland, Div Hematol & Oncol, Ireland Canc Ctr, Cleveland, OH 44106 USA. [Litzow, Mark R.] Mayo Clin, Coll Med, Dept Hematol, Rochester, MN USA. [Wiernik, Peter H.] Montefiore Med Ctr, North Div, Ctr Canc, New York, NY USA. [Wiernik, Peter H.] New York Med Coll, New York, NY USA. [Tallman, Martin S.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL USA. RP Rowe, JM (reprint author), Rambam Med Ctr, Dept Hematol & Bone Marrow Transplantat, IL-31096 Haifa, Israel. EM rowe@jimmy.harvard.edu FU NCI NIH HHS [U10 CA023318, U10 CA013650, U10 CA014548, U10 CA014958, U10 CA017145, U10 CA021115, U10 CA066636, U24 CA114737] NR 37 TC 45 Z9 50 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 1 PY 2010 VL 116 IS 21 BP 5012 EP 5021 DI 10.1002/cncr.25263 PG 10 WC Oncology SC Oncology GA 670CE UT WOS:000283397700017 PM 20629023 ER PT J AU Chan, AT Baba, Y Shima, K Nosho, K Chung, DC Hung, KE Mahmood, U Madden, K Poss, K Ranieri, A Shue, D Kucherlapati, R Fuchs, CS Ogino, S AF Chan, Andrew T. Baba, Yoshifumi Shima, Kaori Nosho, Katsuhiko Chung, Daniel C. Hung, Kenneth E. Mahmood, Umar Madden, Karen Poss, Kirtland Ranieri, Audrey Shue, Daniel Kucherlapati, Raju Fuchs, Charles S. Ogino, Shuji TI Cathepsin B Expression and Survival in Colon Cancer: Implications for Molecular Detection of Neoplasia SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; TUMOR PROGRESSION; MOUSE MODEL; PROTEASE EXPRESSION; KRAS MUTATION; BRAF V600E; CARCINOMA; CYSTEINE AB Background and Aims: Proteases play a critical role in tumorigenesis and are upregulated in colorectal cancer and neoplastic polyps. In animal models, cathepsin B (CTSB)-activatable imaging agents show high enzyme activity within intestinal tumors. Methods: We conducted a prospective cohort study of 558 men and women with colon cancer with tumors that were accessible for immunohistochemical assessment. We used Cox proportional hazards models, stratified by stage, to compute colon cancer-specific and overall mortality according to tumoral expression of CTSB. Results: Among 558 participants, 457 (82%) had tumors that expressed CTSB (CTSB positive) and 101 (18%) had tumors that did not express CTSB (CTSB negative). CTSB expression was not associated with disease stage (P = 0.19). After a median follow-up of 11.6 years, there were 254 total and 155 colon cancer-specific deaths. Compared with participants with CTSB-negative tumors, participants with CTSB-positive tumors experienced a multivariate hazard ratio for colon cancer-specific mortality of 1.99 (95% confidence interval, 1.19-3.34) and overall mortality of 1.71 (95% confidence interval, 1.16-2.50). CTSB expression was independently associated with KRAS (P = 0.01) and BRAF mutation (P = 0.04), but not microsatellite instability status, CpG island methylator phenotype status, PIK3CA mutation, LINE-1 methylation, TP53 expression, or PTGS2 (cyclooxygenase-2) expression. Among 123 individuals with adenomas, 91% expressed CTSB. Conclusions: As assessed by immunohistochemistry, CTSB is expressed in the vast majority of colon cancers, independent of stage, and is significantly associated with higher risk of colon cancer-specific and overall mortality. Impact: These results support the potential of CTSB a target for image detection of neoplastic lesions in humans. Cancer Epidemiol Biomarkers Prev; 19(11); 2777-85. (C)2010 AACR. C1 [Chan, Andrew T.; Chung, Daniel C.; Ranieri, Audrey; Shue, Daniel] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mahmood, Umar] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Baba, Yoshifumi; Shima, Kaori; Nosho, Katsuhiko; Hung, Kenneth E.; Kucherlapati, Raju; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.; Fuchs, Charles S.; Ogino, Shuji] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Baba, Yoshifumi; Shima, Kaori; Nosho, Katsuhiko; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hung, Kenneth E.] Tufts Med Ctr, Dept Med, Boston, MA USA. [Hung, Kenneth E.; Kucherlapati, Raju] Harvard Partners Ctr Genet & Genom, Boston, MA USA. [Madden, Karen; Poss, Kirtland] VisEn Med, Bedford, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 722, Boston, MA 02114 USA. EM achan@partners.org; shuji_ogino@dfci.harvard.edu FU U.S. NIH [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA137148, K07 CA107412, K07 CA122826]; Damon Runyon Cancer Research Foundation FX U.S. NIH grants P01 CA87969, P01 CA55075, P50 CA127003, R01 CA137148, K07 CA107412, and K07 CA122826, and Damon Runyon Cancer Research Foundation. NR 47 TC 23 Z9 25 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2010 VL 19 IS 11 BP 2777 EP 2785 DI 10.1158/1055-9965.EPI-10-0529 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 677KP UT WOS:000283991600010 PM 20833970 ER PT J AU Penney, KL Pyne, S Schumacher, FR Sinnott, JA Mucci, LA Kraft, PL Ma, J Oh, WK Kurth, T Kantoff, PW Giovannucci, EL Stampfer, MJ Hunter, DJ Freedman, ML AF Penney, Kathryn L. Pyne, Saumyadipta Schumacher, Fredrick R. Sinnott, Jennifer A. Mucci, Lorelei A. Kraft, Peter L. Ma, Jing Oh, William K. Kurth, Tobias Kantoff, Philip W. Giovannucci, Edward L. Stampfer, Meir J. Hunter, David J. Freedman, Matthew L. TI Genome-wide Association Study of Prostate Cancer Mortality SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COPY-NUMBER VARIATION; AGGRESSIVENESS LOCI; INTEROBSERVER REPRODUCIBILITY; METASTATIC PROGRESSION; RADICAL PROSTATECTOMY; GLEASON SCORE; RISK LOCUS; SUSCEPTIBILITY; LINKAGE; SCAN AB Background: A pressing clinical issue in prostate cancer is to distinguish which men will have an indolent or aggressive course of disease. Clinical variables such as Gleason grade and stage are useful predictors of lethal cancer; however, the low predictive values of the common Gleason scores, changes in grading over time, and earlier diagnosis of patients due to screening limits their clinical utility. Identifying genetic variants associated with lethal prostate cancer could inform clinical decision making. Methods: We conducted a genome-wide association study, comparing lethal prostate cancer cases to cases surviving at least 10 years beyond their initial diagnosis. Genotyping was done with the Affymetrix 5.0 chip [similar to 500,000 single nucleotide polymorphisms (SNP) and 1,483 copy number variants (CNV)] on DNA from participants in the Physicians' Health Study and Health Professionals Follow-up Study (196 lethal cases, 368 long-term survivors). After excluding SNPs and individuals based on quality control criteria, logistic regression assuming an additive model was done using the PLINK software. Results: No SNP reached genome-wide significance (P <= 1 x 10(-7)); however, three independent SNPs had P < 1 x 10(-5). One top-ranked SNP replicated (P = 0.05) in an independent follow-up study. Although no CNV had genome-wide significance, 14 CNVs showed nominal association with prostate cancer mortality (P < 0.05). Conclusions: No variants were significantly associated at a genome-wide level with prostate cancer mortality. Common genetic determinants of lethal prostate cancer are likely to have odds ratios <2.0. Impact: Genetic markers identified could provide biological insight to improve therapy for men with potentially fatal cancer. Larger studies are necessary to detect the genetic causes of prostate cancer mortality. Cancer Epidemiol Biomarkers Prev; 19(11); 2869-76. (C)2010 AACR. C1 [Pyne, Saumyadipta; Oh, William K.; Kantoff, Philip W.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Penney, Kathryn L.; Mucci, Lorelei A.; Kraft, Peter L.; Kurth, Tobias; Giovannucci, Edward L.; Stampfer, Meir J.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Sinnott, Jennifer A.; Kraft, Peter L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir J.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Penney, Kathryn L.; Sinnott, Jennifer A.; Mucci, Lorelei A.; Ma, Jing; Giovannucci, Edward L.; Stampfer, Meir J.; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Kurth, Tobias] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Oh, William K.] Mt Sinai Sch Med, Div Hematol & Med Oncol, New York, NY USA. [Hunter, David J.; Freedman, Matthew L.] Eli & Edythe L Broad Inst, Cambridge, MA USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 710-C,44 Binney St, Boston, MA 02115 USA. EM freedman@broadinstitute.org RI Kurth, Tobias/A-9243-2012; Oh, William/B-9163-2012 OI Kurth, Tobias/0000-0001-7169-2620; Oh, William/0000-0001-5113-8147 FU French National Research Agency; NIH; Merck; Migraine Research Foundation; Restless Legs Syndrome Foundation; Doris Duke Clinical Scientist Development Award; National Center for Research Resources [U54 RR020278]; National Cancer Institute [CA-34944, CA-40360, CA-097193, CA-55075]; National Heart, Lung, and Blood Institute, Bethesda, MD [HL-26490, HL-34595]; Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE [P50 CA090381-08]; National Research Service Awards [T32 CA009001-34] FX T. Kurth, received within the last 2 years investigator-initiated research funding from the French National Research Agency, the NIH, Merck, and the Migraine Research Foundation; consultant to i3 Drug Safety and World Health Information Science Consultants, LLC; received honoraria from Genzyme, Merck, and Pfizer for educational lectures; and received travel funds from the Restless Legs Syndrome Foundation.; Grant from the Doris Duke Clinical Scientist Development Award. The laboratory work at the Broad Institute Center for Genotyping and Analysis was supported by grant U54 RR020278 from the National Center for Research Resources. The PHS was supported by grants CA-34944, CA-40360, and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute, Bethesda, MD. The HPFS was supported by CA-55075 from the National Cancer Institute. Additional funding was provided by Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (P50 CA090381-08). K. L. Penney was supported by a National Research Service Awards (T32 CA009001-34). NR 44 TC 33 Z9 35 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2010 VL 19 IS 11 BP 2869 EP 2876 DI 10.1158/1055-9965.EPI-10-0601 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 677KP UT WOS:000283991600021 PM 20978177 ER PT J AU Gu, FY Schumacher, FR Canzian, F Allen, NE Albanes, D Berg, CD Berndt, SI Boeing, H Bueno-de-Mesquita, HB Buring, JE Chabbert-Buffet, N Chanock, SJ Clavel-Chapelon, F Dumeaux, V Gaziano, JM Giovannucci, EL Haiman, CA Hankinson, SE Hayes, RB Henderson, BE Hunter, DJ Hoover, RN Johansson, M Key, TJ Khaw, KT Kolonel, LN Lagiou, P Lee, IM LeMarchand, L Lund, E Ma, J Onland-Moret, NC Overvad, K Rodriguez, L Sacerdote, C Sanchez, MJ Stampfer, MJ Stattin, P Stram, DO Thomas, G Thun, MJ Tjonneland, A Trichopoulos, D Tumino, R Virtamo, J Weinstein, SJ Willett, WC Yeager, M Zhang, SMM Kaaks, R Riboli, E Ziegler, RG Kraft, P AF Gu, Fangyi Schumacher, Fredrick R. Canzian, Federico Allen, Naomi E. Albanes, Demetrius Berg, Christine D. Berndt, Sonja I. Boeing, Heiner Bueno-de-Mesquita, H. Bas Buring, Julie E. Chabbert-Buffet, Nathalie Chanock, Stephen J. Clavel-Chapelon, Francoise Dumeaux, Vanessa Gaziano, J. Michael Giovannucci, Edward L. Haiman, Christopher A. Hankinson, Susan E. Hayes, Richard B. Henderson, Brian E. Hunter, David J. Hoover, Robert N. Johansson, Mattias Key, Timothy J. Khaw, Kay-Tee Kolonel, Laurence N. Lagiou, Pagona Lee, I-Min LeMarchand, Loic Lund, Eiliv Ma, Jing Onland-Moret, N. Charlotte Overvad, Kim Rodriguez, Laudina Sacerdote, Carlotta Sanchez, Maria-Jose Stampfer, Meir J. Stattin, Par Stram, Daniel O. Thomas, Gilles Thun, Michael J. Tjonneland, Anne Trichopoulos, Dimitrios Tumino, Rosario Virtamo, Jarmo Weinstein, Stephanie J. Willett, Walter C. Yeager, Meredith Zhang, Shumin M. Kaaks, Rudolf Riboli, Elio Ziegler, Regina G. Kraft, Peter TI Eighteen Insulin-like Growth Factor Pathway Genes, Circulating Levels of IGF-I and Its Binding Protein, and Risk of Prostate and Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ACID-LABILE SUBUNIT; MULTIETHNIC COHORT; COMPREHENSIVE ANALYSIS; SCREENING TRIAL; IGFBP-3 LEVELS; FACTOR (IGF)-I; SERUM-LEVELS; POLYMORPHISMS; ASSOCIATION; METAANALYSIS AB Background: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins. Methods: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium. Results: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 x 10(-4)); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R-2 = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers. Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women. Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes. Cancer Epidemiol Biomarkers Prev; 19(11); 2877-87. (C)2010 AACR. C1 [Gu, Fangyi; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Gu, Fangyi; Buring, Julie E.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Lee, I-Min; Stampfer, Meir J.; Trichopoulos, Dimitrios; Willett, Walter C.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Schumacher, Fredrick R.; Haiman, Christopher A.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, D-6900 Heidelberg, Germany. [Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Allen, Naomi E.; Key, Timothy J.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Albanes, Demetrius; Berg, Christine D.; Berndt, Sonja I.; Chanock, Stephen J.; Hayes, Richard B.; Hoover, Robert N.; Thomas, Gilles; Weinstein, Stephanie J.; Yeager, Meredith; Ziegler, Regina G.] NCI, Bethesda, MD 20892 USA. [Boeing, Heiner] Deutsch Inst Ernahrungsforsch, Dept Epidemiol, Potsdam, Germany. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Buring, Julie E.; Lee, I-Min; Zhang, Shumin M.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. [Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Buring, Julie E.] Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, Boston, MA USA. [Chabbert-Buffet, Nathalie] Hop Tenon, APHP, Dept Gynecol, F-75970 Paris, France. [Chabbert-Buffet, Nathalie] Univ Paris 06, Paris, France. [Clavel-Chapelon, Francoise] Inst Gustave Roussy, INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, F-94805 Villejuif, France. [Clavel-Chapelon, Francoise] Paris S Univ, UMRS 1018, Villejuif, France. [Dumeaux, Vanessa; Lund, Eiliv] Univ Tromso, Inst Community Med, Tromso, Norway. [Gaziano, J. Michael] VA Boston Healthcare Syst, VA Cooperat Studies Programs, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Hankinson, Susan E.; Ma, Jing; Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hayes, Richard B.] NYU, Langone Med Ctr, NYU Canc Inst, Dept Environm Med,Div Epidemiol, New York, NY USA. [Johansson, Mattias] IARC, Lyon, France. [Johansson, Mattias; Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden. [Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge, England. [Kolonel, Laurence N.] Univ Hawaii, Program Epidemiol, Honolulu, HI 96822 USA. [Kolonel, Laurence N.; LeMarchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Lagiou, Pagona] Univ Athens, Sch Med, WHO Collaborating Ctr Food & Nutr Policies, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece. [Onland-Moret, N. Charlotte] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Overvad, Kim] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark. [Rodriguez, Laudina] Hlth & Hlth Care Serv Council, Publ Hlth & Participat Directorate, Oviedo, Asturias, Spain. [Sacerdote, Carlotta] CPO Piemonte Torino, Turin, Italy. [Sacerdote, Carlotta] Human Genet Fdn, Turin, Italy. [Sanchez, Maria-Jose] Andalusian Sch Publ Hlth, Granada, Spain. [Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Tumino, Rosario] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy. [Tumino, Rosario] Civile MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. RP Kraft, P (reprint author), 655 Huntington Ave,Bldg 2,Room 207, Boston, MA 02115 USA. EM pkraft@hsph.harvard.edu RI Clavel-Chapelon, Francoise/G-6733-2014; Gu, Fangyi/I-5957-2014; SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011; Albanes, Demetrius/B-9749-2015; Onland-Moret, N. Charlotte/G-9185-2011; OI SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Sacerdote, Carlotta/0000-0002-8008-5096; Hayes, Richard/0000-0002-0918-661X FU U.S. NIH; National Cancer Institute [U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758]; NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics FX U.S. NIH and the National Cancer Institute (cooperative agreements: U01-CA98233, David J. Hunter; U01-CA98710, Michael J. Thun; U01-CA98216, Elio Riboli and Rudolf Kaaks; and U01-CA98758, Brian E. Henderson; and the Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics). NR 57 TC 33 Z9 37 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2010 VL 19 IS 11 BP 2877 EP 2887 DI 10.1158/1055-9965.EPI-10-0507 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 677KP UT WOS:000283991600022 PM 20810604 ER PT J AU Michor, F Polyak, K AF Michor, Franziska Polyak, Kornelia TI The Origins and Implications of Intratumor Heterogeneity SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID CANCER STEM-CELLS; TUMOR HETEROGENEITY; STOCHASTIC DYNAMICS; MYELOID-LEUKEMIA; SOLID TUMORS; EVOLUTIONARY; MODEL; PROGRESSION; METASTASIS; RESISTANCE AB Human tumors often display startling intratumor heterogeneity in various features including histology, gene expression, genotype, and metastatic and proliferative potential. This phenotypic and genetic heterogeneity plays an important role in neoplasia, cancer progression, and therapeutic resistance. In this issue of the journal (beginning on page 1388), Merlo et al. report their use of molecular data from 239 patients with Barrett's esophagus to evaluate the propensity of major diversity indices for predicting progression to esophageal adenocarcinoma. This work helps elucidate the implications of molecular heterogeneity for the evolution of neoplasia. Cancer Prev Res; 3(11); 1361-4. (C) 2010 AACR. C1 [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Michor, F (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu FU NCI NIH HHS [U54 CA143798, U54CA143798] NR 32 TC 56 Z9 58 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD NOV PY 2010 VL 3 IS 11 BP 1361 EP 1364 DI 10.1158/1940-6207.CAPR-10-0234 PG 4 WC Oncology SC Oncology GA 677KN UT WOS:000283991400001 PM 20959519 ER PT J AU Lee, YJ Karl, DL Maduekwe, UN Rothrock, C Ryeom, S D'Amore, PA Yoon, SS AF Lee, Yoon-Jin Karl, Daniel L. Maduekwe, Ugwuji N. Rothrock, Courtney Ryeom, Sandra D'Amore, Patricia A. Yoon, Sam S. TI Differential Effects of VEGFR-1 and VEGFR-2 Inhibition on Tumor Metastases Based on Host Organ Environment SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MONOCLONAL-ANTIBODY; FACTOR RECEPTOR-2; ANGIOGENESIS; CANCER; THERAPY; CELLS; RAMUCIRUMAB; BEVACIZUMAB; RESISTANCE AB Tumors induce new blood vessel growth primarily from host organ microvascular endothelial cells (EC), and microvasculature differs significantly between the lung and liver. Vascular endothelial growth factor (VEGF or VEGF-A) promotion of tumor angiogenesis is thought to be mediated primarily by VEGF receptor-2 (VEGFR-2). In this study, VEGFR-2 antibody (DC101) inhibited growth of RenCa renal cell carcinoma lung metastases by 26%, whereas VEGFR-1 antibody (MF-1) had no effect. However, VEGFR-2 neutralization had no effect on RenCa liver metastases, whereas VEGFR-1 neutralization decreased RenCa liver metastases by 31%. For CT26 colon carcinoma liver metastases, inhibition of both VEGFR-1 and VEGFR-2 was required to induce growth delay. VEGFR-1 or VEGFR-2 inhibition decreased tumor burden not by preventing the establishment of micrometastases but rather by preventing vascularization and growth of micrometastases by 55% and 43%, respectively. VEGF induced greater phosphorylation of VEGFR-2 in lung ECs and of VEGFR-1 in liver ECs. EC proliferation, migration, and capillary tube formation in vitro were suppressed more by VEGFR-2 inhibition for lung EC and more by VEGFR-1 inhibition for liver EC. Collectively, our results indicate that liver metastases are more reliant on VEGFR-1 than lung metastases to mediate angiogenesis due to differential activity of VEGFRs on liver EC versus lung EC. Thus, therapies inhibiting specific VEGFRs should consider the targeted sites of metastatic disease. Cancer Res; 70(21); 8357-67. (C) 2010 AACR. C1 [Lee, Yoon-Jin; Karl, Daniel L.; Maduekwe, Ugwuji N.; Rothrock, Courtney; Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [D'Amore, Patricia A.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ryeom, Sandra; Yoon, Sam S.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. RP Yoon, SS (reprint author), Univ Penn, Sch Med, Dept Surg, 4 Silverstein,3400 Spruce St, Philadelphia, PA 19104 USA. EM sam.yoon@uphs.upenn.edu FU NIH [5 K12 CA 87723-03, 1 R21 CA117129-01] FX Grant Support; NIH grants 5 K12 CA 87723-03 and 1 R21 CA117129-01 (S.S. Yoon). P.A. D'Amore is a Research to Prevent Blindness Senior Scientific Investigator. NR 34 TC 26 Z9 27 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2010 VL 70 IS 21 BP 8357 EP 8367 DI 10.1158/0008-5472.CAN-10-1138 PG 11 WC Oncology SC Oncology GA 673MJ UT WOS:000283667300014 PM 20978198 ER PT J AU Hall, CA Wang, RS Miao, JY Oliva, E Shen, XY Wheeler, T Hilsenbeck, SG Orsulic, S Goode, S AF Hall, Chad A. Wang, Runsheng Miao, Jiangyong Oliva, Esther Shen, Xiaoyun Wheeler, Thomas Hilsenbeck, Susan G. Orsulic, Sandra Goode, Scott TI Hippo Pathway Effector Yap Is an Ovarian Cancer Oncogene SO CANCER RESEARCH LA English DT Article ID YES-ASSOCIATED PROTEIN; SURFACE EPITHELIUM; SIZE-CONTROL; DROSOPHILA; INHIBITION; INVASION; BIOLOGY; BREAST; CELLS AB The Hippo pathway regulates organ size and tumorigenesis in Drosophila and mammals and is altered in a variety of human cancers, yet it remains unclear if the Hippo pathway is of prognostic significance to cancer patients. Here we show that the key targets of Hippo signaling, transcriptional coactivators Yki and Yap, play a conserved role in promoting ovarian cancer in flies and humans, respectively. Whereas studies linking Yap to cancer in other tissues have focused on overall Yap levels, we show for the first time that subcellular levels of Yap show an exceptionally strong association with poor patient survival. Specifically, high levels of nuclear Yap (nYap), or low levels of cytoplasmic phosphorylated Yap (cpYap), associated with poor survival from ovarian cancer. Patients with both high nYap and low cpYap had similar to 50% lower 5-year survival, and this combination is an independent prognostic marker for survival, with an exceptionally high hazard ratio of 7.8. We find that Yap2 is the predominantly expressed Yap isoform in both the ovarian surface epithelium (OSE) and epithelial ovarian cancers. Overexpression of Yap2 and phosphorylation-defective Yap2-5SA in immortalized OSE cells resulted in increased cell proliferation, resistance to cisplatin-induced apoptosis, faster cell migration, and anchorage-independent growth, whereas Yap knockdown resulted in increased sensitivity to cisplatin-induced apoptosis. Findings argue that the Hippo signaling pathway defines an important pathway in progression of ovarian cancer. Cancer Res; 70(21); 8517-25. (C)2010 AACR. C1 [Hall, Chad A.; Goode, Scott] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Wang, Runsheng; Shen, Xiaoyun; Wheeler, Thomas; Goode, Scott] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Wheeler, Thomas; Hilsenbeck, Susan G.; Goode, Scott] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Hilsenbeck, Susan G.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Goode, Scott] Baylor Coll Med, Dept Mol & Cellular Biol, Program Dev, Program Cell & Mol Biol, Houston, TX 77030 USA. [Miao, Jiangyong; Oliva, Esther; Orsulic, Sandra] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Miao, Jiangyong; Oliva, Esther; Orsulic, Sandra] Harvard Univ, Sch Med, Boston, MA USA. RP Goode, S (reprint author), Baylor Coll Med, Dept Mol & Human Genet, S201,1 Baylor Plaza, Houston, TX 77030 USA. EM sgoode@bcm.edu FU NIH [2RO1 CA087759-06A2, RO1 CA103924, T32 GM008307]; Mary Kay Ash grant [038-03] FX NIH grant 2RO1 CA087759-06A2 and Mary Kay Ash grant 038-03 (S. Goode) and NIH grant RO1 CA103924 (S. Orsulic). C. A. Hall was supported by NIH training grant T32 GM008307. NR 26 TC 82 Z9 89 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2010 VL 70 IS 21 BP 8517 EP 8525 DI 10.1158/0008-5472.CAN-10-1242 PG 9 WC Oncology SC Oncology GA 673MJ UT WOS:000283667300030 PM 20947521 ER PT J AU Vaid, M Sharma, SD Katiyar, SK AF Vaid, Mudit Sharma, Som D. Katiyar, Santosh K. TI Honokiol, a phytochemical from the Magnolia plant, inhibits photocarcinogenesis by targeting UVB-induced inflammatory mediators and cell cycle regulators: development of topical formulation SO CARCINOGENESIS LA English DT Article ID FACTOR-KAPPA-B; SKIN-CANCER; MOUSE SKIN; IN-VIVO; TUMOR-DEVELOPMENT; COX-2 EXPRESSION; HAIRLESS MICE; ACTIVATION; APOPTOSIS; CYCLOOXYGENASE-2 AB To develop newer and more effective chemopreventive agents for skin cancer, we assessed the effect of honokiol, a phytochemical from the Magnolia plant, on ultraviolet (UV) radiation-induced skin tumorigenesis using the SKH-1 hairless mouse model. Topical treatment of mice with honokiol in a hydrophilic cream-based topical formulation before or after UVB (180 mJ/cm(2)) irradiation resulted in a significant protection against photocarcinogenesis in terms of tumor multiplicity (28-60%, P < 0.05 to < 0.001) and tumor volume per tumor-bearing mouse (33-80%, P < 0.05 to 0.001, n = 20). Honokiol also inhibited and delayed the malignant progression of papillomas to carcinomas. To investigate the in vivo molecular targets of honokiol efficacy, tumors and tumor-uninvolved skin samples from the tumor-bearing mice were analyzed for inflammatory mediators, cell cycle regulators and survival signals using immunostaining, western blotting and enzyme-linked immunosorbent assay. Treatment with honokiol significantly inhibited UVB-induced expression of cyclooxygenase-2, prostaglandin E(2) (P < 0.001), proliferating cell nuclear antigen and proinflammatory cytokines, such as tumor necrosis factor-alpha (P < 0.001), interleukin (IL)-1 beta (P < 0.01) and IL-6 (P < 0.001) in the skin as well as in skin tumors. Western blot analysis revealed that honokiol: (i) inhibited the levels of cyclins D1, D2 and E and associated cyclin-dependent kinases (CDKs)2, CDK4 and CDK6, (ii) upregulated Cip/p21 and Kip/p27 and (iii) inhibited the levels of phosphatidylinositol 3-kinase and the phosphorylation of Akt at Ser(473) in UVB-induced skin tumors. Together, our results indicate that honokiol holds promise for the prevention of UVB-induced skin cancer by targeting inflammatory mediators, cell cycle regulators and cell survival signals in UVB-exposed skin. C1 [Vaid, Mudit; Sharma, Som D.; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration FX Veterans Administration Merit Review Award (S.K.K.). NR 47 TC 39 Z9 39 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2010 VL 31 IS 11 BP 2004 EP 2011 DI 10.1093/carcin/bgq186 PG 8 WC Oncology SC Oncology GA 676OS UT WOS:000283922400014 PM 20823108 ER PT J AU Habib, SL Bhandari, BK Sadek, N Abboud-Werner, SL Abboud, HE AF Habib, Samy L. Bhandari, Besant K. Sadek, Nahed Abboud-Werner, Sherry L. Abboud, Hanna E. TI Novel mechanism of regulation of the DNA repair enzyme OGG1 in tuberin-deficient cells SO CARCINOGENESIS LA English DT Article ID HOGG1 SER326CYS POLYMORPHISM; TUMOR-SUPPRESSOR GENE; LUNG-CANCER RISK; EKER RAT MODEL; 3-KINASE/AKT PATHWAY; SCLEROSIS COMPLEX; DAMAGE; TSC2; KIDNEY; PHOSPHORYLATION AB Tuberin (protein encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease in the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in tumour kidney of tuberous sclerosis complex (TSC) patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and kidney cortex of the Eker rat is associated with decreased activator protein 4 (AP4) and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in kidney tumour from Eker rats and the accumulation of significant levels of 8-oxo-deoxyguanosine. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with small interfering RNA (siRNA) also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expression using siRNA resulted in a significant decrease in the protein expression of OGG1. Immunoprecipitation studies show that AP4 is associated with tuberin in cells. Gel shift analysis and chromatin immunoprecipitation identified the transcription factor AP4 as a positive regulator of the OGG1 promoter. AP4 DNA-binding activity is significantly reduced in Tsc2(-/-) as compared with Tsc2(+/+) cells. Transcriptional activity of the OGG1 promoter is also decreased in tuberin-null cells compared with wild-type cells. These data indicate a novel role for tuberin in the regulation of OGG1 through the transcription factor AP4. This regulation may be important in the pathogenesis of kidney tumours in patients with TSC disease. C1 [Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Abboud-Werner, Sherry L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Habib, Samy L.] S Texas Vet Healthcare Syst, Dept Geriatr Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, MSC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM habib@uthscsa.edu FU American Diabetes Association; South Texas Veterans Healthcare System; The National Organization for Research FX American Diabetes Association Research Grant; Merit Review Award and New Investigator Award from the South Texas Veterans Healthcare System to S.L.H.; The authors would like to acknowledge Dr Daniel J.Riley and Dr Anthony Valente for helpful discussions and for critical reading of the manuscript, Dr P.Radicella at Radiobiologie Moleculaire et Cellulaire, France, for providing the OGG1 promoter construct and Dr S.Mitra at the University of Texas M. D. Anderson and Sealy Center for Molecular Science, Galveston, TX for providing the OGG1 antibody. N.S. is a recipient of the Research Fellowship Award from The National Organization for Research, Egypt. NR 44 TC 15 Z9 15 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2010 VL 31 IS 11 BP 2022 EP 2030 DI 10.1093/carcin/bgq189 PG 9 WC Oncology SC Oncology GA 676OS UT WOS:000283922400016 PM 20837600 ER PT J AU Orozco-Gutierrez, JJ Castillo-Martinez, L Orea-Tejeda, A Vazquez-Diaz, O Valdespino-Trejo, A Narvaez-David, R Keirns-Davis, C Carrasco-Ortiz, O Navarro-Navarro, A Sanchez-Santillan, R AF Jose Orozco-Gutierrez, Juan Castillo-Martinez, Lilia Orea-Tejeda, Arturo Vazquez-Diaz, Oscar Valdespino-Trejo, Adrian Narvaez-David, Rene Keirns-Davis, Candace Carrasco-Ortiz, Olin Navarro-Navarro, Adolfo Sanchez-Santillan, Rocio TI Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction SO CARDIOLOGY JOURNAL LA English DT Article DE L-arginine; citrulline; heart failure; blood pressure; right ventricle ID FREE FATTY-ACIDS; PERSISTENT PULMONARY-HYPERTENSION; ENDOTHELIAL DYSFUNCTION; PREGNANCY; EXERCISE; LABOR; CAPACITY; DISEASE; NEWBORN; GLUCOSE AB Background: The effect of L-arginine and L-citrulline on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction (HFpEF) is unknown. We have therefore evaluated, in a randomized clinical trial, the effect of these aminoacids in chronic outstanding and stable patients with HFpEF. Methods and results: All patients underwent an echocardiogram and radioisotopic ventriculography rest/exercise, and were randomized in a consecutive manner to the L-arginine group (n = 15; 8 g/day); and the citrulline malate group (n = 15; 3 g/day). The duration of follow-up was two months. The principal echocardiographic finding was a statistically significant decrease in pulmonary artery pressure in the L-arginine (56.3 +/- 10 vs 44 +/- 16.5 mm Hg, p < 0.05) and the citrulline (56.67 +/- 7.96 vs 47.67 +/- 8.59 mm Hg, p < 0.05) groups. Duration on treadmill and right ventricular ejection fraction post exercise increased, while diastolic and systolic artery pressure decreased significantly in both groups. There were no other statistically significant differences between the groups. Conclusions: Administration of L-arginine and citrulline to patients with HFpEF improved right ventricular function by increasing right ventricular ejection fraction, and probably decreasing systolic pulmonary artery pressure. (Cardiol J 2010; 17, 6: 612-618) C1 [Jose Orozco-Gutierrez, Juan; Castillo-Martinez, Lilia; Orea-Tejeda, Arturo; Vazquez-Diaz, Oscar; Valdespino-Trejo, Adrian; Carrasco-Ortiz, Olin; Navarro-Navarro, Adolfo; Sanchez-Santillan, Rocio] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Heart Failure Clin, Mexico City 03100, DF, Mexico. [Castillo-Martinez, Lilia; Orea-Tejeda, Arturo; Narvaez-David, Rene] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cardiol, Mexico City 03100, DF, Mexico. [Keirns-Davis, Candace] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Orea-Tejeda, A (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Heart Failure Clin, Prov 1218-A Int 402, Mexico City 03100, DF, Mexico. EM artorea@yahoo.com.mx RI Castillo-Martinez, Lilia/H-3750-2013 FU Pronat Laboratories FX We wish to express our gratitude to Pronat Laboratories for their support and generosity and especially to Ing. Sergio Becerril and Lic. Francisco Lopez for donating the aminoacids that made this study possible. NR 36 TC 20 Z9 22 U1 1 U2 8 PU VIA MEDICA PI GDANSK PA UL SWIETOKRZYSKA 73, 80-180 GDANSK, POLAND SN 1897-5593 J9 CARDIOL J JI Cardiol. J. PD NOV PY 2010 VL 17 IS 6 BP 612 EP 618 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 723XL UT WOS:000287540600011 PM 21154265 ER PT J AU Locasale, JW Heiden, MGV Cantley, LC AF Locasale, Jason W. Heiden, Matthew G. Vander Cantley, Lewis C. TI Rewiring of glycolysis in cancer cell metabolism SO CELL CYCLE LA English DT Editorial Material ID PYRUVATE-KINASE; M2 C1 [Locasale, Jason W.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Locasale, Jason W.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Ctr Life Sci, Boston, MA 02215 USA. [Heiden, Matthew G. Vander] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Heiden, Matthew G. Vander] MIT, Koch Inst Integrat Canc Res, Dept Biol, Boston, MA USA. RP Locasale, JW (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM JLocasal@bidmc.harvard.edu; lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 9 TC 13 Z9 14 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV PY 2010 VL 9 IS 21 BP 4253 EP 4253 DI 10.4161/cc.9.21.13925 PG 1 WC Cell Biology SC Cell Biology GA 673HQ UT WOS:000283650500002 PM 21045562 ER PT J AU Afessa, B Anzueto, AR Craven, DE Kollef, MH AF Afessa, Bekele Anzueto, Antonio R. Craven, Donald E. Kollef, Marin H. TI Increased Mortality in Patients Without Ventilator-Associated Pneumonia Response SO CHEST LA English DT Letter ID COATED ENDOTRACHEAL-TUBES; BURDEN C1 [Afessa, Bekele] Mayo Clin, Div Pulm & Crit Care Med, Coll Med, Rochester, MN 55905 USA. [Anzueto, Antonio R.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Anzueto, Antonio R.] Univ Texas Hlth Sci Ctr San Antonio, Univ Hosp, San Antonio, TX 78229 USA. [Craven, Donald E.] Lahey Clin Med Ctr, Boston, MA USA. [Craven, Donald E.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Kollef, Marin H.] Washington Univ, Sch Med, St Louis, MO USA. RP Afessa, B (reprint author), Mayo Clin, Div Pulm & Crit Care Med, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM Afessa.bekele@mayo.edu NR 4 TC 0 Z9 0 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 NOV PY 2010 VL 138 IS 5 BP 1275 EP 1275 DI 10.1378/chest.10-1724 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 681TH UT WOS:000284341700042 ER PT J AU O'Donnell, CR Bankier, AA Stiebellehner, L Reilly, JJ Brown, R Loring, SH AF O'Donnell, Carl R. Bankier, Alexander A. Stiebellehner, Leopold Reilly, John J. Brown, Robert Loring, Stephen H. TI How To Measure Lung Volume? Response SO CHEST LA English DT Letter ID FREQUENCY; GAS C1 [O'Donnell, Carl R.] Beth Israel Deaconess Med Ctr, Dept Pulm & Crit Care Med, Boston, MA 02215 USA. [Bankier, Alexander A.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Loring, Stephen H.] Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. [Stiebellehner, Leopold] Med Univ Vienna, Dept Pulmonol, Vienna, Austria. [Reilly, John J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Brown, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP O'Donnell, CR (reprint author), Beth Israel Deaconess Med Ctr, Dept Pulm & Crit Care Med, Dana 717,330 Brookline Ave, Boston, MA 02215 USA. EM codonne1@bidmc.harvard.edu RI Reilly, John/H-8755-2012 NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2010 VL 138 IS 5 BP 1281 EP 1282 DI 10.1378/chest.10-1607 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 681TH UT WOS:000284341700050 ER PT J AU Anderson, JA Willson, P Peterson, NJ Murphy, C Kent, TA AF Anderson, Jane A. Willson, Pamela Peterson, Nancy J. Murphy, Chris Kent, Thomas A. TI Prototype to Practice Developing and Testing a Clinical Decision Support System for Secondary Stroke Prevention in a Veterans Healthcare Facility SO CIN-COMPUTERS INFORMATICS NURSING LA English DT Article DE Advanced practice nursing; Clinical decision support systems; Electronic medical record; Evidence-based practice; Nursing; Secondary stroke prevention; Usability ID GUIDELINES AB A clinical decision support system that guides nurse practitioners and other healthcare providers in secondary stroke prevention was developed by a multidisciplinary team with funding received from the Veterans Health Administration Office of Nursing Services. This article presents alpha-testing results obtained while using an integrated model for clinical decision support system development that emphasizes end-user perspectives throughout the development process. Before-after and descriptive methods were utilized to evaluate functionality and usability of the prototype among a sample of multidisciplinary clinicians. The predominant functionality feature of the tool is automated prompting and documentation of secondary stroke prevention guidelines in the electronic medical record. Documentation of guidelines was compared among multidisciplinary providers (N = 15) using test case scenarios and two documentation systems, standard versus the prototype. Usability was evaluated with an investigator-developed questionnaire and one open-ended question. The prototype prompted a significant increase (P < .05) in provider documentation for six of 11 guidelines as compared with baseline documentation while using the standard system. Of a possible 56 points, usability was scored high (mean, 48.9 [SD, 6.8]). These results support that guideline prompting has been successfully engineered to produce a usable and useful clinical decision support system for secondary stroke prevention. C1 [Anderson, Jane A.; Murphy, Chris] Baylor Coll Med, Stroke Ctr, Houston, TX 77030 USA. [Anderson, Jane A.; Peterson, Nancy J.; Murphy, Chris; Kent, Thomas A.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Anderson, Jane A.; Willson, Pamela; Peterson, Nancy J.; Murphy, Chris; Kent, Thomas A.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Anderson, Jane A.; Willson, Pamela] Prairie View A&M Univ, Coll Nursing, Houston, TX USA. [Willson, Pamela] Elsevier, Review & Testing, Res, Houston, TX USA. RP Anderson, JA (reprint author), Baylor Coll Med, Stroke Ctr, Houston, TX 77030 USA. EM jane.anderson@med.va.gov OI Kent, Thomas/0000-0002-9877-7584 FU Veterans Health Administration Office of Nursing Services FX This project was funded by the Veterans Health Administration Office of Nursing Services. NR 23 TC 7 Z9 8 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1538-2931 J9 CIN-COMPUT INFORM NU JI CIN-Comput. Inform. Nurs. PD NOV-DEC PY 2010 VL 28 IS 6 BP 353 EP 363 DI 10.1097/NCN.0b013e3181f69c5b PG 11 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Nursing SC Computer Science; Medical Informatics; Nursing GA 675RL UT WOS:000283848300004 PM 20978406 ER PT J AU Weiner, RB Weyman, AE Khan, AM Reingold, JS Chen-Tournoux, AA Scherrer-Crosbie, M Picard, MH Wang, TJ Baggish, AL AF Weiner, Rory B. Weyman, Arthur E. Khan, Abigail May Reingold, Jason S. Chen-Tournoux, Annabel A. Scherrer-Crosbie, Marielle Picard, Michael H. Wang, Thomas J. Baggish, Aaron L. TI Preload Dependency of Left Ventricular Torsion The Impact of Normal Saline Infusion SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE echocardiography; mechanics; cardiac volume; torsion ID INOTROPIC STIMULATION; SYSTOLIC TORSION; APICAL ROTATION; EXERCISE; HEART; MECHANICS; MOTION; ECHOCARDIOGRAPHY; RECOMMENDATIONS; CARDIOMYOPATHY AB Background-Left ventricular (LV) rotation results from contraction of obliquely oriented myocardial fibers. The net difference between systolic apical counterclockwise rotation and basal clockwise rotation is left ventricular torsion (LVT). Although LVT is altered in various cardiac diseases, determinants of LVT are incompletely understood. Methods and Results-LV end-diastolic volume, LV apical and basal rotation, peak systolic LVT, and peak early diastolic untwisting rate were measured by speckle-tracking echocardiography in healthy subjects (n=8) before and after infusion of a weight-based normal saline bolus (2.1 +/- 0.3 L). Saline infusion led to a significant increase in end-diastolic LV internal diameter (45.9 +/- 3.7 versus 47.6 +/- 4.2 mm; P=0.002) and LV end-diastolic volume (90.0 +/- 21.6 versus 98.3 +/- 19.6 mL; P=0.01). Stroke volume (51.3 +/- 10.9 versus 63.0 +/- 15.5 mL; P=0.003) and cardiac output (3.4 +/- 0.8 versus 4.4 +/- 1.5 L/min; P=0.007) increased, whereas there was no change in heart rate and blood pressure. There was a significant increase in the magnitude of peak systolic apical rotation (7.5 +/- 2.4 degrees versus 10.5 +/- 2.8 degrees; P<0.001) but no change in basal rotation (-4.1 +/- 2.3 degrees versus -4.8 +/- 3.1 degrees; P=0.44). Accordingly, peak systolic LVT increased by 33% after saline infusion (11.2 +/- 1.3 degrees versus 14.9 +/- 1.7 degrees; P<0.001). This saline-induced increase in LVT was associated with a marked increase in peak early diastolic untwisting rate (72.3 +/- 21.4 versus 136.8 +/- 30.0 degrees/s; P<0.001). Conclusions-Peak systolic LVT and peak early diastolic untwisting rate are preload-dependent. Changes in LV preload should be considered when interpreting results of future LVT studies. (Circ Cardiovasc Imaging. 2010; 3: 672-678.) C1 [Weiner, Rory B.; Weyman, Arthur E.; Khan, Abigail May; Reingold, Jason S.; Chen-Tournoux, Annabel A.; Scherrer-Crosbie, Marielle; Picard, Michael H.; Wang, Thomas J.; Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org OI Picard, Michael/0000-0002-9264-3243 FU National Center for Research Resources [1 UL1 RR025758-01] FX This study was supported by grant No. 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 28 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2010 VL 3 IS 6 BP 672 EP 678 DI 10.1161/CIRCIMAGING.109.932921 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 680VN UT WOS:000284264400007 PM 20826594 ER PT J AU Messas, E Bel, A Szymanski, C Cohen, I Touchot, B Handschumacher, MD Desnos, M Carpentier, A Menasche, P Hagege, AA Levine, RA AF Messas, Emmanuel Bel, Alain Szymanski, Catherine Cohen, Iris Touchot, Bernard Handschumacher, Mark D. Desnos, Michel Carpentier, Alain Menasche, Philippe Hagege, Albert A. Levine, Robert A. TI Relief of Mitral Leaflet Tethering Following Chronic Myocardial Infarction by Chordal Cutting Diminishes Left Ventricular Remodeling SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE remodeling; myocardial infarction; mitral valve; regurgitation; echocardiography ID 3-DIMENSIONAL ECHOCARDIOGRAPHIC RECONSTRUCTION; DOPPLER-ECHOCARDIOGRAPHY; RING ANNULOPLASTY; VALVE-REPLACEMENT; REGURGITATION; MECHANISM; APPARATUS; SEVERITY; RECOMMENDATIONS; AORTOTOMY AB Background-One of the key targets in treating mitral regurgitation (MR) is reducing the otherwise progressive left ventricular (LV) remodeling that exacerbates MR and conveys adverse prognosis. We have previously demonstrated that severing 2 second-order chordae to the anterior mitral leaflet relieves tethering and ischemic MR acutely. The purpose of this study was to test whether this technique reduces the progression of LV remodeling in the chronic ischemic MR setting. Methods and Results-A posterolateral MI was created in 18 sheep by obtuse marginal branch ligation. After chronic remodeling and MR development at 3 months, 6 sheep were randomized to sham surgery (control group) and 12 to second-order chordal cutting (6 each to anterior leaflet [AntL] and bileaflet [BiL] chordal cutting, techniques that are in clinical application). At baseline, chronic infarction (3 months), and follow-up at a mean of 6.6 months post-myocardial infarction (MI) (euthanasia), we measured LV end-diastolic (EDV) and end-systolic volume (ESV), ejection fraction, wall motion score index, and posterior leaflet (PL) restriction angle relative to the annulus by 2D and 3D echocardiography. All measurements were comparable among groups at baseline and chronic MI. At euthanasia, AntL and BiL chordal cutting limited the progressive remodeling seen in controls. LVESV increased relative to chronic MI by 109 +/- 8.7% in controls versus 30.5 +/- 6.1% with chordal cutting (P<0.01) (LVESV in controls, 82.5 +/- 2.6 mL; in AntL, 60.6 +/- 5.1 mL; in BiL, 61.8 +/- 4.1 mL). LVEDV increased by 63 +/- 2.0% in controls versus 26 +/- 5.5% and 22 +/- 3.4% with chordal cutting (P<0.01). LV ejection fraction and wall motion score index were not significantly different at follow-up among the chordal cutting and control groups. MR progressively increased to moderate in controls but decreased to trace-mild with AntL and BiL chordal cutting (MR vena contracta in controls, 5.9 +/- 1.1 mm; in AntL, 2.6 +/- 0.1 mm; in BiL, 1.7 +/- 0.1 mm; P<0.01). BiL chordal cutting provided greater PL mobility (decreased PL restriction angle to 54.2 +/- 5.0 degrees versus 83 +/- 3.2 degrees with AntL chordal cutting; P<0.01). Conclusions-Reduced leaflet tethering by chordal cutting in the chronic post-MI setting substantially decreases the progression of LV remodeling with sustained reduction of MR over a chronic follow-up. These benefits have the potential to improve clinical outcomes. (Circ Cardiovasc Imaging. 2010; 3: 679-686.) C1 [Messas, Emmanuel] Univ Paris 05, Hop Broussais, Hop Europeen Georges Pompidou, AP HP,Dept Cardiol,INSERM,U633, F-75014 Paris, France. [Handschumacher, Mark D.; Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Messas, E (reprint author), Univ Paris 05, Hop Broussais, Hop Europeen Georges Pompidou, AP HP,Dept Cardiol,INSERM,U633, 6 Rue Didot, F-75014 Paris, France. EM emmanuel.messas@egp.aphp.fr FU Leducq Foundation, Paris, France [07CVD04]; National Institutes of Health, Bethesda [R01, K24 HL67434]; Federation Francaise de Cardiologie FX This work was supported in part by grant 07CVD04 for the Transatlantic Network of Excellence in Mitral Valve Disease from the Leducq Foundation, Paris, France, and by grants R01 and K24 HL67434 from the National Institutes of Health, Bethesda, Md. Dr Szymanski was supported by a grant from the Federation Francaise de Cardiologie. NR 42 TC 19 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2010 VL 3 IS 6 BP 679 EP 686 DI 10.1161/CIRCIMAGING.109.931840 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 680VN UT WOS:000284264400008 PM 20826595 ER PT J AU Kostis, WJ Deng, YZ Pantazopoulos, JS Moreyra, AE Kostis, JB AF Kostis, William J. Deng, Yingzi Pantazopoulos, John S. Moreyra, Abel E. Kostis, John B. CA Myocardial Infarction Data TI Trends in Mortality of Acute Myocardial Infarction After Discharge From the Hospital SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE epidemiology; mortality; myocardial infarction ID POSITIVE PREDICTIVE-VALUE; LONG-TERM MORTALITY; REPERFUSION THERAPY; ST-ELEVATION; HEART; DIAGNOSIS; OUTCOMES; COMMUNITIES; ADMISSION; DISEASE AB Background-We assessed trends in the prognosis of patients with acute myocardial infarction hospitalized in New Jersey hospitals. In recent decades, in-hospital mortality has declined markedly but the decline in longer-term mortality is less pronounced, implying that mortality after discharge has worsened. Methods and Results-Using the Myocardial Infarction Data Acquisition System (MIDAS), we examined the outcomes of 285 397 patients hospitalized for a first acute myocardial infarction between 1986 and 2007. Mortality at discharge decreased by 9.4% from 16.9% to 7.5% (annual change, -0.44; 95% confidence interval, -0.49 to -0.40), but the decrease at 1 year was less pronounced (6.4%) because of an increase in mortality from discharge to 1 year after discharge (from 12.1% to 13.9%; annual change, +0.15; 95% confidence interval, +0.10 to +0.20). Mortality from 30 days after discharge to 1 year, a measure not affected by length of stay, increased by 1.2% (annual change, +0.10; 95% confidence interval, +0.06 to +0.23). The effect was more evident in the older age groups and was due to noncardiovascular mortality, especially from respiratory and renal diseases, septicemia, and cancer. All effects remained statistically significant (P<0.0001) after adjustment for demographics, comorbidities, infarction type, complications, and interventions. Piecewise linear regressions confirmed these trends. Conclusions-Postdischarge mortality of patients with acute myocardial infarction is increasing, primarily because of higher noncardiovascular mortality in the older age groups. (Circ Cardiovasc Qual Outcomes. 2010;3:581-589.) C1 [Kostis, William J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Deng, Yingzi; Pantazopoulos, John S.; Moreyra, Abel E.; Kostis, John B.] UMDNJ Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA. RP Kostis, JB (reprint author), UMDNJ Robert Wood Johnson Med Sch, Dept Med, 1 Robert Wood Johnson Pl, New Brunswick, NJ 08903 USA. EM kostis@umdnj.edu FU Robert Wood Johnson Foundation; Schering-Plough Foundation FX This study was supported by the Robert Wood Johnson Foundation and the Schering-Plough Foundation. NR 30 TC 52 Z9 53 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2010 VL 3 IS 6 BP 581 EP U57 DI 10.1161/CIRCOUTCOMES.110.957803 PG 24 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680VB UT WOS:000284262900005 PM 20923995 ER PT J AU Fang, MC Go, AS Chang, YC Borowsky, LH Pomernacki, NK Udaltsova, N Singer, DE AF Fang, Margaret C. Go, Alan S. Chang, Yuchiao Borowsky, Leila H. Pomernacki, Niela K. Udaltsova, Natalia Singer, Daniel E. TI Warfarin Discontinuation After Starting Warfarin for Atrial Fibrillation SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE anticoagulants; atrial fibrillation; stroke; prevention; warfarin ID STROKE PREVENTION; ANTITHROMBOTIC THERAPY; RISK-FACTORS; ANTICOAGULATION; ASPIRIN; TRIAL; MANAGEMENT; HEMORRHAGE; GUIDELINES; INTENSITY AB Background-Although warfarin is widely recommended to prevent atrial fibrillation-related thromboembolism, many eligible patients do not take warfarin. The objective of this study was to describe factors associated with warfarin discontinuation in patients newly starting warfarin for atrial fibrillation. Methods and Results-We identified 4188 subjects newly starting warfarin in the Anticoagulation and Risk Factors in Atrial Fibrillation Study and tracked longitudinal warfarin use through pharmacy and laboratory databases. Data on patient characteristics, international normalized ratio (INR) tests, and incident hospitalizations for hemorrhage were obtained from clinical and laboratory databases. Multivariable Cox regression analysis was used to identify independent predictors of prolonged warfarin discontinuation, defined as >= 180 consecutive days off warfarin. Within 1 year after warfarin initiation, 26.3% of subjects discontinued therapy despite few hospitalizations for hemorrhage (2.3% of patients). The risk of discontinuation was higher in patients aged <65 years (adjusted hazard ratio [HR], 1.33 [95% CI, 1.03 to 1.72] compared to those aged >= 85 years), patients with poorer anticoagulation control (HR, 1.46 [95% CI, 1.42 to 1.49] for every 10% decrease in time in therapeutic INR range), and patients with lower stroke risk (HR, 2.54 [95% CI, 1.86 to 3.47] for CHADS(2) stroke risk index of 0 compared to 4 to 6). Conclusions-More than 1 in 4 patients newly starting warfarin for atrial fibrillation discontinued therapy in the first year despite a low overall hemorrhage rate. Individuals deriving potentially less benefit from warfarin, including those with younger age, fewer stroke risk factors, and poorer INR control, were less likely to remain on warfarin. Maximizing the benefits of anticoagulation for atrial fibrillation depends on determining which patients are most appropriately initiated and maintained on therapy. (Circ Cardiovasc Qual Outcomes. 2010;3:624-631.) C1 [Fang, Margaret C.; Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Go, Alan S.; Pomernacki, Niela K.; Udaltsova, Natalia] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Chang, Yuchiao; Borowsky, Leila H.; Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Fang, MC (reprint author), Univ Calif San Francisco, Dept Med, 503 Parnassus Ave,Box 0131, San Francisco, CA 94143 USA. EM mfang@medicine.ucsf.edu FU National Institute on Aging [R01 AG15478, K23 AG28978]; National Heart, Lung, and Blood Institute [U19 HL91179, RC2HL101589]; Massachusetts General Hospital (Boston, Mass); Johnson Johnson, Inc.; Daiichi Sankyo, Inc FX Funding for the study was provided by the National Institute on Aging (R01 AG15478 and K23 AG28978); the National Heart, Lung, and Blood Institute (U19 HL91179 and RC2HL101589); and the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital (Boston, Mass). The funding sources had no role in study design, data collection, data analysis, data interpretation, or writing of this manuscript.; Dr Go has received a research grant from Johnson & Johnson, Inc. In the past 2 years, Dr Singer has received a research grant from Daiichi Sankyo, Inc, and consulted for Boehringer Ingelheim, Daiichi Sankyo, Inc, Johnson and Johnson, Inc, Merck and Co, and Sanofi Aventis, Inc. and Bayer Schering Pharma. NR 30 TC 84 Z9 86 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 NOV PY 2010 VL 3 IS 6 BP 624 EP 631 DI 10.1161/CIRCOUTCOMES.110.937680 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680VB UT WOS:000284262900010 PM 20959565 ER PT J AU Maddox, TM Ho, PM Roe, M Dai, D Tsai, TT Rumsfeld, JS AF Maddox, Thomas M. Ho, P. Michael Roe, Matthew Dai, David Tsai, Thomas T. Rumsfeld, John S. TI Utilization of Secondary Prevention Therapies in Patients With Nonobstructive Coronary Artery Disease Identified During Cardiac Catheterization Insights From the National Cardiovascular Data Registry Cath-PCI Registry SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE prevention; coronary disease; epidemiology ID ACUTE MYOCARDIAL-INFARCTION; RISK STRATIFICATION; ANGIOGRAPHY; GUIDELINES; MECHANISMS; OUTCOMES; SITE AB Background-Secondary prevention therapies are indicated for patients with coronary artery disease (CAD). However, patients with nonobstructive CAD may be less likely to receive these therapies compared with patients with obstructive CAD. Therefore, we compared rates of secondary prevention medication prescription between patients with nonobstructive and obstructive CAD. Methods and Results-We conducted a retrospective cohort study of 1 489 745 CAD patients undergoing cardiac catheterization in 786 US centers between 2004 and 2007. We measured rates of aspirin, statin, beta-blocker, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) prescription at hospital discharge among eligible patients; 237 167 (15.9%) patients had nonobstructive CAD and 1 252 578 (84.1%) had obstructive CAD. Compared with obstructive CAD patients, nonobstructive CAD patients had significantly lower rates of rates of aspirin (72.7% versus 90.9%), statin (60.0% versus 80.3%), beta-blocker (57.9% versus 79.4%), and ACEI/ARB (45.9% versus 58.6%; all probability values <0.0001) prescription at hospital discharge. After multivariable adjustment, nonobstructive CAD patients remained significantly less likely to receive prescriptions for aspirin (odds ratio, 0.37; 95% confidence interval, 0.35 to 0.39), statins (odds ratio, 0.45; 95% confidence interval, 0.43 to 0.48), beta-blockers (odds ratio, 0.46; 95% CI, 0.44 to 0.47), or ACEI/ARBs (odds ratio, 0.83; 95% confidence interval, 0.8 to 0.86) compared with obstructive CAD patients. Secondary analyses of selected subgroups supported the primary findings. Conclusions-Patients with nonobstructive CAD were significantly less likely to receive secondary prevention medication prescription at hospital discharge, as compared with patients with obstructive CAD. These findings highlight an opportunity to improve the quality of care for CAD patients with nonobstructive disease. (Circ Cardiovasc Qual Outcomes. 2010;3:632-641.) C1 [Maddox, Thomas M.] Univ Colorado, Denver VAMC, Cardiol Sect 111B, Denver, CO 80220 USA. [Roe, Matthew; Dai, David] Duke Clin Res Inst, Durham, NC USA. RP Maddox, TM (reprint author), Univ Colorado, Denver VAMC, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.maddox@va.gov FU American College of Cardiology; Society for Coronary Angiography and Intervention; Department of Veterans Affairs Health Services Research and Developmen FX This study was supported by the American College of Cardiology and Society for Coronary Angiography and Intervention. The funders had no role in the design and conduct of the study nor collection, management, analysis, and interpretation of the data. The Research and Publications committee for the NCDR Cath-PCI registry reviewed and approved the final version of the manuscript. Drs Maddox and Ho were supported by Department of Veterans Affairs Health Services Research and Development Career Development Awards. NR 21 TC 29 Z9 33 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 NOV PY 2010 VL 3 IS 6 BP 632 EP 641 DI 10.1161/CIRCOUTCOMES.109.906214 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680VB UT WOS:000284262900011 PM 20923997 ER PT J AU Mahoney, EM Wang, K Keo, HH Duval, S Smolderen, KG Cohen, DJ Steg, G Bhatt, DL Hirsch, AT AF Mahoney, Elizabeth M. Wang, Kaijun Keo, Hong H. Duval, Sue Smolderen, Kim G. Cohen, David J. Steg, Gabriel Bhatt, Deepak L. Hirsch, Alan T. CA Reduction Atherothrombosis TI Vascular Hospitalization Rates and Costs in Patients With Peripheral Artery Disease in the United States SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE costs; peripheral artery disease; atherothrombosis ID ST-SEGMENT ELEVATION; CARDIOVASCULAR RISK-FACTORS; ACUTE CORONARY SYNDROMES; HEALTH REACH REGISTRY; LOWER-EXTREMITY; ATHEROTHROMBOSIS; OUTPATIENTS; INTERVENTIONS; CLOPIDOGREL; POPULATION AB Background-Peripheral artery disease (PAD) is common and imposes a high risk of major systemic and limb ischemic events. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international prospective registry of patients at risk of atherothrombosis caused by established arterial disease or the presence of >= 3 atherothrombotic risk factors. Methods and Results-We compared the 2-year rates of vascular-related hospitalizations and associated costs in US patients with established PAD across patient subgroups. Symptomatic PAD at enrollment was identified on the basis of current intermittent claudication with an ankle-brachial index (ABI) < 0.90 or a history of lower-limb revascularization or amputation. Asymptomatic PAD was diagnosed on the basis of an enrollment ABI < 0.90 in the absence of symptoms. Overall, 25 763 of the total 68 236-patient REACH cohort were enrolled from US sites; 2396 (9.3%) had symptomatic and 213 (0.8%) had asymptomatic PAD at baseline. One-and cumulative 2-year follow-up data were available for 2137 (82%) and 1677 (64%) of US REACH patients with either symptomatic or asymptomatic PAD, respectively. At 2 years, mean cumulative hospitalization costs, per patient, were $7445, $7000, $10 430, and $11 693 for patients with asymptomatic PAD, a history of claudication, lower-limb amputation, and revascularization, respectively (P = 0.007). A history of peripheral intervention (lower-limb revascularization or amputation) was associated with higher rates of subsequent procedures at both 1 and 2 years. Conclusions-The economic burden of PAD is high. Recurring hospitalizations and repeat revascularization procedures suggest that neither patients, physicians, nor healthcare systems should assume that a first admission for a lower-extremity PAD procedure serves as a permanent resolution of this costly and debilitating condition. (Circ Cardiovasc Qual Outcomes. 2010;3:642-651.) C1 [Mahoney, Elizabeth M.; Wang, Kaijun; Smolderen, Kim G.; Cohen, David J.] St Lukes Mid Amer Heart & Vasc Inst, Kansas City, MO USA. [Mahoney, Elizabeth M.; Cohen, David J.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. [Smolderen, Kim G.] Tilburg Univ, Ctr Res Psychol & Somat Dis, NL-5000 LE Tilburg, Netherlands. [Keo, Hong H.; Duval, Sue; Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. Univ Paris 07, INSERM U 698, Paris, France. AP HP, Paris, France. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mahoney, EM (reprint author), St Lukes Hosp, Mid Amer Heart & Vasc Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM emahoney1@saint-lukes.org RI Smolderen, Kim/B-8078-2015 FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); American Heart Association Pharmaceutical Roundtable; Daiichi-Sankyo; Eli Lilly; Astra Zeneca; Cytokinetics; Roche; ev3; Schering-Plough; Boston Scientific; Cordis; Medtronic; Servier; Novartis; Heartscape; Medicines Company; Eisai; Ethicon FX The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH Registry is endorsed by the World Heart Federation. A complete list of REACH investigators appears in JAMA, 2006;295:180-189. The REACH Registry enforces a no ghost-writing policy. The manuscript was written and edited by the authors, who take full responsibility for its content.; This study was supported by a grant from Sanofi-Aventis and Bristol-Myers Squibb. Dr Smolderen was supported by an award from the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina.; Dr Mahoney received grant support from Sanofi-Aventis, Bristol-Myers Squibb, Daiichi-Sankyo, and Eli Lilly and received honoraria from Sanofi-Aventis and Bristol-Myers Squibb. Dr Hirsch received research grant support from Bristol-Myers Squibb, Sanofi-Aventis, Astra Zeneca, and Cytokinetics, consulting fees/honoraria from Bristol-Myers Squibb, Sanofi-Aventis, Roche, and ev3, and has been on the speaker's bureau for Bristol-Myers Squibb and Sanofi-Aventis. Dr Cohen received grant support from Eli Lilly, Daiichi-Sankyo, Schering-Plough, and Boston Scientific and consulting fees from Eli Lilly, Cordis, and Medtronic. Dr Steg served as a member of the speakers' bureau for Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sharp and Dohme, Novartis, Nycomed, Sanofi-Aventis, Sankyo, Servier, and ZLB-Behring and received consulting fees/honoraria from Sanofi-Aventis, Servier, Bristol-Myers Squibb, Astra Zeneca, and Novartis. Dr Bhatt received research grants from Astra Zeneca, Heartscape, The Medicines Company, Bristol-Myers Squibb, Sanofi-Aventis, Eisai, and Ethicon. NR 26 TC 68 Z9 72 U1 2 U2 7 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 NOV PY 2010 VL 3 IS 6 BP 642 EP 651 DI 10.1161/CIRCOUTCOMES.109.930735 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680VB UT WOS:000284262900012 PM 20940249 ER PT J AU Lambert-Kerzner, A Havranek, EP Plomondon, ME Albright, K Moore, A Gryniewicz, K Magid, D Ho, PM AF Lambert-Kerzner, Anne Havranek, Edward P. Plomondon, Mary E. Albright, Karen Moore, Ashley Gryniewicz, Kelsey Magid, David Ho, P. Michael TI Patients' Perspectives of a Multifaceted Intervention With a Focus on Technology A Qualitative Analysis SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE hypertension; qualitative; trials ID HEALTH-CARE; HYPERTENSION; MANAGEMENT AB Background-Few studies have investigated the effectiveness of multifaceted interventions from the study participants' perspective. We conducted qualitative interviews to understand patients' experiences with a multifaceted blood pressure (BP) control intervention involving interactive voice response technology, home BP monitoring, and pharmacist-led BP management. In the randomized study, the intervention resulted in clinically significant decreases in BP. Methods and Results-We used insights generated from in-depth interviews from all study participants randomly assigned to the multifaceted intervention or usual care (n = 146) to create a model explaining the observed improvements in health behavior and clinical outcomes. The data were analyzed using qualitative content analysis methods and consultative and reflexive team analysis. Six explanatory factors emerged from the patients' interviews: (1) improved relationships with medical personnel; (2) increased knowledge of hypertension; (3) increased participation in their health care and personal empowerment; (4) greater understanding of the impact of health behavior on BP; (5) high satisfaction with technology used in the intervention; and, for some patients, (6) increased health care utilization. Eighty-six percent of the intervention patients and 62% of the usual care patients stated that study participation had a positive effect on them. Of those expressing a positive effect, 68% (intervention) and 55% (usual care) reached their systolic BP goal. Conclusions-Establishing bidirectional conversations between patients and providers is a key element of successful hypertension management. Home BP monitoring coupled with interactive voice response technology reporting facilitates such conversations. (Circ Cardiovasc Qual Outcomes. 2010;3:668-674.) C1 [Lambert-Kerzner, Anne; Plomondon, Mary E.; Gryniewicz, Kelsey; Ho, P. Michael] Denver Vet Affairs Med Ctr, Denver, CO USA. [Lambert-Kerzner, Anne; Havranek, Edward P.; Plomondon, Mary E.; Albright, Karen; Moore, Ashley; Magid, David; Ho, P. Michael] Univ Colorado Denver, Aurora, CO USA. [Lambert-Kerzner, Anne; Havranek, Edward P.; Moore, Ashley] Denver Hlth Med Ctr, Denver, CO USA. [Magid, David] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. RP Lambert-Kerzner, A (reprint author), DVAMC, 1055 Clermont St, Denver, CO 80220 USA. EM anne.lambert-kerzner@va.gov FU American Heart Association [0535086N]; Colorado Department of Public Health and Environment [99]; VA Health Services Research and Development Award [05-026] FX This work was funded in part by an award from the American Heart Association (0535086N) and from the Colorado Department of Public Health and Environment (CCPD No. 99).; Dr Ho was supported by a VA Health Services Research and Development Award (05-026) and serves as a consultant for Wellpoint, Inc. NR 29 TC 7 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2010 VL 3 IS 6 BP 668 EP 674 DI 10.1161/CIRCOUTCOMES.110.949800 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680VB UT WOS:000284262900015 PM 20923992 ER PT J AU Baggish, AL Weiner, RB Picard, MH Hutter, AM Pope, HG Kanayama, G Hudson, JI AF Baggish, Aaron L. Weiner, Rory B. Picard, Michael H. Hutter, Adolph M. Pope, Harrison G., Jr. Kanayama, Gen Hudson, James I. TI Response to Letter Regarding Article, "Long-Term Anabolic-Androgenic Steroid Use Is Associated With Left Ventricular Dysfunction" SO CIRCULATION-HEART FAILURE LA English DT Letter C1 [Baggish, Aaron L.; Weiner, Rory B.; Picard, Michael H.; Hutter, Adolph M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pope, Harrison G., Jr.; Kanayama, Gen; Hudson, James I.] McLean Hosp, Belmont, MA 02178 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2010 VL 3 IS 6 BP E31 EP E31 DI 10.1161/CIRCHEARTFAILURE.110.958843 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680US UT WOS:000284261600003 ER PT J AU Hobai, IA AF Hobai, Ion A. TI Letter by Hobai Regarding Article, "Long-Term Anabolic-Androgenic Steroid Use Is Associated With Left Ventricular Dysfunction" SO CIRCULATION-HEART FAILURE LA English DT Letter C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Hobai, IA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2010 VL 3 IS 6 BP E30 EP E30 DI 10.1161/CIRCHEARTFAILURE.110.958744 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680US UT WOS:000284261600002 PM 21081736 ER PT J AU Chua, S Hung, J Chung, SY Lin, YC Fu, M Wu, CJ Hang, CL Chai, HT Liu, WH Yang, CH Tsai, TH Chen, CJ Yip, HK AF Chua, Sarah Hung, Judy Chung, Sheng-Ying Lin, Yu-Chun Fu, Morgan Wu, Chiung-Jen Hang, Chi-Ling Chai, Han-Tan Liu, Wen-Hao Yang, Cheng-Hsu Tsai, Tzu-Hsien Chen, Chien-Jen Yip, Hon Kan TI Primary Percutaneous Coronary Intervention Lowers the Incidence of Ischemic Mitral Regurgitation in Patients With Acute ST-Elevated Myocardial Infarction SO CIRCULATION JOURNAL LA English DT Article DE Acute myocardial infarction; Ischemic mitral valve regurgitation; Primary coronary intervention ID HEART-FAILURE; CADILLAC TRIAL; RECOMMENDATIONS; ANGIOPLASTY; PREDICTORS; COMMITTEE AB Background: The impact of primary percutaneous coronary intervention (PCI) for acute ST-elevated myocardial infarction (STEMI) on the incidence of ischemic mitral regurgitation (IMR) is unclear. Methods and Results: Between January 2000 and December 2004, 318 patients presenting with first acute STEMI were enrolled in this study. Two hundred and twelve (66.67%) patients received PCI (PCI group), and 106 age- and Killip class-matched patients received medical management (non-PCI group). The median duration of follow up was 40.46 months. Compared to the non-PCI group, the PCI group had 14.6% (9.9% vs 24.5%) fewer patients with moderate or severe IMR (P<0.001). Univariate analysis demonstrated IMR was significantly associated with advanced age, higher Killip score, and posterior myocardial infarction (MI). Moreover, IMR was strongly associated with a lower left ventricular (LV) ejection fraction, larger left atrial dimension (LAd), and a larger LV end-systolic and LV end-diastolic volumes (LVEDV) (all P<0.01). Multivariate analysis revealed the odds of IMR in the PCI group was 0.208 times those of the non-PCI group (P<0.001). Additionally, moderate or severe IMR was independently correlated with advanced age, inferior MI, Killip class >= 3, larger LAd, and larger LVEDV (all P<0.05). Furthermore, long-term survival time was longer in the PCI group without IMR than in the non-PCI group with IMR (all P<0.01). Conclusions: PCI for first acute STEMI was associated with lower incidence of IMR. Advanced age, inferior MI, Killip class larger LAd and LVEDV were risk factors associated with IMR development. (Circ J 2010; 74: 2386-2392) C1 [Chua, Sarah; Chung, Sheng-Ying; Lin, Yu-Chun; Fu, Morgan; Wu, Chiung-Jen; Hang, Chi-Ling; Chai, Han-Tan; Liu, Wen-Hao; Yang, Cheng-Hsu; Tsai, Tzu-Hsien; Chen, Chien-Jen; Yip, Hon Kan] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Kaohsiung Med Ctr,Div Cardiol, Niao Sung Hsiang, Kaohsiung Hsien, Taiwan. [Hung, Judy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. RP Chua, S (reprint author), Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Kaohsiung Med Ctr,Div Cardiol, 123 Ta Pei Rd, Niao Sung Hsiang, Kaohsiung Hsien, Taiwan. EM chuasr409@hotmail.com; hkyip@adm.cgmh.org.tw NR 28 TC 8 Z9 8 U1 0 U2 0 PU JAPANESE CIRCULATION SOC PI KYOTO PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO, 606-8305, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD NOV PY 2010 VL 74 IS 11 BP 2386 EP 2392 DI 10.1253/circj.CJ-10-0435 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 672YG UT WOS:000283623200026 PM 20890048 ER PT J AU Seton, M AF Seton, Margaret TI How soon after hip fracture surgery should a patient start bisphosphonates? SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Editorial Material ID ZOLEDRONIC ACID; MORTALITY; REPAIR C1 [Seton, Margaret] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Rheumatol Fellowship Program, Boston, MA 02114 USA. [Seton, Margaret] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Seton, M (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Rheumatol Fellowship Program, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 1 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD NOV PY 2010 VL 77 IS 11 BP 751 EP + DI 10.3949/ccjm.77a.10045 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 681FT UT WOS:000284297500003 PM 21048049 ER PT J AU Goldstein, JN Greenberg, SM AF Goldstein, Joshua N. Greenberg, Steven M. TI Should anticoagulation be resumed after intracerebral hemorrhage? SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Review ID FRESH-FROZEN PLASMA; NONVALVULAR ATRIAL-FIBRILLATION; PREDICTS HEMATOMA EXPANSION; VENOUS THROMBOEMBOLISM; INTRACRANIAL HEMORRHAGE; ISCHEMIC-STROKE; RESTARTING ANTICOAGULATION; CONTRAST EXTRAVASATION; BLEEDING COMPLICATIONS; CEREBRAL MICROBLEEDS AB Intracerebral hemorrhage (ICH) is the most feared and the most deadly complication of oral anticoagulant therapy, eg, with warfarin (Coumadin) After such an event, clinicians wonder whether their patients should resume anticoagulant therapy The authors review the management of anticoagulation during and after anticoagulation-associated ICH C1 [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Greenberg, Steven M.] Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Dept Neurol, Boston, MA 02114 USA. [Greenberg, Steven M.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 0 Emerson Pl,Suite 38, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 FU NINDS NIH HHS [K23 NS059774] NR 84 TC 25 Z9 26 U1 0 U2 5 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD NOV PY 2010 VL 77 IS 11 BP 791 EP 799 DI 10.3949/ccjm.77a.10018 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 681FT UT WOS:000284297500008 PM 21048052 ER PT J AU Zakka, LR Keskin, DB Reche, P Ahmed, AR AF Zakka, L. R. Keskin, D. B. Reche, P. Ahmed, A. R. TI Relationship between target antigens and major histocompatibility complex (MHC) class II genes in producing two pathogenic antibodies simultaneously SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Review DE autoantibodies; bullous pemphigoid; epitope spreading; MHC class II genes; mucous membrane pemphigoid; pemphigus vulgaris ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PEMPHIGUS-LIKE ANTIBODIES; CONNECTIVE-TISSUE DISEASE; MULTIPLE-SCLEROSIS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; 1ST-DEGREE RELATIVES; ITALIAN PATIENTS; RECOMBINANT DESMOGLEINS; CLINICAL VARIANTS AB P>In this report, we present 15 patients with histological and immunopathologically proven pemphigus vulgaris (PV). After a mean of 80 months since the onset of disease, when evaluated serologically, they had antibodies typical of PV and pemphigoid (Pg). Similarly, 18 patients with bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) were diagnosed on the basis of histology and immunopathology. After a mean of 60 months since the onset of disease, when their sera were evaluated they were found to have Pg and PV autoantibodies. In both groups of patients the diseases were characterized by a chronic course, which included several relapses and recurrences and were non-responsive to conventional therapy. The major histocompatibility complex class II (MHC II) genes were studied in both groups of patients and phenotypes associated typically with them were observed. Hence, in 33 patients, two different pathogenic autoantibodies were detected simultaneously. The authors provide a computer model to show that each MHC II gene has relevant epitopes that recognize the antigens associated with both diseases. Using the databases in these computer models, the authors present the hypothesis that these two autoantibodies are produced simultaneously due to the phenomena of epitope spreading. C1 [Zakka, L. R.; Ahmed, A. R.] New England Baptist Hosp, Ctr Blistering Dis, Dept Med, Boston, MA 02120 USA. [Keskin, D. B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Reche, P.] Univ Complutense Madrid, Fac Med, Dept Immunol, Immunomedine Grp, Madrid, Spain. RP Ahmed, AR (reprint author), New England Baptist Hosp, Ctr Blistering Dis, Dept Med, 70 Parker Hill Ave, Boston, MA 02120 USA. EM arahmedmd@msn.com RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 NR 145 TC 2 Z9 3 U1 0 U2 2 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 NOV PY 2010 VL 162 IS 2 BP 224 EP 236 DI 10.1111/j.1365-2249.2010.04239.x PG 13 WC Immunology SC Immunology GA 661AP UT WOS:000282694800003 PM 21069937 ER PT J AU Mathenia, J Reyes-Cortes, E Williams, S Molano, I Ruiz, P Watson, DK Gilkeson, GS Zhang, XK AF Mathenia, J. Reyes-Cortes, E. Williams, S. Molano, I. Ruiz, P. Watson, D. K. Gilkeson, G. S. Zhang, X. K. TI Impact of Fli-1 transcription factor on autoantibody and lupus nephritis in NZM2410 mice SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE animal model; autoantibody; Fli-1 transcription factor; lupus; nephritis ID ETS GENE FAMILY; RENAL-DISEASE; MARGINAL ZONE; MRL/LPR MICE; CELL-PROLIFERATION; B-CELLS; EXPRESSION; ERYTHEMATOSUS; MEMBER; GLOMERULONEPHRITIS AB P>The transcription factor Fli-1 is implicated in the pathogenesis of both murine and human lupus. Increased levels of Fli-1 mRNA were present in the peripheral blood lymphocytes from lupus patients; furthermore, transgenic overexpression of Fli-1 in normal mice resulted in the development of a lupus-like disease. Lupus nephritis is a major cause of death in both lupus patients as well as in animal models. In this study, we generated Fli-1 heterozygous knockout (Fli-1+/-) NZM2410 mice (of which the wild-type is a widely used lupus murine model) that expressed decreased levels of Fli-1 and investigated the impact of Fli-1 expression on lupus nephritis development and survival. Ninety-three per cent of the Fli-1+/- NZM2410 mice survived to the age of 52 weeks compared to only 35% of wild-type NZM2410 mice. Autoantibodies, including anti-dsDNA and anti-glomerular basement antigen, in Fli-1+/- NZM2410 mice were statistically significantly lower when compared to wild-type NZM2410 mice at the ages of 30 and 34 weeks. Total B cell and activated B cell populations in the spleens from Fli-1+/- NZM2410 mice were decreased significantly compared to wild-type NZM2410 mice. Fli-1+/- NZM2410 mice also had remarkably diminished proteinuria and decreased renal pathological scores when compared with wild-type NZM2410 mice. Expression of early growth response 1 (Egr-1) was decreased significantly in the kidneys from Fli-1+/- NZM2410 mice when compared to wild-type littermates. Our data indicate that expression of Fli-1 plays an important role in lupus disease development in NZM2410 mice. C1 [Mathenia, J.; Reyes-Cortes, E.; Molano, I.; Gilkeson, G. S.; Zhang, X. K.] Med Univ S Carolina, Div Rheumatol & Immunol, Dept Med, Charleston, SC 29425 USA. [Watson, D. K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Mathenia, J.; Williams, S.; Gilkeson, G. S.; Zhang, X. K.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. [Ruiz, P.] Univ Miami, Sch Med, Miami, FL USA. RP Zhang, XK (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, Dept Med, Suite 912,Jonathan Lucas St MSC637, Charleston, SC 29425 USA. EM zhangjo@musc.edu FU National Institutes of Health [AR054546]; Department of Veterans Affairs FX We thank Sarah Darley and William Zhang for providing excellent technical assistance. This study was supported by National Institutes of Health grants (AR054546 to X.K.Z.) and the Medical Research Service and Research Enhancement Award Programs, Department of Veterans Affairs (to X.K.Z and G. S. G.) NR 36 TC 14 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2010 VL 162 IS 2 BP 362 EP 371 DI 10.1111/j.1365-2249.2010.04245.x PG 10 WC Immunology SC Immunology GA 661AP UT WOS:000282694800017 PM 20731671 ER PT J AU Sun, T Lee, GSM Oh, WK Pomerantz, M Yang, M Xie, WL Freedman, ML Kantoff, PW AF Sun, Tong Lee, Gwo-Shu Mary Oh, William K. Pomerantz, Mark Yang, Ming Xie, Wanling Freedman, Matthew L. Kantoff, Philip W. TI Single-Nucleotide Polymorphisms in p53 Pathway and Aggressiveness of Prostate Cancer in a Caucasian Population SO CLINICAL CANCER RESEARCH LA English DT Article AB Purpose: The tumor suppressor p53 plays a crucial role in maintaining genomic stability and tumor prevention. Mdm2, Mdm4, and Hausp are all critical regulators of the p53 protein. Despite the importance of the p53 pathway in prostate cancer development and progression, little is known about the association of functional single-nucleotide polymorphisms (SNP) in the p53 pathway genes and prostate cancer aggressiveness. Experimental Design: In this study, we analyze the association of SNPs in p53, Mdm2, Mdm4, and Hausp genes with prostate cancer clinicopathologic variables in a large hospital-based Caucasian prostate cancer cohort (N = 4,073). Results: We found that the Mdm2 SNP309 T allele was associated with earlier onset prostate cancer (P = 0.004), higher Gleason scores (P = 0.004), and higher stages in men undergoing a radical prostatectomy (P = 0.011). Both the Mdm4 and Hausp SNPs (rs1380576 and rs1529916) were found to be associated with higher D'Amico risk prostate cancer category at the time of diagnosis (P = 0.023 and P = 0.046, respectively). Mdm4 SNP was also found to be associated with higher Gleason score at radical prostatectomy (P = 0.047). We did not observe any statistically significant association between the p53 Arg72Pro polymorphism and prostate cancer aggressiveness or pathologic variables. Conculsions: These results suggested the importance of these p53 regulators in prostate cancer development and progression. Clin Cancer Res; 16(21); 5244-51. (C)2010 AACR. C1 [Sun, Tong; Lee, Gwo-Shu Mary; Oh, William K.; Pomerantz, Mark; Yang, Ming; Freedman, Matthew L.; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xie, Wanling] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Suite D1230,44 Binney St, Boston, MA 02115 USA. EM philip_kantoff@dfci.harvard.edu RI Oh, William/B-9163-2012; Yang, Ming/G-4705-2012 OI Oh, William/0000-0001-5113-8147; Yang, Ming/0000-0002-7722-7487 FU Specialized Programs of Research Excellence in Prostate Cancer [2 P50 CA090381-06]; Prostate Cancer Foundation FX Specialized Programs of Research Excellence in Prostate Cancer 2 P50 CA090381-06 and Prostate Cancer Foundation. NR 4 TC 21 Z9 22 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 NOV 1 PY 2010 VL 16 IS 21 BP 5244 EP 5251 DI 10.1158/1078-0432.CCR-10-1261 PG 8 WC Oncology SC Oncology GA 673MV UT WOS:000283668500016 PM 20855462 ER PT J AU Makimura, H Stanley, TL Sun, N Connelly, JM Hemphill, LC Grinspoon, SK AF Makimura, Hideo Stanley, Takara L. Sun, Noelle Connelly, Jean M. Hemphill, Linda C. Grinspoon, Steven K. TI The relationship between reduced testosterone, stimulated growth hormone secretion and increased carotid intima-media thickness in obese men SO CLINICAL ENDOCRINOLOGY LA English DT Article ID ADULT GH DEFICIENCY; BODY-MASS INDEX; VISCERAL FAT; OLDER MEN; INSULIN; GLUCOSE; WOMEN; AMPLITUDE; RESPONSIVENESS; ADIPOSITY AB Objective Obesity is associated with reduced testosterone and growth hormone (GH). However, the interrelationship between these axes and their independent contributions to cardiovascular risk is unknown. The objectives of this study were to determine (1) the association between testosterone and GH in obesity, (2) whether excess adiposity mediates this association and (3) the relative contribution of reduced testosterone and GH to increased carotid intima-media thickness (cIMT) in obesity. Design Fifty obese men were studied with GH-releasing hormone-arginine testing, and morning free testosterone (FT) was measured by equilibrium dialysis. Metabolic, anthropometric and cardiovascular risk indices, including cIMT were measured. Twenty-six normal weight men served as controls. Results Obese subjects demonstrated lower mean (+/-SEM) peak stimulated GH (5.9 +/- 0.6 vs 36.4 +/- 3.9 mu g/l; P < 0.0001) and FT (0.41 +/- 0.03 vs 0.56 +/- 0.03 nmol/l; P = 0.0005) compared to controls. GH was significantly associated with FT (r = +0.44; P < 0.0001) and both were inversely related to visceral adipose tissue (VAT) (GH: r = -0.65; P < 0.0001; FT: r = -0.51; P < 0.0001). In multivariate regression analysis controlling for VAT, FT was no longer related to GH. Both GH and FT were associated with cIMT in univariate analysis. However, in multivariate modelling including traditional cardiovascular risk markers, GH (beta = 0.003; P = 0.04) but not FT (P = 0.35) was associated with cIMT. Conclusions These results demonstrate a strong relationship between FT and GH in obesity and suggest that this relationship is more a function of excess adiposity rather than a direct relationship. While reduced FT and GH are both related to increased cIMT, the relationship with reduced GH remains significant controlling for reduced FT and traditional cardiovascular disease risk markers. C1 [Makimura, Hideo; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Makimura, Hideo; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Makimura, Hideo; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Harvard Univ, Sch Med, Boston, MA USA. [Connelly, Jean M.; Hemphill, Linda C.] Massachusetts Gen Hosp, Boston Heart Fdn, Boston, MA 02114 USA. RP Makimura, H (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 211, Boston, MA 02114 USA. EM hmakimura@partners.org FU National Institutes of Health [1R01HL085268-01A1, K24DK064545-06, UL1RR025758] FX National Institutes of Health grant 1R01HL085268-01A1 to SG, K24DK064545-06 to SG, grant UL1RR025758 to the Harvard Catalyst. NR 33 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD NOV PY 2010 VL 73 IS 5 BP 622 EP 629 DI 10.1111/j.1365-2265.2010.03859.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 660IY UT WOS:000282635000010 PM 20681993 ER PT J AU Powe, CE Allen, M Puopolo, KM Merewood, A Worden, S Johnson, LC Fleischman, A Welt, CK AF Powe, Camille E. Allen, Maureen Puopolo, Karen M. Merewood, Anne Worden, Susan Johnson, Lise C. Fleischman, Amy Welt, Corrine K. TI Recombinant human prolactin for the treatment of lactation insufficiency SO CLINICAL ENDOCRINOLOGY LA English DT Article ID MILK-PRODUCTION; BREAST-MILK; MOTHERS; DOMPERIDONE; WOMEN; METOCLOPRAMIDE; OXYTOCIN; PRETERM; INFANTS; RELEASE AB Context Lactation insufficiency has many aetiologies including complete or relative prolactin deficiency. Exogenous prolactin may increase breast milk volume in this subset. We hypothesized that recombinant human prolactin (r-hPRL) would increase milk volume in mothers with prolactin deficiency and mothers of preterm infants with lactation insufficiency. Design Study 1: R-hPRL was administered in an open-label trial to mothers with prolactin deficiency. Study 2: R-hPRL was administered in a randomized, double-blind, placebo-controlled trial to mothers with lactation insufficiency that developed while pumping breast milk for their preterm infants. Patients Study 1: Mothers with prolactin deficiency (n = 5). Study 2: Mothers of premature infants exclusively pumping breast milk (n = 11). Design Study 1: R-hPRL (60 mu g/kg) was administered subcutaneously every 12 h for 28 days. Study 2: Mothers of preterm infants were randomized to receive r-hPRL (60 mu g/kg), placebo or r-hPRL alternating with placebo every 12 h for 7 days. Measurements Change in milk volume. Results Study 1: Peak prolactin (27.9 +/- 17.3 to 194.6 +/- 19.5 mu g/l; P < 0.003) and milk volume (3.4 +/- 1.6 to 66.1 +/- 8.3 ml/day; P < 0.001) increased with r-hPRL administration. Study 2: Peak prolactin increased in mothers treated with r-hPRL every 12 h (n = 3; 79.3 +/- 55.4 to 271.3 +/- 36.7 mu g/l; P < 0.05) and daily (101.4 +/- 61.5 vs 178.9 +/- 45.9 mu g/l; P < 0.04), but milk volume increased only in the group treated with r-hPRL every 12 h (53.5 +/- 48.5 to 235.0 +/- 135.7 ml/day; P < 0.02). Conclusion Twice daily r-hPRL increases milk volume in mothers with prolactin deficiency and in preterm mothers with lactation insufficiency. C1 [Powe, Camille E.; Welt, Corrine K.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Powe, Camille E.; Puopolo, Karen M.] Harvard Univ, Sch Med, Boston, MA USA. [Allen, Maureen; Puopolo, Karen M.; Johnson, Lise C.] Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. [Merewood, Anne] Boston Univ, Sch Med, Div Gen Pediat, Boston, MA 02118 USA. [Worden, Susan] Massachusetts Gen Hosp Children, Dept Pediat, Boston, MA USA. [Fleischman, Amy] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504; Merewood, Anne/0000-0002-7802-9028 FU Food and Drug Administration [FD-R-003014]; March of Dimes Birth Defects Foundation [6-FY04-76]; National Center for Research Resources General Clinical Research Centers [M01-RR-01066] FX We would like to thank the mothers who participated for their extraordinary efforts during the study. We would also like to thank Genzyme Corporation for supplying the recombinant human prolactin. Finally, we thank Dr. Robert Insoft, Dr. Karen K. Miller and Diane Dady-Goldstein, RN, IBCLC, for advice and assistance while serving on our data safety monitoring board. This work was supported by the Food and Drug Administration FD-R-003014, the March of Dimes Birth Defects Foundation research Grant No. 6-FY04-76 and the National Center for Research Resources General Clinical Research Centers Program grant M01-RR-01066. NR 37 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD NOV PY 2010 VL 73 IS 5 BP 645 EP 653 DI 10.1111/j.1365-2265.2010.03850.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 660IY UT WOS:000282635000013 PM 20718766 ER PT J AU Beste, LA Ioannou, GN Larson, MS Chapko, M Dominitz, JA AF Beste, Lauren A. Ioannou, George N. Larson, Meaghan S. Chapko, Michael Dominitz, Jason A. TI Predictors of Early Treatment Discontinuation Among Patients With Genotype 1 Hepatitis C and Implications for Viral Eradication SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Hepatology; Viral Hepatitis; Treatment Duration; Treatment Attrition ID PEGYLATED INTERFERON; VIRUS-INFECTION; ANTIVIRAL THERAPY; PLUS RIBAVIRIN; UNITED-STATES; PREVALENCE; VETERANS; COMPLETION; SYMPTOMS; USERS AB BACKGROUND & AIMS A significant proportion of patients with hepatitis C virus (HCV) infection discontinue anti viral treatment prematurely Risk factors for discontinuation before 48 weeks among patients with genotype 1 HCV vary over the course of therapy We investigated the rates and risk factors for treatment discontinuation within 12 weeks, 12-24 weeks, and 24-48 weeks METHODS We retrospectively evaluated data from all Veterans Affairs (VA) patients with genotype 1 HCV who initiated pegylated interferon and ribavirin therapy from 2002-2007 (n = 11,019) We accounted for appropriate discontinuation because of viral nonresponse RESULTS Overall, 53% of patients completed at least 38 4 weeks of therapy (80% of the projected 48 weeks), 16 5% discontinued early in the setting of viral nonresponse, and 30 9% discontinued de spite viral response or in the absence of virologic data Cirrhosis, diabetes, pretreatment substance use disorder, hemoglobin, and lack of hematopoietic growth factor use independently predicted discontinuation before 12 weeks (P < 05 for all) Among patients with documented early virologic responses, higher baseline levels of creatinine, depression, and lack of growth factor use predicted discontinuation from 12-24 weeks No factors independently predicted discontinuation from 24-48 weeks among patients responding to treatment at 24 weeks CONCLUSIONS Early discontinuation of antiviral therapy is common Use of growth factors was the strongest independent predictor of treatment retention be fore 24 weeks and should be evaluated prospectively Early interventions may also be warranted for other risk factors for early discontinuation, such as pre-existing substance use, depression, cirrhosis, or diabetes C1 VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Beste, Lauren A.; Larson, Meaghan S.; Chapko, Michael; Dominitz, Jason A.] VA Puget Sound Healthcare Syst, NW Hepatitis Resource Ctr C, Seattle, WA USA. [Beste, Lauren A.] VA Puget Sound Healthcare Syst, Div Gen Internal Med, Seattle, WA USA. [Ioannou, George N.; Dominitz, Jason A.] VA Puget Sound Healthcare Syst, Div Gastroenterol, Seattle, WA USA. [Ioannou, George N.; Dominitz, Jason A.] Univ Washington, Sch Med, Seattle, WA USA. [Chapko, Michael] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. RP Beste, LA (reprint author), 1660 S Columbian Way, Seattle, WA 98108 USA. OI Dominitz, Jason/0000-0002-8070-7086 FU VA Puget Sound Health Care System, Seattle, Washington; Department of Veterans Affairs Health Services Research and Development [TPM 61-032]; Northwest Hepatitis C Resource Center Study FX This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington The study was supported by Department of Veterans Affairs Health Services Research and Development research and training funds (TPM 61-032) and the Northwest Hepatitis C Resource Center Study sponsors had no role in the study design, collection, analysis or interpretation of the data or in the writing of the report NR 24 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2010 VL 8 IS 11 BP 972 EP 978 DI 10.1016/j.cgh.2010.07.012 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 690UU UT WOS:000285034800018 PM 20692371 ER PT J AU Baffy, G AF Baffy, Gyorgy TI Negative Outcomes for Intraoperative Blood Transfusion in Patients With Advanced Cirrhosis Post Hoc Ergo Propter Hoc? SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter ID LIVER-DISEASE; SURGERY C1 Harvard Univ, Sch Med, Gastroenterol Sect, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Baffy, G (reprint author), Harvard Univ, Sch Med, Gastroenterol Sect, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 5 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2010 VL 8 IS 11 BP 996 EP 996 DI 10.1016/j.cgh.2010.05.028 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 690UU UT WOS:000285034800022 PM 20541626 ER PT J AU Saokar, A Gee, MS Islam, T Mueller, PR Harisinghani, MG AF Saokar, Anuradha Gee, Michael S. Islam, Tina Mueller, Peter R. Harisinghani, Mukesh G. TI Appearance of primary lymphoid malignancies on lymphotropic nanoparticle-enhanced magnetic resonance imaging using ferumoxtran-10 SO CLINICAL IMAGING LA English DT Article DE Lymphoma; Superparamagnetic iron oxide nanoparticles; Ferumoxtran 10; MRI; Lymphotropic nanoparticle enhanced MRI ID NON-HODGKINS-LYMPHOMA; RADICAL PROSTATECTOMY; NODE DISSECTION; CANCER AB Patients with pathologically confirmed lymphoma/leukemia were retrospectively identified from a large single-institution phase III clinical trial with ferumoxtran-10 Five (2 3%) of 220 patients had lymphoid malignancies involving lymph nodes A subset of patients (n=27) with biopsy-proven nodal metastases from genitourinary or breast cancer was selected as control group Ferumoxtran-10 enhancement patterns and signal-to-noise ratios of lymph nodes involved by metastases and lymphoid malignancy were assessed Like nodal metastases, nodes involved by lymphoid malignancies demonstrate persistent high T2*-signal intensity on lymphotropic nanoparticle-enhanced magnetic resonance imaging (C) 2010 Elsevier Inc All rights reserved C1 [Saokar, Anuradha; Gee, Michael S.; Islam, Tina; Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Massachusetts Gen Hosp,Dept Radiol,Ctr Mol Imagin, Boston, MA 02114 USA. RP Islam, T (reprint author), Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Massachusetts Gen Hosp,Dept Radiol,Ctr Mol Imagin, Boston, MA 02114 USA. NR 10 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD NOV-DEC PY 2010 VL 34 IS 6 BP 448 EP 452 DI 10.1016/j.clinimag.2009.09.008 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 690US UT WOS:000285034600008 PM 21092874 ER PT J AU Sun, HY Alexander, BD Lortholary, O Dromer, F Forrest, GN Lyon, GM Somani, J Gupta, KL del Busto, R Pruett, TL Sifri, CD Limaye, AP John, GT Klintmalm, GB Pursell, K Stosor, V Morris, MI Dowdy, LA Munoz, P Kalil, AC Garcia-Diaz, J Orloff, SL House, AA Houston, SH Wray, D Huprikar, S Johnson, LB Humar, A Razonable, RR Fisher, RA Husain, S Wagener, MM Singh, N AF Sun, Hsin-Yun Alexander, Barbara D. Lortholary, Olivier Dromer, Francoise Forrest, Graeme N. Lyon, G. Marshall Somani, Jyoti Gupta, Krishan L. del Busto, Ramon Pruett, Timothy L. Sifri, Costi D. Limaye, Ajit P. John, George T. Klintmalm, Goran B. Pursell, Kenneth Stosor, Valentina Morris, Michele I. Dowdy, Lorraine A. Munoz, Patricia Kalil, Andre C. Garcia-Diaz, Julia Orloff, Susan L. House, Andrew A. Houston, Sally H. Wray, Dannah Huprikar, Shirish Johnson, Leonard B. Humar, Atul Razonable, Raymund R. Fisher, Robert A. Husain, Shahid Wagener, Marilyn M. Singh, Nina CA Cryptococcal Collaborative TI Unrecognized Pretransplant and Donor-Derived Cryptococcal Disease in Organ Transplant Recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; HEMATOPOIETIC STEM-CELL; SOLID-ORGAN; NEOFORMANS INFECTION; IRON OVERLOAD; LIVER; TRANSMISSION; MENINGITIS; MORTALITY; VIRUS AB Background. Cryptococcosis occurring <= 30 days after transplantation is an unusual event, and its characteristics are not known. Methods. Patients included 175 solid-organ transplant (SOT) recipients with cryptococcosis in a multicenter cohort. Very early-onset and late-onset cryptococcosis were defined as disease occurring <= 30 days or 130 days after transplantation, respectively. Results. Very early-onset disease developed in 9 (5%) of the 175 patients at a mean of 5.7 days after transplantation. Overall, 55.6% (5 of 9) of the patients with very early-onset disease versus 25.9% (43 of 166) of the patients with late-onset disease were liver transplant recipients (Pp. 05). Very early cases were more likely to present with disease at unusual locations, including transplanted allograft and surgical fossa/site infections (55.6% vs 7.2%; P<.001). Two very early cases with onset on day 1 after transplantation (in a liver transplant recipient with Cryptococcus isolated from the lung and a heart transplant recipient with fungemia) likely were the result of undetected pretransplant disease. An additional 5 cases involving the allograft or surgical sites were likely the result of donor-acquired infection. Conclusions. A subset of SOT recipients with cryptococcosis present very early after transplantation with disease that appears to occur preferentially in liver transplant recipients and involves unusual sites, such as the transplanted organ or the surgical site. These patients may have unrecognized pretransplant or donor-derived cryptococcosis. C1 [Sun, Hsin-Yun; Singh, Nina] VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. [Husain, Shahid; Wagener, Marilyn M.; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. [Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA. [Forrest, Graeme N.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Lyon, G. Marshall; Somani, Jyoti] Emory Univ, Atlanta, GA 30322 USA. [del Busto, Ramon] Henry Ford Hosp, Detroit, MI 48202 USA. [Johnson, Leonard B.] St Johns Hosp, Detroit, MI USA. [Pruett, Timothy L.; Sifri, Costi D.] Univ Virginia, Charlottesville, VA USA. [Fisher, Robert A.] Virginia Commonwealth Univ, Richmond, VA USA. [Limaye, Ajit P.] Univ Washington, Seattle, WA 98195 USA. [Klintmalm, Goran B.] Baylor Univ, Med Ctr, Dallas, TX USA. [Pursell, Kenneth] Univ Chicago, Chicago, IL 60637 USA. [Stosor, Valentina] Northwestern Univ, Chicago, IL 60611 USA. [Morris, Michele I.; Dowdy, Lorraine A.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Houston, Sally H.] Tampa Gen Hosp, Tampa, FL 33606 USA. [Kalil, Andre C.] Univ Nebraska, Omaha, NE 68182 USA. [Garcia-Diaz, Julia] Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA. [Orloff, Susan L.] Oregon Hlth & Sci Univ, Portland, OR USA. [Wray, Dannah] Med Univ S Carolina, Charleston, SC 29425 USA. [Huprikar, Shirish] Mt Sinai Med Ctr, New York, NY 10029 USA. [Razonable, Raymund R.] Mayo Clin, Rochester, MN USA. [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Lortholary, Olivier] Hop Necker Enfants Malad, Fac Med Paris Descartes, Paris, France. [Dromer, Francoise] Inst Pasteur, Paris, France. [Gupta, Krishan L.] Postgrad Inst Med Educ & Res, Chandigarh 160012, India. [John, George T.] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Munoz, Patricia] Hosp Gen Univ Gregorio Maranon, Madrid, Spain. [Munoz, Patricia] CIBER Enfermedades Resp, Madrid, Spain. [House, Andrew A.] Univ Western Ontario, London, ON, Canada. [Humar, Atul] Toronto Gen Hosp, Univ Hlth Network, Toronto, ON, Canada. RP Singh, N (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu RI Garcia-Diaz, Julia/D-3555-2011; OI Munoz Garcia, Patricia Carmen/0000-0001-5706-5583; SUN, HSIN-YUN/0000-0003-0074-7721 FU Astellas; Pfizer; Merck; Basilea; National Institutes of Health, National Institute of Allergy and Infectious Diseases [R01 AI 054719-01] FX B. D. A. has served on advisory boards for Abbott, Bristol Myers Squibb, bioMerieux, and has received investigator initiated grants from Astellas and Pfizer. O.L. has served on speaker's bureaus of Astellas, Gilead Sciences, Merck, Schering-Plough, and Pfizer and as a consultant for Astellas and Gilead Sciences. G. F. has received grant support from Astellas. G. M. L. has served on advisory boards for and received grants from Merck and Astellas and on speaker's bureaus of Astellas, Schering-Plough, and Wyeth. A. P. L. has served on consultant boards for Pfizer and Merck and has contracted research for Pfizer. M. I. M. has served on advisory boards for Astellas, Pfizer, and Merck; has received grants from Astellas, Basilea, and Pfizer; and has served on speaker's bureaus of Astellas and Pfizer. P. M. has served on speaker's bureaus of Merck and Novartis and on an advisory board for Pfizer. S. H. H. has served on speaker's bureaus of Astellas and Pfizer. L.B.J. has served on a speaker's bureau of Pfizer. S. H. has received grants from Pfizer, Astellas, and Merck. N.S. has received investigator-initiated grant support from Pfizer. All other authors: no conflicts.; National Institutes of Health, National Institute of Allergy and Infectious Diseases (R01 AI 054719-01 to N.S.) NR 29 TC 27 Z9 27 U1 0 U2 0 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 NOV 1 PY 2010 VL 51 IS 9 BP 1062 EP 1069 DI 10.1086/656584 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 669FC UT WOS:000283331300012 PM 20879857 ER PT J AU Spiegel, B Bolus, R Desai, AA Zagar, P Parker, T Moran, J Solomon, MD Khawar, O Gitlin, M Talley, J Nissenson, A AF Spiegel, Brennan Bolus, Roger Desai, Amar A. Zagar, Philip Parker, Tom Moran, John Solomon, Matthew D. Khawar, Osman Gitlin, Matthew Talley, Jennifer Nissenson, Allen TI Dialysis Practices That Distinguish Facilities with Below- versus Above-Expected Mortality SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID OUTCOMES; PATIENT; CARE; PHYSICIANS; RATIO AB Background and objectives: Mortality rates vary widely among dialysis facilities even after adjustment with standardized mortality ratios (SMRs). This variation may occur because top-performing facilities use practices not shared by others, because the SMR fails to capture key patient characteristics, or both. Practices were identified that distinguish top- from bottom-performing facilities by SMR. Design, setting, participants, & measurements: A cross-sectional survey was performed of staff across three organizations. Staff members rated the perceived quality of their units' patient-, provider-, and facility-level practices using a six-point Likert scale. Facilities were divided into those with above- versus below-expected mortality on the basis of SMRs from U.S. Renal Data Service facility reports. Mean Likert scores were computed for each practice using t tests. Practices that were statistically significant (P <= 0.05) and achieved at least a medium effect size of >= 0.4 were reported. Significant predictors were entered into a linear regression model. Results: Dialysis facilities with below-expected mortality reported that patients in their unit were more activated and engaged, physician communication and interpersonal relationships were stronger, dieticians were more resourceful and knowledgeable, and overall coordination and staff management were superior versus facilities with above-expected mortality. Staff ratings of these practices explained 31% of the variance in SMRs. Conclusions: Patient-, provider-, and facility-level practices partly explain SMR variation among facilities. Improving SMRs may require processes that reflect a coordinated, multidisciplinary environment (i.e., no one group, practice, or characteristic will drive facility-level SMRs). Understanding and improving SMRs will require a holistic view of the facility. Clin J Am Soc Nephrol 5: 2024-2033, 2010. doi: 10.2215/CJN.01620210 C1 [Spiegel, Brennan; Talley, Jennifer] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Spiegel, Brennan; Bolus, Roger; Khawar, Osman] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Spiegel, Brennan; Bolus, Roger; Solomon, Matthew D.; Talley, Jennifer] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Desai, Amar A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Desai, Amar A.; Solomon, Matthew D.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Zagar, Philip] Dialysis Clin Inc, Albuquerque, NM USA. [Parker, Tom] Renal Ventures Management LLC, Lakewood, CO USA. [Moran, John] Satellite Healthcare, Mountain View, CA USA. [Solomon, Matthew D.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Nissenson, Allen] DaVita Inc, Denver, CO USA. RP Spiegel, B (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Amgen, Inc.; Renal Physicians Association; American Nephrology Nurses Association FX Support for this investigator-initiated study was provided by a research grant from Amgen, Inc. Dr. Gitlin is an employee of Amgen, Inc. The principal investigator, Dr. Spiegel, maintained full control over all aspects of the study design, implementation, data collection, data analysis, data interpretation, and manuscript preparation. Dr. Spiegel had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The contributions of individual authors is as follows: AD. study design, study implementation, data collection, data interpretation, and manuscript preparation; R.B. study design, study implementation, data collection, data analysis, and manuscript review; AN study design, data interpretation, and manuscript review; P.Z. data collection/provision, data interpretation, and manuscript review; T.P. data collection/provision, data interpretation, and manuscript review; J.M. data collection/provision, data interpretation, and manuscript review; S.B. study design, data interpretation, and manuscript review; MS. study design, data interpretation, and manuscript review; O.K. study design, data interpretation, and manuscript review; M.G. data interpretation and manuscript preparation; J.T. study implementation and data collection; B.S. study design, study implementation, data collection, data analysis, data interpretation, manuscript preparation, manuscript approval, and guarantor of article. The opinions and assertions contained herein are the sole views of the authors and are not to be construed as official or as reflecting the views of the Department of Veteran Affairs. This study endorsed and supported by the Renal Physicians Association and the American Nephrology Nurses Association. Special thanks to the participating dialysis organizations-DCI; Renal Ventures Management LLC, and Satellite Healthcare. NR 12 TC 16 Z9 16 U1 1 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2010 VL 5 IS 11 BP 2024 EP 2033 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 677UX UT WOS:000284018500018 PM 20876677 ER PT J AU Kutner, NG Zhang, R Huang, YJ Johansen, KL AF Kutner, Nancy G. Zhang, Rebecca Huang, Yijian Johansen, Kirsten L. TI Depressed Mood, Usual Activity Level, and Continued Employment after Starting Dialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; END; VALIDITY; WORK AB Background and objectives: When patients start dialysis, their employment rate declines and disability benefits are an option. With patient sociodemographic and clinical characteristics including disability income status controlled, we investigated the significance of depressed mood and usual activity level as predictors of patients' continued employment after dialysis start. Design, setting, participants, & measurements: Incident patients from 296 randomly selected dialysis clinics were surveyed in the Comprehensive Dialysis Study (CDS). Participants provided information about employment status, disability income status, education, depressive symptoms measured by the Patient Health Questionnaire-2 (PHQ-2), and usual activity level/energy expenditure measured by the Human Activity Profile. Age, gender, race, insurance, diabetes, inability to ambulate or transfer, chronic obstructive pulmonary disease, cardiovascular conditions, and hemoglobin and serum albumin values at treatment start were obtained from US Renal Data System files. Dialysis modality was defined at time of interview. Results: Among 585 CDS participants who worked in the previous year, 191 (32.6%) continued working after dialysis start. On the basis of the PHQ-2 cutoff score >= 3, 12.1% of patients who remained employed had possible or probable depression, compared with 32.8% of patients who were no longer employed. In adjusted analyses, higher Human Activity Profile scores were associated with increased likelihood of continued employment, and there was a borderline association between lower PHQ-2 scores and continued employment. Conclusions: Screening and management of depressive symptoms and support for increased activity level may facilitate patients' opportunity for continued employment after dialysis start, along with generally improving their overall quality of life. Clin J Am Soc Nephrol 5: 2040-2045, 2010. doi: 10.2215/CJN.03980510 C1 [Kutner, Nancy G.] Emory Univ, Dept Rehabil Med, Rehabil Qual Life Special Studies Ctr, Atlanta, GA 30322 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Kutner, NG (reprint author), Emory Univ, Dept Rehabil Med, Rehabil Qual Life Special Studies Ctr, Atlanta, GA 30322 USA. EM nkutner@emory.edu FU National Institutes of Health [HHSN267200715004C, ADB N01-DK-7-5004] FX This study was supported by National Institutes of Health contract HHSN267200715004C, ADB N01-DK-7-5004 (N.G.K.). NR 37 TC 14 Z9 15 U1 0 U2 10 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 NOV PY 2010 VL 5 IS 11 BP 2040 EP 2045 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 677UX UT WOS:000284018500020 PM 20884777 ER PT J AU Vachharajani, TJ Moossavi, S Salman, L Wu, S Maya, ID Yevzlin, AS Agarwal, A Abreo, KD Work, J Asif, A AF Vachharajani, Tushar J. Moossavi, Shahriar Salman, Loay Wu, Steven Maya, Ivan D. Yevzlin, Alex S. Agarwal, Anil Abreo, Kenneth D. Work, Jack Asif, Arif TI Successful Models of Interventional Nephrology at Academic Medical Centers SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PERITONEAL-DIALYSIS CATHETERS; VASCULAR ACCESS CENTER; ARTERIOVENOUS-FISTULA; HEALTH-CARE; PLACEMENT; OUTCOMES; QUALITY; PROGRAM AB The foundation of endovascular procedures by nephrologists was laid in the private practice arena. Because of political issues such as training, credentialing, space and equipment expenses, and co-management concerns surrounding the performance of dialysis-access procedures, the majority of these programs provided care in an outpatient vascular access center. On the basis of the improvement of patient care demonstrated by these centers, several nephrology programs at academic medical centers have also embraced this approach. In addition to providing interventional care on an outpatient basis, academic medical centers have taken a step further to expand collaboration with other specialties with similar expertise (such as with interventional radiologists and cardiologists) to enhance patient care and research. The enthusiastic initiative, cooperative, and mutually collaborative efforts used by academic medical centers have resulted in the successful establishment of interventional nephrology programs. This article describes various models of interventional nephrology programs at academic medical centers across the United States. Clin J Am Soc Nephrol 5: 2130-2136, 2010. doi: 10.2215/CJN.03990510 C1 [Vachharajani, Tushar J.; Moossavi, Shahriar] Wake Forest Univ, Sch Med, Dept Internal Med, Dialysis Access Grp, Winston Salem, NC 27157 USA. [Salman, Loay; Asif, Arif] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Wu, Steven] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Maya, Ivan D.] Univ Alabama, Birmingham, AL USA. [Yevzlin, Alex S.] Univ Wisconsin, Madison, WI USA. [Agarwal, Anil] Ohio State Univ, Columbus, OH 43210 USA. [Abreo, Kenneth D.] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. [Work, Jack] Emory Univ, Dialysis Access Ctr Atlanta, Atlanta, GA 30322 USA. RP Vachharajani, TJ (reprint author), Wake Forest Univ, Sch Med, Dept Internal Med, Dialysis Access Grp, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM tvachhar@wfubmc.edu NR 28 TC 13 Z9 14 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 NOV PY 2010 VL 5 IS 11 BP 2130 EP 2136 DI 10.2215/CJN.03990510 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 677UX UT WOS:000284018500032 PM 20930089 ER PT J AU Sawamura, C Springfield, DS Marcus, KJ Perez-Atayde, AR Gebhardt, MC AF Sawamura, Chigusa Springfield, Dempsey S. Marcus, Karen J. Perez-Atayde, Antonio R. Gebhardt, Mark C. TI Factors Predicting Local Recurrence, Metastasis, and Survival in Pediatric Soft Tissue Sarcoma in Extremities SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Combined Meeting of the International-Society-of-Limb-Salvage (ISOLS)/Musculoskeletal-Tumor-Society (MSTS) CY SEP, 2009 CL Boston, MA SP Int Soc Limb Salvage (ISOLS), Musculoskeletal Tumor Soc (MSTS) ID END RESULTS PROGRAM; PROGNOSTIC-FACTORS; SYNOVIAL SARCOMA; RHABDOMYOSARCOMA; CHEMOTHERAPY; EPIDEMIOLOGY; SURVEILLANCE; CHILDHOOD; CHILDREN; MARGIN AB Background Pediatric soft tissue sarcomas are rare and differ from those in adults regarding the spectrum of diagnoses and treatment. Sarcomas in extremities may have different prognoses from those located elsewhere. Questions/purposes We sought risk factors predicting local recurrence, metastasis, and overall survival and asked whether radiation and chemotherapy influenced local recurrence, metastasis, and overall survival. Methods We retrospectively reviewed all 98 patients aged 18 years or younger diagnosed with soft tissue sarcomas in extremities from 1990 to 2008. Age, tumor size, depth, location, bone or neurovascular involvement, histologic subtypes, unplanned excision, surgical margins, metastasis at diagnosis, and adjuvant treatments were reviewed for each patient. We determined the effect of each prognostic variable on local recurrence, metastasis, and overall survival. Results Ninety-four patients underwent surgical excision and seven patients had local recurrence at a median time of 18.6 months. Radiation therapy reduced the rate of local recurrence. Fourteen patients had metastasis at diagnosis and seven patients later developed metastasis. The median time to metastasis was 20.9 months. Six patients died and the median time to death was 28.0 months. Metastasis at diagnosis was a predictive factor for death. Conclusions When limited to extremities, radiation therapy reduced the rate of local recurrence in pediatric soft tissue sarcomas. Metastases at diagnosis predict death. Level of Evidence Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Gebhardt, Mark C.] Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Boston, MA 02215 USA. [Sawamura, Chigusa] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Springfield, Dempsey S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Marcus, Karen J.] Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Perez-Atayde, Antonio R.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gebhardt, Mark C.] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Gebhardt, MC (reprint author), Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Shapiro CC2-330 Brookline Ave, Boston, MA 02215 USA. EM mgebhardt@bidmc.harvard.edu NR 23 TC 10 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2010 VL 468 IS 11 BP 3019 EP 3027 DI 10.1007/s11999-010-1398-1 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 735TE UT WOS:000288439900026 PM 20544321 ER PT J AU Merlo-Pich, E Alexander, RC Fava, M Gomeni, R AF Merlo-Pich, E. Alexander, R. C. Fava, M. Gomeni, R. TI A New Population-Enrichment Strategy to Improve Efficiency of Placebo-Controlled Clinical Trials of Antidepressant Drugs SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID MAJOR DEPRESSIVE DISORDER; PAROXETINE-CONTROLLED TRIAL; CONTROLLED-RELEASE; PREDICTIVE CHECK; SIGNAL-DETECTION; EFFICACY; MODELS; METAANALYSIS; PERFORMANCE; DULOXETINE AB The rate-limiting factor in the discovery of novel antidepressants is the inefficient methodology of traditional multicenter randomized clinical trials (RCTs). We applied a model-based approach to a large clinical database (five RCTs in major depressive disorder (MDD), involving 1,837 patients from 124 recruitment centers) with two objectives: (i) to learn about the role of center-specific placebo response in RCT failure and (ii) to apply what is learned to improve the efficiency of RCTs by enhancing the detection of treatment effect (TE). Sensitivity analysis indicated that center-specific placebo response was the most relevant predictor of RCT failure. To reduce the statistical "noise" generated by centers with nonplausible, excessively high/low placebo responses, we developed an enrichment-window strategy. Clinical trial simulation was used to assess the enrichment strategy applied before the standard statistical analysis, resulting in an overall reduction in failure of RCTs from similar to 50 to similar to 10%. C1 [Merlo-Pich, E.; Alexander, R. C.] GlaxoSmithKline R&D, Neurosci Ctr Excellence Drug Discovery, Verona, Italy. [Merlo-Pich, E.; Gomeni, R.] GlaxoSmithKline R&D, Pharmacometr, Upper Merion, PA USA. [Fava, M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Merlo-Pich, E (reprint author), GlaxoSmithKline R&D, Neurosci Ctr Excellence Drug Discovery, Verona, Italy. EM emilio.v.merlo-pich@gsk.com NR 50 TC 27 Z9 27 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2010 VL 88 IS 5 BP 634 EP 642 DI 10.1038/clpt.2010.159 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 668UJ UT WOS:000283296500020 PM 20861834 ER PT J AU Bryant, MS Rintala, DH Lai, EC Protas, EJ AF Bryant, M. S. Rintala, D. H. Lai, E. C. Protas, E. J. TI An investigation of two interventions for micrographia in individuals with Parkinson's disease SO CLINICAL REHABILITATION LA English DT Article ID VISUAL FEEDBACK AB Objective: This pilot study was designed to compare a change in micrographia between using grid lines and parallel horizontal lines as visual cues in individuals with Parkinson's disease. Design: Single group pre- and post-test. Setting: Research lab. Participants: Eleven males with Parkinson's disease. Interventions: Practice writing words with parallel and grid lines. The sequence of practising was randomized. Main outcome measures: Length of words. Results: The length of the words after practising with parallel lines was longer than in the initial free writing condition (17.83 +/- 3.93cm vs. 23.36 +/- 5.82 cm, P = 0.008). The length of the words after practising with grid lines was also longer than during free writing (17.83 +/- 3.93cm vs. 22.65 +/- 4.04 cm, P = 0.003). The length of the words after practising with parallel lines was not different from that after practising with grid lines. Conclusion: Improvements in letter size after practising with horizontal parallel lines and grid lines were not different. The addition of vertical lines to form a grid did not appear to improve the writing more than horizontal lines alone in persons with Parkinson's disease who experienced micrographia. C1 [Bryant, M. S.; Protas, E. J.] Univ Texas Med Branch, Sch Hlth Profess, Galveston, TX USA. [Bryant, M. S.; Rintala, D. H.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Lai, E. C.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Lai, E. C.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Bryant, MS (reprint author), 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mon.bryant@yahoo.com FU NICHD NIH HHS [K12 HD055929] NR 9 TC 14 Z9 14 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-2155 J9 CLIN REHABIL JI Clin. Rehabil. PD NOV PY 2010 VL 24 IS 11 BP 1021 EP 1026 DI 10.1177/0269215510371420 PG 6 WC Rehabilitation SC Rehabilitation GA 671UU UT WOS:000283537700006 PM 20554637 ER PT J AU Rubenstein, LZ Ganz, DA AF Rubenstein, Laurence Z. Ganz, David A. TI Falls and Their Prevention Preface SO CLINICS IN GERIATRIC MEDICINE LA English DT Editorial Material C1 [Rubenstein, Laurence Z.] Univ Oklahoma, Coll Med, Reynolds Dept Geriatr Med, Oklahoma City, OK 73104 USA. [Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90095 USA. RP Rubenstein, LZ (reprint author), Univ Oklahoma, Coll Med, Reynolds Dept Geriatr Med, 921 NE 13th St,VAMC 11G, Oklahoma City, OK 73104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD NOV PY 2010 VL 26 IS 4 BP XIII EP XIV DI 10.1016/j.cger.2010.07.007 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 678MK UT WOS:000284079800001 PM 20934609 ER PT J AU Wu, SY Keeler, EB Rubenstein, LZ Maglione, MA Shekelle, PG AF Wu, Shinyi Keeler, Emmett B. Rubenstein, Laurence Z. Maglione, Margaret A. Shekelle, Paul G. TI A Cost-Effectiveness Analysis of a Proposed National Falls Prevention Program SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Falls; Fall prevention; Cost-effectiveness; Medicare; Health policy ID DWELLING OLDER PERSONS; ELDERLY-PEOPLE; RANDOMIZED TRIAL; NURSING-HOME; RISK-FACTORS; COMMUNITY; INJURIES; ADULTS; METAANALYSIS; POPULATION AB Falls are a major health concern for elderly people and cause substantial health care costs The authors used meta-analytic findings on the effectiveness of fall prevention interventions to determine cost-effectiveness of a proposed Medicare fall prevention program for people who experience a recent fall Using published clinical trial data the authors constructed a population-based economic model and estimated that in the base case, the program could prevent a half million people from falling again within a year From the model under most circumstances the cost-effectiveness ratio is less than $1500 per person prevented from experiencing a recurrent fall Paying for a fall prevention program to increase the use of evidence-based interventions would be a cost-effective use of Medicare dollars C1 [Wu, Shinyi] Univ So Calif, Epstein Dept Ind & Syst Engn, Los Angeles, CA 90089 USA. [Wu, Shinyi; Keeler, Emmett B.; Rubenstein, Laurence Z.; Maglione, Margaret A.; Shekelle, Paul G.] RAND Corp, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90401 USA. [Rubenstein, Laurence Z.] Univ Calif Los Angeles, Div Geriatr, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rubenstein, Laurence Z.; Shekelle, Paul G.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Sepulveda Div, Los Angeles, CA 90073 USA. [Rubenstein, Laurence Z.; Shekelle, Paul G.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, W Los Angeles Div, Los Angeles, CA 90073 USA. RP Wu, SY (reprint author), Univ So Calif, Epstein Dept Ind & Syst Engn, 3715 McClintock Ave, Los Angeles, CA 90089 USA. FU National Institute on Aging as part of the UCLA Pepper Center [AG 10415] FX This research was performed by the Southern California Evidence Based Practice Center based at the RAND Corporation Santa Monica CA RAND is under contract with the Centers for Medicare and Medicaid Services (CMS) Dr Keeler was supported by the National Institute on Aging as part of the UCLA Pepper Center Grant AG 10415 NR 47 TC 13 Z9 13 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 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD NOV PY 2010 VL 26 IS 4 BP 751 EP + DI 10.1016/j.cger.2010.07.005 PG 17 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 678MK UT WOS:000284079800012 PM 20934620 ER PT J AU Huppert, JD Siev, J AF Huppert, Jonathan D. Siev, Jedidiah TI Treating Scrupulosity in Religious Individuals Using Cognitive-Behavioral Therapy SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SYMPTOM DIMENSIONS; PREDICTORS AB Scrupulosity, the obsessional fear of thinking or behaving immorally or against one's religious beliefs, is a form of obsessive-compulsive disorder that has been relatively understudied to date. Treating religious patients with scrupulosity raises a number of unique clinical challenges for many clinicians. For example, how does one distinguish normal beliefs from pathological scrupulosity? How does one adapt exposures to a religious patient whose fears are related to sinning? How far should one go in exposures in such cases? How and when does one include clergy in treatment? We address these issues and report a case example of the successful treatment of an ultra-Orthodox Jewish woman using the treatment principles that we recommend for religious individuals with scrupulosity. C1 [Huppert, Jonathan D.] Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. [Siev, Jedidiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Huppert, JD (reprint author), Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. EM huppertj@mscc.huji.ac.il OI Huppert, Jonathan/0000-0002-0537-4701 NR 34 TC 18 Z9 18 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2010 VL 17 IS 4 BP 382 EP 392 PG 11 WC Psychology, Clinical SC Psychology GA 657BO UT WOS:000282386400005 ER PT J AU Polyak, K Kalluri, R AF Polyak, Kornelia Kalluri, Raghu TI The Role of the Microenvironment in Mammary Gland Development and Cancer SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID HUMAN BREAST-CANCER; CARCINOMA IN-SITU; CONTRIBUTE ONCOGENIC SIGNALS; TGF-BETA; EPITHELIAL-CELLS; TUMOR STROMA; MESENCHYMAL TRANSITION; EXTRACELLULAR-MATRIX; MYOEPITHELIAL CELLS; METASTATIC NICHE AB The mammary gland is composed of a diverse array of cell types that form intricate interaction networks essential for its normal development and physiologic function. Abnormalities in these interactions play an important role throughout different stages of tumorigenesis. Branching ducts and alveoli are lined by an inner layer of secretory luminal epithelial cells that produce milk during lactation and are surrounded by contractile myoepithelial cells and basement membrane. The surrounding stroma comprised of extracellular matrix and various cell types including fibroblasts, endothelial cells, and infiltrating leukocytes not only provides a scaffold for the organ, but also regulates mammary epithelial cell function via paracrine, physical, and hormonal interactions. With rare exceptions breast tumors initiate in the epithelial compartment and in their initial phases are confined to the ducts but this barrier brakes down with invasive progression because of a combination of signals emitted by tumor epithelial and various stromal cells. In this article, we overview the importance of cellular interactions and microenvironmental signals in mammary gland development and cancer. C1 [Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Kalluri, Raghu] Beth Israel Deaconess Med Ctr, Dept Med, Div Matrix Biol, Boston, MA 02115 USA. [Kalluri, Raghu] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu FU National Cancer Institute [CA89393, CA116235, CA143233, CA080111]; Department of Defense [W81XWH-07-1-0294, W81XWH-09-1-0131]; Avon Foundation; Susan G. Komen Breast Cancer Research Foundation; Breast Cancer Research Foundation; Novartis; Champalimaud Metastasis Program; [CA125550]; [DK55001] FX The authors thank members of their laboratories for their critical reading of the manuscript and constructive discussions. Work in the authors' laboratories is supported by the National Cancer Institute (CA89393, CA116235, CA143233, and CA080111), Department of Defense (W81XWH-07-1-0294 and W81XWH-09-1-0131), Avon Foundation, Susan G. Komen Breast Cancer Research Foundation, Breast Cancer Research Foundation, and Novartis Oncology grants awarded to KP, and CA125550, DK55001, and Champalimaud Metastasis Program grants awarded to RK. NR 82 TC 109 Z9 113 U1 2 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD NOV PY 2010 VL 2 IS 11 AR a003244 DI 10.1101/cshperspect.a003244 PG 14 WC Cell Biology SC Cell Biology GA 673GI UT WOS:000283646900007 PM 20591988 ER PT J AU Jakobiec, FA Stacy, RC Colby, KA AF Jakobiec, Frederick A. Stacy, Rebecca C. Colby, Kathryn A. TI Pigmented Apocrine Hidrocystoma of the Caruncle SO CORNEA LA English DT Article DE hidrocystoma; apocrine; caruncle; pigmented; gross cystic disease fluid protein-15 ID STEATOCYSTOMA SIMPLEX; TUMORS; DIFFERENTIATION; MARKERS; LESIONS AB Purpose: To describe the clinical and immunopathologic features of the first convincing apocrine hidrocystoma of the caruncle that happened to be pigmented. Methods: Case report with clinical evaluation, ultrasound biomicroscopy, and paraffin-embedded tissue stained with hematoxylin and eosin, periodic acid-Schiff, and immunohistochemical markers. Results: Ultrasound biomicroscopy identified a cyst occurring in a 56-year-old white woman. Histopathologically, it was lined by an inner eosinophilic columnar epithelium that was gross cystic disease fluid protein-15-positive and evinced apical decapitation secretion and periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules. Fontana- and MART-1-positive melanin granules were demonstrated. There was an outer layer of smooth muscle actin-positive myoepithelial cells. An adjacent apocrine gland was discovered with identical staining characteristics but without melanin granules. Conclusions: Classical apocrine gland cysts can exceptionally develop in the caruncle. The light dispersion of cytoplasmic melanin found in the lining cells may have contributed to the cyst's clinical pigmentation, which is otherwise generally regarded as the result of the Tyndall effect, wherein blue wavelengths of light reflect from a colloidal solution of lipofuscin and cell debris. C1 [Jakobiec, Frederick A.; Stacy, Rebecca C.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Eye Pathol, Boston, MA 02114 USA. [Colby, Kathryn A.] Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Eye Pathol, Suite 321,243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu FU Heed Foundation FX Dr. Stacy is supported in part by the Heed Foundation. NR 18 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 2010 VL 29 IS 11 BP 1320 EP 1322 DI 10.1097/ICO.0b013e3181d4fd71 PG 3 WC Ophthalmology SC Ophthalmology GA 669ER UT WOS:000283329800022 PM 20697277 ER PT J AU Willcutt, EG Betjemann, RS McGrath, LM Chhabildas, NA Olson, RK DeFries, JC Pennington, BF AF Willcutt, Erik G. Betjemann, Rebecca S. McGrath, Lauren M. Chhabildas, Nomita A. Olson, Richard K. DeFries, John C. Pennington, Bruce F. TI Etiology and neuropsychology of comorbidity between RD and ADHD: The case for multiple-deficit models SO CORTEX LA English DT Article DE ADHD; Reading disability; Executive functions; Comorbidity; Genetics ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PHONOLOGICAL PROCESSING ABILITIES; LEARNING-DISABLED CHILDREN; DSM-IV SUBTYPES; HYPERACTIVITY DISORDER; READING-DISABILITY; ENVIRONMENTAL-INFLUENCES; GENETIC INFLUENCES; LONGITUDINAL TWIN; WORD RECOGNITION AB Introduction Attention deficit/hyperactivity disorder (ADHD) and reading disability (RD) are complex childhood disorders that frequently co occur but the etiology of this comorbidity remains unknown Method Participants were 457 twin pairs from the Colorado Learning Disabilities Research Center (CLDRC) twin study an ongoing study of the etiology of RD ADHD and related disorders Phenotypic analyses compared groups with and without RD and ADHD on composite measures of six cognitive domains Twin analyses were then used to test the etiology of the relations between the disorders and any cognitive weaknesses Results Phenotypic analyses supported the hypothesis that both RD and ADHD arise from multiple cognitive deficits rather than a single primary cognitive deficit RD was associated independently with weaknesses on measures of phoneme awareness, verbal reasoning and working memory whereas ADHD was independently associated with a heritable weakness in inhibitory control RD and ADHD share a common cognitive deficit in pro cessing speed and twin analyses indicated that this shared weakness is primarily due to common genetic influences that increase susceptibility to both disorders Conclusions Individual differences in processing speed are influenced by genes that also increase risk for RD ADHD and their comorbidity These results suggest that processing speed measures may be useful for future molecular genetic studies of the etiology of comorbidity between RD and ADHD (C) 2010 Elsevier Srl All rights reserved C1 [Willcutt, Erik G.; Chhabildas, Nomita A.; Olson, Richard K.; DeFries, John C.] Univ Colorado, Dept Psychol, UCB 345, Boulder, CO 80309 USA. [Betjemann, Rebecca S.] Regis Univ, Denver, CO USA. [McGrath, Lauren M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pennington, Bruce F.] Univ Denver, Denver, CO 80208 USA. RP Willcutt, EG (reprint author), Univ Colorado, Dept Psychol, UCB 345, Campus Box 345, Boulder, CO 80309 USA. OI McGrath, Lauren/0000-0001-6928-9656 FU NICHD NIH HHS [P50 HD027802, R01 HD038526, R01 HD047264, R01 HD068728]; NIDCD NIH HHS [F31 DC008726]; NIMH NIH HHS [P50 MH079485, R01 MH062120, R01 MH063207, R01 MH063941, R01 MH070037] NR 129 TC 87 Z9 92 U1 4 U2 32 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD NOV-DEC PY 2010 VL 46 IS 10 SI SI BP 1345 EP 1361 DI 10.1016/j.cortex.2010.06.009 PG 17 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 682FA UT WOS:000284385600012 PM 20828676 ER PT J AU Cobb, JP AF Cobb, J. Perren TI MORE for multiple organ dysfunction syndrome: Multiple Organ REanimation, REgeneration, and REprogramming SO CRITICAL CARE MEDICINE LA English DT Article DE MODS; stem cells; critical care; ICU; intensive care; future ID INTENSIVE-CARE-UNIT; MESENCHYMAL STEM-CELLS; MEDICAL ERRORS; PATIENT SAFETY; BONE-MARROW; CRITICAL ILLNESS; IN-VIVO; INJURY; SEPSIS; HEALTH AB Those who care for the critically ill and injured rightfully celebrate the advances made by our field over its first 50 yrs. Advances in systems, tissue, and molecular engineering, together defined as "health engineering," will provide unprecedented opportunities to treat multiple organ dysfunction syndrome in the 21st century. In the future, Multiple Organ REanimation, REgeneration, and REprogramming will be responsible for new treatment approaches for those with multiple organ dysfunction syndrome; several examples are presented here. Thus, as we spent the first 50 yrs of care for the critical ill and injured learning how best to hook humans up to machines, we will spend the next 50 yrs understanding better how to liberate patients from mechanical support. It is difficult to know when these advances will be realized given that the rate of change continues to increase and the seemingly impossible goal of reprogramming fully differentiated cells was accomplished recently by manipulating a few transcription factors. It is not unrealistic to expect that in the next couple of decades that it will be possible to dedifferentiate dysfunctional somatic cells in vivo to a more robust, resistant cell phenotype. Our future should be aimed in part at refining our skill sets and refocusing (even rebranding) critical care as health engineering aimed at Multiple Organ REanimation, REgeneration, and REprogramming. (Crit Care Med 2010; 38: 2242-2246) C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Crit Care Ctr, Boston, MA 02114 USA. [Cobb, J. Perren] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Cobb, JP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Crit Care Ctr, Boston, MA 02114 USA. EM jpcobb@partners.org NR 52 TC 3 Z9 4 U1 1 U2 3 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 NOV PY 2010 VL 38 IS 11 BP 2242 EP 2246 DI 10.1097/CCM.0b013e3181f26a63 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 667YW UT WOS:000283235400021 PM 20711067 ER PT J AU deFoneska, A Kaunitz, JD AF deFoneska, Arushi Kaunitz, Jonathan D. TI Gastroduodenal mucosal defense SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE heat shock proteins; Helicobacter pylori; prostaglandins; proteinase-activated receptors; purinergic signalling; toll-like receptors; trefoil factors ID INTESTINAL ALKALINE-PHOSPHATASE; HELICOBACTER-PYLORI; GASTROINTESTINAL-DISEASES; ADAPTIVE CYTOPROTECTION; GASTRIC NECROSIS; RATS; EXPRESSION; RECEPTOR; CELLS; LIPOPOLYSACCHARIDE AB Purpose of review We have summarized recent findings related to gastroduodenal mucosal defense as well as factors contributing to defensive failure, highlighting findings that illuminate new pathophysiological mechanisms. Recent findings Gastroduodenal bicarbonate secretion is mediated by prostaglandin E receptors and stimulated by the prostone lubiprostone. Toll-like receptor (TLR)4 signaling is protective against gastric injury. Intestinal alkaline phosphatase (IAP) is a chemosensor that regulates the duodenal mucosal surface pH. Lipopolysaccharide (LPS) increases gastric permeability; IAP secreted during fat digestion may detoxify colonic LPS. NADPH oxidase activity mediates ischemia/reperfusion-related gastric mucosal damage. Heat shock protein 70 (HSP70) protects the gastric mucosa through inhibition of apoptosis, proinflammatory cytokines, and cell adhesion molecules (CAMs). HSP90 may be a contributing factor in impaired adaptive cytoprotection. Proteinase-activated receptor-1 (PAR-1) is protective against Helicobacter-induced gastritis, mediated by the suppression of proinflammatory pathways. IKK beta/NF-kappa B signaling decreases chronic Helicobacter-induced inflammation by inhibiting cellular apoptosis and necrosis. Activation of A(2A) adenosine receptors decreases inflammation and gastritis but leads to persistent Helicobacter pylori infection. Summary Enhanced understanding of the mechanisms of gastroduodenal defense and injury provides new insight into potential therapeutic targets, contributing towards the development of better tolerated and more effective therapies. C1 [deFoneska, Arushi; Kaunitz, Jonathan D.] UCLA Sch Med, W Los Angeles VA Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] UCLA Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] UCLA Sch Med, Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] UCLA Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), UCLA Sch Med, W Los Angeles VA Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIH/NIDDK [RO1 DK54221, P30 DK0413] FX We thank Coleen Palileo for her editorial assistance. Supported by VA Merit Review funding, NIH/NIDDK RO1 DK54221, and NIH/NIDDK P30 DK0413. NR 40 TC 28 Z9 29 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2010 VL 26 IS 6 BP 604 EP 610 DI 10.1097/MOG.0b013e32833f1222 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 664SQ UT WOS:000282983200011 PM 20948371 ER PT J AU Cutler, C Antin, JH AF Cutler, Corey Antin, Joseph H. TI Sirolimus immunosuppression for graft-versus-host disease prophylaxis and therapy: an update SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE allogeneic stem cell transplantation; graft-versus-host disease; sirolimus ID STEM-CELL TRANSPLANTATION; CORD BLOOD TRANSPLANTATION; CONDITIONING REGIMEN; GVHD PROPHYLAXIS; TACROLIMUS; RAPAMYCIN; METHOTREXATE; COMBINATION; LEUKEMIA; CYCLOSPORINE AB Purpose of review Sirolimus is being used increasingly as an immunosuppressant in allogeneic hematopoietic stem cell transplantation. This article reviews recent results in sirolimus-based graft-versus-host disease (GVHD) prophylaxis, as well as outcomes using sirolimus for established acute and chronic GVHD. Recent findings In uncontrolled experiments, sirolimus provides good control of steroid-resistant acute or chronic GVHD. Similarly, the addition of sirolimus to GVHD prophylaxis regimens appears to reduce the rate of acute GVHD in the myeloablative and reduced-intensity settings, when used in matched, related, and unrelated donor transplantation. The use of sirolimus in haploidentical transplantation is now being explored as well. Summary Sirolimus should be considered for use in steroid-resistant acute and chronic GVHD. Sirolimus appears promising as primary prophylaxis for GVHD prevention. Randomized trials are currently being performed to determine whether sirolimus-based immunosuppression is superior to traditional GVHD prophylaxis. C1 [Cutler, Corey; Antin, Joseph H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cutler, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu FU Wyeth, Inc.; Stem Cell Cyclists of the Pan-Mass Challenge FX C.C. and J.H.A. report that some research studies have been partially supported by unrestricted grants from Wyeth, Inc. C.C. is supported in part by the Stem Cell Cyclists of the Pan-Mass Challenge. NR 30 TC 21 Z9 21 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD NOV PY 2010 VL 17 IS 6 BP 500 EP 504 DI 10.1097/MOH.0b013e32833e5b2e PG 5 WC Hematology SC Hematology GA 664SJ UT WOS:000282982500003 PM 20717025 ER PT J AU He, WJ Castiblanco, J Walter, EA Okulicz, JF Ahuja, SK AF He, Weijing Castiblanco, John Walter, Elizabeth A. Okulicz, Jason F. Ahuja, Sunil K. TI Mendelian randomization: potential use of genetics to enable causal inferences regarding HIV-associated biomarkers and outcomes SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE biomarker; chemokine; gene; HIV; Mendelian randomization ID HUMAN-IMMUNODEFICIENCY-VIRUS; DUFFY ANTIGEN RECEPTOR; C-REACTIVE PROTEIN; COPY-NUMBER VARIATION; CD4(+) T-CELLS; DISEASE PROGRESSION; ANTIRETROVIRAL THERAPY; PROMOTER POLYMORPHISM; TYPE-1 INFECTION; AIDS SUSCEPTIBILITY AB Purpose of review It is unknown whether biomarkers simply correlate with or are causal for HIV-associated outcomes. Mendelian randomization is a genetic epidemiologic approach used to disentangle causation from association. Here, we discuss the potential use of Mendelian randomization for differentiating whether biomarkers are correlating with or causal for HIV-associated outcomes. Recent findings Mendelian randomization refers to the random allocation of alleles at the time of gamete formation. In observational epidemiology, this refers to the use of genetic variants to estimate a causal effect between a modifiable risk factor and an outcome of interest. A formal Mendelian randomization study using a genetic marker as a proxy for the biomarker has not been conducted in the HIV field. However, in the postgenomic era, this approach is being used increasingly. Examples are evidence for the causal role of BMI in blood pressure and noncausal role of C-reactive protein in coronary heart disease. We discuss the conceptual framework, uses, and limitations of Mendelian randomization in the context of HIV infection as well as specific biomarkers (IL-6, C-reactive protein) and genetic determinants (e. g., in CCR5, chemokine, and DARC genes) that associate with HIV-related outcomes. Summary Making the distinction between correlation and causality has particular relevance when a biomarker (e. g., IL-6) is potentially modifiable, in which case a biomarker-guided targeted treatment strategy may be feasible. Although the tenets of Mendelian randomization rest on strong assumptions, and conducting a Mendelian randomization study in HIV infection presents many challenges, it may offer the potential to identify causal biomarkers for HIV-associated outcomes. C1 [He, Weijing; Castiblanco, John; Ahuja, Sunil K.] S Texas Vet Healthcare Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA. [He, Weijing; Castiblanco, John; Walter, Elizabeth A.; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol Immunol & Biochem, San Antonio, TX 78229 USA. [Okulicz, Jason F.] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. RP Ahuja, SK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Vet Adm Ctr AIDS & HIV Infect, 7703 Floyd Curl Dr MC 7881,Rm 5-065R, San Antonio, TX 78229 USA. EM ahujas@uthscsa.edu OI CASTIBLANCO, JOHN/0000-0003-2556-3697; CASTIBLANCO, JOHN/0000-0002-7965-9822 FU Veterans Administration HIV/AIDS Center of the South Texas Veterans Healthcare System, NIH [R37046326]; Doris Duke Distinguished Clinical Scientist Award; VA MERIT award; Burroughs Wellcome Clinical Scientist Award in Translational Research FX The present work was supported by the Veterans Administration HIV/AIDS Center of the South Texas Veterans Healthcare System, NIH (R37046326), and the Doris Duke Distinguished Clinical Scientist Award to S. K. A. S. K. A. is also supported by a VA MERIT award and the Burroughs Wellcome Clinical Scientist Award in Translational Research. NR 137 TC 1 Z9 1 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD NOV PY 2010 VL 5 IS 6 BP 545 EP 559 DI 10.1097/COH.0b013e32833f2087 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 828NX UT WOS:000295509900014 PM 20978399 ER PT J AU Steven, DW Palevsky, PM AF Weisbord, Steven D. Palevsky, Paul M. TI Strategies for the prevention of contrast-induced acute kidney injury SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE contrast-induced acute kidney injury; prevention; risk factors ID RANDOMIZED CONTROLLED-TRIAL; PERCUTANEOUS CORONARY INTERVENTION; RADIOCONTRAST-INDUCED NEPHROPATHY; INTRAVENOUS N-ACETYLCYSTEINE; ISOTONIC SODIUM-BICARBONATE; ATRIAL-NATRIURETIC-PEPTIDE; SEVERE RENAL-INSUFFICIENCY; MEDIA-INDUCED NEPHROPATHY; DIURESIS DVD TRIAL; HIGH-RISK PATIENTS AB Purpose of review The intravascular administration of iodinated contrast media for diagnostic imaging is a common cause of acute kidney injury and a leading cause of iatrogenic renal disease. The purpose of this review is to describe the principal risk factors for contrast-induced acute kidney injury and to summarize recent data describing the efficacy of various preventive interventions for this condition. Recent findings Whereas earlier studies suggested that certain low-osmolal contrast agents including iohexol and ioxaglate are more nephrotoxic than iso-osmolal iodixanol, recent clinical trials and meta-analyses comparing other low-osmolal contrast agents with iodixanol have found little difference in risk. The provision of prophylactic renal replacement therapy does not ameliorate the risk of contrast-induced acute kidney injury, and likely poses undue risk. Despite some research supporting a benefit of atrial natriuretic peptide, statins, and prostaglandin analogs, additional data from large, adequately powered studies are needed before these agents can be recommended. N-Acetylcysteine and isotonic intravenous bicarbonate have been investigated intensely, yet the data on these interventions are conflicting due to methodological limitations in past studies. Summary Prevention of contrast-induced acute kidney injury involves the identification of high-risk patients, consideration of alternative imaging procedures that do not involve the administration of iodinated contrast, and integration of the cumulative data available on preventive interventions in high-risk patients. C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Univ Drive Div, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Univ Drive Div, Room 7E123 111F-U, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 FU VA Health Services [RCD 03-176-2] FX The views expressed in this article are those of the authors and do not necessarily represent the views of the United States Department of Veterans Affairs. Dr Weisbord is supported by a VA Health Services Research and Development Career Development Transition Award (RCD 03-176-2). NR 111 TC 0 Z9 0 U1 1 U2 1 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 NOV PY 2010 VL 19 IS 6 BP 539 EP 549 DI 10.1097/MNH.0b013e32833d42e3 PG 11 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 664RW UT WOS:000282981200005 ER PT J AU Liu, JF Silver, DP AF Liu, Joyce F. Silver, Daniel P. TI Poly ADP-ribose polymerase inhibitors: science and current clinical development SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE BRCA1; BRCA2; poly ADP-ribose polymerase inhibitor; synthetic lethality ID POLY(ADP-RIBOSE) POLYMERASE; DNA-DAMAGE; HOMOLOGOUS RECOMBINATION; OVARIAN-CARCINOMA; BRCA1 DEFICIENCY; SENSITIVITY; CANCER; REPAIR; TUMORS; CELLS AB Purpose of review Poly ADP-ribose polymerase inhibitors are a promising new area in cancer therapeutics. This review summarizes the current understanding of their mechanism of action, their state of clinical development, and possible mechanisms of resistance. Recent findings Poly ADP-ribose polymerase inhibitors were predicted to cause lethality in cells with lesions in homologous recombination, as well as to be synergistic with cytotoxic chemotherapy. Recent clinical trial results have validated both of these hypotheses. In addition, studies have begun to examine possible mechanisms of resistance. Summary Poly ADP-ribose polymerase inhibitors were developed with the idea of synthetic lethality in mind, a concept from classical genetics that may be a general approach to finding new targets for cancer therapy. They show activity as monotherapy in cancers with defective homologous recombination, and they may potentiate the action of conventional cytotoxic chemotherapy. C1 [Liu, Joyce F.; Silver, Daniel P.] Harvard Univ, Sch Med, Womens Canc Program, Dept Med Oncol, Boston, MA USA. [Silver, Daniel P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. RP Silver, DP (reprint author), Sm 870,1 Jimmy Fund Way, Boston, MA 02115 USA. EM Daniel_Silver@DFCI.Harvard.Edu FU National Cancer Institute in Research Excellence in Breast Cancer at Dana-Farber/Harvard Cancer Center [CA89393]; Cogan Family Foundation; National Cancer Institute Paul Calabresi [K12, CA 087723-07]; American Recovery and Reinvestment Act [NIH 3 U01 CA062490-16S2]; Women's Cancers Executive Council at the Dana-Farber Cancer Institute FX Dr Silver is a paid consultant for Inotek Pharmaceuticals. Dr Liu has no disclosures relevant to this manuscript. Dr Silver gratefully acknowledges support from the National Cancer Institute Specialized Program in Research Excellence in Breast Cancer at Dana-Farber/Harvard Cancer Center (CA89393) and the Cogan Family Foundation; Dr Liu appreciates the support of the National Cancer Institute Paul Calabresi Award (K12) (CA 087723-07), an American Recovery and Reinvestment Act Award (NIH 3 U01 CA062490-16S2), and an award from the Women's Cancers Program Executive Council at the Dana-Farber Cancer Institute. NR 43 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD NOV PY 2010 VL 22 IS 6 BP 567 EP 572 DI 10.1097/CCO.0b013e32833edbf8 PG 6 WC Oncology SC Oncology GA 659WG UT WOS:000282597200005 PM 20739886 ER PT J AU Gerstner, ER Batchelor, TT AF Gerstner, Elizabeth R. Batchelor, Tracy T. TI Imaging and response criteria in gliomas SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE gliomas; MRI; PET; response criteria ID POSITRON-EMISSION-TOMOGRAPHY; HIGH-GRADE GLIOMAS; BEVACIZUMAB PLUS IRINOTECAN; HYPOXIC CELL FRACTION; RECURRENT GLIOBLASTOMA; TUMOR PROGRESSION; BRAIN-TUMORS; RADIATION-THERAPY; PROLONGS SURVIVAL; MALIGNANT GLIOMAS AB Purpose of review To highlight the most recent advances in the imaging of gliomas with a focus on high-grade gliomas. In the last several years, MRI and PET imaging of the brain have moved beyond anatomic imaging and are now capable of probing different aspects of tumor biology and response to treatment. These new techniques are increasingly being incorporated into clinical trials and even into clinical practice. Therefore, it is important to be familiar with the available imaging techniques and their potential uses versus limitations. Recent findings In 2010, updated response assessment criteria for high-grade gliomas were published. It was the first revision to imaging response criteria for gliomas since 1990 and represents an international effort to standardize criteria for clinical trials. Although this revision represents an important development, there are several promising imaging techniques on the horizon such as vascular permeability measurement, perfusion imaging, diffusion imaging, and new PET tracers that will continue to improve our understanding of tumor biology. Summary Advances in neuroimaging of brain tumors are enabling investigators to noninvasively visualize tumor response to treatment over time. As these tools are validated, they will add substantially to our ability to understand glioma biology and response to therapy. C1 [Gerstner, Elizabeth R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Pappas Ctr Neuro Oncol, Boston, MA 02114 USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neuro Oncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM egerstner@partners.org NR 39 TC 13 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD NOV PY 2010 VL 22 IS 6 BP 598 EP 603 DI 10.1097/CCO.0b013e32833de96e PG 6 WC Oncology SC Oncology GA 659WG UT WOS:000282597200010 PM 20689430 ER PT J AU Szymusiak, R AF Szymusiak, Ronald TI Hypothalamic versus neocortical control of sleep SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Article DE adenosine; cytokines; preoptic hypothalamus; sleep homeostasis; synaptic homeostasis ID VENTROLATERAL PREOPTIC NEURONS; SLOW-WAVE ACTIVITY; EYE-MOVEMENT SLEEP; HORMONE-RELEASING-HORMONE; WAKING DISCHARGE PATTERNS; DORSAL RAPHE NUCLEUS; NERVE GROWTH-FACTOR; HOMEOSTATIC REGULATION; SEROTONERGIC NEURONS; PROSTAGLANDIN D-2 AB Purpose of review Regions of the neocortex most strongly activated during waking exhibit increased sleep intensity during subsequent sleep. The novel concept that aspects of sleep homeostasis are determined locally in the cortex contrasts with the established views that global changes in neocortical activity during sleep are achieved through inhibition of ascending arousal systems that originate in the brainstem and hypothalamus. Recent findings Experiments in animals and humans document asymmetries in neocortical electroencephalogram (EEG) slow-wave activity (SWA), a marker of homeostatic sleep need, as a result of functional activity during waking. In addition to local, use-dependent augmentation of EEG SWA and evoked potentials, expression of plasticity-related genes and of sleep-regulatory cytokines and neuromodulators have been shown to be elevated in a use-dependent manner in neocortex. The functional consequences of local sleep are hypothesized to involve regulation of synaptic plasticity, synaptic homeostasis and energy balance. Summary The evidence for use-dependent modulation of neocortical activity during sleep is compelling and provides novel insights into sleep function. However, local changes in neocortex are generally expressed on a background of global sleep. It remains to be determined if events initiated in the cortex have global sleep-promoting effects and how neocortical and hypothalamic mechanisms of sleep control interact. C1 [Szymusiak, Ronald] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 91343 USA. [Szymusiak, Ronald] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Szymusiak, Ronald] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. RP Szymusiak, R (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St,North Hills, Los Angeles, CA 91343 USA. EM rszym@ucla.edu FU Medical Research Service of the Department of Veterans Affairs; National Institute of Mental Health [MH63323] FX The author has no conflicts of interest relevant to the content of this article. Preparation of the article was supported by the U.S. Department of Veterans Affairs. The author has current grant support from the Medical Research Service of the Department of Veterans Affairs and the National Institute of Mental Health MH63323. NR 64 TC 10 Z9 10 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD NOV PY 2010 VL 16 IS 6 BP 530 EP 535 DI 10.1097/MCP.0b013e32833eec92 PG 6 WC Respiratory System SC Respiratory System GA 656UZ UT WOS:000282367400002 PM 20739890 ER PT J AU Tanrikut, C Goldstein, M AF Tanrikut, Cigdem Goldstein, Marc TI Varicocele repair for treatment of androgen deficiency SO CURRENT OPINION IN UROLOGY LA English DT Review DE androgen deficiency; hypogonadism; testosterone; varicocele; varicocelectomy ID INFERTILE MEN; TESTOSTERONE; PARAMETERS; FERTILITY; PLASMA AB Purpose of review The association between varicocele and male infertility is well established. Modern artery and lymphatic-sparing techniques of varicocele repair have been shown to significantly enhance semen quality and increase pregnancy rates. However, the effect of varicocele on testosterone production is less well defined and the possible association with androgen deficiency is controversial. Data regarding the effects of varicocelectomy on serum testosterone levels are limited and conflicting. Recent findings Few studies in the past 18 months have assessed the impact of varicocele repair on serum testosterone levels. The limited data available are culled from a diverse patient population with the goal of evaluating other primary outcome parameters and thus provide a challenge for drawing definitive conclusions. One of the more interesting recent studies uses a rat model of varicocele and varicocelectomy to assess changes in intratesticular testosterone levels. Summary Although the impact of varicocele on testosterone production is not well understood and the utility of varicocelectomy to prevent or reduce deterioration in Leydig cell function remains unproven, recent data suggest an adverse effect of varicocele and possible benefit of repair. Further human clinical studies are warranted to better define these relationships. C1 [Tanrikut, Cigdem] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Tanrikut, Cigdem; Goldstein, Marc] Cornell Univ, Dept Urol, Weill Cornell Med Coll, Ithaca, NY 14853 USA. [Tanrikut, Cigdem; Goldstein, Marc] Cornell Univ, Inst Reprod Med, Ithaca, NY 14853 USA. [Goldstein, Marc] Rockefeller Univ, Populat Council, Ctr Biomed Res, New York, NY 10021 USA. RP Tanrikut, C (reprint author), MGH Fertil Ctr, 55 Fruit St,YAW 10A, Boston, MA 02114 USA. EM ctanrikut@partners.org NR 19 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0963-0643 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD NOV PY 2010 VL 20 IS 6 BP 500 EP 502 DI 10.1097/MOU.0b013e32833f1b5e PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 664EG UT WOS:000282942100008 PM 20852425 ER PT J AU Luxton, DD Skopp, NA Maguen, S AF Luxton, David D. Skopp, Nancy A. Maguen, Shira TI GENDER DIFFERENCES IN DEPRESSION AND PTSD SYMPTOMS FOLLOWING COMBAT EXPOSURE SO DEPRESSION AND ANXIETY LA English DT Article DE depression; PTSD; combat exposure; gender; women ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; SCREEN PC-PTSD; PRIMARY-CARE; SEX-DIFFERENCES; IRAQ; AFGHANISTAN; MILITARY; SELF; PREVALENCE AB Background: This research examined gender as a moderator of the association between combat exposure (CE) and depression as well as CE and PTSD symptoms among a nonclinical sample of Soldiers following deployment in support of operations in Afghanistan and Iraq. Methods: Cases included 6,943 (516 women, 6,427 men) active duty Soldiers that were retrospectively analyzed from a pre- and post-deployment screening database at a large Army installation. Results: Gender moderated the association between CE and depressive and PTSD symptoms such that higher levels of CE were more strongly associated with depression and PTSD symptoms in women compared to men. Female Soldiers also reported higher severity of depressive symptoms compared to male Soldiers, whereas men reported higher levels of CE and a greater number of previous deployments compared to women. Conclusions: CE was a stronger predictor of post-deployment depression and PTSD symptoms for women compared to men. These results provide evidence for gender-based differences in depression and PTSD risk. Screening for degree of CE in addition to symptoms associated with depression and PTSD can help with the care for service members who are returning from deployments to combat zones. Depression and Anxiety 27:1027-1033, 2010. Published 2010 Wiley-Liss, Inc. C1 [Luxton, David D.; Skopp, Nancy A.] Natl Ctr Telehlth & Technol T2, Def Ctr Excellence DCoE Psychol Hlth & Traumat Br, Old Madigan Army Med Ctr, Tacoma, WA 98431 USA. [Maguen, Shira] San Francisco VA Med Ctr, San Francisco, CA USA. [Maguen, Shira] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Luxton, DD (reprint author), Natl Ctr Telehlth & Technol T2, Def Ctr Excellence DCoE Psychol Hlth & Traumat Br, Old Madigan Army Med Ctr, Old Madigan Army Med Ctr Bldg 9933A, Tacoma, WA 98431 USA. EM david.luxton@us.army.mil NR 39 TC 52 Z9 52 U1 2 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD NOV PY 2010 VL 27 IS 11 BP 1027 EP 1033 DI 10.1002/da.20730 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 676EI UT WOS:000283892500006 PM 20721909 ER PT J AU Bhate, K Landeck, L Gonzalez, E Neumann, K Schalock, PC AF Bhate, Ketaki Landeck, Lilla Gonzalez, Ernesto Neumann, Konrad Schalock, Peter C. TI Genital Contact Dermatitis: A Retrospective Analysis SO DERMATITIS LA English DT Article ID DERMATOSES; ALLERGY AB Background: Many topical products are used in the genital region. Allergic contact dermatitis (ACD) may develop from product use or due to treatment of an underlying dermatosis. Objectives: Our goal was to identify the frequency of ACD and identify top allergens in the genital region. Methods: Data were analyzed for 1,238 patients tested between January 1990 and December 2006. Fifteen allergens caused reactions at rates greater than 1%. Thirteen anatomic regions were assessed. Statistical analyses were by chi-square test and Fisher exact test. Adjusted level of significance due to multiple testing was alpha = .002. Results: Of individuals with genital dermatitis (n = 37; aged 24-77 years, 48.6% female), 41% (15 of 37) had at least one positive patch-test result although only 30% (11 of 37) had a final diagnosis of relevant ACD. Mean age was 46 years for males and 41 years for females. The top five allergens were balsam of Peru (10.8%), fragrance mix I (8.1%), tolu balsam (8.1%), phenylmercuric acetate (8.1%), and neomycin (5.4%). Females were more often allergic (50%) compared to males (37%); 59.5% of patients had no positive reactions. Conclusion: Genital dermatitis is rare; the minority tested positively for ACD. The top five allergens were present in toiletries and cosmetics used on genital skin. The top three allergens are fragrance related, underscoring the importance of using fragrance-free products on mucosal skin. C1 [Bhate, Ketaki] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Charite, Dept Biometry & Clin Epidemiol, D-13353 Berlin, Germany. RP Bhate, K (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 14 TC 8 Z9 8 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1710-3568 J9 DERMATITIS JI Dermatitis PD NOV-DEC PY 2010 VL 21 IS 6 BP 317 EP 320 DI 10.2310/6620.2010.10048 PG 4 WC Dermatology SC Dermatology GA 704XP UT WOS:000286089200003 PM 21144343 ER PT J AU Yeung, CK Shek, SY Chan, HHL AF Yeung, Chi K. Shek, Samantha Y. Chan, Henry H. L. TI Hair Removal with Neodymium-Doped Yttrium Aluminum Garnet Laser and Pneumatic Skin Flattening in Asians SO DERMATOLOGIC SURGERY LA English DT Article AB BACKGROUND Based on the "gate theory" of pain transmission, pneumatic skin flattening (PSF) may reduce pain during laser hair removal. OBJECTIVE To compare the pain, efficacy, and adverse effects after laser hair reduction using PSF with that using a dynamic cooling device (DCD) in Asians. METHODS Twelve participants (skin types III-IV) received laser hair removal with a PSF device on the right axilla and DCD on the other side. Pain was assessed based on a visual analogue scale. Hair regrowth was rated based on photographs taken before treatment and in follow-up visits at 8 and 36 weeks. RESULTS Sixty-seven percent of participants felt less pain in the PSF side than the DCD side right after laser treatment. On a scale of 1 to 10, the immediate mean pain score was 5.7 +/- 2.0 for the PSF side and 6.5 +/- 1.5 for the DCD side (p=.09). Seventy-five percent of the participants preferred treatments with PSF. Efficacy of hair reduction was similar on both sides 8 and 36 weeks after treatment. CONCLUSION PSF decreases pain sensation during laser hair removal while allowing higher energy densities in Asian patients. The equal efficacy and complication rate of PSF indicates that it is a feasible alternative to DCD at lower cost. Candela Corp, Wayland, Massachusetts, loaned the pneumatic skin flattening device used for this study. C1 [Yeung, Chi K.; Shek, Samantha Y.; Chan, Henry H. L.] Univ Hong Kong, Dept Med, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H. L.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Chan, HHL (reprint author), Dermatol & Laser Ctr, 13-F,Club Lusitano,16 Ice House St, Hong Kong, Hong Kong, Peoples R China. EM hhlchan@hkucc.hku.hk RI Yeung, Chi Keung/L-4795-2013; Chan, Henry Hin Lee/L-2267-2013 NR 12 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD NOV PY 2010 VL 36 IS 11 BP 1664 EP 1670 DI 10.1111/j.1524-4725.2010.01715.x PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 669BY UT WOS:000283322600004 PM 20961348 ER PT J AU Custis, T Beynet, D Carranza, D Greco, J Lask, GP Kim, J AF Custis, Trenton Beynet, David Carranza, Dafnis Greco, Joseph Lask, Gary P. Kim, Jenny TI Comparison of Treatment of Melomental Fold Rhytides with Cross-Linked Hyaluronic Acid Combined with OnabotulinumtoxinA and Cross-Linked Hyaluronic Acid Alone SO DERMATOLOGIC SURGERY LA English DT Article ID TOXIN TYPE-A AB BACKGROUND Hyaluronic acid and onabotulinumtoxinA combination therapy has been shown to have greater clinical effectiveness than hyaluronic acid alone for glabellar furrowing, but this is not well documented for melomental fold rhytides. OBJECTIVE To compare the efficacy of intradermal cross-linked hyaluronic acid (HA) and onabotulinumtoxinA combination therapy with the efficacy of cross-linked HA monotherapy in patients with melomental fold rhytides. METHODS AND MATERIALS Twenty-two patients received combination therapy to a melomental fold area while also receiving cross-linked HA and a placebo saline injection to the contralateral side. Blinded physician evaluators and patient self-evaluators clinically and photographically assessed responses during standard intervals over 12 months. RESULTS The melomental folds treated with combination therapy had significantly greater aesthetic improvement than the monotherapy-treated side at 2 weeks and 1 month upon physician photographic review. Furthermore, the median time for return to pretreatment rhytides was 6.5 weeks longer in the combination therapy side. Patient assessment also revealed improvement over baseline for the combination therapy at 1 month. CONCLUSION Cross-linked HA and onabotulinumtoxinA combination therapy to melomental fold rhytides may provide better overall aesthetic results and longer duration of aesthetic improvement than cross-linked HA monotherapy. David Beynet, Gary P. Lask and Jenny Kim are consultants for Allergan. The authors received the cross-linked HA and onabotulinumtoxinA for the study from Allergan, Inc. (Irvine, CA). This was an investigator-initiated study and no scientific input was received from Allergan Inc. C1 [Custis, Trenton; Beynet, David; Carranza, Dafnis; Greco, Joseph; Lask, Gary P.; Kim, Jenny] Univ Calif Los Angeles, Div Dermatol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Beynet, David; Kim, Jenny] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Dermatol, Los Angeles, CA USA. [Lask, Gary P.] Indianer Lask & Rosenzweig Dermatol Grp, Encino, CA USA. RP Kim, J (reprint author), Univ Calif Los Angeles, Div Dermatol, David Geffen Sch Med, 52-121 Ctr Hlth Sci,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM JeKim@mednet.ucla.edu NR 9 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD NOV PY 2010 VL 36 IS 3 SI SI BP 1852 EP 1858 DI 10.1111/j.1524-4725.2010.01741.x PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 669UZ UT WOS:000283377000010 PM 20969662 ER PT J AU Gallagher, A Madan, N Stemmer-Rachamimov, A Thiele, EA AF Gallagher, Anne Madan, Neel Stemmer-Rachamimov, Anat Thiele, Elizabeth A. TI Progressive calcified tuber in a young male with tuberous sclerosis complex SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID EPILEPSY; CT AB Tubers are the most common brain lesions in tuberous sclerosis complex (TSC), and typically remain stable in size and appearance. We present the case of a young male with global developmental impairment and autistic features as well as multiple and mixed daily seizures. The patient had a prominent right frontal cortical tuber characterized by a calcified component, which changed on consecutive magnetic resonance imaging between the age of 4 and 11 years, at which time the patient underwent a lesionectomy. A poor long-term outcome is reported since the patient presents an intractable mixed seizure disorder status post-epilepsy surgery and no significant neuropsychological improvements. Histopathology findings show typical characteristics of tubers in TSC as well as numerous calcifications within the resected nodular lesion. This case supports the notion that tubers with calcified components are not necessarily static lesions and can change with time. Investigation of the relationship between the presence of calcification in tubers and epileptogenecity in a large group of patients would provide insights into the pathogenesis of the seizures and cognitive impairment and hopefully, eventually provide better treatment options for patients with TSC. C1 [Gallagher, Anne; Thiele, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, Boston, MA 02114 USA. [Madan, Neel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuropathol Serv, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Canadian Institutes of Health Research; Carol and James Herscot Center for Tuberous Sclerosis Complex FX We are grateful to the Radiology Educational Media Services of the Massachusetts General Hospital for their help with graphic illustrations. This work was supported by scholarships from the Canadian Institutes of Health Research, awarded to Dr Anne Gallagher, as well as the Carol and James Herscot Center for Tuberous Sclerosis Complex. NR 14 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD NOV PY 2010 VL 52 IS 11 BP 1062 EP 1065 DI 10.1111/j.1469-8749.2010.03792.x PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 660ZE UT WOS:000282688800023 PM 21175459 ER PT J AU Keenan, HA Sun, JK Levine, J Doria, A Aiello, LP Eisenbarth, G Bonner-Weir, S King, GL AF Keenan, Hillary A. Sun, Jennifer K. Levine, Jared Doria, Alessandro Aiello, Lloyd P. Eisenbarth, George Bonner-Weir, Susan King, George L. TI Residual Insulin Production and Pancreatic beta-Cell Turnover After 50 Years of Diabetes: Joslin Medalist Study SO DIABETES LA English DT Article ID INCIDENCE TRENDS; TYPE-1; COMPLICATIONS; RISK; AUTOANTIBODIES; DETERMINES; WORLDWIDE; DURATION; RATHER; EUROPE AB OBJECTIVE-To evaluate the extent of pancreatic beta-cell function in a large number of insulin-dependent diabetic patients with a disease duration of 50 years or longer (Medalists). RESEARCH DESIGN AND METHODS-Characterization of clinical and biochemical parameters and beta-cell function of 411 Medalists with correlation with postmortem morphologic findings of 9 Medalists. RESULTS-The Medalist cohort, with a mean +/- SD disease duration and age of 56.2 +/- 5.8 and 67.2 +/- 7.5 years, respectively, has a clinical phenotype similar to type 1 diabetes (type 1 diabetes): mean +/- SD onset at 11.0 +/- 6.4 years, EMI at 26.0 +/- 5.1 kg/m(2), insulin dose of 0.46 +/- 0.2 u/kg, similar to 94% positive for DR3 and/or DR4, and 29.5% positive for either IA2 or glutamic acid decarboxylase (GAD) autoantibodies. Random serum C-peptide levels showed that more than 67.4% of the participants had levels in the minimal (0.03-0.2 nmol/l) or sustained range (>= 0.2 nmol/l). Parameters associated with higher random C-peptide were lower hemoglobin A1C, older age of onset, higher frequency of HLA DR3 genotype, and responsiveness to a mixed-meal tolerance test (MMTT). Over half of the Medalists with fasting C-peptide >0.17 nmol/l responded in MMTT by a twofold or greater rise over the course of the test compared to fasting. Postmortem examination of pancreases from nine Medalists showed that all had insulin+ beta-cells with some positive for TUNEL staining, indicating apoptosis. CONCLUSIONS-Demonstration of persistence and function of insulin-producing pancreatic cells suggests the possibility of a steady state of turnover in which stimuli to enhance endogenous beta cells could be a viable therapeutic approach in a significant number of patients with type 1 diabetes, even for those with chronic duration. Diabetes 59:2846-2853, 2010 C1 [Keenan, Hillary A.; Sun, Jennifer K.; Levine, Jared; Doria, Alessandro; Aiello, Lloyd P.; Bonner-Weir, Susan; King, George L.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Keenan, Hillary A.; Levine, Jared; Doria, Alessandro; Bonner-Weir, Susan; King, George L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sun, Jennifer K.; Aiello, Lloyd P.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Sun, Jennifer K.; Aiello, Lloyd P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Eisenbarth, George] Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA. RP King, GL (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM George.King@joslin.harvard.edu FU Juvenile Diabetes Research Foundation [8-2005-358, 8-2008-363, 25-2008-383]; National Institutes of Health [K12-16335, T32-DK-007260, R24-DK-083957 01, P30-DK-036836-23]; Brehm Foundation; Beatson Foundation; Eli Lilly [F3Z US X024] FX This study is supported by grants from the Juvenile Diabetes Research Foundation 8-2005-358, 8-2008-363, 25-2008-383; National Institutes of Health K12-16335, T32-DK-007260, R24-DK-083957 01, P30-DK-036836-23, Brehm Foundation, Beatson Foundation; and Eli Lilly (F3Z US X024). NR 28 TC 161 Z9 163 U1 2 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD NOV PY 2010 VL 59 IS 11 BP 2846 EP 2853 DI 10.2337/db10-0676 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 679BC UT WOS:000284133400021 PM 20699420 ER PT J AU Mori, MA Liu, M Bezy, O Almind, K Shapiro, H Kasif, S Kahn, CR AF Mori, Marcelo A. Liu, Manway Bezy, Olivier Almind, Katrine Shapiro, Hagit Kasif, Simon Kahn, C. Ronald TI A Systems Biology Approach Identifies Inflammatory Abnormalities Between Mouse Strains Prior to Development of Metabolic Disease SO DIABETES LA English DT Article ID ADIPOSE-TISSUE INFLAMMATION; DIABETES-RELATED TRAITS; INSULIN-RESISTANCE; HUMAN OBESITY; FATTY-ACIDS; T-CELLS; MICE; PATHOGENESIS; EXPRESSION; MECHANISM AB OBJECTIVE-Type 2 diabetes and obesity are increasingly affecting human populations around the world. Our goal was to identify early molecular signatures predicting genetic risk to these metabolic diseases using two strains of mice that differ greatly in disease susceptibility. RESEARCH DESIGN AND METHODS We integrated metabolic characterization, gene expression, protein-protein interaction networks, RT-PCR, and flow cytometry analyses of adipose, skeletal muscle, and liver tissue of diabetes-prone C57BL/6NTac (B6) mice and diabetes-resistant 129S6/SvEvTac (129) mice at 6 weeks and 6 months of age. RESULTS At 6 weeks of age, B6 mice were metabolically indistinguishable from 129 mice, however, adipose tissue showed a consistent gene expression signature that differentiated between the strains. In particular, immune system gene networks and inflammatory biomarkers were upregulated in adipose tissue of B6 mice, despite a low normal fat mass. This was accompanied by increased T-cell and macrophage infiltration. The expression of the same networks and biomarkers, particularly those related to T-cells, further increased in adipose tissue of B6 mice, but only minimally in 129 mice, in response to weight gain promoted by age or high-fat diet, further exacerbating the differences between strains. CONCLUSIONS Insulin resistance in mice with differential susceptibility to diabetes and metabolic syndrome is preceded by differences in the inflammatory response of adipose tissue. This phenomenon may serve as an early indicator of disease and contribute to disease susceptibility and progression. Diabetes 59:2960-2971, 2010 C1 [Mori, Marcelo A.; Bezy, Olivier; Almind, Katrine; Shapiro, Hagit; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Liu, Manway; Kasif, Simon] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu FU National Institutes of Health [DK-082659, DK-033201, DK-060837]; Joslin Diabetes and Endocrinology Research Center [DK-036836]; National Human Genome Research Institute [R01 HG003367-01A1]; National Institutes of Health, National Center for Biomedical Computing [U54 LM008748] FX M.A.M., O.B., K.A., and C.R.K. were supported by grants from the National Institutes of Health: DK-082659, DK-033201, and DK-060837 (Diabetes Genome Anatomy Project), as well as the Joslin Diabetes and Endocrinology Research Center cores (DK-036836) and the Mary K. Iacocca Professorship. The work of M.L. and S.K. was supported by grants from the National Human Genome Research Institute (R01 HG003367-01A1) and the National Institutes of Health (U54 LM008748) National Center for Biomedical Computing. NR 42 TC 36 Z9 36 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2010 VL 59 IS 11 BP 2960 EP 2971 DI 10.2337/db10-0367 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 679BC UT WOS:000284133400035 PM 20713682 ER PT J AU Nelson, KM Boyko, EJ Koepsell, T AF Nelson, Karin M. Boyko, Edward J. Koepsell, Thomas TI All-Cause Mortality Risk Among a National Sample of Individuals With Diabetes SO DIABETES CARE LA English DT Article ID CORONARY HEART-DISEASE; PHYSICAL-ACTIVITY; TIME-SCALE; FOLLOW-UP; ADULTS; HEALTH; WOMEN; PREDICTORS; MELLITUS; CHOICE AB OBJECTIVE- Little is known about the relative contributions of modifiable risk factors to overall diabetes mortality. The purpose of the current study is to 1) assess the association between modifiable risk factors and all-cause mortality among a nationally representative sample of individuals with diabetes and 2) determine the population-attributable risk percent (PAR%) for these factors. RESEARCH DESIGN AND METHODS- We analyzed data from a nationally representative sample of 1,507 adults over the age of 17 years with a self-reported diagnosis of diabetes from the Third National Health and Nutrition Examination Survey (NHANES III) mortality study. Our main outcome measures were all-cause mortality and PAR%. We used the Cox proportional hazard analysis to determine hazard ratios (HRs) for known diabetes risks and calculated PAR%. RESULTS- Among adults with diabetes, the HRs for all-cause mortality were significant for individuals who had an A1C >= 8% (HR 1.65, 95% CI 1.11-2.45) or reported no regular physical activity (1.58, 1.24-2.02) or current tobacco use (1.77, 1.15-2.73). The population-attributable risk was 15.3% for A1C value >= 8%, 16.4% for no regular physical activity, and 7.5% for current tobacco use. CONCLUSIONS- Health systems may consider prioritizing care to include smoking cessation, increasing physical activity, and moderate glycemic control among patients with diabetes. This study suggests that focusing on these areas may result in significant reductions in mortality in individuals with diabetes. C1 [Nelson, Karin M.; Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA USA. [Nelson, Karin M.; Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA USA. [Nelson, Karin M.; Boyko, Edward J.; Koepsell, Thomas] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Nelson, Karin M.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Koepsell, Thomas] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA. RP Nelson, KM (reprint author), VA Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA USA. EM karin.nelson@va.gov FU Epidemiologic Research and Information Center VA Puget Sound Health Care System, Seattle, Washington FX This study was supported by the Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle, Washington. NR 24 TC 18 Z9 18 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2010 VL 33 IS 11 BP 2360 EP 2364 DI 10.2337/dc10-0846 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683ZI UT WOS:000284516400013 PM 20739687 ER PT J AU Yang, QH Liu, TB Shrader, P Yesupriya, A Chang, MH Dowling, NF Ned, RM Dupuis, J Florez, JC Khoury, MJ Meigs, JB AF Yang, Quanhe Liu, Tiebin Shrader, Peter Yesupriya, Ajay Chang, Man-Huei Dowling, Nicole F. Ned, Renee M. Dupuis, Josee Florez, Jose C. Khoury, Muin J. Meigs, James B. CA MAGIC Investigators TI Racial/Ethnic Differences in Association of Fasting Glucose-Associated Genomic Loci With Fasting Glucose, NOMA-B, and Impaired Fasting Glucose in the US Adult Population SO DIABETES CARE LA English DT Article ID TYPE-2 DIABETES RISK; PLASMA-GLUCOSE; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; HOMEOSTASIS; VARIANTS; MTNR1B; MEN AB OBJECTIVE- To estimate allele frequencies and the marginal and combined effects of novel fasting glucose (FG)-associated single nucleotide polymorphisms (SNPs) on PG levels and on risk of impaired FG (IFG) among non-Hispanic white, non-Hispanic black, and Mexican Americans. RESEARCH DESIGN AND METHODS- DNA samples from 3,024 adult fasting participants in the National Health and Nutrition Examination Survey (NHANES) III (1991-1994) were genotyped for 16 novel FG-associated SNPs in multiple genes. We determined the allele frequencies and influence of these SNPs alone and in a weighted genetic risk score on FG, homeostasis model assessment of beta-cell function (HOMA-B), and IFG by race/ethnicity, while adjusting for age and sex. RESULTS- All allele frequencies varied significantly by race/ethnicity. A weighted genetic risk score, based on 16 SNPs, was associated with a 0.022 mmol/l (95% CI 0.009-0.035), 0.036 mmol/l (0.019-0.052), and 0.033 mmol/l (0.020-0.046) increase in FG levels per risk allele among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. Adjusted odds ratios for IFG were 1.78 for non-Hispanic whites (95% CI 1.00-3.17), 2.40 for non-Hispanic blacks (1.07-5.37), and 2.39 for Mexican Americans (1.37-4.14) when we compared the highest with the lowest quintiles of genetic risk score (P = 0.365 for testing heterogeneity of effect across race/ethnicity). CONCLUSIONS- We conclude that allele frequencies of 16 novel FG-associated SNPs vary significantly by race/ethnicity, but the influence of these SNPs on PG levels, HOMA-B, and IFG were generally consistent across all racial/ethnic groups. C1 [Yang, Quanhe; Liu, Tiebin; Yesupriya, Ajay; Chang, Man-Huei; Dowling, Nicole F.; Ned, Renee M.; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee] Harvard Univ, Massachusetts Gen Hosp,Diabet Unit, Ctr Human Genet Res & Diadetes Res Ctr,Med Sch, Program Med & Populat Genet,Broad Inst,Dept Med, Boston, MA USA. RP Yang, QH (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. EM qay0@cdc.gov RI Ned, Renee/D-3746-2009 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616, NIDDK K24 DK080140, K23 DK65978]; Massachusetts General Hospital; Doris Duke Charitable Foundation; GlaxoSmithKline FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK078616 (to J.B.M.), NIDDK K24 DK080140 (to J.B.M.), a NIDDK Research Career Award K23 DK65978 (to J.C.F.), a Massachusetts General Hospital Physician Scientist Development Award, and a Doris Duke Charitable Foundation Clinical Scientist Development Award (to J.C.F.).; J.B.M. currently has research grants from GlaxoSmithKline and serves on a consultancy board for Interleukin Genetics. No other potential conflicts of interest relevant to this article were reported. NR 25 TC 9 Z9 9 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2010 VL 33 IS 11 BP 2370 EP 2377 DI 10.2337/dc10-0898 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683ZI UT WOS:000284516400015 PM 20805255 ER PT J AU Downs, JS Arslanian, S de Bruin, WB Copeland, VC Doswell, W Herman, W Lain, K Mansfield, J Murray, PJ White, N Charron-Prochownik, D AF Downs, Julie S. Arslanian, Silva de Bruin, Waendi Bruine Copeland, Valire Carr Doswell, Willa Herman, William Lain, Kristine Mansfield, Joan Murray, Pamela J. White, Neil Charron-Prochownik, Denise TI Implications of Type 2 Diabetes on Adolescent Reproductive Health Risk An Expert Model SO DIABETES EDUCATOR LA English DT Article ID AFRICAN-AMERICAN CHILDREN; PRE-CONCEPTION CARE; PRECONCEPTION CARE; CONGENITAL-MALFORMATIONS; PREGNANCY OUTCOMES; GLYCEMIC CONTROL; EPIDEMIC; MELLITUS; WOMEN; BEHAVIORS C1 [Downs, Julie S.; de Bruin, Waendi Bruine] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Arslanian, Silva; Murray, Pamela J.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Copeland, Valire Carr; Doswell, Willa; Charron-Prochownik, Denise] Univ Pittsburgh, Pittsburgh, PA USA. [Herman, William] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Lain, Kristine] Univ Kentucky, Lexington, KY USA. [Mansfield, Joan] Harvard Univ, Sch Med, Joslin Diabet Clin Boston, Boston, MA USA. [White, Neil] Washington Univ, St Louis Childrens Hosp, St Louis, MO 63110 USA. RP Downs, JS (reprint author), Carnegie Mellon Univ, SDS PH 208, Pittsburgh, PA 15213 USA. EM downs@cmu.edu FU NIH/NICHD [R01 HD044097] FX This work was supported by grant R01 HD044097 (NIH/NICHD). The authors gratefully acknowledge the assistance of Patricia Schmitt, Mandy Holbrook, and Charlotte Fitzgerald in helping to make possible the expert panel discussion and translation of those findings into this article. NR 57 TC 7 Z9 7 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD NOV-DEC PY 2010 VL 36 IS 6 BP 911 EP 919 DI 10.1177/0145721710383586 PG 9 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 687OY UT WOS:000284789000005 PM 20944055 ER PT J AU Osborn, CY Bains, SS Egede, LE AF Osborn, Chandra Y. Bains, Sujeev S. Egede, Leonard E. TI Health Literacy, Diabetes Self-Care, and Glycemic Control in Adults with Type 2 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID SOCIAL SUPPORT; ELDERLY PERSONS; KNOWLEDGE; OUTCOMES; ASSOCIATION; MORTALITY; EDUCATION AB Background: Although limited health literacy is a barrier to disease management and has been associated with poor glycemic control, the mechanisms underlying the relationships between health literacy and diabetes outcomes are unknown. We examined the relationships between health literacy, determinants of diabetes self-care, and glycemic control in adults with type 2 diabetes. Methods: Patients with diabetes were recruited from an outpatient primary care clinic. We collected information on demographics, health literacy, diabetes knowledge, diabetes fatalism, social support, and diabetes self-care, and hemoglobin A1c values were extracted from the medical record. Structural equation models tested the predicted pathways linking health literacy to diabetes self-care and glycemic control. Results: No direct relationship was observed between health literacy and diabetes self-care or glycemic control. Health literacy had a direct effect on social support (r = -0.20, P < 0.05) and through social support had an indirect effect on diabetes self-care (r = -0.07) and on glycemic control (r = -0.01). More diabetes knowledge (r = 0.22, P < 0.05), less fatalism (r = -0.22, P < 0.05), and more social support (r = 0.27, P < 0.01) were independent, direct predictors of diabetes self-care and through self-care were related to glycemic control (r = -0.20, P < 0.05). Conclusions: Our findings suggest health literacy has an indirect effect on diabetes self-care and glycemic control through its association with social support. This suggests that for patients with limited health literacy, enhancing social support would facilitate diabetes self-care and improved glycemic control. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Bains, Sujeev S.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Osborn, Chandra Y.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Sch Med, Vanderbilt Eskind Diabet Ctr, Diabet Res & Training Ctr, Nashville, TN 37212 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK [P60 DK020593] FX C.Y.O. is supported by a Diversity Supplement Award (NIDDK P60 DK020593). NR 35 TC 37 Z9 39 U1 4 U2 18 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD NOV PY 2010 VL 12 IS 11 BP 913 EP 919 DI 10.1089/dia.2010.0058 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 682IT UT WOS:000284395500009 PM 20879964 ER PT J AU Boyko, EJ Gerstein, HC Mohan, V Yusuf, S Sheridan, P Anand, S Shaw, JE AF Boyko, E. J. Gerstein, H. C. Mohan, V. Yusuf, S. Sheridan, P. Anand, S. Shaw, J. E. CA DREAM Trial Investigators TI Effects of ethnicity on diabetes incidence and prevention: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial SO DIABETIC MEDICINE LA English DT Article DE Asian; ethnicity; Latino; prevention; rosiglitazone; thiazolidinedione ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE MODIFICATION; INSULIN-RESISTANCE; MELLITUS; RISK; AMERICANS; ATHEROSCLEROSIS; PREVALENCE; METFORMIN; WHITES AB P>Aims Risk of Type 2 diabetes varies by ethnicity, but whether ethnicity remains important among those who have impaired glucose tolerance or impaired fasting glucose is uncertain. Whether the effect of thiazolidinedione treatment on diabetes prevention in persons with non-diabetic dysglycaemia varies by ethnicity is also not known. We addressed these questions using data collected in the DREAM trial. Methods A 2-by-2 factorial double-blind randomized controlled trial to compare the effects of rosiglitazone and ramipril on the primary outcome of diabetes or death in persons meeting criteria for impaired glucose tolerance or impaired fasting glucose. The effect of these interventions by ethnicity was estimated using Cox regression analysis. Results Of 5269 adults, 2365 were randomly assigned to rosiglitzone and 2634 to placebo. South Asians showed a higher hazard for the primary outcome compared with Europeans (hazard ratio, 95% confidence interval 2.21, 1.41-3.47) adjusted for age, gender, BMI, waist-hip ratio and geographic region. A lesser increase in risk was seen in Black people (1.37, 1.04-1.81). A significant reduction in risk of the primary outcome with rosiglitazone treatment assignment was seen in all ethnic groups, but the treatment effect significantly differed by ethnicity (P = 0.0242), with South Asians experiencing a smaller, and Latinos a larger preventive effect. Conclusions Ethnicity is an important risk factor for Type 2 diabetes in dysglycaemic persons. All ethnic groups experienced a large significant reduction in diabetes risk because of rosiglitazone. The magnitude of this reduction differed by ethnicity. Given the post hoc nature of this analysis, further confirmation of these findings is needed. C1 [Boyko, E. J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Boyko, E. J.; Shaw, J. E.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Gerstein, H. C.; Yusuf, S.; Sheridan, P.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada. [Mohan, V.] Madras Diabet Res Fdn & Dr Mohans Diabet Specialt, Madras, Tamil Nadu, India. [Anand, S.] McMaster Univ, Dept Med, Hamilton, ON, Canada. RP Boyko, EJ (reprint author), 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM eboyko@u.washington.edu RI Shaw, Jonathan/E-7388-2010 OI Shaw, Jonathan/0000-0002-6187-2203 FU Canadian Institutes of Health Research [MCT41548]; Sanofi-Aventis; Glaxo SmithKline; King Pharmaceuticals FX Support was provided by grants from the Canadian Institutes of Health Research (MCT41548), Sanofi-Aventis, Glaxo SmithKline and King Pharmaceuticals. SA holds the Michael G. DeGroote and Heart and Stroke Foundation of Ontario Chair in Population Health and the May Cohen Eli Lilly Endowed Chair in Women's Health Research, McMaster University. NR 22 TC 6 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD NOV PY 2010 VL 27 IS 11 BP 1226 EP 1232 DI 10.1111/j.1464-5491.2010.03064.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 666YX UT WOS:000283160200002 PM 20950379 ER PT J AU Patti, ME Goldfine, AB AF Patti, M. E. Goldfine, A. B. TI Hypoglycaemia following gastric bypass surgery-diabetes remission in the extreme? SO DIABETOLOGIA LA English DT Editorial Material DE Clinical; Gastro-entero pancreatic factors; Human; Hypoglycaemia; Insulin secretion in vivo; Insulin sensitivity and resistance; Islet cells; Islet hormones; Metabolism; Pathophysiology ID HYPERINSULINEMIC HYPOGLYCEMIA; BARIATRIC SURGERY; ISLET HYPERPLASIA; MANAGEMENT; SECRETION; MORTALITY; THERAPY; GLUCOSE; TRIAL AB Postprandial hypoglycaemia is increasingly recognised as a complication of gastric bypass surgery. While post-bypass hypoglycaemia is often responsive to dietary modification, a subset of individuals develop life-threatening neuroglycopenia, with loss of consciousness, seizures and motor vehicle accidents. Such patients require complex nutritional and medical management strategies to reduce postprandial insulin secretion and stabilise glucose excursions, using medications including acarbose, octreotide and diazoxide, and frequent monitoring of glucose values. In an article in this issue of Diabetologia, nationwide registry data from Sweden were used to assess the frequency of severe hypoglycaemia and potentially related diagnoses (e.g. confusion, syncope, seizures, accidental death) following obesity surgery. Relative risk of hypoglycaemia and related diagnoses were two- to sevenfold higher in the post-gastric bypass population, but absolute risk was small. While these data underscore that hypoglycaemia is an important complication of gastric bypass, many questions regarding frequency, pathogenesis and optimal therapy remain unanswered. Given that hypoglycaemia is usually evaluated in the outpatient setting, more precise assessments of hypoglycaemia frequency will require prospective longitudinal studies in post-bypass cohorts. Until such data are available, practitioners should have a higher awareness of symptoms consistent with neuroglycopenia in patients with a history of bariatric surgery. Understanding the beneficial and challenging metabolic consequences of bariatric surgery is a key imperative for the diabetes community, as such data may yield novel insights into mechanisms by which bariatric surgery can lead to diabetes remission. C1 [Patti, M. E.; Goldfine, A. B.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Patti, M. E.; Goldfine, A. B.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Patti, ME (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU NIDDK NIH HHS [DK062948, RC1 DK086108, DK70648] NR 18 TC 20 Z9 21 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2010 VL 53 IS 11 BP 2276 EP 2279 DI 10.1007/s00125-010-1884-8 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656HS UT WOS:000282320400002 PM 20730413 ER PT J AU Cotsapas, C Prokunina-Olsson, L Welch, C Saxena, R Weaver, C Usher, N Guiducci, C Bonakdar, S Turner, N LaCroix, B Hall, JL AF Cotsapas, C. Prokunina-Olsson, L. Welch, C. Saxena, R. Weaver, C. Usher, N. Guiducci, C. Bonakdar, S. Turner, N. LaCroix, B. Hall, J. L. TI Expression analysis of loci associated with type 2 diabetes in human tissues SO DIABETOLOGIA LA English DT Article DE Colon; eQTL; HHEX; IDE; Liver; mRNA; Pancreas; SLC30A8; SNP; Type 2 diabetes ID GENOMICS; TCF7L2 AB Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetes-associated regions in three relevant human tissues. We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n = 50), colon (n = 195) and liver (n = 50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling. Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver. This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined. C1 [Welch, C.; Weaver, C.; Usher, N.; Turner, N.; LaCroix, B.; Hall, J. L.] Lillehei Heart Inst, Dept Med, Minneapolis, MN 55455 USA. [Cotsapas, C.; Saxena, R.; Guiducci, C.; Bonakdar, S.] Broad Inst, Cambridge, MA USA. [Prokunina-Olsson, L.] NIH, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Cotsapas, C.; Saxena, R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hall, J. L.] Univ Minnesota, Ctr Dev Biol, Minneapolis, MN USA. [Cotsapas, C.; Saxena, R.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Hall, JL (reprint author), Lillehei Heart Inst, Dept Med, 4-280 NHH,312 Church St SE, Minneapolis, MN 55455 USA. EM jlhall@umn.edu OI Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Cotsapas, Chris/0000-0002-7772-5910 FU NCI/NIH; NIH [1R21DK078029-01] FX We are grateful to S. Schmechel and S. Bowell for help with procurement of tissues from the University of Minnesota Tissue Procurement Facility. We would also like to thank M. Carlson for help in preparing samples for the analysis. The study was supported by an intramural research programme of NCI/NIH and by NIH grant 1R21DK078029-01 (to J. L. Hall). NR 10 TC 12 Z9 12 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2010 VL 53 IS 11 BP 2334 EP 2339 DI 10.1007/s00125-010-1861-2 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656HS UT WOS:000282320400011 PM 20703447 ER PT J AU Akiba, Y Kaunitz, JD AF Akiba, Yasutada Kaunitz, Jonathan D. TI Lafutidine, a Protective H(2) Receptor Antagonist, Enhances Mucosal Defense in Rat Esophagus SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Esophageal blood flow; Interstitial pH; Capsaicin-sensitive afferent nerves; Pepsin; Interstitial acidification ID SENSITIVE AFFERENT NEURONS; CARBONIC-ANHYDRASES; REFLUX ESOPHAGITIS; ACID INJURY; BLOOD-FLOW; LOW PH; DUODENUM; MEDIATE; PEPSIN; NERVES AB Luminal acid or CO(2) induces a hyperemic response in the esophagus, via activation of acid sensors on capsaicin-sensitive afferent nerves (CSAN). Since disruption of the hyperemic response to luminal CO(2) acidifies the interstitium of the esophageal mucosa, the hyperemic response may maintain interstitial pH (pH(int)). We hypothesized that acid-related hyperemia maintains pH(int), preventing acid-induced injury in the esophageal mucosa. We examined the effects of capsaicin (Cap) or lafutidine (Laf), a mucosal protective H(2) antagonist, on the regulation of pH(int) and blood flow in rat esophagus using ratiometric microimaging and laser-Doppler measurements of the lower esophageal mucosa of living rats. The esophagus was topically superfused with pH 7.0 buffer, or a pH 1.0 or pH 1.0 + pepsin (1 mg/ml) solution with or without Laf. Cap (30 or 100 A mu M) or Laf (0.1 or 1 mM) dose-dependently increased blood flow, accompanied by increased pH(int). The pH 1.0 solution increased blood flow without pH(int) change, whereas Laf (1 mM) increased blood flow and pH(int) during acid exposure. The effects of Laf were abolished by ablation of CSAN. Perfusion of the acidified pepsin solution gradually decreased pH(int), inhibited by Laf perfusion. Activation of CSAN by Laf with or without acid, accompanied by hyperemia, increased pH(int), preventing acidified pepsin-induced interstitial acidification. Stimulation of the capsaicin pathway with compounds such as Laf enhances mucosal protection from acid-related injury in the upper gastrointestinal tract. C1 [Akiba, Yasutada; Kaunitz, Jonathan D.] W Los Angeles Vet Affairs Med Ctr, Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Brentwood Biomed Res Inst, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU Taiho Pharmaceutical Co.; NIH-NIDDK [R01 DK54221]; Veterans Affairs FX We thank Coleen Palileo for her assistance with manuscript preparation. This work was supported by a research grant from Taiho Pharmaceutical Co., Veterans Affairs Merit Review Award, and NIH-NIDDK R01 DK54221 (J. Kaunitz). NR 25 TC 7 Z9 7 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 NOV PY 2010 VL 55 IS 11 BP 3063 EP 3069 DI 10.1007/s10620-010-1379-y PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 668VP UT WOS:000283300400009 PM 20824506 ER PT J AU Richardson, P Henderson, L Davila, JA Kramer, JR Fitton, CP Chen, GJ El-Serag, HB AF Richardson, Peter Henderson, Louise Davila, Jessica A. Kramer, Jennifer R. Fitton, Conar P. Chen, G. John El-Serag, Hashem B. TI Surveillance for Hepatocellular Carcinoma: Development and Validation of an Algorithm to Classify Tests in Administrative and Laboratory Data SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Algorithm; Liver cancer; Cirrhosis; Screening; Ultrasound; Alpha fetoprotein; VA ID MANAGEMENT; STAGE AB The purpose of alpha-fetoprotein (AFP) and abdominal ultrasound (US) cannot be discerned in administrative data. We developed an algorithm to identify AFP and US used as surveillance tests for hepatocellular carcinoma (HCC). We evaluated 300 AFP and 301 US tests from a VA database. Surveillance predictors in the administrative files (diagnoses, labs) were examined in logistic regression models. We calculated model-based probabilities of HCC surveillance status, and developed classification procedures using single and multiple imputation methods. The predictors of surveillance intent for AFP were absence of alcoholism, abdominal pain, ascites, diabetes and high AST levels. For US, the predictors of surveillance were prior AFP testing and HIV status and absence of abdominal pain, ascites, or drug dependence. For AFP classification, single imputation compared favorably with multiple imputation, both showing robustness in discrimination and calibration. For US both approaches were less robust in discrimination and calibration which was more moderate in multiple imputation than single imputation. Predictive algorithms in administrative files can be used to identify AFP performed for HCC surveillance, however, the intent of US is more difficult to identify. C1 [El-Serag, Hashem B.] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Richardson, Peter; Davila, Jessica A.; Kramer, Jennifer R.; Fitton, Conar P.; Chen, G. John; El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Richardson, Peter; Davila, Jessica A.; Kramer, Jennifer R.; Fitton, Conar P.; Chen, G. John; El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA. [El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Henderson, Louise] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. RP El-Serag, HB (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU Houston VA HSR&D Center of Excellence [HFP90-020]; National Cancer Institute [R01-CA-125487] FX Financial support: This work was supported in part by the Houston VA HSR&D Center of Excellence (HFP90-020) and the National Cancer Institute (R01-CA-125487). NR 13 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2010 VL 55 IS 11 BP 3241 EP 3251 DI 10.1007/s10620-010-1387-y PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 668VP UT WOS:000283300400033 PM 20844957 ER PT J AU Gorgun, G Hideshima, T Anderson, KC AF Goerguen, G. Hideshima, T. Anderson, K. C. TI MLN-8237 SO DRUGS OF THE FUTURE LA English DT Article DE Aurora Kinase A Inhibitor; Oncolytic ID AURORA-A KINASE; MITOTIC SPINDLE; CENTROSOME AMPLIFICATION; COLORECTAL CANCERS; MULTIPLE-MYELOMA; PROTEIN-KINASE; HUMAN OVARIAN; CELLS; OVEREXPRESSION; PHOSPHORYLATION AB Aurora serine/threonine-protein kinases localize in the centrosome and play a crucial role in cell division by regulating chromatid segregation in mitotic cells; moreover, defective chromatid segregation causes genetic instability, leading to tumorigenesis. Aurora kinases were first identified in Xenopus Eg2, yeast lpl1 and Drosophila aurora. The human genome expresses three members of the mitotic Aurora kinase family: Aurora kinase A, B and C. Although Aurora kinase A and 13 are highly homologous, their localization and function differ during mitosis. Aurora kinase A and B have been extensively studied due to their overexpression in tumor cells. Since high AURKA gene expression has been correlated with centrosome amplification and Aurora kinase A is required for cytokinesis, defective Aurora kinase A may cause aneuploidy characteristic of tumors. Thus, inhibition of Aurora kinase A may prove to be therapeutically beneficial, and several inhibitors of Aurora kinase A ore being tested in early-phase clinical trials. MLN-8237, a selective inhibitor of Aurora kinase A, is currently in phase I/II clinical trials in both adult and childhood solid tumors and hematological malignancies. Here we review the biology of Aurora kinase A and the role of MLN-8237 as a novel therapeutic agent for cancer. C1 [Goerguen, G.; Hideshima, T.; Anderson, K. C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Gorgun, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M557, Boston, MA 02115 USA. EM gullu_gorgun@dfci.harvard.edu NR 65 TC 2 Z9 2 U1 0 U2 2 PU PROUS SCIENCE, SA-THOMSON REUTERS PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD NOV PY 2010 VL 35 IS 11 BP 903 EP 908 DI 10.1358/dof.2010.35.11.1529824 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 754QS UT WOS:000289872300003 ER PT J AU Ganda, OP Fonseca, VA AF Ganda, Om P. Fonseca, Vivian A. TI SALT SENSITIVITY, INSULIN RESISTANCE, AND PUBLIC HEALTH IN INDIA SO ENDOCRINE PRACTICE LA English DT Article ID METABOLIC SYNDROME; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; DEVELOPING-COUNTRIES; ASIAN INDIANS; SODIUM-INTAKE; RISK-FACTORS; HYPERTENSION; POPULATION; PREVALENCE AB Objective: To provide a current overview of the worldwide prevalence and pattern of cardiovascular disease and discuss the role of sodium intake and salt sensitivity, with a focus on the Asian Indian population. Methods: An extensive search of the literature from PubMed and the Cochrane Library was undertaken. Moreover, the pathophysiologic basis of the relationship between sodium intake and insulin sensitivity in various populations was reviewed. Results: High blood pressure is the most common cause of cardiovascular disease and mortality globally. Although salt sensitivity is a frequent determinant of hypertension, a strong link between salt sensitivity and cardiovascular disease associated with insulin resistance has not received adequate attention. This may be particularly relevant to the public health challenges of increasing prevalences of obesity, diabetes, and cardiometabolic syndrome in India where, according to recent estimates, approximately 60% of the world's cases of cardiovascular disease occur and the salt consumption is among the highest in any large population. Conclusion: There is evidence for a strong link between increased salt sensitivity and insulin resistance leading to metabolic syndrome and cardiovascular disease. This relationship may be particularly relevant to the escalating epidemic of cardiovascular disease in the southern Asian Indian population. A broad-based community action to achieve at least a modest restriction of salt intake can yield important health benefits and is urgently needed. (Endocr Pract. 2010;16:940-944) C1 [Ganda, Om P.] Beth Israel Deaconess Med Ctr, Dept Med, Sect Clin Res, Joslin Diabet Ctr, Boston, MA 02215 USA. [Ganda, Om P.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Fonseca, Vivian A.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. RP Ganda, OP (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Sect Clin Res, Joslin Diabet Ctr, Boston, MA 02215 USA. EM om.ganda@joslin.harvard.edu FU National Institutes of Health [DK 36836] FX This work was supported in part by the National Institutes of Health grant DK 36836. NR 35 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CLIN ENDOCRINOL PI JACKSONVILLE PA 1000 RIVERSIDE AVE, STE 205, JACKSONVILLE, FL 32204 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD NOV-DEC PY 2010 VL 16 IS 6 BP 940 EP 944 DI 10.4158/EP10103.OR PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 704BI UT WOS:000286025700003 PM 20439237 ER PT J AU Shi, J Mehta, AJ Hang, JQ Zhang, HX Dai, HL Su, L Eisen, EA Christiani, DC AF Shi, Jing Mehta, Amar J. Hang, Jing-qing Zhang, Hongxi Dai, Helian Su, Li Eisen, Ellen A. Christiani, David C. TI Chronic Lung Function Decline in Cotton Textile Workers: Roles of Historical and Recent Exposures to Endotoxin SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE byssinosis; China; chronic obstructive lung disease; cotton textile workers; occupational health; organic dusts; pulmonary function ID PULMONARY-FUNCTION; RESPIRATORY SYMPTOMS; RESPONSE RELATIONSHIPS; BACTERIAL-ENDOTOXIN; DUST; EPIDEMIOLOGY; VARIABILITY; INDUSTRY; DISEASE; DESIGN AB BACKGROUND: Long-term occupational exposure to cotton dust that contains endotoxin is associated with chronic respiratory symptoms and excessive decline in forced expiratory volume in 1 sec (FEV(1)), but the mechanisms of endotoxin-related chronic airflow obstruction remain unclear. OBJECTIVE: In the current study, we examined temporal aspects of the exposure-response relationship between airborne endotoxin exposure, longitudinal change in FEV(1), and respiratory symptoms in a cohort of Chinese cotton textile workers. METHODS: This prospective cohort study followed 447 cotton textile workers from 1981 to 2006. at approximately 5-year intervals. We used a generalized estimating equations approach to model FEV(1) level and respiratory symptoms as a function of past exposure (cumulative exposure up to the start of the most recent 5-year survey interval) and cumulative exposure (within the most recent interval) to endotoxins, after adjusting for other covariates. Models were stratified by active versus retired work status and by years employed before the baseline survey (< 5 and >= 5 years). RESULTS AND CONCLUSIONS: Past exposure to endotoxin was associated with reduced FEV(1) level among retired cotton workers. Among all cotton workers, past exposure was more strongly associated with reduced FEV(1) for those hired < 5 years before baseline than for those who were hired >= 5 years after baseline. Recent endotoxin exposure was significantly associated with byssinosis, chronic bronchitis, and chronic cough. C1 [Shi, Jing; Mehta, Amar J.; Su, Li; Eisen, Ellen A.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Shi, Jing] China Inst Ind Relat, Dept Safety Engn, Beijing, Peoples R China. [Hang, Jing-qing; Zhang, Hongxi; Dai, Helian] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Eisen, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave,Bldg 1-1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institute for Occupational Safety and Health [R01-OH02421]; National Institute of Environmental Health Sciences, National Institutes of Health [ES-00002] FX This study was supported by grants from the National Institute for Occupational Safety and Health (R01-OH02421) and from the National Institute of Environmental Health Sciences, National Institutes of Health (ES-00002). NR 43 TC 23 Z9 23 U1 0 U2 3 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 NOV PY 2010 VL 118 IS 11 BP 1620 EP 1624 DI 10.1289/ehp.0901178 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 674CR UT WOS:000283711800036 PM 20797932 ER PT J AU Wirth, KE Tchetgen, EJT Murray, M AF Wirth, Kathleen E. Tchetgen, Eric J. Tchetgen Murray, Megan TI Adjustment for Missing Data in Complex Surveys Using Doubly Robust Estimation Application to Commercial Sexual Contact Among Indian Men SO EPIDEMIOLOGY LA English DT Article ID HIV-INFECTION; LOGISTIC-REGRESSION; RISK-FACTORS; WORKERS; BEHAVIOR; VIOLENCE; MODELS; SPREAD; TRIAL AB Background: The Demographic and Health Survey program routinely collects nationally representative information on HIV-related risk behaviors in many countries, using face-to-face interviews and a complex sampling scheme. If respondents skip questions about behaviors perceived as socially undesirable, such interviews may introduce bias. We sought to implement a doubly robust estimator to correct for dependent missing data in this context. Methods: We applied 3 methods of adjustment for nonresponse on self-reported commercial sexual contact data from the 2005-2006 India Demographic Health Survey to estimate the prevalence of sexual contact between sexually active men and female sex workers. These methods were inverse-probability weighted regression, outcome regression, and doubly robust estimation-a recently-described approach that is more robust to model misspecification. Results: Compared with an unadjusted prevalence of 0.9% for commercial sexual contact prevalence (95% confidence interval = 0.8%-1.0%), adjustment for nonresponse using doubly robust estimation yielded a prevalence of 1.1% (1.0%-1.2%). We found similar estimates with adjustment by outcome regression and inverse-probability weighting. Marital status was strongly associated with item nonresponse, and correction for nonresponse led to a nearly 80% increase in the prevalence of commercial sexual contact among unmarried men (from 6.9% to 12.1%-12.4%). Conclusions: Failure to correct for nonresponse produced a bias in self-reported commercial sexual contact. To facilitate the application of these methods (including the doubly robust estimator) to complex survey data settings, we provide analytical variance estimators and the corresponding SAS and MATLAB code. These variance estimators remain valid regardless of whether the modeling assumptions are correct. C1 [Wirth, Kathleen E.; Tchetgen, Eric J. Tchetgen; Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tchetgen, Eric J. Tchetgen] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Murray, Megan] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Murray, Megan] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Wirth, KE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 641 Huntington Ave, Boston, MA 02115 USA. EM kwirth@hsph.harvard.edu FU US National Institutes of Health [AI 007433] FX Supported by the US National Institutes of Health (AI 007433). NR 30 TC 3 Z9 3 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2010 VL 21 IS 6 BP 863 EP 871 DI 10.1097/EDE.0b013e3181f57571 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 659XL UT WOS:000282600600018 PM 20881599 ER PT J AU Vendrame, M Maski, KP Chatterjee, M Heshmati, A Krishnamoorthy, K Tan, WH Kothare, SV AF Vendrame, Martina Maski, Kiran P. Chatterjee, Madhumouli Heshmati, Arezou Krishnamoorthy, Kalpathy Tan, Wen-Hann Kothare, Sanjeev V. TI Epilepsy in Prader-Willi syndrome: Clinical characteristics and correlation to genotype SO EPILEPSY & BEHAVIOR LA English DT Article DE Imprinting; UBE3A; CHRNA7; Uniparental disomy; Febrile seizures; Epilepsy; Prader-Willi syndrome ID MATERNAL UNIPARENTAL DISOMY; DIAGNOSTIC-CRITERIA; ANGELMAN-SYNDROME; INFANTILE SPASMS; BEUREN-SYNDROME; DELETION; MECHANISMS; PHENOTYPE; PREVALENCE; CONSENSUS AB Prader-Willi syndrome (PWS) is a genomic imprinting disease secondary to the loss of a functional paternal copy of 15q11-q13. Unlike its related imprinting disorder, Angelman syndrome, PWS has not been regarded as a risk factor for epilepsy. A retrospective analysis of 92 patients with PWS identified 24 (26%) with seizures. Twenty-two of these (92%) were affected by focal epilepsy and only two (8%) had generalized epilepsy. The most common seizure type was staring spells (67%). Correlation to genotype analysis showed deletions were more common in patients with epilepsy than in patients without epilepsy. The epilepsy syndromes were easy to control with a single antiepileptic drug in most cases. Three patients (11%) had had febrile seizures. These findings suggest that PWS may be a risk factor for epilepsy, which can manifest with focal features. Patients with PWS with a deletion genotype showed a trend toward developing seizures compared with patients with other genotypes in our series, even though this difference did not achieve statistical significance. (C) 2010 Elsevier Inc. All rights reserved. C1 [Kothare, Sanjeev V.] Childrens Hosp, Dept Neurol, Div Epilepsy & Clin Neurophysiol, Boston, MA 02115 USA. [Heshmati, Arezou; Krishnamoorthy, Kalpathy] Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA. [Tan, Wen-Hann] Childrens Hosp, Div Genet, Boston, MA 02115 USA. RP Kothare, SV (reprint author), Childrens Hosp, Dept Neurol, Div Epilepsy & Clin Neurophysiol, FE9,300 Longwood Ave, Boston, MA 02115 USA. EM Sanjeev.kothare@childrens.harvard.edu OI Kothare, Sanjeev/0000-0001-7849-6649 NR 37 TC 10 Z9 10 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2010 VL 19 IS 3 BP 306 EP 310 DI 10.1016/j.yebeh.2010.07.007 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 696OV UT WOS:000285451600018 PM 20727826 ER PT J AU Goto, S Ogawa, H Takeuchi, M Flather, MD Bhatt, DL AF Goto, Shinya Ogawa, Hisao Takeuchi, Masaru Flather, Marcus D. Bhatt, Deepak L. CA J LANCELOT Investigators TI Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease SO EUROPEAN HEART JOURNAL LA English DT Article DE E5555; Atherothrombosis; Thrombin; PAR-1; Acute coronary syndrome; Coronary artery disease ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; VASCULAR-DISEASE; EVENT RATES; ATHEROTHROMBOSIS; CLOPIDOGREL; ASPIRIN; OUTPATIENTS; PREVALENCE; PLATELETS AB Two multicentre, randomized, double-blind, placebo-controlled Phase II studies assessed the safety and efficacy of the oral protease-activated receptor 1 (PAR-1) antagonist E5555 in addition to standard therapy in Japanese patients with acute coronary syndrome (ACS) or high-risk coronary artery disease (CAD). Patients with ACS (n = 241) or high-risk CAD (n = 263) received E5555 (50, 100, or 200 mg) or placebo once daily for 12 (ACS patients) or 24 weeks (CAD patients). The incidence of TIMI major, minor, and minimal bleeds requiring medical attention was similar in the placebo and combined E5555 (atopaxar) groups (ACS: 6.6% placebo vs. 5.0% E5555; CAD: 1.5% placebo vs. 1.5% E5555). There were no TIMI major bleeds and three CURE major bleeds (two with placebo; one with 100 mg E5555). There was a numerical increase in 'any' TIMI bleeding with the E5555 200 mg dose (ACS: 16.4% placebo vs. 23.0% E5555, P = 0.398; CAD: 4.5% placebo vs. 13.2% E5555, P = 0.081). The rate of major cardiovascular adverse events in the combined E5555 group was not different from placebo (ACS: 6.6% placebo vs. 5.0% E5555, P = 0.73; CAD: 4.5% placebo vs. 1.0% E5555, P = 0.066). There was a statistically significant dose-dependent increase in liver function abnormalities and QTcF with E5555. At trough dosing levels in both populations, mean inhibition of platelet aggregation was > 90% with 100 and 200 mg E5555, and 20-60% with 50 mg E5555. E5555 (50, 100, and 200 mg) did not increase clinically significant bleeding, although there was a higher rate of any TIMI bleeding with the highest two doses. All doses tested achieved a significant level of platelet inhibition. There was a significant dose-dependent increase in liver function abnormalities and QTcF. Although further study is needed, PAR-1 antagonism may have the potential to be a novel pathway for platelet inhibition to add on to the current standard of care therapy. C1 [Goto, Shinya] Tokai Univ, Sch Med, Dept Med Cardiol, Kanagawa 2591143, Japan. [Ogawa, Hisao] Kumamoto Univ, Sch Med, Kumamoto 860, Japan. [Takeuchi, Masaru] Eisai & Co Ltd, Frontier Prod Creat Unit, Bunkyo Ku, Tokyo, Japan. [Flather, Marcus D.] Royal Brompton & Harefield NHS Fdn Trust, London, England. [Flather, Marcus D.] Univ London Imperial Coll Sci Technol & Med, London, England. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Goto, S (reprint author), Tokai Univ, Sch Med, Dept Med Cardiol, 143 Shimokasuya, Kanagawa 2591143, Japan. EM shinichi@is.icc.u-tokai.ac.jp FU Eisai; Eisai Co., Ltd, in Japan; Eisai Product Creation Systems; Astra Zeneca; Bristol-Myers Squibb; Ethicon; Heartscape; Sanofi-aventis; The Medicines Company; Pfizer; Ono; Otsuka; Sankyo; Daiichi; Takeda; Asteras; Kowa; Ministry of Health, Labour and Welfare (Japan); Astellas; Banyu; Bayer Yakuhin; Boehringer Ingelheim; Chugai; Daiichi Sankyo; Dainippon Sumitomo; Get Bros; Guidant Japan; Japan Lifeline; Kyowa Hakko Kirin; Mitsubishi Tanabe; Mochida; Nihon Kohden; Nihon Schering; Novartis; Pharmacia; Sanwa Kagaku Kenkyusho; Schering-Plough; Sionogi; Sumitomo; Tanabe; Teijin; Toa Eiyo; Japan Heart Foundation; Smoking Research Foundation; Eli Lilly FX We thank the CEC members (Dr Shunichi Miyazaki, Kinki University in Osaka, Dr Hiroyuki Daida, Juntendo University in Tokyo, Dr Kazuo Kimura, Yokohama City University in Kanagawa, and Dr Takeshi Kimura, Kyoto University in Kyoto). We also thank Hideaki Miyagishi who is an employee of Eisai Co., Ltd, for performing the statistical analyses and all of the investigators who participated in both clinical studies (Appendix 2). This manuscript was prepared with editorial support from Heather Sharrock and Ian Marshall of Choice Pharma Ltd, UK. Choice Pharma received payments for this work from Eisai. The first draft of the manuscript was written by the authors and agreed upon by all authors prior to submission.; J-LANCELOT studies were sponsored by Eisai Co., Ltd, in Japan. Funding to pay the Open Access publication charges for this article was provided by Eisai Product Creation Systems.; D.L.B. receives research grants from Astra Zeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, sanofi-aventis, and The Medicines Company. S.G. received research grants from Pfizer, sanofi-aventis, Ono, Eisai, Otsuka, Sankyo, Daiichi, Takeda, Asteras, Kowa, and Astra Zeneca. S.G. received honoraria from sanofi-aventis, Eisai, Otsuka, Daiichi Sankyo, and Schering-Plough. H.O. has received grant support for the past 5 years from the Ministry of Health, Labour and Welfare (Japan), and grant support and lecturer's fees from Astellas, Astra Zeneca, Banyu, Bayer Yakuhin, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Get Bros, Guidant Japan, Japan Lifeline, Kowa, Kyowa Hakko Kirin, Mitsubishi Tanabe, Mochida, Nihon Kohden, Nihon Schering, Novartis, Otsuka, Pfizer, Pharmacia, Sankyo, sanofi-aventis, Sanwa Kagaku Kenkyusho, Schering-Plough, Sionogi, Sumitomo, Takeda, Tanabe, Teijin, Toa Eiyo, Japan Heart Foundation, and Smoking Research Foundation over the past 5 years. M.D.F. has received honorarium payments from Eisai for attending meetings and has received research grants and honoraria for attending meetings from sanofi-aventis, Bristol-Myers Squibb, Novartis, and Eli Lilly. NR 30 TC 91 Z9 99 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 NOV PY 2010 VL 31 IS 21 BP 2601 EP 2613 DI 10.1093/eurheartj/ehq320 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 676QA UT WOS:000283926500013 PM 20805115 ER PT J AU Kumbhani, DJ Bhatt, DL AF Kumbhani, Dharam J. Bhatt, Deepak L. TI Platelet activation: yet another strike against routine TRANSFUSION SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; BLOOD-TRANSFUSION; CRITICALLY-ILL; ANEMIA C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, 75 Francis St, Boston, MA 02115 USA. EM DLBHATTMD@POST.HARVARD.EDU NR 18 TC 6 Z9 6 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 NOV PY 2010 VL 31 IS 22 BP 2712 EP 2714 DI 10.1093/eurheartj/ehq268 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 683FK UT WOS:000284456900007 PM 20736242 ER PT J AU Hiemenz, JW Raad, II Maertens, JA Hachem, RY Saah, AJ Sable, CA Chodakewitz, JA Severino, ME Saddier, P Berman, RS Ryan, DM DiNubile, MJ Patterson, TF Denning, DW Walsh, TJ AF Hiemenz, J. W. Raad, I. I. Maertens, J. A. Hachem, R. Y. Saah, A. J. Sable, C. A. Chodakewitz, J. A. Severino, M. E. Saddier, P. Berman, R. S. Ryan, D. M. DiNubile, M. J. Patterson, T. F. Denning, D. W. Walsh, T. J. TI Efficacy of caspofungin as salvage therapy for invasive aspergillosis compared to standard therapy in a historical cohort SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; LIVER-TRANSPLANT RECIPIENTS; ALTERNATIVE TRIAL DESIGNS; STEM-CELL TRANSPLANTATION; FUNGAL-INFECTIONS; HEMATOLOGIC MALIGNANCIES; PULMONARY ASPERGILLOSIS; COLLOIDAL DISPERSION; ANTIFUNGAL THERAPY; PROGNOSTIC-FACTORS AB In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of a parts per thousand yen1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy. C1 [Hiemenz, J. W.] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL 32610 USA. [Raad, I. I.; Hachem, R. Y.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Maertens, J. A.] Univ Hosp Gasthuisberg, Leuven, Belgium. [Saah, A. J.; Sable, C. A.; Chodakewitz, J. A.; Severino, M. E.; Saddier, P.; Berman, R. S.; Ryan, D. M.; DiNubile, M. J.] Merck Res Labs, West Point, PA USA. [Patterson, T. F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Patterson, T. F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Denning, D. W.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Walsh, T. J.] NCI, Bethesda, MD 20892 USA. RP Hiemenz, JW (reprint author), Univ Florida, Coll Med, Div Hematol Oncol, POB 100278, Gainesville, FL 32610 USA. EM john.hiemenz@medicine.ufl.edu OI Denning, David/0000-0001-5626-2251 FU Merck Co., Inc. FX Merck & Co., Inc., which markets caspofungin under the brand name Cancidas, sponsored and funded this study. Current and former employees of the sponsor (indicated on the title page) may own stock or stock options in the company. All non-Merck authors have served as investigators on Merck studies. The sponsor formally reviewed a penultimate draft. All co-authors approved an essentially final version of the manuscript. NR 45 TC 13 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD NOV PY 2010 VL 29 IS 11 BP 1387 EP 1394 DI 10.1007/s10096-010-1013-0 PG 8 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 671LL UT WOS:000283507500009 PM 20703506 ER PT J AU Juillerat, P Pittet, V Vader, JP Burnand, B Gonvers, JJ de Saussure, P Mottet, C Seibold, F Rogler, G Sagmeister, M Felley, C Michetti, P Froehlich, F AF Juillerat, Pascal Pittet, Valerie Vader, John-Paul Burnand, Bernard Gonvers, Jean-Jacques de Saussure, Philippe Mottet, Christian Seibold, Frank Rogler, Gerhard Sagmeister, Markus Felley, Christian Michetti, Pierre Froehlich, Florian CA Swiss IBD Cohort Study Grp TI Infliximab for Crohn's disease in the Swiss IBD Cohort Study: clinical management and appropriateness SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE antitumor necrosis factor alpha; appropriateness; Cohort Study; Crohn's disease; inflammatory bowel disease; infliximab; therapy; treatment ID UPPER GASTROINTESTINAL ENDOSCOPY; INFLAMMATORY-BOWEL-DISEASE; QUALITY-OF-CARE; CRITERIA; UNDERUSE; THERAPY; OVERUSE AB Objective Antitumor necrosis factor a agents have significantly improved the management of Crohn's disease (CD), but not all patients benefit from this therapy. We used data from the Swiss Inflammatory Bowel Disease Cohort Study and predefined appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients. Methods EPACT II (European Panel on the Appropriateness of CD Therapy, 2007; www.epact.ch) appropriateness criteria have been developed using a formal explicit panel process combining evidence from the published literature and expert opinion. Questionnaires relating to EPACT II criteria were used at enrollment and follow-up of all Swiss Inflammatory Bowel Disease Cohort Study patients. A step-by-step analysis of all possible indications for IFX therapy in a given patient allowed identification of the most appropriate indication and final classification in a single appropriateness category (appropriate, uncertain, inappropriate). Results Eight hundred and twenty-one CD patients were prospectively enrolled between November 2006 and March 2009. IFX was administered to 146 patients (18%) at enrollment and was most frequently used for complex fistulizing disease and for the maintenance of remission induced by biological therapy. IFX therapy was considered appropriate in 44%, uncertain in 44%, and inappropriate in 10% of patients. Conclusion In this cohort, 9 out of 10 indications for IFX therapy were clinically generally acceptable (appropriate or uncertain) according to EPACT II criteria. Uncertain indications resulted mainly from the current more liberal use of IFX in clinical practice as compared with the EPACT II criteria. Eur J Gastroenterol Hepatol 22:1352-1357 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Juillerat, Pascal; Gonvers, Jean-Jacques; Mottet, Christian; Felley, Christian; Michetti, Pierre; Froehlich, Florian] CHU Vaudois, Dept Gastroenterol & Hepatol, Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland. [Juillerat, Pascal; Pittet, Valerie; Vader, John-Paul; Burnand, Bernard] CHU Vaudois, Healthcare Evaluat Unit, Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland. [Juillerat, Pascal; Pittet, Valerie; Vader, John-Paul; Burnand, Bernard] Univ Lausanne, Lausanne, Switzerland. [de Saussure, Philippe] Univ Hosp Geneva, Dept Gastroenterol & Hepatol, Geneva, Switzerland. [Seibold, Frank] Tiefenau Hosp, Dept Gastroenterol, Bern, Switzerland. [Rogler, Gerhard] Univ Zurich Hosp, Div Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland. [Sagmeister, Markus] Kantonsspital St Gallen, Div Gastroenterol, St Gallen, Switzerland. [Froehlich, Florian] Univ Basel, Dept Gastroenterol & Hepatol, Basel, Switzerland. RP Juillerat, P (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM pjuillerat@partners.org RI Schappi Tempia-Caliera, Michela/A-7619-2012; Schappi, Michela/D-5363-2012; Rogler, Gerhard/O-5308-2015 OI Schappi Tempia-Caliera, Michela/0000-0002-9860-7294; Rogler, Gerhard/0000-0002-1733-9188 FU Swiss National Science Foundation [3347CO-108792/1, PBLAP3-124341] FX The authors gratefully acknowledge the contribution of all the gastroenterologists and investigators who are listed in the Appendix, and Susan Giddons for editorial assistance. This study was supported by the Swiss National Science Foundation, Grant numbers 3347CO-108792/1 and PBLAP3-124341. There was no conflict of interest to declare. NR 24 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD NOV PY 2010 VL 22 IS 11 BP 1352 EP 1357 DI 10.1097/MEG.0b013e32833eaa8a PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 664TE UT WOS:000282984600012 PM 20964261 ER PT J AU Ponikowski, P Mitrovic, V O'Connor, CM Dittrich, H Cotter, G Massie, BM Givertz, MM Chen, E Murray, M Weatherley, BD Fujita, KP Metra, M AF Ponikowski, Piotr Mitrovic, Veselin O'Connor, Christopher M. Dittrich, Howard Cotter, Gad Massie, Barry M. Givertz, Michael M. Chen, Erluo Murray, Meredith Weatherley, Beth D. Fujita, Kenji P. Metra, Marco TI Haemodynamic effects of rolofylline in the treatment of patients with heart failure and impaired renal function SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Haemodynamic effects; Heart failure; Renal failure ID A(1) RECEPTOR ANTAGONIST; SYSTOLIC DYSFUNCTION; PULMONARY-ARTERY; CONTROLLED TRIAL; KIDNEY-FUNCTION; BG9719 CVT-124; ADENOSINE; PRESSURE; FUROSEMIDE; TOLVAPTAN AB The direct effects of adenosine A1 receptor antagonists on haemodynamic parameters in patients with acute heart failure (HF) remain largely unknown. We evaluated the haemodynamic effects of the AA(1)RA rolofylline in 59 HF patients with concomitant renal impairment (estimated creatinine clearance 20-80 mL/min). Placebo or rolofylline 30 mg was administered as a 4 h infusion followed by intravenous (i.v.) loop diuretic administration. Haemodynamic measurements were carried out hourly up to 8 h post-dosing by pulmonary artery catheterization. Urine output, fractional excretion of sodium, potassium, urea, and uric acid, and blood urea nitrogen (BUN) and creatinine levels were also measured. In both groups, the changes from baseline in all haemodynamic indices except mean pulmonary artery pressure (PAP) were not clinically significant. Mean [95% confidence interval (CI)] PAP showed a placebo-adjusted decrease with rolofylline of -1.5 (-4.1, 1.1)mmHg at Hour 4 and -3.5 mmHg (95% CI: -6.2, -0.2) at Hour 8. There was a significant increase with rolofylline in diuresis [placebo-corrected mean (95% CI) change of 68 (20, 116)mL/h at Hour 2-4 and 103 (21, 185)mL/h at Hour 4-8] and in fractional excretion of sodium, potassium, and uric acid. Placebo-corrected changes in plasma levels of creatinine and BUN with rolofylline were non-significant. Single administration of rolofylline in patients with HF and impaired renal function produced a slight decrease in mean PAP and consistently increased diuresis and natriuresis without compromising renal function, both before and after administration of i.v. loop diuretics. C1 [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Dept Heart Dis, PL-50891 Wroclaw, Poland. [Mitrovic, Veselin] Max Planck Inst Physiol & Clin Res, Kerckhoff Klin, D-6350 Bad Nauheim, Germany. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, CA USA. [Dittrich, Howard] NovaCardia, San Diego, CA USA. [Cotter, Gad; Weatherley, Beth D.] Momentum Res, Durham, NC USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, Erluo; Murray, Meredith] Merck & Co Inc, Upper Gwynedd, PA USA. [Fujita, Kenji P.] Merck & Co Inc, Rahway, NJ 07065 USA. [Metra, Marco] Univ Brescia, Div Cardiol, Dept Expt & Appl Med, Brescia, Italy. RP Ponikowski, P (reprint author), Med Univ, Clin Mil Hosp, Dept Heart Dis, Weigla 5, PL-50891 Wroclaw, Poland. EM piotrponikowski@4wsk.pl RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568 FU Merck; NovaCardia/Merck; Merck Co.; NovaCardia, Inc. FX P.P. has received honoraria from Merck and Biogen. V.M. has no conflicts. C.M.O'.C is a consultant and has received grant support from Merck. H.C.D. is/was a stockholder/consultant of the company (NovaCardia/Merck) that sponsored the study. G.C. is an employee of Momentum Research who received payments from Merck for the conduct of the study. B.M.M. has been a consultant to NovaCardia and Merck prior to and during the trial (payments from Merck<$ 10 000) and has received speaking honoraria for presentations during satellite symposia (<$ 10 000). M.M.G. has received research support from Merck & Co. E.C. and M. M. are employees of Merck and hold Merck stock options. B.D.W. is an employee of Momentum Research Inc., which has provided consulting services to Merck, Corthera, Celladon, Bio-heart, and Nile Therapeutics. K.P.F. is an employee of Merck & Co. M.M. has received honoraria for participation to meetings and as a member of the executive board from Cardiokine, Corthera, Merck, and Servier.; This study was funded by NovaCardia, Inc. As of September 2007, NovaCardia is a wholly owned subsidiary of Merck & Co, Inc. NR 35 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD NOV PY 2010 VL 12 IS 11 BP 1238 EP 1246 DI 10.1093/eurjhf/hfq137 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 673PB UT WOS:000283674300014 PM 20823097 ER PT J AU O'Dushlaine, CT Morris, D Moskvina, V Gill, M Corvin, A Wilson, JF Cavalleri, GL AF O'Dushlaine, Colm T. Morris, Derek Moskvina, Valentina Gill, Michael Corvin, Aiden Wilson, James F. Cavalleri, Gianpiero L. CA Int Schizophrenia Consortium TI Population structure and genome-wide patterns of variation in Ireland and Britain SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE GWAS; population genetic structure; homozygosity; linkage disequilibrium; haplotype diversity ID LINKAGE DISEQUILIBRIUM; COMPLEX DISEASES; IRISH POPULATION; BRITISH-ISLES; ASSOCIATION; DIVERSITY; EUROPE; SCHIZOPHRENIA; SUBSTRUCTURE; HOMOZYGOSITY AB Located off the northwestern coast of the European mainland, Britain and Ireland were among the last regions of Europe to be colonized by modern humans after the last glacial maximum. Further, the geographical location of Britain, and in particular of Ireland, is such that the impact of historical migration has been minimal. Genetic diversity studies applying the Y chromosome and mitochondrial systems have indicated reduced diversity and an increased population structure across Britain and Ireland relative to the European mainland. Such characteristics would have implications for genetic mapping studies of complex disease. We set out to further our understanding of the genetic architecture of the region from the perspective of (i) population structure, (ii) linkage disequilibrium (LD), (iii) homozygosity and (iv) haplotype diversity (HD). Analysis was conducted on 3654 individuals from Ireland, Britain (with regional sampling in Scotland), Bulgaria, Portugal, Sweden and the Utah HapMap collection. Our results indicate a subtle but clear genetic structure across Britain and Ireland, although levels of structure were reduced in comparison with average cross-European structure. We observed slightly elevated levels of LD and homozygosity in the Irish population compared with neighbouring European populations. We also report on a cline of HD across Europe with greatest levels in southern populations and lowest levels in Ireland and Scotland. These results are consistent with our understanding of the population history of Europe and promote Ireland and Scotland as relatively homogenous resources for genetic mapping of rare variants. European Journal of Human Genetics (2010) 18, 1248-1254; doi: 10.1038/ejhg.2010.87; published online 23 June 2010 C1 [Int Schizophrenia Consortium] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [O'Dushlaine, Colm T.; Morris, Derek; Gill, Michael; Corvin, Aiden] Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin, Ireland. [O'Dushlaine, Colm T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Psychiat & Neurodev Genet Unit, Boston, MA USA. [O'Dushlaine, Colm T.] Stanley Ctr Psychiat Res, Broad Inst, Cambridge, MA USA. [Moskvina, Valentina; Gill, Michael] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Cardiff, S Glam, Wales. [Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. RP Cavalleri, GL (reprint author), Royal Coll Surgeons Ireland, Dublin 2, Ireland. EM jim.wilson@hgu.mrc.ac.uk; gcavalleri@rcsi.ie RI Cavalleri, Gianpiero/A-6632-2010; Wilson, James F/A-5704-2009; OI Escott-Price, Valentina/0000-0003-1784-5483; Cavalleri, Gianpiero/0000-0002-9802-0506; Wilson, James F/0000-0001-5751-9178; Corvin, Aiden/0000-0001-6717-4089; Morris, Derek/0000-0002-3413-570X; Gill, Michael/0000-0003-0206-5337 FU Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02]; Royal Society; Science Foundation Ireland FX We acknowledge the use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council Grant G0000934 and the Wellcome Trust Grant 068545/Z/02. CTO'D was funded by a post-doctoral fellowship for the Irish Research Council for Science Engineering and Technology, JW by the Royal Society and AC from Science Foundation Ireland. We thank three anonymous reviewers for their constructive and helpful comments. NR 41 TC 28 Z9 28 U1 1 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV PY 2010 VL 18 IS 11 BP 1248 EP 1254 DI 10.1038/ejhg.2010.87 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 668ZE UT WOS:000283314700014 PM 20571510 ER PT J AU Kyriakakis, E Cavallari, M Andert, J Philippova, M Koella, C Bochkov, V Erne, P Wilson, SB Mori, L Biedermann, BC Resink, TJ De Libero, G AF Kyriakakis, Emmanouil Cavallari, Marco Andert, Jan Philippova, Maria Koella, Christoph Bochkov, Valery Erne, Paul Wilson, S. Brian Mori, Lucia Biedermann, Barbara C. Resink, Therese J. De Libero, Gennaro TI Invariant natural killer T cells: Linking inflammation and neovascularization in human atherosclerosis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Angiogenesis; CD1 molecules; Cell migration; Inflammation; Invariant NKT cells ID SMOOTH-MUSCLE-CELLS; NKT CELLS; PLAQUE NEOVASCULARIZATION; MONOCLONAL-ANTIBODY; APOE(-/-) MICE; DEFICIENT MICE; FOAM-CELLS; DISEASE; LESIONS; IL-8 AB Atherosclerosis, a chronic inflammatory lipid storage disease of large arteries, is complicated by cardiovascular events usually precipitated by plaque rupture or erosion. Inflammation participates in lesion progression and plaque rupture. Identification of leukocyte populations involved in plaque destabilization is important for effective prevention of cardiovascular events. This study investigates CD1d-expressing cells and invariant NKT cells (iNKT) in human arterial tissue, their correlation with disease severity and symptoms, and potential mechanisms for their involvement in plaque formation and/or destabilization. CD1d-expressing cells were present in advanced plaques in patients who suffered from cardiovascular events in the past and were most abundant in plaques with ectopic neovascularization. Confocal microscopy detected iNKT cells in plaques, and plaque-derived iNKT cell lines promptly produced proinflammatory cytokines when stimulated by CD1d-expressing APC-presenting alpha-galactosylceramide lipid antigen. Furthermore, iNKT cells were diminished in the circulating blood of patients with symptomatic atherosclerosis. Activated iNKT cell-derived culture supernatants showed angiogenic activity in a human microvascular endothelial cell line HMEC-1-spheroid model of in vitro angiogenesis and strongly activated human microvascular endothelial cell line HMEC-1 migration. This functional activity was ascribed to IL-8 released by iNKT cells upon lipid recognition. These findings introduce iNKT cells as novel cellular candidates promoting plaque neovascularization and destabilization in human atherosclerosis. C1 [Kyriakakis, Emmanouil; Philippova, Maria; Resink, Therese J.] Univ Basel Hosp, Lab Signal Transduct, Dept Biomed, CH-4031 Basel, Switzerland. [Cavallari, Marco; Mori, Lucia; De Libero, Gennaro] Univ Basel Hosp, Dept Biomed, Expt Immunol Lab, CH-4031 Basel, Switzerland. [Andert, Jan; Biedermann, Barbara C.] Cantonal Hosp Bruderholz, Univ Dept Med, Bruderholz, Switzerland. [Koella, Christoph] Cantonal Hosp Bruderholz, Dept Surg, Bruderholz, Switzerland. [Bochkov, Valery] Med Univ Vienna, Dept Vasc Biol & Thrombosis Res, Vienna, Austria. [Erne, Paul] Cantonal Hosp Luzern, Div Cardiol, Luzern, Switzerland. [Wilson, S. Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA USA. RP Resink, TJ (reprint author), Univ Basel Hosp, Lab Signal Transduct, Dept Biomed, CH-4031 Basel, Switzerland. EM Therese-J.Resink@unibas.ch OI Kyriakakis, Emmanouil/0000-0002-6796-0431 FU EEC [005206]; Swiss National Science Foundation [3100A0-109918, 3100-118096, 310000-118468/1]; Herzkreislauf Stiftung; Swiss Cardiology Foundation; Stiftung fur Medizinische Forschung, Basel, Switzerland FX This study was supported by EEC grant MOLSTROKE (Molecular basis of vascular events leading to thrombotic stroke) LSHM-CT-2004 Contract Number 005206 (to T. J. R., B. C. B. and G. D. L.), the Swiss National Science Foundation grants 3100A0-109918 (to G. D. L.), 3100-118096 (to B. C. B.) and 310000-118468/1 (to T. J. R.), Herzkreislauf Stiftung (to T. J. R., P. E.), Swiss Cardiology Foundation (to T. J. R., P. E.), and the Stiftung fur Medizinische Forschung, Basel, Switzerland (to B. C. B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Ed Palmer for reading the manuscript and helpful discussions. NR 49 TC 30 Z9 30 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2010 VL 40 IS 11 BP 3268 EP 3279 DI 10.1002/eji.201040619 PG 12 WC Immunology SC Immunology GA 678FH UT WOS:000284059000031 PM 21061446 ER PT J AU Solomon, VR Haq, W Smilkstein, M Srivastava, K Puri, SK Katti, SB AF Solomon, V. R. Haq, W. Smilkstein, M. Srivastava, Kumkum Puri, Sunil K. Katti, S. B. TI 4-Aminoquinoline derived antimalarials: Synthesis, antiplasmodial activity and heme polymerization inhibition studies SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE 4-Aminoquinoline; Thiourea; Antimalarial agents; Heme polymerization ID HEMATIN POLYMERIZATION; PLASMODIUM-FALCIPARUM; RETAIN ACTIVITY; IN-VITRO; CHLOROQUINE; DESIGN; DERIVATIVES; MECHANISM; BINDING; DRUGS AB A new series of 4-aminoquinoline derivatives have been synthesized and found to be active against both susceptible and resistant strains of Plasmodium falciparum in vitro. Compound 1-[3-(7-chloro-quinolin-4-ylamino)-propyl]-3-cyclopropyl-thiourea (7) exhibited superior in vitro activity against resistant strains of P. falciparum as compared to chloroquine (CQ). All the compounds showed resistance factor between 0.59 and 4.31 as against 5.05 for CQ. Spectroscopic studies suggested that this class of compounds act on heme polymerization target. (C) 2010 Elsevier Masson SAS. All rights reserved. C1 [Solomon, V. R.; Haq, W.; Katti, S. B.] Cent Drug Res Inst, Med & Proc Chem Div, Lucknow 226001, Uttar Pradesh, India. [Srivastava, Kumkum; Puri, Sunil K.] Cent Drug Res Inst, Div Parasitol, Lucknow 226001, Uttar Pradesh, India. [Smilkstein, M.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Katti, SB (reprint author), Cent Drug Res Inst, Med & Proc Chem Div, MG Rd, Lucknow 226001, Uttar Pradesh, India. EM setu_katti@yahoo.com RI Viswas, V. Raja Solomon/F-6654-2011 OI Viswas, V. Raja Solomon/0000-0002-9863-4452 FU CDRI; CSIR, New Delhi FX The authors thank the Director, CDRI for the support and the SAIF for the spectral data. One of the authors (V. R. Solomon) thanks the CSIR, New Delhi for Senior Research Fellowship. CDRI communication no. 7912 NR 31 TC 18 Z9 18 U1 0 U2 4 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD NOV PY 2010 VL 45 IS 11 BP 4990 EP 4996 DI 10.1016/j.ejmech.2010.07.068 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 676KZ UT WOS:000283911300035 PM 20805010 ER PT J AU Chen, LC McKenna, JT Bolortuya, Y Winston, S Thakkar, MM Basheer, R Brown, RE McCarley, RW AF Chen, Lichao McKenna, James T. Bolortuya, Yunren Winston, Stuart Thakkar, Mahesh M. Basheer, Radhika Brown, Ritchie E. McCarley, Robert W. TI Knockdown of orexin type 1 receptor in rat locus coeruleus increases REM sleep during the dark period SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE diurnal; hypocretin; narcolepsy; RNA interference; siRNA ID EYE-MOVEMENT SLEEP; HYPOCRETIN OREXIN; SUPRACHIASMATIC NUCLEUS; IMAGE-ANALYSIS; WAKING CYCLE; CIRCADIAN REGULATION; DORSOLATERAL PONS; BEHAVIORAL STATE; IMPULSE ACTIVITY; MAMMALIAN-CELLS AB The locus coeruleus (LC) regulates sleep/wakefulness and is densely innervated by orexinergic neurons in the lateral hypothalamus. Here we used small interfering RNAs (siRNAs) to test the role of LC orexin type 1 receptor (OxR1) in sleep-wake control. In sleep studies, bilateral OxR1 siRNA injections led to an increase of time spent in rapid eye movement (REM) sleep, which was selective for the dark (active) period, peaked at approximately 30% of control during the second dark period after injection and then disappeared after 4 days. Cataplexy-like episodes were not observed. The percentage time spent in wakefulness and non-REM (NREM) sleep and the power spectral profile of NREM and REM sleep were unaffected. Control animals, injected with scrambled siRNA, had no sleep changes after injection. Quantification of the knockdown revealed that unilateral microinjection of siRNAs targeting OxR1 into the rat LC on two consecutive days induced a 45.5% reduction of OxR1 mRNA in the LC 2 days following the injections when compared with the contralateral side receiving injections of control (scrambled) siRNAs. This reduction disappeared 4 days after injection. Similarly, unilateral injection of OxR1 siRNA into the LC revealed a marked (33.5%) reduction of OxR1 staining 2 days following injections. In contrast, both the mRNA level and immunohistochemical staining for tyrosine hydroxylase were unaffected. The results indicate that a modest knockdown of OxR1 is sufficient to induce observable sleep changes. Moreover, orexin neurons, by acting on OxR1 in the LC, play a role in the diurnal gating of REM sleep. C1 [Chen, Lichao; McKenna, James T.; Bolortuya, Yunren; Winston, Stuart; Basheer, Radhika; Brown, Ritchie E.; McCarley, Robert W.] Harvard Univ, Res Serv, VA Boston Healthcare Syst, Sch Med, Brockton, MA 02301 USA. [Chen, Lichao; McKenna, James T.; Bolortuya, Yunren; Winston, Stuart; Basheer, Radhika; Brown, Ritchie E.; McCarley, Robert W.] Harvard Univ, Dept Psychiat, Sch Med, Brockton, MA 02301 USA. [Thakkar, Mahesh M.] Univ Missouri, Harry S Truman Mem Vet Hosp, Dept Neurol, Columbia, MO USA. RP Chen, LC (reprint author), Harvard Univ, Res Serv, VA Boston Healthcare Syst, Sch Med, Brockton, MA 02301 USA. EM lichao_chen@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Brown, Ritchie/0000-0002-7164-4132 FU VA; NIMH [062522, 39683, 01798, NS059831] FX This study was supported by VA (Merit Award to R.W.M.) and NIMH grants 062522, 39683, 01798, NS059831 (M.M.T.). We thank Mike Leonard and Courtney Earle for their technical assistance. We also thank Dr. Robert Strecker for the support of his VA MERIT grant, and his effort in providing the staff and resources needed to perform surgery and sleep data analysis for this project. NR 79 TC 24 Z9 24 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2010 VL 32 IS 9 BP 1528 EP 1536 DI 10.1111/j.1460-9568.2010.07401.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 673VO UT WOS:000283692500012 PM 21089218 ER PT J AU Haraldsdottir, S Gudnason, T Sigurdsson, AF Gudjonsdottir, J Lehman, SJ Eyjolfsson, K Scheving, SS Gibson, CM Hoffmann, U Jonsdottir, B Andersen, K AF Haraldsdottir, Sigurdis Gudnason, Thorarinn Sigurdsson, Axel F. Gudjonsdottir, Jonina Lehman, Sam J. Eyjolfsson, Kristjan Scheving, Sigurpall S. Gibson, C. Michael Hoffmann, Udo Jonsdottir, Birna Andersen, Karl TI Diagnostic accuracy of 64-slice multidetector CT for detection of in-stent restenosis in an unselected, consecutive patient population SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE 64-Slice CT; In-stent restenosis; Diagnostic accuracy; Coronary angiography ID MULTISLICE COMPUTED-TOMOGRAPHY; CORONARY-ARTERY DISEASE; DUAL-SOURCE CT; BALLOON ANGIOPLASTY; ANGIOGRAPHY; PATENCY AB Objectives: To investigate the diagnostic accuracy of 64-slice multidetector computed tomography (64-CT) for detection of in-stent restenosis (ISR) in an unselected, consecutive patient population. Background: Detection of in-stent restenosis by cardiac CT would be a major advance for the evaluation of patients suspected of having ISR. However, the diagnostic accuracy of current generation 64-CT in this context is not fully established. Methods: We conducted a prospective study on patients with stable angina or acute coronary syndrome with no prior history of coronary artery disease. Six months after percutaneous coronary intervention (PCI) with stent placement they underwent a 64-CT scan (Toshiba Multi-Slice Aquilion 64) and consequently a repeat coronary angiography for comparison. Cardiac CT data sets were analyzed for the presence of in-stent restenosis by two independent expert readers blinded to the coronary angiographic data. Results: Ninety-three patients with a total of 140 stents were evaluated. Males comprised 82% of the study group and the mean age was 63 +/- 10 years. The mean time from PCI to the repeat coronary angiography was 208 +/- 37 days and the mean time from 64-CT to repeat coronary angiography was 3.7 +/- 4.9 days. The restenosis rate according to coronary angiography was 26%. Stent diameter, strut thickness, heart rate and body mass index (BMI) significantly affected image quality. The sensitivity, specificity, positive and negative predictive values of 64-CT for detection of in-stent restenosis were 27%, 95%, 67% and 78%, respectively. Conclusions: Current generation, 64-slice CT, remains limited in its ability to accurately detect in-stent restenosis. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Gudnason, Thorarinn; Sigurdsson, Axel F.; Eyjolfsson, Kristjan; Scheving, Sigurpall S.; Andersen, Karl] Landspitali Univ Hosp, IS-101 Reykjavik, Iceland. [Haraldsdottir, Sigurdis] Boston Med Ctr, Boston, MA 02118 USA. [Gudjonsdottir, Jonina; Jonsdottir, Birna] Rontgen Domus Med, IS-101 Reykjavik, Iceland. [Lehman, Sam J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Andersen, K (reprint author), Landspitali Univ Hosp, IS-101 Reykjavik, Iceland. EM sigurdisha@gmail.com; thorgudn@landspitali.is; axelfsig@landspitali.is; jonina@rd.is; slehman@partners.org; kristey@landspitali.is; sigurpal@landspitali.is; mgibson@perfuse.org; uhoffmann@partners.org; birna@rd.is; andersen@landspitali.is FU National Institute of Health, Maryland, USA; Icelandic Society of Cardiology, Reykjavik, Iceland; Landspitali University Hospital, Reykjavik, Iceland FX Sources of funding: National Institute of Health, Maryland, USA; Research Fund of the Icelandic Society of Cardiology, Reykjavik, Iceland; Research Fund of Landspitali University Hospital, Reykjavik, Iceland. NR 18 TC 13 Z9 18 U1 0 U2 6 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 NOV PY 2010 VL 76 IS 2 BP 188 EP 194 DI 10.1016/j.ejrad.2009.05.030 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 675NU UT WOS:000283838200015 PM 19570632 ER PT J AU Goetti, R Feuchtner, G Stolzmann, P Desbiolles, L Fischer, MA Karlo, C Baumueller, S Scheffel, H Alkadhi, H Leschka, S AF Goetti, Robert Feuchtner, Gudrun Stolzmann, Paul Desbiolles, Lotus Fischer, Michael Alexander Karlo, Christoph Baumueller, Stephan Scheffel, Hans Alkadhi, Hatem Leschka, Sebastian TI High-pitch dual-source CT coronary angiography: systolic data acquisition at high heart rates SO EUROPEAN RADIOLOGY LA English DT Article DE High-pitch; Computed tomography; Systolic reconstruction; Coronary arteries; Heart rate; Radiation dose ID SPIRAL COMPUTED-TOMOGRAPHY; IMAGE QUALITY; DIAGNOSTIC-ACCURACY; RADIATION-EXPOSURE; ROW CT; WINDOWS; SPEED; AORTA AB To assess the effect of systolic data acquisition for electrocardiography (ECG)-triggered high-pitch computed tomography (CT) on motion artefacts of coronary arteries in patients with high heart rates (HRs). Eighty consecutive patients (15 women, age 67 +/- 14 years) with HR a parts per thousand yen70 bpm underwent CT angiography of the thoracic aorta (CTA) on 128-slice dual-source CT in ECG-triggered high-pitch acquisition mode (pitch = 3.2) set at 60% (group A, n = 40) or 30% (group B, n = 40) of the RR interval. Two blinded readers graded coronary artery image quality on a three-point scale. Radiation doses were calculated. Inter-observer agreement in grading image quality of the 1,154 coronary segments was good (kappa = 0.62). HRs were similar in groups A and B (85 +/- 13 bpm vs 85 +/- 14 bpm, p not significant). Significantly fewer coronary segments with non-diagnostic image quality occurred (i.e. score 3) in group B than in group A [2.8% (16/579) vs 8.3% (48/575), p < 0.001]. Seventeen patients (42.5%) of group A and 12 patients (30.0%) of group B had at least one non-diagnostic segment. Effective radiation doses were 2.3 +/- 0.3 mSv for chest CTA. A systolic acquisition window for high-pitch dual-source CTA in patients with high HRs (a parts per thousand yen70 bpm) significantly improves coronary artery image quality at a low radiation dose. C1 [Leschka, Sebastian] Kantonsspital, Inst Radiol, CH-9007 St Gallen, Switzerland. [Goetti, Robert; Feuchtner, Gudrun; Stolzmann, Paul; Desbiolles, Lotus; Fischer, Michael Alexander; Karlo, Christoph; Baumueller, Stephan; Scheffel, Hans; Alkadhi, Hatem; Leschka, Sebastian] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. [Stolzmann, Paul; Scheffel, Hans; Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Leschka, S (reprint author), Kantonsspital, Inst Radiol, Rorschacherstr 95, CH-9007 St Gallen, Switzerland. EM sebastian.leschka@kssg.ch RI Goetti, Robert/I-8961-2012 NR 30 TC 27 Z9 33 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD NOV PY 2010 VL 20 IS 11 BP 2565 EP 2571 DI 10.1007/s00330-010-1838-z PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 657PP UT WOS:000282425100003 PM 20585785 ER PT J AU Giove, TJ Sena-Esteves, M Eldred, WD AF Giove, Thomas J. Sena-Esteves, Miguel Eldred, William D. TI Transduction of the inner mouse retina using AAVrh8 and AAVrh10 via intravitreal injection SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE adeno-associated virus; AAV; inner retina; inner nuclear layer; horizontal cells; retina; retinal gene delivery ID LEBER CONGENITAL AMAUROSIS; ADENOASSOCIATED VIRAL VECTORS; HIGH-EFFICIENCY TRANSDUCTION; MEDIATED GENE-TRANSFER; PHOTORECEPTOR DEGENERATION; VIRUS; THERAPY; SEROTYPES; DISEASE; CELLS AB Adeno-associated virus (AAV) is a proven, safe and effective vector for gene delivery in the retina. There are over 100 serotypes of AAV, and AAV2 through AAV9 have been evaluated in the retina. Each AAV serotype has different cell tropism and transduction efficiency. Intravitreal injections of AAV into the eye tend to transduce cells in the ganglion cell layer (GCL), while subretinal injections tend to transduce retinal pigment epithelium and photoreceptors. Efficient transduction of the inner retina beyond the GCL is not well established with the current methodologies and serotypes used to date. In this study, we compared the cellular tropism of AAVrh8 and AAVrh10 vectors encoding enhanced green fluorescent protein (EGFP) using intravitreal injections. We found that AAVrh8 largely transduced cells in the GCL and also amacrine cells in the inner nuclear layer (INL), as well as Muller and horizontal cells. Inner retinal transduction with AAVrh10 was similar to AAVrh8. but AAVrh10 appeared to also transduce bipolar cells. The transduction efficiency as measured by the intensity of EGFP signal was 3.5 fold higher in horizontal cells transduced with AAVrh10 than AAVrh8. Glial fibrillary accessory protein (GFAP) levels were increased in Muller cells in transduced areas for both serotypes. The results of this study suggest that AAVrh8 and AAVrh10 may be excellent vector candidates to deliver genetic material to the INL, particularly for amacrine and horizontal cells, however they may also cause cellular stress as shown by increased glial GFAP expression. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Giove, Thomas J.; Eldred, William D.] Boston Univ, Dept Biol, Lab Visual Neurobiol, Boston, MA 02215 USA. [Sena-Esteves, Miguel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. [Sena-Esteves, Miguel] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02129 USA. RP Eldred, WD (reprint author), Boston Univ, Dept Biol, Lab Visual Neurobiol, 5 Cummington St, Boston, MA 02215 USA. EM eldred@bu.edu FU NIH [EY004785] FX We would like to thank Zarmina Khankel and Felicitas B. Eldred for their technical assistance and Jamit Argawal for the creation of the custom Image J plugin used in determining our thresholds for normalization. This research was supported by NIH EY004785 to W.D. Eldred. NR 41 TC 9 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2010 VL 91 IS 5 BP 652 EP 659 DI 10.1016/j.exer.2010.08.011 PG 8 WC Ophthalmology SC Ophthalmology GA 675JL UT WOS:000283826300012 PM 20723541 ER PT J AU Bandyopadhyay, S Huang, XD Lahiri, DK Rogers, JT AF Bandyopadhyay, Sanghamitra Huang, Xudong Lahiri, Debomoy K. Rogers, Jack T. TI Novel drug targets based on metallobiology of Alzheimer's disease SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE APP; A beta; iron responsive element; metal chelators; screening ID AMYLOID PRECURSOR PROTEIN; IRON-RESPONSIVE ELEMENT; ALPHA-SECRETASE CLEAVAGE; INDUCED OXIDATIVE STRESS; TRANSGENIC MOUSE MODEL; 3 HISTIDINE-RESIDUES; APP MESSENGER-RNA; REDOX-ACTIVE IRON; BETA-PEPTIDE; A-BETA AB Importance of the field: Increased localization of Zn, Fe, Cu and Al within the senile plaques (SP) exacerbates amyloid beta (A beta)-mediated oxidative damage, and acts as catalyst for A beta aggregation in Alzheimer's disease (AD). Thus, disruption of aberrant metal-peptide interactions via chelation therapy holds considerable promise as a rational therapeutic strategy against Alzheimer's amyloid pathogenesis. Areas covered in this review: The complexities of metal-induced genesis of SP are reviewed. The recent advances in the molecular mechanism of action of metal chelating agents are discussed with critical assessment of their potential to become drugs. What the reader will gain: Taking into consideration the interaction of metals with the metal-responsive elements on the Alzheimer's amyloid precursor protein (APP), readers will gain understanding of several points to bear in mind when developing a screening campaign for AD-therapeutics. Take home message: A functional iron-responsive element (IRE) RNA stem loop in the 5' untranslated region (UTR) of the APP transcript regulates neural APP translation. Desferrioxamine, clioquinol, tetrathiolmolybdate, dimercaptopropanol, VK-28, and natural antioxidants, such as curcumin and ginko biloba need critical evaluation as AD therapeutics. There is a necessity for novel screens (related to metallobiology) to identify therapeutics effective in AD. C1 [Bandyopadhyay, Sanghamitra] CSIR, Indian Inst Toxicol Res, Lucknow, Uttar Pradesh, India. [Huang, Xudong] Brigham & Womens Hosp, Boston, MA 02114 USA. [Huang, Xudong] Harvard Univ, Sch Med, Conjugate & Med Chem Lab, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Lahiri, Debomoy K.] Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat,Lab Mol Neurogenet, Indianapolis, IN 46202 USA. [Huang, Xudong; Rogers, Jack T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huang, Xudong; Rogers, Jack T.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Huang, Xudong; Rogers, Jack T.] Genet & Aging Res Unit, Neurochem Lab, Boston, MA 02115 USA. RP Bandyopadhyay, S (reprint author), CSIR, Indian Inst Toxicol Res, Lucknow, Uttar Pradesh, India. EM sanghmitra@iitr.res.in; jtrogers@rics.bwh.harvard.edu OI Bandyopadhyay, Sanghamitra /0000-0002-1490-3599 NR 230 TC 32 Z9 33 U1 2 U2 14 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD NOV PY 2010 VL 14 IS 11 BP 1177 EP 1197 DI 10.1517/14728222.2010.525352 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 664MH UT WOS:000282964500005 PM 20942746 ER PT J AU Johnson, N Shapiro, GI AF Johnson, Neil Shapiro, Geoffrey I. TI Cyclin-dependent kinases (cdks) and the DNA damage response: rationale for cdk inhibitor-chemotherapy combinations as an anticancer strategy for solid tumors SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE chemotherapy; cyclin-dependent kinase; DNA damage ID STRAND-BREAK REPAIR; CHRONIC LYMPHOCYTIC-LEUKEMIA; FLAVOPIRIDOL-INDUCED APOPTOSIS; RNA-POLYMERASE-II; DINACICLIB SCH 727965; CANCER-CELL-LINES; END RESECTION; IN-VIVO; S-PHASE; P-TEFB AB Importance of the field: The eukaryotic cell division cycle is a tightly regulated series of events coordinated by the periodic activation of multiple cyclin-dependent kinases (cdks). Small-molecule cdk-inhibitory compounds have demonstrated preclinical synergism with DNA-damaging agents in solid tumor models. An improved understanding of how cdks regulate the DNA damage response now provides an opportunity for optimization of combinations of cdk inhibitors and DNA damaging chemotherapy agents that can be translated to clinical settings. Areas covered in this review: Here, we discuss novel work uncovering multiple roles for cdks in the DNA-damage-response network. First, they activate DNA damage checkpoint and repair pathways. Later their activity is turned off, resulting in cell cycle arrest, allowing time for DNA repair to occur. Recent clinical data on cdk inhibitor-DNA-damaging agent combinations are also discussed. What the reader will gain: Readers will learn about novel areas of cdk biology, the complexity of DNA damage signaling networks and clinical implications. Take home message: New data demonstrate that cdks are 'master' regulators of DNA damage checkpoint and repair pathways. Cdk inhibition may therefore provide a means of potentiating the clinical activity of DNA-damaging chemotherapeutic agents for the treatment of cancer. C1 [Johnson, Neil; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Johnson, Neil; Shapiro, Geoffrey I.] Brigham & Womens Hosp, Boston, MA 02215 USA. [Johnson, Neil; Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 810A,44 Binney St, Boston, MA 02215 USA. EM geoffrey_shapiro@dfci.harvard.edu FU NIH [R01 CA090687, P50 CA089393, P50 CA090578]; Susan G Komen Post-Doctoral Fellowship [KG080773]; Schering-Plough (Merck); Cyclacel, Ltd. FX The authors are supported by NIH grants R01 CA090687, P50 CA089393 [Dana-Farber/Harvard Cancer Center (DF/HCC) Specialized Program of Research Excellence (SPORE) in Breast Cancer], P50 CA090578 (DF/HCC SPORE in Lung Cancer) and Susan G Komen Post-Doctoral Fellowship Award KG080773. GI Shapiro receives funding for the conduct of clinical trials with cdk inhibitors, including trials sponsored by Schering-Plough (Merck) and Cyclacel, Ltd. NR 125 TC 35 Z9 35 U1 1 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD NOV PY 2010 VL 14 IS 11 BP 1199 EP 1212 DI 10.1517/14728222.2010.525221 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 664MH UT WOS:000282964500006 PM 20932174 ER PT J AU Baxt, LA Goldberg, MB AF Baxt, Leigh A. Goldberg, Marcia B. TI Anaerobic environment of the intestine primes pathogenic Shigella for infection SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Article DE diarrhea; enteric infection; FNR; intestine; oxygen; Shigella flexneri; TTSS; type three secretion system ID III SECRETION SYSTEMS; BACTERIAL VIRULENCE; PROTEINS; INHIBITORS; FLEXNERI; FNR AB Marteyn et al. have investigated the role of oxygen and the regulator FNR in infection by the intracellular enteric pathogen Shigella flexneri. FNR is active under anaerobic conditions like those present in the lumen of the distal intestine. FNR causes elongation of a secretion apparatus required for bacterial entry into cells and represses secretion of proteins that trigger entry. Higher oxygen levels present at the intestinal cell surface are sufficient to inactivate FNR, thereby derepressing secretion. Thus, bacteria are 'primed' in the anaerobic environment of the lumen, and entry is triggered by the aerobic conditions at the intestinal cell surface. FNR is conserved among many enteric pathogens, suggesting that regulation of virulence in response to oxygen may be widely conserved. C1 [Baxt, Leigh A.; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. [Baxt, Leigh A.; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Cambridge, MA 02139 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [R01 AI081724] NR 20 TC 2 Z9 2 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD NOV PY 2010 VL 8 IS 11 BP 1225 EP 1229 DI 10.1586/ERI.10.123 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 686GG UT WOS:000284684200010 PM 21073287 ER PT J AU Kosinski, MA Lipsky, BA AF Kosinski, Mark A. Lipsky, Benjamin A. TI Current medical management of diabetic foot infections SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE empiric therapy; foot infections; multidrug-resistant organisms; osteomyelitis polymicrobial infections; severity of infection; soft-tissue infections ID RESISTANT-STAPHYLOCOCCUS-AUREUS; SKIN-STRUCTURE INFECTIONS; IN-VITRO ACTIVITY; GRAM-POSITIVE ORGANISMS; SOFT-TISSUE INFECTIONS; LENGTH-OF-STAY; COMPLICATED SKIN; RISK-FACTORS; LOWER-EXTREMITY; LINEZOLID THERAPY AB Foot infections are a serious complication of diabetes associated with substantial morbidity and occasional mortality. Antibiotic therapy for mild infections in patients who have not recently received antibiotic therapy can often be directed at just staphylococci and streptococci. Empiric therapy for infections that are chronic, moderate or severe, or that occur in patients who have failed previous antibiotic treatment, should usually be more broad spectrum. Bone infection also complicates a substantial percentage of diabetic foot wounds and increases the likelihood of treatment failure, requiring lower extremity amputation. An increasing body of evidence supports the effectiveness of nonsurgical treatment of diabetic foot osteomyelitis in selected patients, although the optimal choice of agent, route of administration and duration of therapy have yet to be defined. This article examines the potential role of standard and newer antibiotics that may be appropriate for treating diabetic foot infections, including ertapenem, vancomycin, moxifloxacin, daptomycin, telavancin and tigecycline, as well as several investigational agents, such as dalbavancin, ceftobiprole and nemonoxacin. C1 [Kosinski, Mark A.] New York Coll Podiatr Med, Div Med Sci, New York, NY 10035 USA. [Lipsky, Benjamin A.] VA Puget Sound Hlth Care Syst, Primary Care Clin & Antibiot Res, Seattle, WA 98108 USA. [Lipsky, Benjamin A.] Univ Washington, Sch Med, Seattle, WA 98108 USA. RP Kosinski, MA (reprint author), New York Coll Podiatr Med, Div Med Sci, 53 E 124th St, New York, NY 10035 USA. EM mkosins@nycpm.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 FU Merck; Pfizer; Schering-Plough/Bayer; Cubist; Wyeth; TaiGen; Innocoll FX Mark Kosinski has received speaker fees from Merck. Benjamin Lipsky has received research funding consultant or speaker fees from Merck, Pfizer, Schering-Plough/Bayer, Cubist, Wyeth, TaiGen and Innocoll. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 113 TC 14 Z9 15 U1 0 U2 11 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD NOV PY 2010 VL 8 IS 11 BP 1293 EP 1305 DI 10.1586/ERI.10.122 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 686GG UT WOS:000284684200016 PM 21073293 ER PT J AU Sano, M AF Sano, Mary TI ICAD 2010: detection may hold the key to treatment SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review AB The Alzheimer's Association International Conference on Alzheimer's Disease was held on July 10-15 in Honolulu (HI, USA). Over 3800 attendees participated, attending sessions that included more than 1700 posters and 200 oral presentations. The meeting, first organized in 1988 by Khalid Iqbal and Bengt Winblad, became an annual event in 2009, and under the current design includes not only well-established themes of interest, but investigator-initiated sessions also. The Alzheimer's Association started managing the conference in 2000 in partnership with the founders, and abstracts for the meeting are published in the association's journal, Alzheimer's & Dementia. Key themes of this year's conference included validation of biomarkers, drug development, the value of screening for cognitive loss and dementia and the proposal of a new criteria for Alzheimer's disease. C1 Mt Sinai Sch Med, James J Peters Vet Adm Med Ctr, Dept Psychiat, Alzheimer Dis Res Ctr, Bronx, NY 10468 USA. RP Sano, M (reprint author), Mt Sinai Sch Med, James J Peters Vet Adm Med Ctr, Dept Psychiat, Alzheimer Dis Res Ctr, 130 W Kingsbridge Rd,Code 150,Rm 1F01, Bronx, NY 10468 USA. EM mary.sano@mssm.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD NOV PY 2010 VL 10 IS 11 BP 1659 EP 1661 DI 10.1586/ERN.10.150 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 686GJ UT WOS:000284684500010 PM 20977323 ER PT J AU George, MS AF George, Mark S. TI Transcranial magnetic stimulation for the treatment of depression SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE depression; TMS; transcranial magnetic stimulation; treatment-resistant ID TREATMENT-RESISTANT DEPRESSION; MOTOR CORTEX STIMULATION; HEALTHY-YOUNG MEN; RANDOMIZED CONTROLLED-TRIAL; DEEP BRAIN-REGIONS; MAJOR DEPRESSION; ELECTROCONVULSIVE-THERAPY; PREFRONTAL CORTEX; CORTICAL EXCITABILITY; BIPOLAR DEPRESSION AB Repeated daily left prefrontal transcranial magnetic stimulation (TMS) was first proposed as a potential treatment for depression in 1993. Multiple studies from researchers around the world since then have repeatedly demonstrated that TMS has antidepressant effects greater than sham treatment, and that these effects are clinically meaningful. A large industry-sponsored trial, published in 2007, resulted in US FDA approval in October 2008. Most recently, a large NIH-sponsored trial, with a more rigorous sham technique, found that a course of treatment (3-5 weeks) was statistically and clinically significant in reducing depression. However, consistently showing statistically and clinically significant antidepressant effects, and gaining regulatory approval, is merely the beginning for this new treatment. As with any new treatment involving a radically different approach, there are many unanswered questions about TMS, and the field is still rapidly evolving. These unanswered questions include the appropriate scalp location, understanding the mechanisms of action, refining the 'dose' (frequency, train, number of stimuli/day and pattern of delivery), understanding whether and how TMS can be combined with medications or talking/exposure therapy, or both, and how to deliver maintenance TMS. This article summarizes the available clinical information, and discusses key areas where more research is needed. TMS reflects a paradigm shift in treating depression. It is a safe, relatively noninvasive, focal brain stimulation treatment that does not involve seizures or implanted wires, and does not have drug-drug interactions or systemic side effects. C1 [George, Mark S.] Med Univ S Carolina, Inst Psychiat, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Inst Psychiat, 502 N,67 President St, Charleston, SC 29425 USA. EM georgem@musc.edu FU Glaxo-Smith-Kline; Jazz Pharmaceuticals; Brainsway FX Mark George reports no equity or other direct financial investment in any device or pharmaceutical firm. Within the past 3 years he has: served as a paid consultant to Glaxo-Smith-Kline, Jazz Pharmaceuticals, Cyberonics and Neuropace; received research grants from Glaxo-Smith-Kline, Jazz Pharmaceuticals and Brainsway; served as an unpaid consultant to Brainsonix, Brainsway, Neuronetics and NeoStim; and been the editor-in-chief of a journal published by Elsevier, entitled Brain Stimulation. The Medical University of South Carolina holds patents in the area of combining TMS with functional brain imaging. The total compensation from any company in a single year has been less than US$10,000. The total combined compensation from all consulting activities is less than 10% of his university salary. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 124 TC 38 Z9 39 U1 6 U2 20 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD NOV PY 2010 VL 10 IS 11 BP 1761 EP 1772 DI 10.1586/ERN.10.95 PG 12 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 686GJ UT WOS:000284684500020 PM 20977332 ER PT J AU Rouvas, AA Papakostas, TD Ntouraki, A Douvali, M Vergados, I Ladas, ID AF Rouvas, A. A. Papakostas, T. D. Ntouraki, A. Douvali, M. Vergados, I. Ladas, I. D. TI Angiographic and OCT features of retinal angiomatous proliferation SO EYE LA English DT Article DE fluorescein angiography; indocyanine green angiography; optical coherence tomography; retinal angiomatous proliferation ID OCCULT CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; TYPE-3 NEOVASCULARIZATION; ANASTOMOSES; DETACHMENTS; DRUSEN; SIGN AB Background To propose a classification system for retinal angiomatous proliferation (RAP) on the basis of the indocyanine green angiography (ICG). Methods Retrospective chart review of 55 eyes of 55 patients presenting with RAP. Fluorescein angiography (FA), ICG and optical coherence tomography (OCT) were used to evaluate the patients. Results All RAP lesions appeared as occult or minimally classic CNV on FA without clear evidence of pigment epithelium detachment (PED). We were able to identify five different patterns of RAP on the basis of ICG. These were focal (27.2%), irregular (21.8%), circular (21.8%), multifocal (18.2%), and combined (10.9%) hyperfluorescence. The sudden termination of retinal vessel course sign was observed in 14 of 55 eyes (25.4%), which had a circular or irregular pattern on the ICG. Only the circular RAP exhibited a late hypofluorescence ('wash out') with staining of the surrounding tissue on the ICG. Forty eight of 55 eyes (86%) had PED according to the OCT. Out of these 48 eyes, 19 had intraretinal fluid (IRF) alone, and the rest had IRF and subretinal fluid. The eight eyes (14%) without PED belonged to the focal hyperfluorescence group and the fluid was located intraretinally in cystic spaces. In addition, in four eyes (7%) with coexisting CNV a band of tissue beneath the RAP protruding in the PED was observed. Conclusion We propose a classification system for RAP on the basis of ICG and present the angiographic and OCT findings of these lesions. These data may further aid in the early diagnosis of RAP and can be also used for prognosis and clinical course documentation. Eye (2010) 24, 1633-1643; doi: 10.1038/eye.2010.134; published online 29 October 2010 C1 [Rouvas, A. A.; Ntouraki, A.; Douvali, M.; Vergados, I.] Univ Athens, Sch Med, Dept Ophthalmol 1, Attikon Gen Hosp, Athens 12462, Greece. [Papakostas, T. D.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Rouvas, AA (reprint author), Univ Athens, Sch Med, Dept Ophthalmol 1, Attikon Gen Hosp, 1 Rimini Str, Athens 12462, Greece. EM rallex@hol.gr NR 14 TC 12 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD NOV PY 2010 VL 24 IS 11 BP 1633 EP 1643 DI 10.1038/eye.2010.134 PG 11 WC Ophthalmology SC Ophthalmology GA 678WF UT WOS:000284112900001 PM 21068770 ER PT J AU Subramanian, ML Abedi, G Ness, S Ahmed, E Fenberg, M Daly, MK Houranieh, A Feinberg, EB AF Subramanian, M. L. Abedi, G. Ness, S. Ahmed, E. Fenberg, M. Daly, M. K. Houranieh, A. Feinberg, E. B. TI Bevacizumab vs ranibizumab for age-related macular degeneration: 1-year outcomes of a prospective, double-masked randomised clinical trial SO EYE LA English DT Article DE bevacizumab; ranibizumab; Avastin; Lucentis; macular degeneration ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL BEVACIZUMAB; CHOROIDAL NEOVASCULARIZATION; AVASTIN TREATMENT; EYE DISEASE; SHORT-TERM; THERAPY; SAFETY; VERTEPORFIN; PEGAPTANIB AB Purpose To report 1-year visual and anatomic outcomes of a prospective, double-masked randomised clinical trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration (AMD). Methods Patients who met inclusion criteria were randomised 2 : 1 to bevacizumab or ranibizumab. All subjects and investigators (except for the pharmacist responsible for study assignments) were masked to treatment arms. Visual acuity was taken on Early Treatment Diabetic Retinopathy Study chart. Patients were given either bevacizumab or ranibizumab every month for the first 3 months, followed by an optical coherence tomography-guided, variable-dosing treatment schedule. Main outcomes measured included visual acuity, foveal thickness, and total number of injections over the 1-year treatment period. Results In total, 15 patients received bevacizumab and 7 patients received ranibizumab. The average pre-operative visual acuity was 34.9 letters in the bevacizumab group, and 32.7 letters in the ranibizumab group. At 1-year follow-up, mean vision was 42.5 letters in the bevacizumab group, and 39.0 letters in the ranibizumab group. Two-tailed t-test failed to showed statistical significance between the two groups (P = 0.5). Patients in the bevacizumab group underwent an average of eight injections, whereas patients in the ranibizumab group underwent a mean of four injections (P = 0.001). Conclusion The 1-year outcomes of a prospective, double-masked, randomised clinical trial comparing bevacizumab with ranibizumab failed to show a difference in visual and anatomic outcomes between the two treatments for choroidal neovascularisation in AMD. Total injections given over the treatment period were significantly different between the two groups. Further studies with larger sample sizes are warranted. Eye (2010) 24, 1708-1715; doi: 10.1038/eye.2010.147; published online 1 October 2010 C1 [Subramanian, M. L.; Abedi, G.; Ness, S.; Ahmed, E.; Fenberg, M.; Daly, M. K.; Feinberg, E. B.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Subramanian, M. L.; Abedi, G.; Ness, S.; Ahmed, E.; Fenberg, M.; Daly, M. K.; Houranieh, A.; Feinberg, E. B.] Vet Affairs Boston Healthcare Syst, Surg Serv, Jamaica Plain, MA USA. RP Subramanian, ML (reprint author), Boston Univ, Sch Med, Dept Ophthalmol, 85 E Concord St,8826, Boston, MA 02118 USA. EM manju.subramanian@bmc.org FU Veterans Affairs Boston Healthcare System, Jamaica Plain, MA, USA; VA Boston FX Al Ozonoff, with the Department of Biostatistics in the Boston University School of Public Health, was consulted during the protocol preparation phase of this study. Gheorghe Doros, with the Department of Biostatistics in the Boston University School of Public Health, aided in the statistical analysis of the data. This article is the result of work supported with resources and the use of facilities at the Veterans Affairs Boston Healthcare System, Jamaica Plain, MA, USA. The VA Boston funded the cost of medications for this study. NR 37 TC 43 Z9 45 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD NOV PY 2010 VL 24 IS 11 BP 1708 EP 1715 DI 10.1038/eye.2010.147 PG 8 WC Ophthalmology SC Ophthalmology GA 678WF UT WOS:000284112900011 PM 20885427 ER PT J AU van Ham, TJ Mapes, J Kokel, D Peterson, RT AF van Ham, Tjakko J. Mapes, James Kokel, David Peterson, Randall T. TI Live imaging of apoptotic cells in zebrafish SO FASEB JOURNAL LA English DT Article DE neuronal cell death; in vivo microscopy; vertebrate model; neurotoxicity; p53; DNA damage response ID DNA FRAGMENTATION; GENE-EXPRESSION; DEATH; EMBRYO; PHOSPHATIDYLSERINE; NEURONS; BRAIN; MODEL AB Many debilitating diseases, including neurodegenerative diseases, involve apoptosis. Several methods have been developed for visualizing apoptotic cells in vitro or in fixed tissues, but few tools are available for visualizing apoptotic cells in live animals. Here we describe a genetically encoded fluorescent reporter protein that labels apoptotic cells in live zebrafish embryos. During apoptosis, the phospholipid phosphatidylserine (PS) is exposed on the outer leaflet of the plasma membrane. The calcium-dependent protein Annexin V (A5) binds PS with high affinity, and biochemically purified, fluorescently labeled A5 probes have been widely used to detect apoptosis in vitro. Here we show that secreted A5 fused to yellow fluorescent protein specifically labels apoptotic cells in living zebrafish. We use this fluorescent probe to characterize patterns of apoptosis in living zebrafish larvae and to visualize neuronal cell death at single-cell resolution in vivo.-Van Ham, T. J., Mapes, J., Kokel, D., Peterson, R. T. Live imaging of apoptotic cells in zebrafish. FASEB J. 24, 4336-4342 (2010). www.fasebj.org C1 [van Ham, Tjakko J.; Kokel, David; Peterson, Randall T.] Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [van Ham, Tjakko J.; Kokel, David; Peterson, Randall T.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med,Dept Med, Charlestown, MA 02129 USA. [van Ham, Tjakko J.; Kokel, David; Peterson, Randall T.] Broad Inst, Cambridge, MA USA. [Mapes, James] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. RP Peterson, RT (reprint author), Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, 149 13th St, Charlestown, MA 02129 USA. EM peterson@cvrc.mgh.harvard.edu RI van Ham, Tjakko/I-2382-2013; van Ham, Tjakko/A-1989-2015 OI van Ham, Tjakko/0000-0002-2175-8713 FU National Institutes of Health (NIH) [NS063733, MH086867]; NIH/National Cancer for Research Resources Centers of Biomedical Research Excellence in Obesity and Cardiovascular Disease [P20 RR021954] FX The authors thank the members of the R.T.P. laboratory for technical assistance and advice, Lindsay Cade for graphical expertise, Ding Xue (University of Colorado, Boulder, CO, USA) for helpful comments, David Langenau and Myron Ignatius (Massachusetts General Hospital Cancer Center, Charlestown, MA, USA) for p53 mutant animals, Chetana Satchidanandan (Institute of Genomics and Integrative Biology, Delhi, India) and Martin Distel and Reinhard Koester (Helmholtz Institute, Munich, Germany) for transgenic animals, the Koichi Kawakami laboratory (National Institute of Genetics, Mishima, Japan) for reagents, Anne Hart for use of equipment, the Michael L. Nonet laboratory (Washington University, St. Louis, MO, USA) for plasmids, and Iain Drummond (Massachusetts General Hospital, Charlestown, MA, USA) for advice on microscopy. This work was supported by National Institutes of Health (NIH) grants NS063733 and MH086867. This work was supported in part by the NIH/National Cancer for Research Resources Centers of Biomedical Research Excellence in Obesity and Cardiovascular Disease, grant P20 RR021954. NR 35 TC 42 Z9 44 U1 0 U2 16 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2010 VL 24 IS 11 BP 4336 EP 4342 DI 10.1096/fj.10-161018 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 675UA UT WOS:000283861100021 PM 20601526 ER PT J AU Patel, SM Iqbal, N Kaul, S Ratcliffe, SJ Rickels, MR Reilly, MP Scattergood, T Basu, A Fuller, C Cappola, AR AF Patel, Shrita M. Iqbal, Nayyar Kaul, Shailja Ratcliffe, Sarah J. Rickels, Michael R. Reilly, Muredach P. Scattergood, Theresa Basu, Arpita Fuller, Carissa Cappola, Anne R. TI Effects of metformin and leuprolide acetate on insulin resistance and testosterone levels in nondiabetic postmenopausal women: a randomized, placebo-controlled trial SO FERTILITY AND STERILITY LA English DT Article DE Testosterone; insulin resistance; polycystic ovary syndrome; metabolic syndrome; aging; elderly; women ID POLYCYSTIC-OVARY-SYNDROME; CORONARY-ARTERY-DISEASE; METABOLIC SYNDROME; GLUCOSE DISPOSAL; ENDOGENOUS ANDROGENS; HORMONE AGONIST; HEART-DISEASE; SERUM; SUPPRESSION; SECRETION AB Objective: To determine whether insulin sensitizers lower androgen levels and whether androgen suppression improves insulin resistance in nondiabetic postmenopausal women. Design: Randomized, double-blind, placebo-controlled study. Setting: Clinical and Translational Research Center of a university hospital. Patient(s): Thirty-five postmenopausal women aged 50-79 years with insulin resistance and higher T levels. Intervention(s): Subjects were randomized to metformin plus leuprolide acetate (LA) placebo, LA plus metformin placebo, or LA placebo plus metformin placebo in a 1: 1: 1 fashion during a 12-week period. Main Outcome Measure(s): Insulin sensitivity (M) assessed by euglycemic hyperinsulinemic clamp and free T by equilibrium dialysis. Result(s): In those randomized to metformin, free T decreased by 19% compared with placebo, along with an expected improvement in M. Total Talso decreased significantly, whereas sex hormone-binding globulin (SHBG) did not change. In those randomized to LA, the percent change in M was not different from placebo, despite a 48% relative decrease in free T levels. Conclusion(s): These data are the first to establish a causal link between insulin resistance and T in postmenopausal women. They confirm that treatment of insulin resistance decreases T production in this population and demonstrate that pharmacologic lowering of T does not affect insulin resistance. (Fertil Steril (R) 2010; 94: 2161-6. (C) 2010 by American Society for Reproductive Medicine.) C1 [Patel, Shrita M.; Kaul, Shailja; Rickels, Michael R.; Scattergood, Theresa; Basu, Arpita; Fuller, Carissa; Cappola, Anne R.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Patel, Shrita M.; Ratcliffe, Sarah J.; Cappola, Anne R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Iqbal, Nayyar] Univ Penn, Sch Med, Sect Endocrinol Diabet & Metab, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Reilly, Muredach P.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. RP Cappola, AR (reprint author), Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, 764 CRB,415 Curie Blvd, Philadelphia, PA 19104 USA. EM acappola@mail.med.upenn.edu RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Ratcliffe, Sarah/0000-0002-6644-8284 FU National Institute on Aging [K23 AG19161]; National Center for Research Resources [UL1RR024134]; National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK19525]; John A. Hartford Foundation; University of Pennsylvania Institute for Diabetes, Obesity, and Metabolism FX Supported by K23 AG19161 from the National Institute on Aging, UL1RR024134 from the National Center for Research Resources, P30 DK19525 from the National Institute of Diabetes and Digestive and Kidney Diseases, the John A. Hartford Foundation, and the University of Pennsylvania Institute for Diabetes, Obesity, and Metabolism. The views expressed are those of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 31 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2010 VL 94 IS 6 BP 2161 EP 2166 DI 10.1016/j.fertnstert.2010.01.064 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 670QC UT WOS:000283441400042 PM 20226444 ER PT J AU Zhang, YQ Zhang, HM Shi, Y Lustgarten, M Li, Y Qi, WB Zhang, BX Van Remmen, H AF Zhang, Yiqiang Zhang, Hong-Mei Shi, Yun Lustgarten, Michael Li, Yan Qi, Wenbo Zhang, Bin-Xian Van Remmen, Holly TI Loss of manganese superoxide dismutase leads to abnormal growth and signal transduction in mouse embryonic fibroblasts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE MnSOD; Oxidative stress; ROS; Signal transduction; Free radicals ID REACTIVE OXYGEN; OXIDATIVE STRESS; MITOCHONDRIAL-FUNCTION; KNOCKOUT MICE; MUTANT MICE; LIFE-SPAN; MAMMALIAN TARGET; FREE-RADICALS; CELLS; CA2+ AB Manganese superoxide dismutase (MnSOD) in the mitochondria plays an important role in cellular defense against oxidative damage. Homozygous MnSOD knockout (Sod2(-/-)) mice are neonatal lethal, indicating the essential role of MnSOD in early development. To investigate the potential cellular abnormalities underlying the aborted development of Sod2(-/-) mice, we examined the growth of isolated mouse embryonic fibroblasts (MEFs) from Sod2(-/-) mice. We found that the proliferation of Sod2(-/-) MEFs was significantly decreased compared with wild-type MEFs despite the absence of morphological differences. The Sod2(-/-) MEFs produced less cellular ATP, had lower O(2) consumption, generated more superoxide, and expressed less Prdx3 protein. Furthermore, the loss of MnSOD dramatically altered several markers involved in cell proliferation and growth, including decreased growth stimulatory function of mTOR signaling and enhanced growth inhibitory function of GSK-3 beta signaling. Interestingly, the G-protein-coupled receptor-mediated intracellular Ca(2+) signal transduction was also severely suppressed in Sod2(-/-) MEFs. Finally, the ratio of microtubule-associated protein light chain 3 (LC3)-II/LC3-I, an index of autophagic activity, was increased in Sod2(-/-)MEFs, consistent with a reduction in mTOR signal transduction. These data demonstrate that MnSOD deficiency results in alterations in several key signaling pathways, which may contribute to the lethal phenotype of Sod2(-/-) mice. Published by Elsevier Inc. C1 [Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Zhang, Yiqiang; Shi, Yun; Lustgarten, Michael; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Zhang, Yiqiang; Li, Yan; Qi, Wenbo; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Zhang, Yiqiang; Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Zhang, Hong-Mei; Zhang, Bin-Xian] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Zhang, Hong-Mei] Fourth Mil Med Univ, Dept Clin Oncol, Xijing Hosp, Xian 710032, Peoples R China. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu FU Department of Veterans Affairs FX The authors thank Corinne Price for help in editing the manuscript. This study was supported by a Department of Veterans Affairs Merit Grant to H.V.R. NR 65 TC 30 Z9 31 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2010 VL 49 IS 8 BP 1255 EP 1262 DI 10.1016/j.freeradbiomed.2010.07.006 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 654YN UT WOS:000282207300001 PM 20638473 ER PT J AU Stoffel, EM Chittenden, A AF Stoffel, Elena M. Chittenden, Anu TI Genetic Testing for Hereditary Colorectal Cancer: Challenges in Identifying, Counseling, and Managing High-Risk Patients SO GASTROENTEROLOGY LA English DT Review ID MISMATCH-REPAIR GENES; LYNCH-SYNDROME; COLON-CANCER; MICROSATELLITE INSTABILITY; COST-EFFECTIVENESS; SCREENING PRACTICES; GERMLINE MUTATIONS; PREDICTIVE MODELS; PREDISPOSITION; IDENTIFICATION C1 [Stoffel, Elena M.] Dana Farber Canc Inst, Div Populat Sci, Canc Risk & Prevent Clin, Boston, MA 02115 USA. RP Stoffel, EM (reprint author), Dana Farber Canc Inst, Div Populat Sci, Canc Risk & Prevent Clin, 44 Binney St, Boston, MA 02115 USA. EM estoffel@partners.org FU NCI NIH HHS [K07 CA120448] NR 32 TC 11 Z9 11 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2010 VL 139 IS 5 BP 1436 EP + DI 10.1053/j.gastro.2010.09.018 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 673HW UT WOS:000283651100010 PM 20858494 ER PT J AU Schreiner, MA Weiss, DG Lieberman, DA AF Schreiner, Mitchal A. Weiss, David G. Lieberman, David A. TI Proximal and Large Hyperplastic and Nondysplastic Serrated Polyps Detected by Colonoscopy Are Associated With Neoplasia SO GASTROENTEROLOGY LA English DT Article DE Serrated Polyps; Hyperplastic Polyps; Colon Surveillance; Advanced Neoplasia ID CPG ISLAND METHYLATION; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; KRAS MUTATIONS; RISK-FACTORS; ADENOMAS; BRAF; SURVEILLANCE; PREVALENCE; PATHWAYS AB BACKGROUND & AIMS: The family of serrated lesions includes hyperplastic polyps and sessile serrated adenomas without dysplasia, as well as traditional serrated adenoma with dysplasia. We investigated whether detection of proximal nondysplastic serrated polyps (ND-SP) at screening and surveillance colonoscopies is associated with advanced neoplasia. METHODS: The study included 3121 asymptomatic patients (aged 50-75 years) who had screening colonoscopies; 1371 had subsequent surveillance. The proximal colon was defined as segments proximal to the descending colon. Large ND-SP were defined as > 10 mm. We compared rates of detection of any neoplasia and advanced neoplasia at screening and surveillance colonoscopies (within 5.5 years) in patients with and without proximal or large ND-SP. RESULTS: At baseline screening, 248 patients (7.9%) had at least 1 proximal ND-SP. They were more likely than patients with no proximal ND-SP to have advanced neoplasia (17.3% vs 10.0%; odds ratio [OR], 1.90; 95% confidence interval [CI], 1.33-2.70). Patients with large ND-SP (n = 44) were also more likely to have synchronous advanced neoplasia (OR, 3.37; 95% CI, 1.71-6.65). During surveillance, 39 patients with baseline proximal ND-SP and no neoplasia were more likely to have neoplasia compared with subjects who did not have polyps (OR, 3.14; 95% CI, 1.59-6.20). Among patients with advanced neoplasia at baseline, those with proximal ND-SP (n = 43) were more likely to have advanced neoplasia during surveillance (OR, 2.17; 95% CI, 1.03-4.59). CONCLUSIONS: Detection of proximal and large ND-SP at a screening colonoscopy is associated with an increased risk for synchronous advanced neoplasia. Detection of proximal ND-SP in a baseline colonoscopy is associated with an increased risk for interval neoplasia during surveillance. C1 [Schreiner, Mitchal A.; Lieberman, David A.] Portland VA Med Ctr, Portland, OR 97239 USA. [Schreiner, Mitchal A.; Lieberman, David A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Weiss, David G.] Perry Point VA Med Ctr, Perry Point, MD USA. RP Lieberman, DA (reprint author), Portland VA Med Ctr, P3 GI,1037 SW Vet Hosp Rd, Portland, OR 97239 USA. EM lieberma@ohsu.edu FU Department of Veterans Affairs [380] FX Supported by the Department of Veterans Affairs Cooperative Study Program (#380) and the Department of Veterans Affairs with statistical support for the study (DGW). NR 29 TC 115 Z9 116 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2010 VL 139 IS 5 BP 1497 EP 1502 DI 10.1053/j.gastro.2010.06.074 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 673HW UT WOS:000283651100024 PM 20633561 ER PT J AU Corradini, E Schmidt, PJ Meynard, D Garuti, C Montosi, G Chen, SZ Vukicevic, S Pietrangelo, A Lin, HY Babitt, JL AF Corradini, Elena Schmidt, Paul J. Meynard, Delphine Garuti, Cinzia Montosi, Giuliana Chen, Shanzhuo Vukicevic, Slobodan Pietrangelo, Antonello Lin, Herbert Y. Babitt, Jodie L. TI BMP6 Treatment Compensates for the Molecular Defect and Ameliorates Hemochromatosis in Hfe Knockout Mice SO GASTROENTEROLOGY LA English DT Article DE Hemochromatosis; HFE; Bone Morphogenetic Protein ID HEPCIDIN EXPRESSION; HEREDITARY HEMOCHROMATOSIS; IRON-METABOLISM; MOUSE MODEL; PROTEIN; OVERLOAD; LIVER; ELEMENTS; HEMOJUVELIN; REGULATOR AB BACKGROUND & AIMS: Abnormal hepcidin regulation is central to the pathogenesis of HFE hemochromatosis. Hepatic bone morphogenetic protein 6 (BMP6)-SMAD signaling is a main regulatory mechanism controlling hepcidin expression, and this pathway was recently shown to be impaired in Hfe knockout (Hfe(-/-)) mice. To more definitively determine whether HFE regulates hepcidin expression through an interaction with the BMP6-SMAD signaling pathway, we investigated whether hepatic Hfe overexpression activates the BMP6-SMAD pathway to induce hepcidin expression. We then investigated whether excess exogenous BMP6 administration overcomes the BMP6-SMAD signaling impairment and ameliorates hemochromatosis in Hfe(-/-) mice. METHODS: The BMP6-SMAD pathway and the effects of neutralizing BMP6 antibody were examined in Hfe transgenic mice (Hfe Tg) compared with wild-type (WT) mice. Hfe(-/-) and WT mice were treated with exogenous BMP6 and analyzed for hepcidin expression and iron parameters. RESULTS: Hfe Tg mice exhibited hepcidin excess and iron deficiency anemia. Hfe Tg mice also exhibited increased hepatic BMP6-SMAD target gene expression compared with WT mice, whereas anti-BMP6 antibody administration to Hfe Tg mice improved the hepcidin excess and iron deficiency. In Hfe(-/-) mice, supraphysiologic doses of exogenous BMP6 improved hepcidin deficiency, reduced serum iron, and redistributed tissue iron to appropriate storage sites. CONCLUSIONS: HFE interacts with the BMP6-SMAD signaling pathway to regulate hepcidin expression, but HFE is not necessary for hepcidin induction by BMP6. Exogenous BMP6 treatment in mice compensates for the molecular defect underlying Hfe hemochromatosis, and BMP6-like agonists may have a role as an alternative therapeutic strategy for this disease. C1 [Corradini, Elena; Meynard, Delphine; Chen, Shanzhuo; Lin, Herbert Y.; Babitt, Jodie L.] Harvard Univ, Program Membrane Biol, Sch Med, Nephrol Div,Ctr Syst Biol,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Corradini, Elena; Garuti, Cinzia; Montosi, Giuliana; Pietrangelo, Antonello] Univ Hosp Modena & Reggio Emilia, Ctr Hemochromatosis, Modena, Italy. [Schmidt, Paul J.] Childrens Hosp Boston, Dept Pathol, Boston, MA USA. [Vukicevic, Slobodan] Univ Zagreb, Sch Med, Ctr Translat & Clin Res, Lab Mineralized Tissues, Zagreb 41001, Croatia. RP Babitt, JL (reprint author), Harvard Univ, Program Membrane Biol, Sch Med, Nephrol Div,Ctr Syst Biol,Massachusetts Gen Hosp, 185 Cambridge St,CPZN-8218, Boston, MA 02114 USA. EM babitt.jodie@mgh.harvard.edu RI meynard, delphine/B-4236-2014; Corradini, Elena/O-4167-2016; Pietrangelo, Antonello/K-1517-2016 OI Corradini, Elena/0000-0001-9477-2164; Pietrangelo, Antonello/0000-0002-7411-935X FU Massachusetts Biomedical Research Corporation (MBRC) at Massachusetts General Hospital; National NIH [K01 DK074410]; Italian University and Research Council [PRIN-08]; Telethon; MZOS [108-1080327-0320]; NIH [RO1 DK069533, RO1 DK071837, K08 DK075846, RO1 DK087727]; National Kidney Foundation; Massachusetts General Hospital FX E.C. was supported in part by a Tosteson Postdoctoral Fellowship Award from the Massachusetts Biomedical Research Corporation (MBRC) at Massachusetts General Hospital. P.J.S. was supported in part by National NIH grant K01 DK074410. C.G., G.M., and A.P. were supported by the Italian University and Research Council grant PRIN-08 and the Telethon 2010 grant. S. V. was supported in part by MZOS grant 108-1080327-0320. H.Y.L. was supported in part by NIH grants RO1 DK069533 and RO1 DK071837. J.L.B. was supported in part by NIH grants K08 DK075846 and RO1 DK087727, by the Satellite Dialysis Young Investigator Grant of the National Kidney Foundation, and by a Claflin Distinguished Scholar Award from the Massachusetts General Hospital. NR 40 TC 49 Z9 51 U1 3 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2010 VL 139 IS 5 BP 1721 EP 1729 DI 10.1053/j.gastro.2010.07.044 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 673HW UT WOS:000283651100047 PM 20682319 ER PT J AU Telford, JJ Carr-Locke, DL Baron, TH Poneros, JM Bounds, BC Kelsey, PB Schapiro, RH Huang, CS Lichtenstein, DR Jacobson, BC Saltzman, JR Thompson, CC Forcione, DG Gostout, CJ Brugge, WR AF Telford, Jennifer J. Carr-Locke, David L. Baron, Todd H. Poneros, John M. Bounds, Brenna C. Kelsey, Peter B. Schapiro, Robert H. Huang, Christopher S. Lichtenstein, David R. Jacobson, Brian C. Saltzman, John R. Thompson, Christopher C. Forcione, David G. Gostout, Christopher J. Brugge, William R. TI A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/108th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-25, 2007 CL Washington, DC SP Amer Gastroenterol Assoc, Amer Assoc Study Liver Dis, Amer Soc Gastrointestinal Endoscopy, Soc Surg Alimentary Tract ID COMMON BILE-DUCT; WALLSTENTS; CHOLECYSTITIS; MANAGEMENT; PLACEMENT; EFFICACY AB Background: The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. Objective: To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. Design: Multicenter randomized trial. Setting: Four teaching hospitals. Patients: Adults with inoperable distal malignant biliary obstruction. Interventions: Uncovered or partially covered SEMS insertion. Main Outcome Measures: Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. Results: From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively (P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups (P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively (P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated (P = .0061). Limitations: Intended sample size was not reached. Allocation to treatment groups was unequal. Conclusions: There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration. (Clinical trial registration number: NCT01047332.) (Gastrointest Endosc 2010;72:907-14.) C1 [Telford, Jennifer J.] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. [Carr-Locke, David L.] New York Presbyterian Hosp, Beth Israel Med Ctr, New York, NY 10003 USA. [Baron, Todd H.; Gostout, Christopher J.] Mayo Clin, Rochester, MN USA. [Bounds, Brenna C.; Kelsey, Peter B.; Schapiro, Robert H.; Forcione, David G.; Brugge, William R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huang, Christopher S.; Lichtenstein, David R.; Jacobson, Brian C.] Boston Univ, Med Ctr, Boston, MA USA. [Saltzman, John R.; Thompson, Christopher C.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Telford, JJ (reprint author), Univ British Columbia, Pacific Gastroenterol Associates, 770-1190 Hornby St, Vancouver, BC V6Z 2K5, Canada. OI Jacobson, Brian/0000-0001-7064-2357; Huang, Christopher/0000-0003-0582-7499 NR 17 TC 92 Z9 94 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2010 VL 72 IS 5 BP 907 EP 914 DI 10.1016/j.gie.2010.08.021 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 678SU UT WOS:000284101500001 PM 21034891 ER PT J AU Egede, LE Grubaugh, AL Ellis, C AF Egede, Leonard E. Grubaugh, Anouk L. Ellis, Charles TI The effect of major depression on preventive care and quality of life among adults with diabetes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Major depression; Preventive care; Quality of life; Adults with diabetes ID RISK-FACTOR SURVEY; SELF-CARE; MEDICATION ADHERENCE; COMORBID DEPRESSION; GLYCEMIC CONTROL; US ADULTS; TYPE-2; METAANALYSIS; INDIVIDUALS; SYMPTOMS AB Objective: To examine the association between major depression and preventive care practices and quality-of-life indices among adults with diabetes. Methods: Data from 16,754 participants with diabetes in the 2006 Behavioral Risk Factor Surveillance Survey were examined. Multiple logistic regression was used to assess the independent association between the presence of major depression and a range of (1) preventive care behaviors and (2) quality-of-life indices, after accounting for relevant covariates. Results: With regard to preventive care practices, women with major depression were less likely to have received a mammogram in the past 2 years [OR 0.60 (95% Cl 0.45-0.79) for women age 40 years and older and OR 0.52 (95% Cl 0.37-0.71) for women age 50 and older] relative to their counterparts without major depression. With regard to quality-of-life indices, individuals with major depression were less likely to perceive their health as good [OR 0.24 (95% Cl 0.19-0.31)], to report being satisfied with life [OR 0.10 (95% Cl 0.07-0.14)] and to report receiving needed social support [OR 0.29 (95% Cl 0.22-0.38)] relative to individuals without major depression. Individuals with major depression were also more likely to report one or more poor physical and poor mental health days in the past 30 days [OR 4.36 (95% Cl 3.33-5.72) and OR 9.77 (95% Cl 7.81-12.22), respectively] than those without major depression. Conclusions: Major depression in adults with diabetes is associated with decreases in a wide range of quality-of-life indices as well as preventive self-care practices that were not entirely limited to diabetes-specific disease management. (c) 2010 Elsevier Inc. All rights reserved. C1 [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Grubaugh, Anouk L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Ellis, Charles] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Egede, Leonard E.; Grubaugh, Anouk L.; Ellis, Charles] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. EM egedel@musc.edu FU SC HSRD [REA 08-261]; Veterans Health Administration Health Services Research and Development program [07-015-2, 07-012-3] FX This work represents work supported by the use of facilities at the Charleston, SC HSR&D Funded Center for Disease Prevention and Health Interventions for Diverse Populations (REA 08-261).; Dr. Grubaugh and Dr. Ellis are both supported by a career development award (CDA2 #07-015-2 and CDA #07-012-3, respectively) from the Veterans Health Administration Health Services Research and Development program. NR 42 TC 22 Z9 23 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2010 VL 32 IS 6 BP 563 EP 569 DI 10.1016/j.genhosppsych.2010.08.002 PG 7 WC Psychiatry SC Psychiatry GA 693PC UT WOS:000285235000001 PM 21112446 ER PT J AU Kilbourne, AM Teh, CF Welsh, D Pincus, HA Lasky, E Perron, B Bauer, MS AF Kilbourne, Amy M. Teh, Carrie Farmer Welsh, Deborah Pincus, Harold Alan Lasky, Elaine Perron, Brian Bauer, Mark S. TI Implementing composite quality metrics for bipolar disorder: towards a more comprehensive approach to quality measurement SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Mood disorders-bipolar; Quality of care; Quality improvement; Co-occurring conditions ID HEALTH-CARE; OF-CARE; RACIAL-DIFFERENCES; POPULATION; PERFORMANCE; PREVALENCE; DIAGNOSIS; OUTCOMES; COSTS; TRIAL AB Objective: We implemented a set of processes of care measures for bipolar disorder that reflect psychosocial, patient preference and continuum of care approaches to mental health, and examined whether veterans with bipolar disorder receive care concordant with these practices. Method: Data from medical record reviews were used to assess key processes of care for 433 VA mental health outpatients with bipolar disorder. Both composite and individual processes of care measures were operationalized. Results: Based on composite measures, 17% had documented assessment of psychiatric symptoms (e.g., psychotic, hallucinatory), 28% had documented patient treatment preferences (e.g., reasons for treatment discontinuation), 56% had documented substance abuse and psychiatric comorbidity assessment, and 62% had documentation of adequate cardiometabolic assessment. No-show visits were followed up 20% of the time, and monitoring of weight gain was noted in only 54% of the patient charts. In multivariate analyses, history of homelessness (OR=1.61; 95% Cl=1.05-2.46) and nonwhite race (OR=1.74; 95%Cl=1.02-2.98) were associated with documentation of psychiatric symptoms and comorbidities, respectively. Conclusions: Only half of patients diagnosed with bipolar disorder received care in accordance with clinical practice guidelines. High-quality treatment of bipolar disorder includes not only adherence to treatment guidelines but also patient-centered care processes. Published by Elsevier Inc. C1 [Kilbourne, Amy M.; Welsh, Deborah; Perron, Brian] VA Ann Arbor HSR&D Ctr Excellence, Ann Arbor, MI 48105 USA. [Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Teh, Carrie Farmer; Pincus, Harold Alan] RAND Corp, Pittsburgh, PA 15213 USA. [Pincus, Harold Alan] New York Presbyterian Hosp, New York, NY 10032 USA. [Pincus, Harold Alan] Columbia Univ, Irving Inst Clin & Translat Res, New York, NY 10032 USA. [Pincus, Harold Alan] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Lasky, Elaine] VA Pittsburgh Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Perron, Brian] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Boston, MA 02132 USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA 02132 USA. RP Kilbourne, AM (reprint author), VA Ann Arbor HSRD SMITREC, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 02-283]; National Institute of Mental Health [MH 74509, MH 79994, T32 MH19986] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (IIR 02-283) and by the National Institute of Mental Health (MH 74509; MH 79994, T32 MH19986). The funding source had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. All authors warrant having no actual or perceived conflicts of interest - financial or nonfinancial - in the procedures described in 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 37 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2010 VL 32 IS 6 BP 636 EP 643 DI 10.1016/j.genhosppsych.2010.09.011 PG 8 WC Psychiatry SC Psychiatry GA 693PC UT WOS:000285235000012 PM 21112457 ER PT J AU Liu, HD Chi, AWS Arnett, KL Chiang, MY Xu, LW Shestova, O Wang, HF Li, YM Bhandoola, A Aster, JC Blacklow, SC Pear, WS AF Liu, Hudan Chi, Anthony W. S. Arnett, Kelly L. Chiang, Mark Y. Xu, Lanwei Shestova, Olga Wang, Hongfang Li, Yue-Ming Bhandoola, Avinash Aster, Jon C. Blacklow, Stephen C. Pear, Warren S. TI Notch dimerization is required for leukemogenesis and T-cell development SO GENES & DEVELOPMENT LA English DT Article DE Notch; transcription; c-Myc; lymphocyte; T-ALL; leukemia ID BETA-SELECTION CHECKPOINT; DELTA-LIKE 4; PRE-TCR; C-MYC; LINEAGE COMMITMENT; THYMOCYTE DIFFERENTIATION; SIGNALING CONTROLS; COLORECTAL-CANCER; PROGENITOR CELLS; GENE-EXPRESSION AB Notch signaling regulates myriad cellular functions by activating transcription, yet how Notch selectively activates different transcriptional targets is poorly understood. The core Notch transcriptional activation complex can bind DNA as a monomer, but it can also dimerize on DNA-binding sites that are properly oriented and spaced. However, the significance of Notch dimerization is unknown. Here, we show that dimeric Notch transcriptional complexes are required for T-cell maturation and leukemic transformation but are dispensable for T-cell fate specification from a multipotential precursor. The varying requirements for Notch dimerization result from the differential sensitivity of specific Notch target genes. In particular, c-Myc and pre-T-cell antigen receptor alpha (Ptcra) are dimerization-dependent targets, whereas Hey1 and CD25 are not. These findings identify functionally important differences in the responsiveness among Notch target genes attributable to the formation of higher-order complexes. Consequently, it may be possible to develop a new class of Notch inhibitors that selectively block outcomes that depend on Notch dimerization (e.g., leukemogenesis). C1 [Liu, Hudan; Chiang, Mark Y.; Xu, Lanwei; Shestova, Olga; Pear, Warren S.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Liu, Hudan; Xu, Lanwei; Shestova, Olga; Pear, Warren S.] Univ Penn, Inst Med & Engn, Philadelphia, PA 19104 USA. [Liu, Hudan; Chi, Anthony W. S.; Xu, Lanwei; Shestova, Olga; Bhandoola, Avinash; Pear, Warren S.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Arnett, Kelly L.; Wang, Hongfang; Aster, Jon C.; Blacklow, Stephen C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Arnett, Kelly L.; Blacklow, Stephen C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chiang, Mark Y.] Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Li, Yue-Ming] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA. RP Pear, WS (reprint author), Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. EM wpear@mail.med.upenn.edu RI Arnett, Kelly/C-4816-2012; Liu, Hudan/K-6037-2012; Su, Hexiu/O-4913-2014; OI Arnett, Kelly/0000-0001-5117-3647 FU National Institute of Health [R01AG02666, RC1HL099758, P01CA119070, R01AI047833, T32-DK07780, T32-CA009140]; Leukemia and Lymphoma Society; Lymphoma Research Foundation; NCI [K08 CA120544-01]; American Cancer Society FX We are grateful to B. Reizis for providing reagents, C. Romany and K. Toscano for retroviral production, and members of the Pear laboratory, T. Kadesch, and G. Qing for advice and comments on the manuscript. We thank William Demuth for cell sorting. This work was supported by grants from the National Institute of Health to Y.L. (R01AG02666), A. B. (RC1HL099758), S. C. B. (P01CA119070), J.C.A. (P01CA119070), and W. S. P. (R01AI047833, P01CA119070), and a Leukemia and Lymphoma Society SCOR Award to J.C.A., S. C. B., and W. S. P. Individual support was provided by an NIH-funded Institutional Research Training Grant (T32-DK07780) and a Fellow Award from the Lymphoma Research Foundation to H. L., an NIH-funded Institutional Research Training Grant (T32-CA009140) to A. W. S. C., a career development award from the NCI (K08 CA120544-01) to M.Y.C., a Fellow Award from the American Cancer Society to K. L. A., and a Fellow Award from the Leukemia and Lymphoma Society to H.W. NR 64 TC 31 Z9 31 U1 1 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV PY 2010 VL 24 IS 21 BP 2395 EP 2407 DI 10.1101/gad.1975210 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 673JU UT WOS:000283656400005 PM 20935071 ER PT J AU Sebro, R Hoffman, TJ Lange, C Rogus, JJ Risch, NJ AF Sebro, Ronnie Hoffman, Thomas J. Lange, Christoph Rogus, John J. Risch, Neil J. TI Testing for Non-Random Mating: Evidence for Ancestry-Related Assortative Mating in the Framingham Heart Study SO GENETIC EPIDEMIOLOGY LA English DT Article DE population stratification; non-random mating; Hardy-Weinberg equilibrium ID HARDY-WEINBERG EQUILIBRIUM; GENOME-WIDE ASSOCIATION; GENOTYPING ERRORS; STRATIFICATION; POPULATION AB Population stratification leads to a predictable phenomenon-a reduction in the number of heterozygotes compared to that calculated assuming Hardy-Weinberg Equilibrium (HWE). We show that population stratification results in another phenomenon-an excess in the proportion of spouse-pairs with the same genotypes at all ancestrally informative markers, resulting in ancestrally related positive assortative mating. We use principal components analysis to show that there is evidence of population stratification within the Framingham Heart Study, and show that the first principal component correlates with a North-South European cline. We then show that the first principal component is highly correlated between spouses (r = 0.58, p = 0.0013), demonstrating that there is ancestrally related positive assortative mating among the Framingham Caucasian population. We also show that the single nucleotide polymorphisms loading most heavily on the first principal component show an excess of homozygotes within the spouses, consistent with similar ancestry-related assortative mating in the previous generation. This nonrandom mating likely affects genetic structure seen more generally in the North American population of European descent today, and decreases the rate of decay of linkage disequilibrium for ancestrally informative markers. Genet. Epidemiol. 34:674-679, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Sebro, Ronnie; Hoffman, Thomas J.; Risch, Neil J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Sebro, Ronnie] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lange, Christoph] Univ Bonn, Inst Genom Math, D-5300 Bonn, Germany. [Lange, Christoph] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. [Rogus, John J.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Risch, Neil J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Risch, Neil J.] Kaiser Permanente, Div Res, Oakland, CA USA. RP Sebro, R (reprint author), Univ Calif San Francisco, Inst Human Genet, 513 Parnassus Ave,Suite S965,Box 0794, San Francisco, CA 94143 USA. EM rsebro@radmail.ucsf.edu FU Howard Hughes Medical Institute; NIH [R25CA112355]; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195]; Boston University [N01-HC-25195] FX Contract grant sponsor: Howard Hughes Medical Institute Pre-Doctoral Fellowship.; Ronnie Sebro was supported by a Howard Hughes Medical Institute Pre-Doctoral Fellowship. Thomas J. Hoffmann was supported by NIH R25CA112355 training grant. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195). This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. The authors thank Dr. Nan Laird, Solandra Craig and two anonymous reviewers for their helpful comments. NR 16 TC 15 Z9 15 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2010 VL 34 IS 7 BP 674 EP 679 DI 10.1002/gepi.20528 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 677BZ UT WOS:000283965400004 PM 20842694 ER PT J AU Watt, T Burlina, AP Cazzorla, C Schonfeld, D Banikazemi, M Hopkin, RJ Martins, AM Sims, K Beitner-Johnson, D O'Brien, F Feldt-Rasmussen, U AF Watt, Torquil Burlina, Alessandro P. Cazzorla, Chiara Schoenfeld, Dorothee Banikazemi, Maryam Hopkin, Robert J. Martins, Ana Maria Sims, Katherine Beitner-Johnson, Dana O'Brien, Fanny Feldt-Rasmussen, Ulla TI Agalsidase beta treatment is associated with improved quality of life in patients with Fabry disease: Findings from the Fabry Registry SO GENETICS IN MEDICINE LA English DT Article DE lysosomal storage disease; alpha galactosidase A deficiency; SF-36 (R) Health Survey; enzyme replacement therapy; health status indicator ID ENZYME REPLACEMENT THERAPY; CLINICAL-MANIFESTATIONS; RHEUMATOID-ARTHRITIS; ALPHA-GALACTOSIDASE; OUTCOME SURVEY; DOUBLE-BLIND; HEALTH; MALES; FEMALES; TRIAL AB Purpose: To evaluate the effect of agalsidase beta on longitudinal health-related quality of life in patients with Fabry disease. Methods: The SF-36 (R) Health Survey was used to measure health-related quality of life in Fabry Registry patients. Seventy-one men and 59 women who were treated with agalsidase beta (median dose: 1.0 mg/kg/2 weeks) and who had baseline and at least 2 yearly posttreatment health-related quality of life measurements were included in these analyses. A repeated measures model was used to analyze change in score from baseline. Results: Men improved in the physical component summary and in all eight scales of the SF-36 after 1 and 2 years and in the mental component summary after 1 year of agalsidase beta treatment (P < 0.05). Women improved in the mental component summary and in six of the eight scales after 1 and/or 2 years of treatment. Patients whose baseline SF-36 scores were below the median showed the greatest improvements. These responses were comparable with or greater than the published effects of various treatments for multiple sclerosis, rheumatoid arthritis, central neuropathic pain, and Gaucher disease. Conclusion: Long-term treatment with agalsidase beta resulted in substantial improvements in health-related quality of life in both men and women; the effect was more pronounced in men. Genet Med 2010:12(11):703 712. C1 [Watt, Torquil; Feldt-Rasmussen, Ulla] Natl Univ Hosp, Dept Endocrinol, DK-2100 Copenhagen, Denmark. [Burlina, Alessandro P.] San Bassano Hosp, Dept Neurol, Bassano Del Grappa, Italy. [Cazzorla, Chiara] Univ Padua, Dept Neurosci, Padua, Italy. [Schoenfeld, Dorothee] Univ Wurzburg, Dept Med, Wurzburg, Germany. [Banikazemi, Maryam] Columbia Univ, Dept Pediat, Div Clin Genet, Coll Phys & Surg, New York, NY 10027 USA. [Hopkin, Robert J.] Cincinnati Childrens Hosp, Div Human Genet, Cincinnati, OH USA. [Martins, Ana Maria] Univ Fed Sao Paulo, Inatos Metab CREIM, Sao Paulo, Brazil. [Sims, Katherine] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Beitner-Johnson, Dana; O'Brien, Fanny] Genzyme Corp, Dept Biomed Data Sci & Informat, Cambridge, MA USA. RP Feldt-Rasmussen, U (reprint author), Natl Univ Hosp, Dept Endocrinol, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. EM ufeldt@rh.dk OI Hopkin, Robert/0000-0003-0770-5516 FU Genzyme Corporation; Genzyme FX The Fabry Registry is sponsored by Genzyme Corporation. U.F.-R., K.S., R.J.H., M. B., A.M., and A.P.B. serve on the Genzyme-sponsored Fabry Registry Boards of Advisors. D.B.-J. and F.O.B. are full-time employees of Genzyme Corporation. T.W. has received unrestricted grants from Genzyme for other research projects. NR 35 TC 31 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV PY 2010 VL 12 IS 11 BP 703 EP 712 DI 10.1097/GIM.0b013e3181f13a4a PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 678UD UT WOS:000284105800007 PM 20885332 ER PT J AU Scheuner, MT McNeel, TS Freedman, AN AF Scheuner, Maren T. McNeel, Timothy S. Freedman, Andrew N. TI Population prevalence of familial cancer and common hereditary cancer syndromes. The 2005 California Health Interview Survey SO GENETICS IN MEDICINE LA English DT Article DE family history; cancer; hereditary cancer syndrome; prevalence of familial risk ID NONPOLYPOSIS COLORECTAL-CANCER; LYNCH-SYNDROME; OVARIAN-CANCER; HISTORY; RISK; PREVENTION; REGISTRIES; CRITERIA AB Purpose: Family history guides cancer prevention and genetic testing. We sought to estimate the population prevalence of increased familial risk for breast, ovarian, endometrial, prostate, and colorectal cancers and hereditary cancer syndromes that include these cancers. Methods: Using the 2005 California Health Interview Survey data, a weak, moderate, or strong familial cancer risk was assigned to 33,187 respondents. Guidelines were applied to identify individuals with hereditary breast-ovarian cancer and hereditary nonpolyposis colon cancer. Results: Among respondents without a personal history of cancer, familial breast cancer was most prevalent; 7% had a moderate and 5% a strong familial risk. Older individuals and women were more likely to report family history of cancer. Generally, whites had the highest prevalence, and Asians and Latinos had the lowest prevalence. Among women without a personal history of breast or ovarian cancer, 2.5% met criteria for hereditary breast-ovarian cancer, and among individuals without a personal history of colorectal, endometrial or ovarian cancer, 1.1% met criteria for hereditary nonpolyposis colon cancer. Conclusions: We provide population-based prevalence estimates for moderate and strong familial risk for five common cancers and hereditary breast-ovarian cancer and hereditary nonpolyposis colon cancer. Such estimates are helpful in planning and evaluation of genetic services and prevention programs, and assessment of cancer surveillance and prevention strategies. Genet Med 2010:12(11):726-735. C1 [Scheuner, Maren T.] RAND Corp, Santa Monica, CA USA. [Scheuner, Maren T.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Scheuner, Maren T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [McNeel, Timothy S.] Informat Management Serv Inc, Silver Spring, MD USA. [Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Scheuner, MT (reprint author), 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM scheuner@rand.org FU National Cancer Institute at the National Institutes of Health FX This work was supported by a contract from the National Cancer Institute at the National Institutes of Health. NR 25 TC 30 Z9 30 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV PY 2010 VL 12 IS 11 BP 726 EP 735 DI 10.1097/GIM.0b013e3181f30e9e PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 678UD UT WOS:000284105800010 PM 20921897 ER PT J AU Paintlia, AS Paintlia, MK Singh, AK Orak, JK Singh, I AF Paintlia, Ajaib S. Paintlia, Manjeet K. Singh, Avtar K. Orak, John K. Singh, Inderjit TI Activation of PPAR-gamma and PTEN Cascade Participates in Lovastatin-Mediated Accelerated Differentiation of Oligodendrocyte Progenitor Cells SO GLIA LA English DT Article DE lovastatin; EAE/MS; oligodendrocyte progenitors; PPAR-gamma/PTEN; RhoA-ROCK; differentiation; remyelination ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COA REDUCTASE INHIBITOR; MULTIPLE-SCLEROSIS; GENE-EXPRESSION; PROTEIN-KINASE; IN-VITRO; CYCLE PROGRESSION; GROWTH-ARREST; GLIAL-CELLS AB Previously, we and others documented that statins including-lovastatin (LOV) promote the differentiation of oligodendrocyte progenitor cells (OPCs) and remyelination in experimental autoimmune encephalomyelitis (EAE), an multiple sclerosis (MS) model. Conversely, some recent studies demonstrated that statins negatively influence oligodendrocyte (OL) differentiation in vitro and remyelination in a cuprizone-CNS demyelinating model. Therefore, herein, we first investigated the cause of impaired differentiation of OLs by statins in vitro settings. Our observations indicated that the depletion of cholesterol was detrimental to LOV treated OPCs under cholesterol/serum-deprived culture conditions similar to that were used in conflicting studies. However, the depletion of geranylgeranyl-pp under normal cholesterol homeostasis conditions enhanced the phenotypic commitment and differentiation of LOV-treated OPCs ascribed to inhibition of RhoA-Rho kinase. Interestingly, this effect of LOV was associated with increased activation and expression of both PPAR-g and PTEN in OPCs as confirmed by various pharmacological and molecular based approaches. Furthermore, PTEN was involved in an inhibition of OPCs proliferation via PI3K-Akt inhibition and induction of cell cycle arrest at G1 phase, but without affecting their cell survival. These effects of LOV on OPCs in vitro were absent in the CNS of normal rats chronically treated with LOV concentrations used in EAE indicating that PPAR-g induction in normal brain may be tightly regulated-providing evidences that statins are therapeutically safe for humans. Collectively, these data provide initial evidence that statin-mediated activation of the PPAR-gamma-PTEN cascade participates in OL differentiation, thus suggesting new therapeutic-interventions for MS or related CNS-demyelinating diseases. (C) 2010 Wiley-Liss, Inc. C1 [Paintlia, Ajaib S.; Paintlia, Manjeet K.; Orak, John K.; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NIH [NS-22576, NS-34741, NS-37766, NS-038236]; Dialysis Clinic Inc. [C06-RR015455, C06-RR018823] FX Grant sponsor: NIH; Grant numbers: NS-22576, NS-34741, NS-37766, and NS-038236; Contract grant sponsor: Dialysis Clinic Inc.; Contract grant numbers: C06-RR015455 and C06-RR018823. NR 57 TC 23 Z9 24 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD NOV PY 2010 VL 58 IS 14 BP 1669 EP 1685 DI 10.1002/glia.21039 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 664VH UT WOS:000282990600003 PM 20578043 ER PT J AU Malo, MS Alam, SN Mostafa, G Zeller, SJ Johnson, PV Mohammad, N Chen, KT Moss, AK Ramasamy, S Faruqui, A Hodin, S Malo, PS Ebrahimi, F Biswas, B Narisawa, S Millan, JL Warren, HS Kaplan, JB Kitts, CL Hohmann, EL Hodin, RA AF Malo, M. S. Alam, S. Nasrin Mostafa, G. Zeller, S. J. Johnson, P. V. Mohammad, N. Chen, K. T. Moss, A. K. Ramasamy, S. Faruqui, A. Hodin, S. Malo, P. S. Ebrahimi, F. Biswas, B. Narisawa, S. Millan, J. L. Warren, H. S. Kaplan, J. B. Kitts, C. L. Hohmann, E. L. Hodin, R. A. TI Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota SO GUT LA English DT Article ID GENE-EXPRESSION; GASTROINTESTINAL-TRACT; KNOCKOUT MICE; RAT; DIARRHEA; PATTERN; FLORA; LIPOPOLYSACCHARIDE; TOXICITY; COLITIS AB Background and aims The intestinal microbiota plays a critical role in maintaining human health; however, the mechanisms governing the normal homeostatic number and composition of these microbes are largely unknown. Previously it was shown that intestinal alkaline phosphatase (IAP), a small intestinal brush border enzyme, functions as a gut mucosal defence factor limiting the translocation of gut bacteria to mesenteric lymph nodes. In this study the role of IAP in the preservation of the normal homeostasis of the gut microbiota was investigated. Methods Bacterial culture was performed in aerobic and anaerobic conditions to quantify the number of bacteria in the stools of wild-type (WT) and IAP knockout (IAP-KO) C57BL/6 mice. Terminal restriction fragment length polymorphism, phylogenetic analyses and quantitative real-time PCR of subphylum-specific bacterial 16S rRNA genes were used to determine the compositional profiles of microbiotas. Oral supplementation of calf IAP (cIAP) was used to determine its effects on the recovery of commensal gut microbiota after antibiotic treatment and also on the colonisation of pathogenic bacteria. Results IAP-KO mice had dramatically fewer and also different types of aerobic and anaerobic microbes in their stools compared with WT mice. Oral supplementation of IAP favoured the growth of commensal bacteria, enhanced restoration of gut microbiota lost due to antibiotic treatment and inhibited the growth of a pathogenic bacterium (Salmonella typhimurium). Conclusions IAP is involved in the maintenance of normal gut microbial homeostasis and may have therapeutic potential against dysbiosis and pathogenic infections. C1 [Malo, M. S.; Alam, S. Nasrin; Mostafa, G.; Mohammad, N.; Chen, K. T.; Moss, A. K.; Ramasamy, S.; Faruqui, A.; Hodin, S.; Malo, P. S.; Ebrahimi, F.; Biswas, B.; Hodin, R. A.] Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Zeller, S. J.; Johnson, P. V.; Hohmann, E. L.] Harvard Univ, Div Infect Dis, Dept Med, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. [Warren, H. S.] Harvard Univ, Infect Dis Unit, Dept Pediat, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. [Warren, H. S.] Harvard Univ, Infect Dis Unit, Dept Med, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. [Kitts, C. L.] Calif Polytech State Univ San Luis Obispo, Environm Biotechnol Inst, San Luis Obispo, CA USA. RP Malo, MS (reprint author), Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Jackson 812,55 Fruit St, Boston, MA 02114 USA. EM mmalo@partners.org OI Kuhnen, Angela/0000-0003-4944-9143 FU NIH [R01DK050623, R01DK047186]; MGH Department of Surgery; Bill and Melinda Gates Foundation FX This work was supported by NIH grants R01DK050623 and R01DK047186 to RAH, a Junior Faculty Award to MSM from the MGH Department of Surgery and a Grand Challenge Exploration Grant from the Bill and Melinda Gates Foundation to MSM. NR 37 TC 55 Z9 60 U1 4 U2 28 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD NOV PY 2010 VL 59 IS 11 BP 1476 EP 1484 DI 10.1136/gut.2010.211706 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 664LZ UT WOS:000282963100010 PM 20947883 ER PT J AU Muller, S Schaffer, T Flogerzi, B Seibold-Schmid, B Schnider, J Takahashi, K Darfeuille-Michaud, A Vazeille, E Schoepfer, AM Seibold, F AF Mueller, Stefan Schaffer, Thomas Flogerzi, Beatrice Seibold-Schmid, Beatrice Schnider, Jasmin Takahashi, Kazue Darfeuille-Michaud, Arlette Vazeille, Emilie Schoepfer, Alain M. Seibold, Frank TI Mannan-binding lectin deficiency results in unusual antibody production and excessive experimental colitis in response to mannose-expressing mild gut pathogens SO GUT LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS; ESCHERICHIA-COLI; INNATE IMMUNITY; ILEAL MUCOSA; INFECTION; MICE; RECOGNITION AB Background In Crohn's disease (CD) the deficiency of mannan-binding lectin (MBL) is associated with an increased prevalence of anti-Saccharomyces cerevisiae antibodies (ASCA) and with complicated phenotypes of the disease. However, the role of MBL in intestinal inflammation is currently unclear. A study was undertaken to analyse local MBL expression in human intestine and the consequences of MBL deficiency in experimental colitis and yeast infection. Methods ASCA were measured by ELISA. MBL was assessed by ELISA and quantitative PCR. Wild type and MBL-deficient mice were administered dextran sulfate sodium (DSS) in the presence or absence of viable Candida albicans or adhesive invasive Escherichia coli (AIEC). Mice were infected with C albicans to assess generation of anti-yeast mannan antibodies. Results MBL expression was virtually undetectable in the intestinal mucosa of both healthy controls and patients with CD, irrespective of macroscopic inflammation, indicating that systemic MBL must be responsible for the reduced risk of complicated disease in MBL-competent patients with CD. MBL-deficient mice showed enhanced DSS colitis upon oral challenge with C albicans or AIEC. C albicans could be recovered from the kidneys of colitic/C albicans-fed MBL-deficient, but not wild type mice. Infection with C albicans induced high titres of anti-C albicans mannan IgM and IgG in MBL-deficient mice but only a modest and transient IgM response with no class switch to IgG in wild type mice. Cross-reactive ASCA IgM continuously increased in MBL-deficient mice but rapidly declined after transient induction in wild type mice. In MBL-deficient mice, increased C albicans dissemination correlated with reduced early retention in the circulation. Conclusions These results suggest that systemic MBL helps to prevent excessive inflammation upon access of normally mild pathogens across the damaged intestinal epithelium. Lack of this innate defence promotes antibody responses with cross-reactive potential against common mannan epitopes. These interpretations are compatible with the increased prevalence of ASCA and complicated disease phenotypes in MBL-deficient patients with CD. C1 [Mueller, Stefan; Schaffer, Thomas; Flogerzi, Beatrice; Seibold-Schmid, Beatrice; Schnider, Jasmin; Schoepfer, Alain M.; Seibold, Frank] Univ Bern, Dept Clin Res, Div Gastroenterol, CH-3010 Bern, Switzerland. [Takahashi, Kazue] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Programs Dev Immunol, Boston, MA USA. [Darfeuille-Michaud, Arlette; Vazeille, Emilie] Univ Auvergne, Ctr Biomed Rech & Valorisat, Clermont Ferrand, France. [Schoepfer, Alain M.] McMaster Univ, Farncombe Family Inst Digest Hlth Res, Hamilton, ON, Canada. [Seibold, Frank] Univ Hosp Bern, Dept Visceral Surg & Med, Div Gastroenterol, CH-3010 Bern, Switzerland. RP Muller, S (reprint author), Univ Bern, Dept Clin Res, Div Gastroenterol, Murtenstr 35, CH-3010 Bern, Switzerland. EM stefan.mueller@dkf.unibe.ch FU Swiss National Science Foundation [SNSF 3200B0-107527/1] FX This work was supported by the Swiss National Science Foundation grant number SNSF 3200B0-107527/1 to FS. NR 48 TC 28 Z9 28 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD NOV PY 2010 VL 59 IS 11 BP 1493 EP 1500 DI 10.1136/gut.2010.208348 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 664LZ UT WOS:000282963100012 PM 20682699 ER PT J AU Rauh-Hain, JA Growdon, WB Schorge, JO Goodman, AK Boruta, DM McCann, C Horowitz, NS del Carmen, MG AF Rauh-Hain, J. Alejandro Growdon, Whitfield B. Schorge, John O. Goodman, A. K. Boruta, David M. McCann, Christopher Horowitz, Neil S. del Carmen, Marcela G. TI Prognostic determinants in patients with stage IIIC and IV uterine papillary serous carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Uterine papillary serous carcinoma; Optimal cytoreduction ID HER-2/NEU OVEREXPRESSION; CYTOREDUCTIVE SURGERY; ENDOMETRIAL CANCER; CLEAR-CELL; CHEMOTHERAPY; RADIOTHERAPY; CISPLATIN; UPSC; CYCLOPHOSPHAMIDE; DOXORUBICIN AB Objective. The aim of this study was to evaluate the survival impact of cytoreductive surgery and other prognostic determinants in patients with stage IIIC and IV uterine papillary serous carcinoma (UPSC). Methods. All patients with FIGO stage IIIC and IV UPSC who underwent surgical staging at the two participating institutions, between January 1, 1995 and December 31, 2007, were identified from the tumor registry database. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox regression analysis. Results. Analysis of 79 patients with stage IIIC-IV disease was performed. Optimal cytoreduction was associated with a median survival of 36 months, compared with 12 months for patients who underwent a suboptimal surgical effort (p = 0.001), and a disease-free survival (DFS) of 21 months vs. 10 months (p = 0.001), respectively. Regression analysis identified stage (HR = 2.4, p = 0.03), absence of visible residual disease (HR = 0.5, p = 0.03), and chemotherapy (HR = 0.1, p<0.001) as independent predictors of OS. Conclusions. Cytoreduction to no gross residual disease and the use of platinum therapy are associated with a significant survival benefit for patients with stage IIIC-IV UPSC. Recommended management for this group of patients should consist of maximal surgical cytoreduction followed by platinum-based chemotherapy, preferably in combination with paclitaxel. Adjuvant radiation therapy should also be considered. (C) 2010 Elsevier Inc. All rights reserved. C1 [Rauh-Hain, J. Alejandro; Growdon, Whitfield B.; Schorge, John O.; Goodman, A. K.; Boruta, David M.; McCann, Christopher; del Carmen, Marcela G.] Harvard Univ, Div Gynecol Oncol Vincent Obstet & Gynecol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Rauh-Hain, J. Alejandro; Horowitz, Neil S.] Harvard Univ, Div Gynecol Oncol, Brigham & Womens Hosp, Sch Med, Boston, MA 02114 USA. RP del Carmen, MG (reprint author), Harvard Univ, Div Gynecol Oncol Vincent Obstet & Gynecol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 34 TC 16 Z9 18 U1 0 U2 2 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 NOV PY 2010 VL 119 IS 2 BP 299 EP 304 DI 10.1016/j.ygyno.2010.07.010 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 667PO UT WOS:000283206300025 PM 20691465 ER PT J AU Jacobson, CA Ritz, J AF Jacobson, Caron A. Ritz, Jerome TI B-cell-directed therapy for chronic graft-versus-host disease SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material ID MINOR HISTOCOMPATIBILITY ANTIGEN; EXCESS BAFF; RITUXIMAB; TRANSPLANTATION; HOMEOSTASIS; ACTIVATION C1 [Jacobson, Caron A.; Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Jacobson, CA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu FU NCI NIH HHS [P01 CA142106] NR 21 TC 5 Z9 6 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2010 VL 95 IS 11 BP 1811 EP 1813 DI 10.3324/haematol.2010.032227 PG 3 WC Hematology SC Hematology GA 682YF UT WOS:000284438200005 PM 21037328 ER PT J AU Price, M Norris, DM AF Price, Marilyn Norris, Donna Marie TI Firearm Laws: A Primer for Psychiatrists SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE firearm; guns; homicide; legislation; suicide; violence ID MENTAL-ILLNESS; VIOLENT BEHAVIOR; GUN OWNERSHIP; HANDGUN VIOLENCE; SUBSTANCE-ABUSE; UNITED-STATES; RISK-FACTOR; SUICIDE; SCHIZOPHRENIA; HEALTH AB Persons with mental illness or substance abuse have been perceived by the public to pose an increased risk of violence to themselves and others. As a result, federal and state laws have restricted the right of certain categories of persons with mental illness or substance abuse to possess, register, license, retain, or carry a firearm. Clinicians should be familiar with the specific firearm statutes of their own states, which describe the disqualifying mental health/substance abuse history and the role and responsibility of the psychiatrist in the process. State statutes vary widely in terms of the definitions of, and reporting requirements relating to, prohibited persons with mental illness or substance abuse. States also vary in the duration of the prohibition and in the timing of the appeals process. Some of the statutes have specific provisions for the removal of a firearm when a prohibited person is identified. States may maintain a mental health database that is used to determine firearm eligibility and may forward information to the National Instant Criminal Background Check System. The National Instant Criminal Background Check System Improvement Amendments Act of 2007 will likely increase the number of persons identified as belonging to the prohibited class. (HARV REV PSYCHIATRY 2010;18:326-335.) C1 [Price, Marilyn] Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. [Norris, Donna Marie] Harvard Univ, Sch Med, Program Psychiat & Law, Beth Israel Deaconess Hosp, Boston, MA USA. [Price, Marilyn; Norris, Donna Marie] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Price, M (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM mprice3@partners.org NR 65 TC 7 Z9 7 U1 1 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 2010 VL 18 IS 6 BP 326 EP 335 DI 10.3109/10673229.2010.527520 PG 10 WC Psychiatry SC Psychiatry GA 680WF UT WOS:000284267500003 PM 21080771 ER PT J AU Glezer, A Brendel, RW AF Glezer, Anna Brendel, Rebecca Weintraub TI Beyond Emergencies: The Use of Physical Restraints in Medical and Psychiatric Settings SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE law; physical restraint; risk management AB Physical restraints, such as locked-door seclusion and two-or four-point leather restraints, are frequently used in both the medical and psychiatric settings. Efforts are currently under way to reduce the use of physical restraints in psychiatric settings; various institutional, state, and federal policies are place. However, using these same restraints in the context of providing medical care for psychiatric patients is more complicated, as it is uncertain which principles and regulations apply in a particular setting. For example, is the restraint governed by the policies that regulate the psychiatric application of restraints, by those that regulate the medical application of restraints, or by both? This article reviews the principles and regulations governing the use of restraints on psychiatric patients, with specific attention to the use of restraints in providing medical treatment to that patient population. Also addressed are general principles of risk management to help avoid negative outcomes and to reduce the risk of litigation for unauthorized or unlawful restraint. A case example is used to illustrate these concepts. (HARV REV PSYCHIATRY 2010;18:353-358.) C1 [Glezer, Anna] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Glezer, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM aglezer@partners.org NR 14 TC 4 Z9 4 U1 5 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 2010 VL 18 IS 6 BP 353 EP 358 DI 10.3109/10673229.2010.527514 PG 6 WC Psychiatry SC Psychiatry GA 680WF UT WOS:000284267500005 PM 21080773 ER PT J AU Saleh, FM Grudzinskas, AJ Malin, HM Dwyer, RG AF Saleh, Fabian M. Grudzinskas, Albert J., Jr. Malin, H. Martin Dwyer, R. Gregg TI The Management of Sex Offenders: Perspectives for Psychiatry SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE paraphilias; risk management; sex offender; sexual predator laws ID PHARMACOLOGICAL-TREATMENT; PARAPHILIAS; RECIDIVISM; BEHAVIOR; INTERVENTIONS; METAANALYSIS; INSTRUMENTS; ACETATE AB In the effort to identify and manage sex offenders, the differences between legal and medical/psychiatric terminology and approaches are readily apparent. This article discusses the different definitions and approaches of the two fields and considers both the behaviors that create risk to others and the strategies for reducing that risk. Particular attention is paid to the subcategory of paraphilic sex offenders. Treatment goals, modalities, and efficacies are discussed, as are evolving legal strategies for risk control and the need for interaction between law and medicine/psychiatry in order to accomplish common goals of risk management. (HARV REV PSYCHIATRY 2010;18:359-368.) C1 [Saleh, Fabian M.] Massachusetts Gen Hosp, Law & Psychiat Serv, Dept Psychiat, Boston, MA 02114 USA. [Saleh, Fabian M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Grudzinskas, Albert J., Jr.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Dwyer, R. Gregg] Univ S Carolina, Sch Med, Dept Psychiat, Columbia, SC 29208 USA. [Malin, H. Martin] Inst Adv Study Human Sexual, San Francisco, CA USA. RP Saleh, FM (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, Dept Psychiat, 15 Parkman St, Boston, MA 02114 USA. EM fsaleh@partners.org NR 64 TC 4 Z9 4 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 2010 VL 18 IS 6 BP 359 EP 368 DI 10.3109/10673229.2010.533003 PG 10 WC Psychiatry SC Psychiatry GA 680WF UT WOS:000284267500006 PM 21080774 ER PT J AU Schouten, R AF Schouten, Ronald TI Terrorism and the Behavioral Sciences SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE analysis; deradicalization; intelligence; interrogation; profiling; radicalization; terrorism; violence ID RADICALIZATION; PATHWAYS; VIOLENCE; BOMBERS; WORDS AB Terrorism has existed for millennia and is a phenomenon well-known to many parts of the world. Americans were forced to recognize this phenomenon, and our vulnerability to it, by two sets of events in 2001: the attacks on New York City and Washington, DC, and the anthrax mailings that followed shortly thereafter. Psychiatry, psychology, and other behavioral and social sciences have been looked to for assistance in collecting and analyzing intelligence data, understanding terrorism, and developing strategies to combat terrorism. In addition to reviewing areas in which the behavioral sciences have made contributions in addressing this problem, this article discusses the developing roles for behavioral scientists in this field. (HARV REV PSYCHIATRY 2010;18:369-378.) C1 [Schouten, Ronald] Massachusetts Gen Hosp, Law & Psychiat Serv, Dept Psychiat, Boston, MA 02114 USA. [Schouten, Ronald] Harvard Univ, Sch Med, Boston, MA USA. RP Schouten, R (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM rschouten@partners.org NR 52 TC 4 Z9 4 U1 1 U2 20 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 2010 VL 18 IS 6 BP 369 EP 378 DI 10.3109/10673229.2010.533005 PG 10 WC Psychiatry SC Psychiatry GA 680WF UT WOS:000284267500007 PM 21080775 ER PT J AU Peterson, ED Roe, MT Chen, AY Fonarow, GC Lytle, BL Cannon, CP Rumsfeld, JS AF Peterson, Eric D. Roe, Matthew T. Chen, Anita Y. Fonarow, Gregg C. Lytle, Barbara L. Cannon, Christopher P. Rumsfeld, John S. TI The NCDR ACTION Registry-GWTG: transforming contemporary acute myocardial infarction clinical care SO HEART LA English DT Database Review ID ACUTE CORONARY SYNDROMES; INTERVENTION OUTCOMES NETWORK; RAPID RISK STRATIFICATION; QUALITY IMPROVEMENT; ST-ELEVATION; EARLY IMPLEMENTATION; ACC/AHA GUIDELINES; WRITING COMMITTEE; AMERICAN-COLLEGE; ADVERSE OUTCOMES AB Aims The NCDR ACTION Registry-GWTG collects detailed in-hospital clinical, process-of-care and outcomes data for patients admitted with acute myocardial infarction (AMI) in the USA. The registry is a national AMI surveillance system that contributes to the scientific enquiry process of AMI care through the facilitation of local and national quality improvement efforts. Interventions No treatments are mandated, participating centres receive routine quality-of-care and outcomes performance feedback reports and access to quality of care tools, such as dosing algorithms and standing orders. Population AMI patients are retrospectively identified. No informed consent is required, as data are anonymised. From January 2007 to date, 147 165 records have been submitted from 383 participating US hospitals. Patients with a primary diagnosis of ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction are eligible for enrolment in the registry. These patients must have ischemic symptoms and electrocardiogram changes, and/or positive cardiac markers within 24 hours of initial presentation. Baseline data Approximately 350 fields encompassing patient demographics, medical history and risk factors, hospital presentation, initial cardiac status, medications and associated doses, reperfusion strategy, procedures, laboratory values, and outcomes. Data are manually entered by study personnel; there are non-financial incentives at the hospital level. Completeness within the registry is noteworthy with most fields at less than 5% missing. Endpoints Main outcome measures include American College of Cardiology/American Heart Association myocardial infarction performance indicators, as well as in-hospital patient outcomes. Data are available for research by application to: http://www.ncdr.com. C1 [Peterson, Eric D.; Roe, Matthew T.; Chen, Anita Y.; Lytle, Barbara L.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Peterson, ED (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM peter016@mc.duke.edu FU Society of Chest Pain Centers; Society of Hospital Medicine; American College of Emergency Physicians; Bristol-Myers Squibb/Sanofi Pharmaceuticals; Schering-Plough Corporation; Agency for Healthcare Research and Quality (AHRQ) [U18HS016964] FX The ACTION Registry-GWTG is an initiative of the American College of Cardiology Foundation and the American Heart Association, with partnering support from the Society of Chest Pain Centers, the Society of Hospital Medicine and the American College of Emergency Physicians. The registry is sponsored by the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership and Schering-Plough Corporation. This project was supported by grant number U18HS016964 from the Agency for Healthcare Research and Quality (AHRQ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHRQ. The funding source had no role in the design or implementation of the study, or in the decision to seek publication. NR 17 TC 57 Z9 61 U1 0 U2 1 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 NOV PY 2010 VL 96 IS 22 BP 1798 EP 1802 DI 10.1136/hrt.2010.200261 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 668VC UT WOS:000283298700004 PM 20736202 ER PT J AU Zhu, X Fu, WY Xu, SH AF Zhu Xin Fu Wenyu Xu Shenhua TI Clinicopathologic Significance of Cytokine Levels in Esophageal Squamous Cell Carcinoma SO HEPATO-GASTROENTEROLOGY LA English DT Article DE Esophageal squamous cell carcinoma; Cytokines; IFN-Y; TNF-alpha; IL-2; IL-4; IL-5; IL-10 ID INTERFERON-GAMMA; IFN-GAMMA; CANCER; TH2; EXPRESSION; IMBALANCE; SURVIVAL AB Background/Aims: Treatment's effect on esophageal squamous cell carcinoma (ESCC) patients' immune functions may influence outcomes. Here, we address the scarcity of information about immune responses of treated and untreated ESCC patients. Methodology: Levels of IFN-Y, TNF-alpha, IL-2, IL4, IL-5 and IL-10 were detected in 36 untreated patients (UPs), and 82 treated patients (TPs) with ESCC, and in 70 healthy controls, using cytometric bead arrays. Results: Levels of IL-2, IL-4 and IL-5 were higher (p<0.001), and TNF-a was lower (p<0.01), in UPs than in controls; IFN-Y, IL-2, IL-4, IL-5 and IL-10 levels were higher in TPs than in controls (p<0.001); IFN-Y, TNF-alpha and IL-10 levels were higher in TPs than in UPs (p<0.05); IFN-Y/IL-4 ratios of UPs were lower than controls (p<0.05). Levels did not significantly differ by age or weight index, but did differ by clinical stages, differentiation degree and tumor location. Patients' survival was affected by clinical stage (p=0.001), differentiation degree (p=0.012), tumor location (p=0.043) and lymph node involvement (p=0.039); clinical stage was an independent prognostic factor (p=0.014). Conclusions: We found that Thl/Th2 imbalance and immune function turbulence correlate with differentiation degree, clinical stage and tumor location. Moreover, clinical stage is currently the best predictor of survival. C1 [Zhu Xin; Xu Shenhua] Zhejiang Canc Hosp, Zhejiang Canc Res Inst, Hangzhou 310031, Zhejiang, Peoples R China. [Fu Wenyu] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Fu Wenyu] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Xu, SH (reprint author), Zhejiang Canc Hosp, Zhejiang Canc Res Inst, 38 Guangji Rd, Hangzhou 310031, Zhejiang, Peoples R China. EM xu_shenhua@126.com FU Chinese Ministry of Health and Zhejiang Province [WKJ2006-2-009] FX This research was supported by the Co-constructing Scientific Research Fund of Chinese Ministry of Health and Zhejiang Province (WKJ2006-2-009). NR 21 TC 0 Z9 0 U1 0 U2 0 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 NOV-DEC PY 2010 VL 57 IS 104 BP 1416 EP 1422 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 725ZR UT WOS:000287685900017 ER PT J AU Golden-Mason, L Cox, AL Randall, JA Cheng, LL Rosen, HR AF Golden-Mason, Lucy Cox, Andrea L. Randall, Jessica A. Cheng, Linling Rosen, Hugo R. TI Increased Natural Killer Cell Cytotoxicity and NKp30 Expression Protects Against Hepatitis C Virus Infection in High-Risk Individuals and Inhibits Replication In Vitro SO HEPATOLOGY LA English DT Article ID CD56(+) T-CELLS; NK CELLS; ACTIVATING RECEPTOR; CYTOLYTIC FUNCTION; HUMAN HEPATOCYTES; PERIPHERAL-BLOOD; ENVELOPE PROTEIN; HCV INFECTION; CORE PROTEIN; FREQUENCY AB CD56(pos) natural killer (NK)/natural T (NT) cells are important innate effectors providing the first line of defense against viral infection. Enhanced NK activity has been shown to protect from human immunodeficiency virus-1 infection. However, the role played by these innate effectors in protection against or development of hepatitis C virus (HCV) infection is unknown. We characterized CD56(pos) populations in 11 injection drug users (IDUs) who remained uninfected despite being repeatedly exposed to HCV. NK profiles in exposed but uninfected (EU) individuals were compared with preinfection samples (median 90 days prior to HCV seroconversion) collected from 14 IDUs who were exposed and subsequently became infected (EI) and unexposed normal control subjects (n = 8). Flow cytometric analysis of CD56(pos) populations demonstrated that EUs had a higher proportion of CD56(low) mature (P = 0.0011) NK cells compared with El subjects. Bead-isolated NKs (>90% purity) from EUs had significantly higher interleukin-2 (IL-2) induced cytolytic activity against the NK-sensitive cell line K562 at an effector-to-target ratio of 10:1 (P < 0.0001). NKp30, a natural cytotoxicity receptor involved in NK activation, is highest on NK/NT cells in EUs relative to infected subjects. Using the JFH-1 infection system, we demonstrated that NKp30(high) cells in the absence of exogenous stimulation significantly reduce infection of hepatocytes. Conclusion: CD56(pos) populations in EUs are enriched for effector NKs displaying enhanced IL-2 induced cytolytic activity and higher levels of the natural cytotoxicity receptor NKp30-activating receptor. In addition, NKp30(high) cells are more effective in preventing infection of Huh-7.5 cells than their NKp30(low/neg) counterparts. These data support the hypothesis that NK cells contribute to anti-HCV defense in vivo in the earliest stages of infection, providing innate protection from HCV acquisition. (HEPATOLOGY 2010;52:1581-1589) C1 [Golden-Mason, Lucy; Randall, Jessica A.; Cheng, Linling; Rosen, Hugo R.] Univ Colorado, Dept Med, Div GI Hepatol, Aurora, CO 80045 USA. [Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado, Integrated Dept Immunol, Denver, CO 80202 USA. [Golden-Mason, Lucy; Rosen, Hugo R.] Natl Jewish Hosp, Denver, CO USA. [Cox, Andrea L.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. RP Rosen, HR (reprint author), Univ Colorado, Dept Med, Div GI Hepatol, Acad Off Bldg 1,12631 E 17th Ave B-158, Aurora, CO 80045 USA. EM hugo.rosen@ucdenver.edu FU National Institutes of Health [U19 AI40035, RO1 DK060590, U19 A 1066328] FX Supported by National Institutes of Health Grants U19 AI40035 (to A. L. C.) and RO1 DK060590 and U19 A 1066328 (HCV center grant; to H. R. R.). NR 43 TC 58 Z9 60 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2010 VL 52 IS 5 BP 1581 EP 1589 DI 10.1002/hep.23896 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 674RH UT WOS:000283764800008 PM 20812318 ER PT J AU Lennerz, JKM Kuter, DJ Hasserjian, R Iafrate, J AF Lennerz, Jochen K. M. Kuter, David J. Hasserjian, Robert Iafrate, John TI Massive Hepatomegaly and Involvement by Janus Kinase 2-Positive Myeloproliferative Neoplasm SO HEPATOLOGY LA English DT Editorial Material ID MYELOFIBROSIS; CELLS C1 [Lennerz, Jochen K. M.; Hasserjian, Robert; Iafrate, John] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA 02114 USA. [Lennerz, Jochen K. M.; Kuter, David J.; Iafrate, John] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Lennerz, JKM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM JLennerz@partners.org NR 6 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2010 VL 52 IS 5 BP 1855 EP 1856 DI 10.1002/hep.23913 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 674RH UT WOS:000283764800035 PM 20890944 ER PT J AU Weinreb, I Simpson, RH Skalova, A Perez-Ordonez, B Dardick, I Chetty, R Hunt, JL AF Weinreb, Ilan Simpson, Roderick H. Skalova, Alena Perez-Ordonez, Bayardo Dardick, Irving Chetty, Runjan Hunt, Jennifer L. TI Ductal adenomas of salivary gland showing features of striated duct differentiation ('striated duct adenoma'): a report of six cases SO HISTOPATHOLOGY LA English DT Article DE basal cells; canalicular adenoma; ductal adenoma; myoepithelial; striated duct ID PAROTID-GLAND; CANALICULAR ADENOMAS; BASAL-CELL; HYPERPLASIA; CARCINOMA; SPECTRUM AB Aims: To describe a salivary adenoma composed largely of unilayered ducts resembling striated ducts, and to differentiate it from similar adenomas, including canalicular and intercalated duct adenoma. Methods and results: Six unilayered ductal adenomas were identified in parotid (four) and palate (two). They were encapsulated, ranged from 0.5 to 3.0 cm and composed of closely apposed ducts with virtually no stroma. The ducts varied in size and showed cysts up to 0.1 cm. The cells were eosinophilic and bland. Prominent cell membranes, reminiscent of 'striations' of normal striated ducts, were seen. The typical epithelial 'beading' pattern with abundant stroma of canalicular adenoma was absent. The tumours expressed keratins (six of six) and S100 (five of six). Smooth muscle actin (SMA) revealed no myoepithelial cells. Two tumours showed focal bilayered ducts with calponin or smooth muscle myosin heavy chain, but the tumours were largely unilayered. Only isolated cells in three tumours were positive with p63; a pattern identical to striated ducts. In contrast, the normal excretory and intercalated ducts all contained diffuse bilayering with basal or myoepithelial markers. Conclusions: Striated duct adenomas are unilayered ductal tumours that recapitulate normal striated ducts. C1 [Weinreb, Ilan; Perez-Ordonez, Bayardo; Dardick, Irving; Chetty, Runjan] Univ Toronto, Dept Pathol, Univ Hlth Network, Toronto, ON, Canada. [Simpson, Roderick H.] Royal Devon & Exeter Hosp, Dept Histopathol, Exeter EX2 5DW, Devon, England. [Skalova, Alena] Charles Univ Prague, Fac Med, Dept Pathol, Plzen, Czech Republic. [Hunt, Jennifer L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hunt, Jennifer L.] Harvard Univ, Sch Med, Boston, MA USA. RP Weinreb, I (reprint author), Univ Toronto, Dept Pathol, Univ Hlth Network, Toronto, ON, Canada. EM weinrebi@yahoo.ca NR 18 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD NOV PY 2010 VL 57 IS 5 BP 707 EP 715 DI 10.1111/j.1365-2559.2010.03682.x PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 681MQ UT WOS:000284320300006 PM 21054495 ER PT J AU Gupta, R Ejebe, K Butler, J Lettre, G Lyon, H Guiducci, C Wilks, R Bennett, F Forrester, T Tayo, B Musunuru, K Hirschhorn, J Kathiresan, S Cooper, RS McKenzie, CA AF Gupta, R. Ejebe, K. Butler, J. Lettre, G. Lyon, H. Guiducci, C. Wilks, R. Bennett, F. Forrester, T. Tayo, B. Musunuru, K. Hirschhorn, J. Kathiresan, S. Cooper, R. S. McKenzie, C. A. TI Association of common DNA sequence variants at 33 genetic loci with blood lipids in individuals of African ancestry from Jamaica SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; POPULATION; DISEASE; RISK AB The relevance of loci associated with blood lipids recently identified in European populations in individuals of African ancestry is unknown. We tested association between lipid traits and 36 previously described single-nucleotide polymorphisms (SNPs) in 1,466 individuals of African ancestry from Spanish Town, Jamaica. For the same allele and effect direction as observed in individuals of European ancestry, SNPs at three loci (1p13, 2p21, and 19p13) showed statistically significant association (p < 0.05) with LDL, two loci (11q12 and 20q13) showed association with HDL cholesterol, and two loci (11q12 and 2p24) showed association with triglycerides. The most significant association was between a SNP at 1p13 and LDL cholesterol (p = 4.6 x 10(-8)). This SNP is in a linkage disequilibrium region containing four genes (CELSR2, PSRC1, MYBPHL, and SORT1) and was recently shown to relate to risk for myocardial infarction. Overall, the results of this study suggest that much of the genetic variation which influences blood lipids is shared across ethnic groups. C1 [Bennett, F.; Forrester, T.; McKenzie, C. A.] Univ W Indies, Trop Metab Res Unit, Res Inst Trop Med, Kingston 7, Jamaica. [Gupta, R.; Ejebe, K.; Musunuru, K.; Kathiresan, S.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Gupta, R.; Ejebe, K.; Musunuru, K.; Kathiresan, S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lettre, G.] Univ Montreal, Montreal, PQ, Canada. [Lettre, G.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Butler, J.; Lyon, H.; Hirschhorn, J.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Wilks, R.] Univ W Indies, Epidemiol Res Unit, Res Inst Trop Med, Kingston 7, Jamaica. [Tayo, B.; Cooper, R. S.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. RP McKenzie, CA (reprint author), Univ W Indies, Trop Metab Res Unit, Res Inst Trop Med, Kingston 7, Jamaica. EM colin.mckenzie02@uwimona.edu.jm RI Ejebe, Kenechi/I-9238-2016 OI Ejebe, Kenechi/0000-0002-6090-8657 FU NIH [HL53353 Cooper (PI)]; NHLBI [NIH R01 HL087676]; National Center for Research Resources [U54 RR020278] FX Our chief acknowledgement is to the participants in the Spanish Town Study for their willingness to contribute to the study. We also thank the Research Nurses, Laboratory technologists and drivers at TMRU for their invaluable technical assistance. Investigators of this work were partially supported by grants from the NIH [HL53353 Cooper (PI)]. Genotyping was funded by NIH R01 HL087676 from the NHLBI STAMPEED Genomics Research Program. Replication genotyping was also supported by The Broad Institute Center for Genotyping and Analysis through grant U54 RR020278 from the National Center for Research Resources. NR 13 TC 4 Z9 5 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2010 VL 128 IS 5 BP 557 EP 561 DI 10.1007/s00439-010-0887-3 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 666EC UT WOS:000283094100009 PM 20839009 ER PT J AU Bosco, DA Lemay, N Ko, HK Zhou, HR Burke, C Kwiatkowski, TJ Sapp, P McKenna-Yasek, D Brown, RH Hayward, LJ AF Bosco, Daryl A. Lemay, Nathan Ko, Hae Kyung Zhou, Hongru Burke, Chris Kwiatkowski, Thomas J., Jr. Sapp, Peter McKenna-Yasek, Diane Brown, Robert H., Jr. Hayward, Lawrence J. TI Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules SO HUMAN MOLECULAR GENETICS LA English DT Article ID RNA-BINDING PROTEIN; FRONTOTEMPORAL LOBAR DEGENERATION; MESSENGER-RNA; NUCLEAR-LOCALIZATION; DENDRITIC SPINES; IN-VIVO; TDP-43; TLS; GENE; EWS AB Mutations in the RNA-binding protein FUS (fused in sarcoma) are linked to amyotrophic lateral sclerosis (ALS), but the mechanism by which these mutants cause motor neuron degeneration is not known. We report a novel ALS truncation mutant (R495X) that leads to a relatively severe ALS clinical phenotype compared with FUS missense mutations. Expression of R495X FUS, which abrogates a putative nuclear localization signal at the C-terminus of FUS, in HEK-293 cells and in the zebrafish spinal cord caused a striking cytoplasmic accumulation of the protein to a greater extent than that observed for recessive (H517Q) and dominant (R521G) missense mutants. Furthermore, in response to oxidative stress or heat shock conditions in cultures and in vivo, the ALS-linked FUS mutants, but not wild-type FUS, assembled into perinuclear stress granules in proportion to their cytoplasmic expression levels. These findings demonstrate a potential link between FUS mutations and cellular pathways involved in stress responses that may be relevant to altered motor neuron homeostasis in ALS. C1 [Bosco, Daryl A.; Lemay, Nathan; Ko, Hae Kyung; Zhou, Hongru; Burke, Chris; Sapp, Peter; McKenna-Yasek, Diane; Brown, Robert H., Jr.; Hayward, Lawrence J.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Kwiatkowski, Thomas J., Jr.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Bosco, DA (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, Room LRB 603,55 Lake Ave N, Worcester, MA 01655 USA. EM daryl.bosco@umassmed.edu; lawrence.hayward@umassmed.edu FU ALS Association; ALS Therapy Alliance; National Institute for Neurological Disease and Stroke [1RC2NS070342, 1RC1NS068391, R01NS050557, U01NS05225]; Angel Fund; ALS; Pierre L. de Bourgknecht ALS Research Foundation FX This work was supported by the ALS Association (D. A. B., R. H. B. and L.J.H.); ALS Therapy Alliance (D. A. B., R. H. B. and L.J.H.); National Institute for Neurological Disease and Stroke (1RC2NS070342, 1RC1NS068391, R01NS050557 and U01NS05225 to R. H. B. and 1RC1NS068391 to L.J.H.); Angel Fund (R. H. B.); Project ALS (R. H. B.); Pierre L. de Bourgknecht ALS Research Foundation (R. H. B.); and Al-Athel ALS Foundation (R.H.B.). NR 63 TC 187 Z9 193 U1 1 U2 14 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 NOV 1 PY 2010 VL 19 IS 21 BP 4160 EP 4175 DI 10.1093/hmg/ddq335 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 661TR UT WOS:000282751500004 PM 20699327 ER PT J AU Toney, JH Kaplowitz, H Pu, RS Qi, F Chang, G AF Toney, Jeffrey H. Kaplowitz, Hank Pu, Rongsun Qi, Feng Chang, George TI Science and Human Rights: A Bridge Towards Benefiting Humanity SO HUMAN RIGHTS QUARTERLY LA English DT Article ID BACILLUS-ANTHRACIS; DIVERSITY AB Three case studies involving scientists from different disciplines that contribute their expertise to advancing human rights in the US and abroad are discussed. Scientific research can have a greater impact on society if directed towards solving problems relevant to human rights. Progress in science and technology can be abused, leading to violations of human rights, but can also benefit humanity. Scientists have an opportunity to play an active role in preserving human rights. C1 [Toney, Jeffrey H.] Kean Univ, Coll Nat Appl & Hlth Sci, Union Township, NJ USA. [Toney, Jeffrey H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Toney, Jeffrey H.] MIT, Cambridge, MA 02139 USA. [Kaplowitz, Hank] Kean Univ, Human Rights Inst, Union Township, NJ USA. [Kaplowitz, Hank] Kean Univ, Dept Psychol, Union Township, NJ USA. [Pu, Rongsun] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Qi, Feng] Kean Univ, Dept Geol & Meteorol, Union Township, NJ USA. [Chang, George] Kean Univ, Dept Comp Sci, Union Township, NJ USA. [Toney, Jeffrey H.] Montclair State Univ, Montclair, NJ 07043 USA. RP Toney, JH (reprint author), Kean Univ, Coll Nat Appl & Hlth Sci, Union Township, NJ USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0275-0392 J9 HUM RIGHTS QUART JI Hum. Rights Q. PD NOV PY 2010 VL 32 IS 4 BP 1008 EP 1017 PG 10 WC Political Science; Social Issues SC Government & Law; Social Issues GA 682IK UT WOS:000284394400007 ER PT J AU Shin, JH Smith, D Swiercz, W Staley, K Rickard, JT Montero, J Kurgan, LA Cios, KJ AF Shin, Joo-Heon Smith, David Swiercz, Waldemar Staley, Kevin Rickard, J. Terry Montero, Javier Kurgan, Lukasz A. Cios, Krzysztof J. TI Recognition of Partially Occluded and Rotated Images With a Network of Spiking Neurons SO IEEE TRANSACTIONS ON NEURAL NETWORKS LA English DT Article DE Image recognition; partially occluded and rotated images; spiking neurons; synaptic plasticity rule ID TIMING-DEPENDENT PLASTICITY; DRIVEN SYNAPTIC PLASTICITY; OBJECT RECOGNITION; NEURAL-NETWORKS; VISUAL-ATTENTION; FACE RECOGNITION; MODEL; INFORMATION; STORAGE; CORTEX AB In this paper, we introduce a novel system for recognition of partially occluded and rotated images. The system is based on a hierarchical network of integrate-and-fire spiking neurons with random synaptic connections and a novel organization process. The network generates integrated output sequences that are used for image classification. The proposed network is shown to provide satisfactory predictive performance given that the number of the recognition neurons and synaptic connections are adjusted to the size of the input image. Comparison of synaptic plasticity activity rule (SAPR) and spike timing dependant plasticity rules, which are used to learn connections between the spiking neurons, indicates that the former gives better results and thus the SAPR rule is used. Test results show that the proposed network performs better than a recognition system based on support vector machines. C1 [Shin, Joo-Heon; Cios, Krzysztof J.] Virginia Commonwealth Univ, Dept Comp Sci, Richmond, VA 23284 USA. [Smith, David] Univ Colorado, Denver, CO 80204 USA. [Swiercz, Waldemar; Staley, Kevin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Swiercz, Waldemar; Staley, Kevin] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rickard, J. Terry] Distributed Infin Inc, Larkspur, CO 80118 USA. [Montero, Javier] Univ Complutense Madrid, Dept Stat & Operat Res, Fac Math, E-28040 Madrid, Spain. [Kurgan, Lukasz A.] Univ Alberta, Dept Elect & Comp Engn, Edmonton, AB T6G 2M7, Canada. [Cios, Krzysztof J.] IITiS Polish Acad Sci, PL-44100 Gliwice, Poland. RP Shin, JH (reprint author), Virginia Commonwealth Univ, Dept Comp Sci, Med Coll Virginia Campus, Richmond, VA 23284 USA. EM shinjh2@vcu.edu; dizzyd@dizzyd.com; wswiercz@partners.org; kstaley@partners.org; terry.rickard@gmail.com; monty@mat.ucm.es; lkur-gan@ece.ualberta.ca; kcios@vcu.edu RI Kurgan, Lukasz/B-5721-2009; Montero, Javier/H-1704-2015 OI Kurgan, Lukasz/0000-0002-7749-0314; Montero, Javier/0000-0001-8333-2155 FU NIH [1R01NS064675-01] FX Manuscript received November 2, 2009; revised February 19, 2010; accepted April 20, 2010. Date of current version November 3, 2010. The work of K. J. Cios was supported by NIH, under Grant 1R01NS064675-01. NR 56 TC 12 Z9 14 U1 0 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1045-9227 J9 IEEE T NEURAL NETWOR JI IEEE Trans. Neural Netw. PD NOV PY 2010 VL 21 IS 11 BP 1697 EP 1709 DI 10.1109/TNN.2010.2050600 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Hardware & Architecture; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 676UM UT WOS:000283944100001 PM 21047704 ER PT J AU Hong, XM Wang, CX Thompson, J Allen, B Malik, WQ Ge, XH AF Hong, Xuemin Wang, Cheng-Xiang Thompson, John Allen, Ben Malik, Wasim Q. Ge, Xiaohu TI On Space-Frequency Correlation of UWB MIMO Channels SO IEEE TRANSACTIONS ON VEHICULAR TECHNOLOGY LA English DT Article DE Channel modeling; diversity order; multiple input-multiple output (MIMO); space-frequency (SF) correlation; ultrawideband (UWB) ID BANDWIDTH INDOOR CHANNEL; WIDE-BAND SYSTEMS; FADING CHANNELS; ULTRAWIDEBAND CHANNELS; SPATIAL CORRELATION; STATISTICAL-MODEL; DIVERSITY; TIME; PROPAGATION; SIMULATION AB Conventional multiple-input-multiple-output (MIMO) channel correlation models focus on describing the complex amplitude correlation of resolvable multipath components (MPCs). It has recently been shown that the time-of-arrival (ToA) correlation of resolvable MPCs, which has largely been ignored in the literature so far, is important for characterizing the space-frequency (SF) correlation of MIMO channels in the ultrawideband (UWB) regime. The proposal of ToA correlation brings forth the following open questions: What is the fundamental difference between amplitude and ToA correlations? Are they mutually replaceable? What impact do they have on system performance? Is this impact related to channel bandwidth? This paper systematically answers the above questions. We demonstrate that, compared with a conventional model that only considers amplitude correlation, a UWB MIMO channel model taking into account both amplitude and ToA correlations leads to different theoretical maximum diversity order, numerical structure of the SF channel covariance matrix, spatial correlation function, and diversity performance. We conclude that ToA correlation is a necessary complement to amplitude correlation when the channel bandwidth exceeds 500 MHz, i.e., UWB channels. This new insight serves as the motivation for more realistic modeling of UWB MIMO channels and the inspiration for designing advanced UWB MIMO systems to fully exploit the SF channel correlation properties. C1 [Hong, Xuemin; Wang, Cheng-Xiang] Heriot Watt Univ, Joint Res Inst Signal & Image Proc, Sch Engn & Phys Sci, Edinburgh EH14 4AS, Midlothian, Scotland. [Thompson, John] Heriot Watt Univ, Joint Res Inst Signal & Image Proc, Inst Digital Commun, Edinburgh EH9 3JL, Midlothian, Scotland. [Allen, Ben] Univ Bedfordshire, Dept Comp Sci & Technol, Luton LU1 3JU, Beds, England. [Malik, Wasim Q.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Malik, Wasim Q.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Ge, Xiaohu] Huazhong Univ Sci & Technol, Elect & Informat Engn Dept, Wuhan 430074, Peoples R China. RP Hong, XM (reprint author), Heriot Watt Univ, Joint Res Inst Signal & Image Proc, Sch Engn & Phys Sci, Edinburgh EH14 4AS, Midlothian, Scotland. EM x.hong@hw.ac.uk; cheng-xiang.wang@hw.ac.uk; john.thompson@ed.ac.uk; ben.Allen@beds.ac.uk; wqm@mit.edu; xhge@mail.hust.edu.cn RI Malik, Wasim/C-9982-2011; Ge, Xiaohu/N-8504-2015 OI Ge, Xiaohu/0000-0002-3204-5241 FU Scottish Funding Council; Heriot-Watt University; Research Councils U. K. for the U.K.-China; National Natural Science Foundation of China [60872007]; National 863 High Technology Program of China [2009AA01Z239]; International Science and Technology Collaboration Program of China [0903] FX The work of X. Hong, C.-X. Wang (corresponding author), and J. S. Thompson was supported by the Scottish Funding Council for the Joint Research Institute in Signal and Image Processing between the University of Edinburgh and Heriot-Watt University, as part of the Edinburgh Research Partnership in Engineering and Mathematics. The work of X. Hong, C.-X. Wang, and X. Ge was supported by the Research Councils U. K. for the U.K.-China Science Bridges: R&D on(B)4G Wireless Mobile Communications. The work of X. Ge was also supported in part by the National Natural Science Foundation of China under Grant 60872007, by the National 863 High Technology Program of China under Grant 2009AA01Z239, and by the International Science and Technology Collaboration Program of China under Grant 0903. The review of this paper was coordinated by Prof. R. C. Qiu. NR 44 TC 10 Z9 10 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9545 EI 1939-9359 J9 IEEE T VEH TECHNOL JI IEEE Trans. Veh. Technol. PD NOV PY 2010 VL 59 IS 9 BP 4201 EP 4213 DI 10.1109/TVT.2010.2075947 PG 13 WC Engineering, Electrical & Electronic; Telecommunications; Transportation Science & Technology SC Engineering; Telecommunications; Transportation GA 678NZ UT WOS:000284087700001 ER PT J AU Kreslavsky, T Gleimer, M Garbe, AI von Boehmer, H AF Kreslavsky, Taras Gleimer, Michael Garbe, Annette I. von Boehmer, Harald TI alpha beta versus gamma delta fate choice: counting the T-cell lineages at the branch point SO IMMUNOLOGICAL REVIEWS LA English DT Review DE alpha beta T cells; gamma delta T cells; lineage choice; T-cell receptor; Id3; PLZF ID ANTIGEN RECEPTOR GENES; HELIX PROTEIN ID3; THYMOCYTE DEVELOPMENT; PRE-TCR; SELECTION CHECKPOINT; BETA/GAMMA-DELTA; INTERFERON-GAMMA; IGE PRODUCTION; MUTANT MICE; ZINC-FINGER AB Both alpha beta and gamma delta T cells develop in the thymus from a common progenitor. Historically distinguished by their T-cell receptor (TCR), these lineages are now defined on the basis of distinct molecular programs. Intriguingly, in many transgenic and knockout systems these programs are mismatched with the TCR type, leading to the development of gamma delta lineage cells driven by alpha beta TCR and vice versa. These puzzling observations were recently explained by the demonstration that TCR signal strength, rather than TCR type per se, instructs lineage fate, with stronger TCR signal favoring gamma delta and weaker signal favoring alpha beta lineage fates. These studies also highlighted the ERK (extracellular signal regulated kinase)-Egr (early growth response)-Id3 (inhibitor of differentiation 3) axis as a potential molecular switch downstream of TCR that determines lineage choice. Indeed, removal of Id3 was sufficient to redirect TCR gamma delta transgenic cells to the alpha beta lineage, even in the presence of strong TCR signal. However, in TCR non-transgenic Id3 knockout mice the overall number of gamma delta lineage cells was increased due to an outgrowth of a V gamma 1V delta 6.3 subset, suggesting that not all gamma delta T cells depend on this molecular switch for lineage commitment. Thus, the gamma delta lineage may in fact be a collection of two or more lineages not sharing a common molecular program and thus equipollent to the alpha beta lineage. TCR signaling is not the only factor that is required for development of alpha beta and gamma delta lineage cells; other pathways, such as signaling from Notch and CXCR4 receptors, cooperate with the TCR in this process. C1 [Kreslavsky, Taras; Gleimer, Michael; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Lymphocyte Biol, Boston, MA 02115 USA. [Garbe, Annette I.] Tech Univ Dresden, Fac Med, MTZ, Inst Physiol Chem, Dresden, Germany. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Lymphocyte Biol, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu RI Garbe, Annette/A-4824-2014 FU National Institutes of Health [R01 A145846, R01 A151378] FX We are grateful to Valentina Schmidt for technical assistance. We thank Professor Anthony Capobianco for providing c-Myc retrovirus and Professor Jerry Adams for vav-bcl2 transgenic mice. These studies were supported by National Institutes of Health Grants R01 A145846 and R01 A151378. NR 106 TC 24 Z9 25 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD NOV PY 2010 VL 238 BP 169 EP 181 DI 10.1111/j.1600-065X.2010.00947.x PG 13 WC Immunology SC Immunology GA 671MB UT WOS:000283509100013 PM 20969592 ER PT J AU Strome, M Lott, DG AF Strome, Marshall Lott, David G. TI Anti-alpha beta-T-cell receptor antibodies in the setting of laryngeal transplantation SO IMMUNOTHERAPY LA English DT Review DE alpha beta-TCR; anti-alpha beta-TCR antibody; chimerism; composite tissue allograft; laryngeal transplantation; tolerance ID COMPOSITE-TISSUE ALLOGRAFTS; DONOR BONE-MARROW; MONOCLONAL-ANTIBODY; CARDIAC ALLOGRAFTS; ACCELERATED REJECTION; TARGETED THERAPY; DIRECTED THERAPY; RAT RECIPIENTS; LYMPHOCYTES-T; CLONAL ANERGY AB Inhibiting T-cell activation is critically important to the induction of transplantation tolerance. Monoclonal antibodies directed against the alpha beta-T-cell receptor have been shown to cause selective immunodepletion of this T-cell population and can provide long-term allograft acceptance. This article discusses the role of this promising immunosuppressive agent in scientific research and clinical utilization. Specifically, the article focuses on its efficacy and mechanism of tolerance induction in solid tissue and composite tissue allograft transplantation with a particular focus on laryngeal transplantation. C1 [Strome, Marshall; Lott, David G.] New York Head & Neck Inst, New York, NY USA. RP Lott, DG (reprint author), Massachusetts Gen Hosp, Ctr Laryngeol Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM dlott@partners.org NR 53 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD NOV PY 2010 VL 2 IS 6 BP 835 EP 845 DI 10.2217/IMT.10.72 PG 11 WC Immunology SC Immunology GA 700AU UT WOS:000285705300012 PM 21091115 ER PT J AU Lo, M Murray, GL Khoo, CA Haake, DA Zuerner, RL Adler, B AF Lo, Miranda Murray, Gerald L. Khoo, Chen Ai Haake, David A. Zuerner, Richard L. Adler, Ben TI Transcriptional Response of Leptospira interrogans to Iron Limitation and Characterization of a PerR Homolog SO INFECTION AND IMMUNITY LA English DT Article ID FERRIC CITRATE TRANSPORT; OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI; PATHOGENIC LEPTOSPIRA; BACILLUS-SUBTILIS; FUR HOMOLOGS; SEROVAR LAI; NEISSERIA-MENINGITIDIS; BINDING PROTEIN; VIRULENCE GENES AB Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur homologs; we have constructed a mutation in one of these, la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects of la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte L. biflexa and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of la1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the la1857 mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence. C1 [Lo, Miranda; Murray, Gerald L.; Khoo, Chen Ai; Adler, Ben] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. [Zuerner, Richard L.] USDA ARS, Infect Bacterial Dis Res Unit, Natl Anim Dis Ctr, Ames, IA 50010 USA. [Adler, Ben] Monash Univ, Australian Res Council, Ctr Excellence Struct & Funct Microbial Genom, Clayton, Vic 3800, Australia. [Adler, Ben] Monash Univ, Victorian Bioinformat Consortium, Clayton, Vic 3800, Australia. RP Adler, B (reprint author), Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia. EM Ben.Adler@med.monash.edu.au FU National Health and Medical Research Council; Australian Research Council, Canberra, Australia; National Institute of Allergy and Infectious Diseases [AI-34431]; VA Medical Research Funds FX This work was supported by the National Health and Medical Research Council and the Australian Research Council, Canberra, Australia (to B.A.), by Public Health Service grant AI-34431 from the National Institute of Allergy and Infectious Diseases (to D.A.H.), and by VA Medical Research Funds (to D.A.H.). G.L.M. is the recipient of a NHMRC Peter Doherty Fellowship. NR 73 TC 30 Z9 31 U1 1 U2 6 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 NOV PY 2010 VL 78 IS 11 BP 4850 EP 4859 DI 10.1128/IAI.00435-10 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 665RB UT WOS:000283052100044 PM 20805337 ER PT J AU Lee, BY Wiringa, AE Bailey, RR Goyal, V Tsui, B Lewis, GJ Muder, RR Harrison, LM AF Lee, Bruce Y. Wiringa, Ann E. Bailey, Rachel R. Goyal, Vishal Tsui, Becky Lewis, G. Jonathan Muder, Robert R. Harrison, Lee M. TI The Economic Effect of Screening Orthopedic Surgery Patients Preoperatively for Methicillin-Resistant Staphylococcus aureus SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HOSPITAL-ACQUIRED INFECTION; JOINT-REPLACEMENT SURGERY; NASAL CARRIAGE; COLONIZATION; MRSA; PNEUMONIA; MUPIROCIN; MORTALITY; EPIDEMIOLOGY; SURVEILLANCE AB BACKGROUND AND OBJECTIVE. Patients undergoing orthopedic surgery are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, which can result in increased morbidity, hospital lengths of stay, and medical costs. We sought to estimate the economic value of routine preoperative MRSA screening and decolonization of orthopedic surgery patients. METHODS. A stochastic decision-analytic computer simulation model was used to evaluate the economic value of implementing this strategy (compared with no preoperative screening or decolonization) among orthopedic surgery patients from both the third-party payer and hospital perspectives. Sensitivity analyses explored the effects of varying MRSA colonization prevalence, the cost of screening and decolonization, and the probability of decolonization success. RESULTS. Preoperative MRSA screening and decolonization was strongly cost-effective (incremental cost-effectiveness ratio less than $6,000 per quality-adjusted life year) from the third-party payer perspective even when MRSA prevalence was as low as 1%, decolonization success was as low as 25%, and decolonization costs were as high as $300 per patient. In most scenarios this strategy was economically dominant (ie, less costly and more effective than no screening). From the hospital perspective, preoperative MRSA screening and decolonization was the economically dominant strategy for all scenarios explored. CONCLUSIONS. Routine preoperative screening and decolonization of orthopedic surgery patients may under many circumstances save hospitals and third-party payers money while providing health benefits. Infect Control Hosp Epidemiol 2010; 31(11): 1130-1138 C1 [Lee, Bruce Y.] Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR Grp, Publ Hlth Computat & Operat Res PHICOR, Pittsburgh, PA 15213 USA. [Lee, Bruce Y.; Wiringa, Ann E.; Bailey, Rachel R.; Goyal, Vishal; Tsui, Becky; Lewis, G. Jonathan] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Lee, Bruce Y.; Wiringa, Ann E.; Bailey, Rachel R.; Goyal, Vishal; Tsui, Becky; Lewis, G. Jonathan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Harrison, Lee M.] Univ Pittsburgh, Infect Dis Epidemiol Res Unit, Sch Med, Pittsburgh, PA 15213 USA. [Muder, Robert R.] Vet Affairs Pittsburgh Hlth Syst, Div Infect Dis, Pittsburgh, PA USA. RP Lee, BY (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR Grp, Publ Hlth Computat & Operat Res PHICOR, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM byl1@pitt.edu OI Slayton, Rachel/0000-0003-4699-8040 FU National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) [U01-GM070708-05]; Pennsylvania Department of Health FX National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) through grant U01-GM070708-05 and the Pennsylvania Department of Health. NR 62 TC 17 Z9 19 U1 0 U2 3 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 NOV PY 2010 VL 31 IS 11 BP 1130 EP 1138 DI 10.1086/656591 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 675OV UT WOS:000283840900006 PM 20923285 ER PT J AU Diegelmann, J Seiderer, J Niess, JH Haller, D Goke, B Reinecker, HC Brand, S AF Diegelmann, Julia Seiderer, Julia Niess, Jan-Hendrik Haller, Dirk Goeke, Burkhard Reinecker, Hans-Christian Brand, Stephan TI Expression and Regulation of the Chemokine CXCL16 in Crohn's Disease and Models of Intestinal Inflammation SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/108th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-25, 2007 CL Washington, DC SP Amer Gastroenterol Assoc, Amer Assoc Study Liver Dis, Amer Soc Gastrointestinal Endoscopy, Soc Surg Alimentary Tract DE Crohn's disease; ulcerative colitis; inflammatory bowel disease; chemokine; CXCL16; CXCR6; mouse model; intestinal inflammation; intestinal epithelial cells; cytokine; signaling ID COLORECTAL-CANCER CELLS; EPITHELIAL-CELLS; BOWEL-DISEASE; RECEPTOR CXCR6; PROTEIN-KINASE; TNF-ALPHA; T-CELLS; ACTIVATION; LIGAND; FRACTALKINE AB Background: CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria and is a strong chemoattractant for CXCR6+ T cells. In this study, we determined the so far unknown expression and signal transduction of the novel CXCL16-CXCR6 chemokine ligand receptor system in intestinal inflammation in vivo and in vitro. Methods: CXCL16 mRNA was measured by quantitative PCR in human colonic biopsies of patients with Crohn's disease (CD) as well as in the TNF Delta ARE mouse model of ileitis and in murine cytomegalovirus (MCMV) induced colitis. CXCL16 serum levels were analyzed by ELISA. CXCL16-induced signal transduction was analyzed in intestinal epithelial cells with phospho-specific antibodies for mitogen-activated protein (MAP) kinases and Akt. Results: We found an inverse expression pattern of CXCL16 and CXCR6, with highest CXCL16 mRNA expression in the proximal murine small intestine and the highest CXCR6 mRNA expression in the distal colon. CXCL16 and CXCR6 mRNA were expressed in colorectal cancer (CRC) derived intestinal epithelial cell (IEC) lines. CRC-expressed CXCR6 was functional, as demonstrated by CXCL16-induced MAP kinase and Akt activation. Intestinal CXCL16 expression was elevated in the TNF Delta ARE mouse model of ileitis and in MCMV-induced colitis (P < 0.05) and in the sera and colons of patients with CD (P < 0.05), where its expression correlated highly with CXCR6 and IL-8 levels (r = 0.85 and 0.89, respectively). Conclusions: CRC-derived IECs express the functional CXCL16 receptor CXCR6. CXCL16 mRNA and protein expression is up-regulated in intestinal inflammation in vitro and in CD patients, suggesting an important role for this chemokine in intestinal inflammation. C1 [Niess, Jan-Hendrik] Univ Ulm, Dept Internal Med 1, D-7900 Ulm, Germany. [Haller, Dirk] Tech Univ Munich, ZIEL Res Ctr Nutr & Food Sci, Munich, Germany. [Reinecker, Hans-Christian] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Reinecker, Hans-Christian] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA. [Reinecker, Hans-Christian] Harvard Univ, Sch Med, Boston, MA USA. Univ Munich, Dept Internal Med Grosshadern 2, Munich, Germany. RP Brand, S (reprint author), Univ Munich, Dept Med 2, Univ Hosp Munich Grosshadern, Marchioninistr 15, D-81377 Munich, Germany. EM stephan.brand@med.uni-muenchen.de RI Niess, Jan /E-8361-2017 OI Niess, Jan /0000-0001-6902-5650 FU NIDDK NIH HHS [P01 DK033506, DK 51003, DK33506, DK068181, R01 DK051003, R01 DK068181, P30 DK043351] NR 45 TC 20 Z9 20 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2010 VL 16 IS 11 BP 1871 EP 1881 DI 10.1002/ibd.21306 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 679AA UT WOS:000284130600011 PM 20848509 ER PT J AU Shi, Y Buffenstein, R Pulliam, DA Van Remmen, H AF Shi, Yun Buffenstein, Rochelle Pulliam, Daniel A. Van Remmen, Holly TI Comparative Studies of Oxidative Stress and Mitochondrial Function in Aging SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2010 CL Seattle, WA SP Soc Integrat & Comparat Biol ID HYDROGEN-PEROXIDE PRODUCTION; FREE-RADICAL PRODUCTION; LONGEST-LIVING RODENT; MAXIMUM LIFE-SPAN; NAKED MOLE-RAT; BUTYL-ALPHA-PHENYLNITRONE; HUMAN SKELETAL-MUSCLE; AGE-RELATED-CHANGES; SHORT-LIVED RAT; PROTEIN OXIDATION AB The oxidative stress theory and its correlate the mitochondrial theory of aging are among the most studied and widely accepted of all hypotheses of the mechanism of aging. To date, most of the supporting evidence for these theories has come from investigations using common model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and laboratory rodents. However, comparative data from a wide range of endotherms provide equivocal support as to whether oxidative stress is merely a correlate, rather than a determinant, of species' maximum lifespan. The great majority of studies in this area have been devoted to the relationship between reactive oxygen species and maximal longevity in young adult organisms, with little emphasis on mitochondrial respiratory efficiency, age-related alterations in mitochondrial physiology or oxidative damage. The advantage of studying a broader spectrum of species is the broad range of virtually every biological phenotype/ trait, such as lifespan, body weight and metabolic rate. Here we summarize the results from a number of comparative studies in an effort to correlate oxidant production and oxidative damage among many species with their maximal lifespan and briefly discuss the pitfalls and limitations. Based on current information, it is not possible to accept or dispute the oxidative stress theory of aging, nor can we exclude the possibility that private mechanisms might offer an explanation for the longevity of exceptionally long-lived animal models. Thus, there is need for more thorough and controlled investigations with more unconventional animal models for a deeper understanding of the role of oxidative stress in longevity. C1 [Shi, Yun; Buffenstein, Rochelle; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Shi, Yun; Buffenstein, Rochelle; Pulliam, Daniel A.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Buffenstein, Rochelle; Pulliam, Daniel A.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Van Remmen, Holly] S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. RP Shi, Y (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu NR 71 TC 10 Z9 10 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD NOV PY 2010 VL 50 IS 5 BP 869 EP 879 DI 10.1093/icb/icq079 PG 11 WC Zoology SC Zoology GA 673QM UT WOS:000283678100016 PM 21558246 ER PT J AU Thompson, BT Ranieri, VM Finfer, S Barie, PS Dhainaut, JF Douglas, IS Gardlund, B Marshall, JC Rhodes, A AF Thompson, B. Taylor Ranieri, V. Marco Finfer, Simon Barie, Philip S. Dhainaut, Jean-Francois Douglas, Ivor S. Gardlund, Bengt Marshall, John C. Rhodes, Andrew CA PROWESS Shock Steering Comm TI Statistical analysis plan of PROWESS SHOCK study SO INTENSIVE CARE MEDICINE LA English DT Letter ID ACTIVATED PROTEIN-C; SEVERE SEPSIS; SURVIVING SEPSIS; CONTROLLED-TRIAL; SEPTIC SHOCK; CAMPAIGN C1 [Ranieri, V. Marco] Univ Turin, Osped S Giovanni Battista Molinette, Turin, Italy. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Finfer, Simon] Univ Sydney, George Inst Int Hlth, Sydney, NSW 2006, Australia. [Barie, Philip S.] P713A Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA. [Dhainaut, Jean-Francois] Cochin Port Royal Univ, Paris, France. [Douglas, Ivor S.] Denver Hlth, Denver, CO USA. [Douglas, Ivor S.] Univ Colorado, Denver, CO 80202 USA. [Gardlund, Bengt] Karolinska Univ Hosp, Dept Infect Dis, S-14186 Huddinge, Sweden. [Marshall, John C.] St Michaels Hosp, Dept Surg & Crit Care Med, Toronto, ON M5B 1W8, Canada. RP Ranieri, VM (reprint author), Univ Turin, Osped S Giovanni Battista Molinette, Turin, Italy. EM marco.ranieri@unito.it OI Douglas, Ivor/0000-0002-4541-1431 NR 8 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD NOV PY 2010 VL 36 IS 11 BP 1972 EP 1973 DI 10.1007/s00134-010-1977-3 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 661DB UT WOS:000282702100025 ER PT J AU Butler, MO Ansen, S Tanaka, M Imataki, O Berezovskaya, A Mooney, MM Metzler, G Milstein, MI Nadler, LM Hirano, N AF Butler, Marcus O. Ansen, Sascha Tanaka, Makito Imataki, Osamu Berezovskaya, Alla Mooney, Mary M. Metzler, Genita Milstein, Matthew I. Nadler, Lee M. Hirano, Naoto TI A panel of human cell-based artificial APC enables the expansion of long-lived antigen-specific CD4(+) T cells restricted by prevalent HLA-DR alleles SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE adoptive therapy; artificial APC; CD4; Foxp3; HLA-DR; K562 ID HUMAN CYTOMEGALOVIRUS; METASTATIC MELANOMA; PRESENTING CELLS; COSTIMULATORY MOLECULES; APLASTIC-ANEMIA; PROTEIN PP65; RESPONSES; LYMPHOCYTES; THERAPY; PEPTIDE AB Many preclinical experiments have attested to the critical role of CD4(+) T cell help in CD8(+) cytotoxic T lymphocyte (CTL)-mediated immunity. Recent clinical trials have demonstrated that reinfusion of CD4(+) T cells can induce responses in infectious diseases and cancer. However, few standardized and versatile systems exist to expand antigen-specific CD4(+) T-h for clinical use. K562 is a human erythroleukemic cell line, which lacks expression of HLA class I and class II, invariant chain and HLA-DM but expresses adhesion molecules such as intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. With this unique immunologic phenotype, K562 has been tested in clinical trials of cancer immunotherapy. Previously, we created a K562-based artificial antigen-presenting cell (aAPC) that generates ex vivo long-lived HLA-A2-restricted CD8(+) CTL with a central/effector memory phenotype armed with potent effector function. We successfully generated a clinical version of this aAPC and conducted a clinical trial where large numbers of anti-tumor CTL are reinfused to cancer patients. In this article, we shifted focus to CD4(+) T cells and developed a panel of novel K562-derived aAPC, where each expresses a different single HLA-DR allele, invariant chain, HLA-DM, CD80, CD83 and CD64; takes up soluble protein by endocytosis and processes and presents CD4(+) T-cell peptides. Using this aAPC, we were able to determine novel DR-restricted CD4(+) T-cell epitopes and expand long-lived CD4(+) T-cells specific for multiple antigens without growing bystander Foxp3(+) regulatory T cells. Our results suggest that K562-based aAPC may serve as a translatable platform to generate both antigen-specific CD8(+) CTL and CD4(+) T-h. C1 [Butler, Marcus O.; Ansen, Sascha; Tanaka, Makito; Imataki, Osamu; Berezovskaya, Alla; Mooney, Mary M.; Metzler, Genita; Milstein, Matthew I.; Nadler, Lee M.; Hirano, Naoto] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Butler, Marcus O.; Ansen, Sascha; Tanaka, Makito; Imataki, Osamu; Nadler, Lee M.; Hirano, Naoto] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Butler, Marcus O.; Ansen, Sascha; Tanaka, Makito; Imataki, Osamu; Nadler, Lee M.; Hirano, Naoto] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hirano, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Naoto_Hirano@dfci.harvard.edu FU Cancer Research Institute; National Institutes of Health [CA87720, K22CA129240, R01CA148673]; American Society of Hematology FX Cancer Research Institute to M.O.B., M.T., O.I. and L.M.N.; National Institutes of Health (CA87720 to M.O.B, K22CA129240 and R01CA148673 to N.H.; American Society of Hematology Scholar Award. NR 52 TC 20 Z9 20 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2010 VL 22 IS 11 BP 863 EP 873 DI 10.1093/intimm/dxq440 PG 11 WC Immunology SC Immunology GA 689TU UT WOS:000284953300002 PM 21059769 ER PT J AU Boergermann, JH Kopf, J Yu, PB Knaus, P AF Boergermann, J. H. Kopf, J. Yu, P. B. Knaus, P. TI Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Dorsomorphin; LDN-193189; BMP signalling; p38; Akt ID ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR-BETA; STEM-CELLS; PHOSPHORYLATION; DIFFERENTIATION; RECEPTORS; PATHWAYS; MSK1; CREB AB Bone morphogenetic proteins (BMPs) are key regulators of cell fate decisions during embryogenesis and tissue homeostasis. BMPs signal through a coordinated assembly of two types of transmembrane serine/threonine kinase receptors to induce Smad1/5/8 plus non-Smad pathways, such as MAPK and Akt. The recent discovery of BMP receptor inhibitors opened new avenues to study specific BMP signalling and to delineate this effect from TGF-beta and Activin signalling. Here we present comprehensive and quantitative analyses on both canonical and non-Smad mediated BMP signalling under Dorsomorphin (DM) and LDN-193189 (LDN) treatment conditions. We demonstrate for the first time, that both compounds affect not only the Smad but also the non-Smad signalling pathways induced by either BMP2, BMP6 or GDF5. The activation of p38, ERK1/2 and Akt in C2C12 cells was inhibited by DM and LDN. In addition "off-target" effects on all branches of BMP non-Smad signalling are presented. From this we conclude that the inhibition of BMP receptors by DM and more efficiently by LDN-193189 affects all known BMP induced signalling cascades. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Boergermann, J. H.; Kopf, J.; Knaus, P.] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany. [Yu, P. B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Yu, P. B.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Yu, P. B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Knaus, P (reprint author), Free Univ Berlin, Inst Chem & Biochem, Thielallee 63, D-14195 Berlin, Germany. EM knaus@chemie.fu-berlin.de OI Yu, Paul/0000-0003-2145-4944 FU Knaus lab; Deutsche Forschungsgemeinschaft [SFB760]; BSRT FX We thank members of the Knaus lab for vivid discussions and support and Matheusz Kolanczyk for helpful advice. BMP2 was a generous gift from Walter Sebald (Wurzburg), BMP6 from Slobodan Vukicevic (Zagreb) and GDF5 (BioPharm, Heidelberg). This work was supported by the Deutsche Forschungsgemeinschaft (research grant SFB760 to PK and a BSRT fellowship to JK). NR 25 TC 64 Z9 65 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD NOV PY 2010 VL 42 IS 11 BP 1802 EP 1807 DI 10.1016/j.biocel.2010.07.018 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 673YA UT WOS:000283698900010 PM 20691279 ER PT J AU Zhao, SJ Wang, YB Cao, L Ouellette, MM Freeman, JW AF Zhao, Shujie Wang, Yubao Cao, Lin Ouellette, Michel M. Freeman, James W. TI Expression of oncogenic K-ras and loss of Smad4 cooperate to induce the expression of EGFR and to promote invasion of immortalized human pancreas ductal cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE pancreatic cancer; cell signaling; K-ras; EGFR; TGF-beta; Smad4 ID EPIDERMAL-GROWTH-FACTOR; TGF-BETA; CANCER CELLS; ADENOCARCINOMA; PROGRESSION; METASTASIS; MUTATIONS; PATHWAYS; TRANSFORMATION; INACTIVATION AB Activating mutation of K-ras and inactivation of DPC4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC). A separate common event in PDAC progression is increased expression of phosphotyrosine kinase receptors (PTKRs). In our study, we examined whether activating mutations of K-ras and loss of Smad4 play a role in causing the aberrant expression of PTKRs. Immortalized human pancreas ductal cells (HPNE) were genetically modified by expressing oncogenic K-ras and/or by shRNA knockdown of Smad4. EGFR and erbB2 protein levels but not Ron or IGF-1R were substantially upregulated in HPNE cells that express K-ras((GD12)). The increased expression of EGFR in HPNE cells that expressed K-ras((GD12)) was mediated by both stabilizing EGFR protein and by increasing EGFR transcription. TGF-beta signaling partially suppressed K-ras((GD12)) induced EGFR transcription in Smad4 intact HPNE cells; whereas knockdown of Smad4 in cells expressing K-ras((GD12)) further enhanced expression of EGFR and erbB2. The upregulation of EGFR and erbB2 was associated with an increase of invasion, which was blocked by a kinase inhibitor of EGFR. Our study indicates for the first time, that oncogenic ras and loss of Smad signaling cooperate to upregulate EGFR and erbB2, which plays a role in promoting invasion. C1 [Zhao, Shujie; Wang, Yubao; Cao, Lin; Freeman, James W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol & Oncol, San Antonio, TX 78229 USA. [Zhao, Shujie; Cao, Lin; Freeman, James W.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. [Ouellette, Michel M.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Eppley Inst, Omaha, NE USA. RP Freeman, JW (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol & Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM freemanjw@uthscsa.edu FU NIH [R21CA125713, RO1CA069122]; VA Merit Award FX Grant sponsor: NIH; Grant numbers: R21CA125713, RO1CA069122; Grant sponsor: VA Merit Award NR 38 TC 17 Z9 17 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2010 VL 127 IS 9 BP 2076 EP 2087 DI 10.1002/ijc.25412 PG 12 WC Oncology SC Oncology GA 659AO UT WOS:000282539600009 PM 20473902 ER PT J AU Becker, AE Arrindell, AH Perloe, A Fay, K Striegel-Moore, RH AF Becker, Anne E. Arrindell, Adrienne Hadley Perloe, Alexandra Fay, Kristen Striegel-Moore, Ruth H. TI A Qualitative Study of Perceived Social Barriers to Care for Eating Disorders: Perspectives from Ethnically Diverse Health Care Consumers SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE ethnicity; stereotypes; stigma; eating disorders; access to care ID PHOBIC ANOREXIA-NERVOSA; BULIMIA-NERVOSA; GASTROINTESTINAL PRACTICE; SCREENING-PROGRAM; TREATMENT-SEEKING; COMMUNITY SAMPLE; MENTAL-ILLNESS; WHITE WOMEN; BLACK-WOMEN; HONG-KONG AB Objective: The study aim was to identify and describe health consumer perspectives on social barriers to care for eating disorders in an ethnically diverse sample. Method: We conducted an exploratory secondary analysis of qualitative data comprising transcripts from semi-structured interviews with past and prospective consumers of eating disorder treatment (n = 32). Transcripts were inputted into NVivo 8 for coding, sorting, and quantifying thematic content of interest within strata defined by ethnic minority and non-minority participants. We then examined the influence of key social barriers including stigma and social stereotypes on perceived impact on care. Results: The majority of respondents (78%) endorsed at least one social barrier to care for an eating or weight concern. Perceived stigma (or shame) and social stereotyping identified both within social networks and among clinicians had adversely impacted care for 59% and 19% of respondents, respectively. Discussion: Social barriers to care for eating and weight related concerns may be prevalent in the U.S. and impact both ethnic minority and non-minority health care consumers. (C) 2009 by Wiley Periodicals, Inc. C1 [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Becker, Anne E.; Arrindell, Adrienne Hadley; Perloe, Alexandra; Fay, Kristen] Massachusetts Gen Hosp, Dept Psychiat, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Fay, Kristen] Tufts Univ, Eliot Pearson Dept Child Dev, Medford, MA 02155 USA. [Striegel-Moore, Ruth H.] Wesleyan Univ, Dept Psychol, Middletown, CT USA. RP Becker, AE (reprint author), 641 Huntington Ave, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu OI weissman, ruth/0000-0001-6121-4641 FU Harvard Medical School; NIMH [K23 MH068575] FX Supported by the Irene Pollin Fellowship in memory of Cherry Adler from Harvard Medical School and K23 MH068575 from the NIMH. NR 64 TC 31 Z9 31 U1 3 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2010 VL 43 IS 7 BP 633 EP 647 DI 10.1002/eat.20755 PG 15 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 666GK UT WOS:000283102300009 PM 19806607 ER PT J AU Baker, JH Mitchell, KS Neale, MC Kendler, KS AF Baker, Jessica H. Mitchell, Karen S. Neale, Michael C. Kendler, Kenneth S. TI Eating Disorder Symptomatology and Substance Use Disorders: Prevalence and Shared Risk in a Population Based Twin Sample SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE bulimia nervosa; anorexia nervosa; disordered eating; substance use disorders; comorbidity; prevalence; twin study; genetics ID DEFINED BULIMIA-NERVOSA; ANOREXIA-NERVOSA; MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; ALCOHOL-ABUSE; DRUG-ABUSE; WOMEN; DEPENDENCE; ASSOCIATION; COMORBIDITY AB Objective: Research shows a significant association between eating disorders (ED) and substance use disorders (SUD). The objective of this study is to examine the prevalence, chronology, and possibility of shared familial risk between SUD and ED symptomatology. Method: Subjects included 1,206 monozygotic and 877 dizygotic adult female twins. ED symptomatology included anorexia (AN) and bulimia nervosa (BN) diagnosis, symptoms associated with diagnostic criteria, and BN symptom count. SOD included alcohol, illicit drug, and caffeine abuse/dependence. Generalized estimated equation modeling was used to examine phenotypic associations, and Choleksy decompositions were used to delineate the contribution of genes and environment to comorbidity. Results: There were no significant differences between SOD prevalence in women with AN and BN. Women with BN reported BN preceded SOD development while the reverse was true for AN. Twin analyses showed possible familial overlap between BN symptomatology and all SOD examined. Discussion: Results suggest an important difference in the chronology of EDs and SUDs. Women with BN may be turning to substances to dampen bulimic urges. Women with AN may be engaging in substance use initially in an effort to lose weight. Results also suggest familial factors contribute to the comorbidity between BN and SOD. (C) 2010 by Wiley Periodicals, Inc. C1 [Baker, Jessica H.; Mitchell, Karen S.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Baker, Jessica H.; Mitchell, Karen S.; Neale, Michael C.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA. [Mitchell, Karen S.] Vet Affairs Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA USA. [Neale, Michael C.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23284 USA. RP Baker, JH (reprint author), Virginia Commonwealth Univ, Dept Psychol, Box 842018, Richmond, VA 23284 USA. EM bakerjh@mymail.vcu.edu FU National Institute of Health [MH/AA-49492, AA/DA-09095, T32-MH-020030, MH-20030]; National Institute of Drug Abuse [T32-DA-007027, DA-18673]; Rachel Brown Banks Endowment Fund FX Supported by MH/AA-49492, AA/DA-09095, T32-MH-020030, MH-20030, National Institute of Health; T32-DA-007027, DA-18673, National Institute of Drug Abuse; and Rachel Brown Banks Endowment Fund. NR 40 TC 26 Z9 27 U1 5 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2010 VL 43 IS 7 BP 648 EP 658 DI 10.1002/eat.20856 PG 11 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 666GK UT WOS:000283102300010 PM 20734312 ER PT J AU Woo, BKP Harwood, DG Melrose, RJ Mandelkern, MA Campa, OM Walston, A Sultzer, DL AF Woo, Benjamin K. P. Harwood, Dylan G. Melrose, Rebecca J. Mandelkern, Mark A. Campa, Olivia M. Walston, Amy Sultzer, David L. TI Executive deficits and regional brain metabolism in Alzheimer's disease SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer's disease; positron emission tomography; executive function ID AMERICAN-NEUROPSYCHIATRIC-ASSOCIATION; FUNCTIONAL IMPAIRMENT; PREFRONTAL CORTEX; FDG-PET; DYSFUNCTION; HYPOMETABOLISM; INVOLVEMENT; COMMITTEE; MEMORY; APATHY AB Objective: Executive deficits are common in patients with Alzheimer's disease (AD), contribute prominently to clinical disability, and may be associated with frontal lobe pathology. This study examined regional brain hypometabolism associated with executive dysfunction in patients with AD. Methods: Forty-one patients with probable AD underwent [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at rest. Neuropsychological measures of executive control included the Conceptualization (Conc) and Initiation/Perseveration (TIP) subscales of the Mattis Dementia Rating Scale (DRS), the Wechsler Adult Intelligence Scale (WAIS) Similarities subtest, the Tower test, and the Ruff Figural Fluency test (Ruff). Voxel-based analyses were conducted using statistical parametric mapping (SPM2) to measure the correlation between regional cerebral metabolism and executive measures. Correlations independent of global cognitive impairment were identified by including Mini-Mental State Examination (MMSE) score as a covariate in the model. Results: Executive deficits, as measured by poor performances on the DRS I/P and Conc subscales, were associated with hypometabolism in the bilateral mid-dorsolateral frontal region. Activity in posterior cortical regions also contributed uniquely to some aspects of executive functioning, as lower resting metabolism in parietal or temporal cortex was correlated with poor performance on four of the five executive measures. After controlling for global cognitive score, there were significant extra-frontal correlations with hypometabolism in insula, occipital lobe, and temporal cortex. Conclusions: Some but not all executive deficits in AD are associated with neural activity in the dorsolateral frontal cortex. Activities in distributed neural systems that include parietal and temporal cortex also contribute to some executive abilities. The pathophysiology of executive dysfunction is complex and includes abnormalities not limited to a single region. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Woo, Benjamin K. P.; Harwood, Dylan G.; Melrose, Rebecca J.; Walston, Amy; Sultzer, David L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Woo, Benjamin K. P.; Harwood, Dylan G.; Melrose, Rebecca J.; Campa, Olivia M.; Walston, Amy; Sultzer, David L.] Vet Affairs Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA USA. [Mandelkern, Mark A.] Vet Affairs Greater Los Angeles Healthcare Syst, Nucl Med Serv, Los Angeles, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Woo, BKP (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. EM bkpwoo@gmail.com OI Woo, Benjamin/0000-0002-0127-4850 FU National Institute of Mental Health [R01 MH56031]; Department of Veterans Affairs FX This work was supported by the National Institute of Mental Health (R01 MH56031) and by the Department of Veterans Affairs. NR 43 TC 15 Z9 16 U1 2 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD NOV PY 2010 VL 25 IS 11 BP 1150 EP 1158 DI 10.1002/gps.2452 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 674RM UT WOS:000283765300008 PM 20069587 ER PT J AU Chew, I Post, MD Carinelli, SG Campbell, S Di, Y Soslow, RA Oliva, E AF Chew, Ivy Post, Miriam D. Carinelli, Silvestro G. Campbell, Sharon Di, Ye Soslow, Robert A. Oliva, Esther TI p16 Expression in Squamous and Trophoblastic Lesions of the Upper Female Genital Tract SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE p16; Squamous cell carcinoma; Endometrioid adenocarcinoma with squamous differentiation; Placental site nodule; Placental site trophoblastic tumor ID CERVICAL INTRAEPITHELIAL NEOPLASIA; HUMAN PAPILLOMAVIRUS DETECTION; BENIGN CYSTIC TERATOMA; CELL-CYCLE CONTROL; CANCER STUDY-GROUP; ENDOCERVICAL ADENOCARCINOMAS; ENDOMETRIAL CARCINOMAS; DIFFERENTIAL-DIAGNOSIS; OVARIAN-CARCINOMA; PRB EXPRESSION AB p16, a surrogate marker for human papillomavirus (HPV) infection, is uniformly present in HPV-related carcinomas. This study aims to further characterize p16 expression in trophoblastic lesions and squamous lesions of the upper female genital tract, as little data exists. p16 immunostaining was performed on sections from ichthyosis uteri (1), primary uterine corpus squamous cell carcinoma (UCSCC) (2), primary ovarian SCC (OSCC) (5; 2 associated with a dermoid cyst), endometrial endometrioid adenocarcinoma with extensive squamous differentiation (EC-SD) (5), ovarian endometrioid adenocarcinoma with extensive squamous differentiation (OC-SD) (4), placental site nodule (5), and placental site trophoblastic tumor (PSTT) (6). We evaluated the percentage of positive cytoplasmic and nuclear staining (focal = <10%, multifocal = 10% to 50%, and diffuse = >50%) and staining intensity (weak, moderate, and strong). HPV-DNA analysis by polymerase chain reaction was performed on 5 OSCC. Ichthyosis uteri, all UCSCC and 1 OSCC (arising in a dermoid) were negative; the other dermoid-associated OSCC showed focal moderate staining, the remaining OSCC displayed strong (100%), diffuse (2), or multifocal (1) p16 positivity. Three of the 5 EC-SD cases showed strong diffuse staining of the squamous component. The glandular component focally showed strong p16 positivity (2), with variably intense focal staining in 3 cases. The squamous component of all OC-SD showed focal moderate staining, with variable staining of the glandular component. Overall, 3 EC-SD had 80% to 90% p16 positivity. Five of the 5 placental site nodules and 4 of the 6 PSTT showed focal weak staining, whereas 2 PSTT were p16 negative. HPV-DNA analysis was negative in 3 of the 5 OSCC, the other 2 cases being technical failures. p16 is expressed in OSCC and in the squamous and glandular components of EC-SD and OC-SD. As p16 is negative in UCSCC, it may help to identify the origin of SCC diffusely involving the corpus and cervix, and suggests different pathogeneses for SCC of the upper female genital tract, likely to be unrelated to HPV infection. In contrast to earlier data, we found weak and focal p16 expression in trophoblastic lesions. Thus, when considering the differential diagnosis of cervical SCC and trophoblastic lesions, only strong diffuse p16 staining should be considered helpful. C1 [Chew, Ivy; Campbell, Sharon; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Di, Ye] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Post, Miriam D.] Univ Colorado, Dept Pathol, Denver, CO 80202 USA. [Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Carinelli, Silvestro G.] Fdn Osped Policlin, Dept Pathol, Milan, Italy. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol Warren 251A, 55 Fruit St, Boston, MA 02114 USA. EM eoliva@partners.org OI Soslow, Robert/0000-0002-7269-5898 NR 82 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD NOV PY 2010 VL 29 IS 6 BP 513 EP 522 DI 10.1097/PGP.0b013e3181e2fe70 PG 10 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 668JK UT WOS:000283264400002 PM 20881863 ER PT J AU Elkin, PL Liebow, M Bauer, BA Chaliki, S Wahner-Roedler, D Bundrick, J Lee, M Brown, SH Froehling, D Bailey, K Famiglietti, K Kim, R Hoffer, E Feldman, M Barnett, GO AF Elkin, Peter L. Liebow, Mark Bauer, Brent A. Chaliki, Swarna Wahner-Roedler, Dietlind Bundrick, John Lee, Mark Brown, Steven H. Froehling, David Bailey, Kent Famiglietti, Kathleen Kim, Richard Hoffer, Ed Feldman, Mitchell Barnett, G. Octo TI The introduction of a diagnostic decision support system (DXplain (TM)) into the workflow of a teaching hospital service can decrease the cost of service for diagnostically challenging Diagnostic Related Groups (DRGs) SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Review DE Expert systems; Clinical decision support; Medical education; Medical economics ID PROGRAM AB Background: In an era of short inpatient stays, residents may overlook relevant elements of the differential diagnosis as they try to evaluate and treat patients. However, if a resident's first principal diagnosis is wrong, the patient's appropriate evaluation and treatment may take longer, cost more, and lead to worse outcomes. A diagnostic decision support system may lead to the generation of a broader differential diagnosis that more often includes the correct diagnosis, permitting a shorter, more effective, and less costly hospital stay. Methods: We provided residents on General Medicine services access to DXplain, an established computer-based diagnostic decision support system, for 6 months. We compared charges and cost of service for diagnostically challenging cases seen during the fourth through sixth month of access to DXplain (intervention period) to control cases seen in the 6 months before the system was made available. Results: 564 cases were identified as diagnostically challenging by our criteria during the intervention period along with 1173 cases during the control period. Total charges were $1281 lower (p=.006), Medicare Part A charges $1032 lower (p=0.006) and cost of service $990 lower (p=0.001) per admission in the intervention cases than in control cases. Conclusions: Using DXplain on all diagnostically challenging cases might save our medical center over $2,000,000 a year on the General Medicine Services alone. Using clinical diagnostic decision support systems may improve quality and decrease cost substantially at teaching hospitals. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Elkin, Peter L.] Mt Sinai Sch Med, Ctr Biomed Informat, New York, NY 10029 USA. [Liebow, Mark; Bauer, Brent A.; Chaliki, Swarna; Wahner-Roedler, Dietlind; Bundrick, John; Lee, Mark; Froehling, David; Bailey, Kent] Mayo Clin, Coll Med, Rochester, MN USA. [Brown, Steven H.] Vanderbilt Univ, Nashville, TN USA. [Brown, Steven H.] Vet Adm, Nashville, TN USA. [Famiglietti, Kathleen; Kim, Richard; Hoffer, Ed; Feldman, Mitchell; Barnett, G. Octo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Elkin, PL (reprint author), Mt Sinai Sch Med, Ctr Biomed Informat, 1 Gustave L Levy Pl,Box 1023, New York, NY 10029 USA. EM peter.elkin@mssm.edu FU National Library of Medicine [LM06918]; Centers for Disease Control and Prevention [PH000022, HK00014]; Laboratory of Computer Science, Massachusetts General Hospital FX This work has been supported in part by a grant from the National Library of Medicine LM06918, and grants from the Centers for Disease Control and Prevention PH000022 and HK00014 and in part by no-cost access to DXplain from the Laboratory of Computer Science, Massachusetts General Hospital. NR 22 TC 22 Z9 24 U1 3 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD NOV PY 2010 VL 79 IS 11 BP 772 EP 777 DI 10.1016/j.ijmedinf.2010.09.004 PG 6 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 673GO UT WOS:000283647700003 PM 20951080 ER PT J AU Boutrus, R Ab-Raad, R Niemierko, A Brachtel, EF Rizk, L Kelada, A Taghian, AG AF Boutrus, Rimoun Ab-Raad, Rita Niemierko, Andrzej Brachtel, Elena F. Rizk, Levi Kelada, Alexandra Taghian, Alphonse G. TI DOES LYMPHOVASCULAR INVASION PREDICT REGIONAL NODAL FAILURE IN BREAST CANCER PATIENTS WITH ZERO TO THREE POSITIVE LYMPH NODES TREATED WITH CONSERVING SURGERY AND RADIOTHERAPY? IMPLICATIONS FOR REGIONAL RADIATION SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY NOV 01-05, 2009 CL Chicago, IL SP Amer Soc Therapeut Radiat & Oncol DE Breast cancer; Breast-conserving therapy; Regional nodal failure; Lymphovascular invasion; Regional irradiation ID 20-YEAR FOLLOW-UP; CONSERVATIVE SURGERY; VESSEL INVASION; THERAPY; IRRADIATION; MASTECTOMY; PATTERNS AB Purpose: To examine the relationship between lymphovascular invasion (LVI) and regional nodal failure (RNF) in breast cancer patients with zero to three positive nodes treated with breast-conservation therapy (BCT). Methods and Materials: The records of 1,257 breast cancer patients with zero to three positive lymph nodes were reviewed. All patients were treated with BCT at Massachusetts General Hospital from 1980 to December 2003. Lymphovascular invasion was diagnosed by hematoxylin and eosin stained sections and in some cases supported by immunohistochemical stains. Regional nodal failure was defined as recurrence in the ipsilateral supraclavicular, axillary, or internal mammary lymph nodes. Regional nodal failure was diagnosed by clinical and/or radiologic examination. Results: The median follow-up was 8 years (range, 0.1-21 years). Lymphovascular invasion was present in 211 patients (17%). In univariate analysis, patients with LVI had a higher rate of RNF (3.32% vs. 1.15%; p = 0.02). In multivariate analysis, only tumor size, grade, and local failure were significant predictors of RNF (p = 0.049, 0.013, and 0.0001, respectively), whereas LVI did not show a significant relationship with RNF (hazard ratio = 2.07; 95% CI, 0.8-5.5; p = 0.143). The presence of LVI in the T2/3 population did not increase the risk of RNF over that for those with no LVI (p = 0.15). In addition, patients with Grade 3 tumors and positive LVI did not have a higher risk of RNF than those without LVI (p = 0.96). Conclusion: These results suggest that LVI can not be used as a sole indicator for regional nodal irradiation in breast cancer patients with zero to three positive lymph nodes treated with BCT. (C) 2010 Elsevier Inc. C1 [Boutrus, Rimoun; Ab-Raad, Rita; Niemierko, Andrzej; Rizk, Levi; Kelada, Alexandra; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Brachtel, Elena F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox Bldg 302, Boston, MA 02114 USA. EM ataghian@partners.org NR 23 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2010 VL 78 IS 3 BP 793 EP 798 DI 10.1016/j.ijrobp.2009.08.049 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 661MB UT WOS:000282731300022 PM 20171799 ER PT J AU Li, HK Hubbard, LD Danis, RP Esquivel, A Florez-Arango, JF Ferrier, NJ Krupinski, EA AF Li, Helen K. Hubbard, Larry D. Danis, Ronald P. Esquivel, Adol Florez-Arango, Jose F. Ferrier, Nicola J. Krupinski, Elizabeth A. TI Digital versus Film Fundus Photography for Research Grading of Diabetic Retinopathy Severity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2008 CL Ft Lauderdale, FL SP Assoc Res Vision & Opthalmol ID DIAGNOSIS; PROGRAM; SYSTEM; CAMERA AB PURPOSE. To assess agreement between digital and film photography for research classification of diabetic retinopathy severity. METHODS. Digital and film photographs from a 152-eye cohort with a full spectrum of Early Treatment Diabetic Retinopathy Study (ETDRS) severity levels were assessed for repeatability of grading within each image medium and for agreement on ETDRS discrete severity levels, ascending severity thresholds, and presence or absence of diabetic retinopathy index lesions, between digital and 35-mm slides (film). Digital photographs were color balanced to match film. RESULTS. There was substantial agreement (kappa = 0.61, kappa(w) [linear weighted] = 0.87) in classification of ETDRS diabetic retinopathy severity levels between digital images and film. Marginal homogeneity analyses found no significant difference in frequency distributions on the severity scale (P = 0.21, Bhapkar test). The kappa results ranged from 0.72 to 0.95 for presence or absence of eight ascending diabetic retinopathy severity thresholds. Repeatability of grading between readers viewing digital images was equal to or better than that obtained with film (pair-wise interreader kappa for digital images ranged from 0.47 to 0.57 and for film from 0.43 to 0.57. The kappa results for identifying diabetic retinopathy lesions ranged from moderate to almost perfect. Moderate agreement of intraretinal microvascular abnormalities and venous beading between digital images and film accounted for slightly lower concordance for severity thresholds >= 47 and for slightly lower interreader agreement within digital and film images at severity thresholds >= 43 and >= 47. CONCLUSIONS. Under controlled circumstances, digital photography can equal the reliability of 35-mm slides for research classification of ETDRS severity level. (Invest Ophthalmol Vis Sci. 2010;51:5846-5852) DOI:10.1167/iovs.09-4803 C1 [Li, Helen K.; Florez-Arango, Jose F.] Univ Texas Hlth Sci Ctr, Sch Biomed Informat, Houston, TX USA. [Li, Helen K.] Thomas Jefferson Univ, Dept Ophthalmol, Philadelphia, PA 19107 USA. [Hubbard, Larry D.; Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Ferrier, Nicola J.] Univ Wisconsin, Dept Mech Engn, Madison, WI 53706 USA. [Ferrier, Nicola J.] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53706 USA. [Esquivel, Adol] Houston Vet Affairs Med Ctr, Houston, TX USA. [Esquivel, Adol] Baylor Coll Med, Houston, TX 77030 USA. [Florez-Arango, Jose F.] Univ De Antioquia, Medellin, Colombia. [Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Li, HK (reprint author), Community Retina Grp, 1400 Hermann Dr, Houston, TX 77004 USA. EM hlimed@mac.com OI Florez-Arango, Jose F/0000-0001-9083-0195 NR 31 TC 9 Z9 9 U1 0 U2 0 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 NOV PY 2010 VL 51 IS 11 BP 5846 EP 5852 DI 10.1167/iovs.09-4803 PG 7 WC Ophthalmology SC Ophthalmology GA 672BQ UT WOS:000283558400057 PM 20484593 ER PT J AU van der Giessen, AG Toepker, MH Donelly, PM Bamberg, F Schlett, CL Raffle, C Irlbeck, T Lee, H van Walsum, T Maurovich-Horvat, P Gijsen, FJH Wentzel, JJ Hoffmann, U AF van der Giessen, Alina G. Toepker, Michael H. Donelly, Patrick M. Bamberg, Fabian Schlett, Christopher L. Raffle, Christopher Irlbeck, Thomas Lee, Hang van Walsum, Theo Maurovich-Horvat, Pal Gijsen, Frank J. H. Wentzel, Jolanda J. Hoffmann, Udo TI Reproducibility, Accuracy, and Predictors of Accuracy for the Detection of Coronary Atherosclerotic Plaque Composition by Computed Tomography An Ex Vivo Comparison to Intravascular Ultrasound SO INVESTIGATIVE RADIOLOGY LA English DT Article DE coronary artery angiography; x-ray computed tomography; intravascular ultrasonography; plaque detection ID MULTIDETECTOR ROW CT; ELECTRON-BEAM CT; DIAGNOSTIC-ACCURACY; ARTERY-DISEASE; INTRACORONARY ULTRASOUND; STABLE ANGINA; ANGIOGRAPHY; QUANTIFICATION; RESOLUTION; CALCIUM AB Purpose: To determine the reproducibility, accuracy, and predictors of accuracy of computed tomography (CT) angiography to detect and characterize coronary atherosclerotic plaque as compared with intravascular ultrasound. Methods: Ten ex vivo human coronary arteries were imaged in a moving phantom by dual-source CT (collimation: 0.6 mm, reconstructed slice thickness: 0.4 mm) and intravascular ultrasound (IVUS). Coregistered crosssections were assessed at 0.4 mm intervals for the presence and composition of atherosclerotic plaque (noncalcified, mixed, and calcified) on CT and IVUS by independent readers to determine reader agreement and diagnostic accuracy. Quantitative measurements of lumen and plaque area, plaque eccentricity, and intimal thickness on IVUS were used to determine predictors for the detection of noncalcified plaque by CT. Results: Within 1002 coregistered cross-sections, the interobserver agreement to detect plaque on CT was K = 0.48, K = 0.42, and K = 1.00 for noncalcified, mixed, and calcified plaque; respectively. The sensitivity and specificity of CT was 57% out of 84% for noncalcified, 32% of 92% for mixed, and 56% of 93% for calcified plaque when compared with IVUS; respectively. Misclassification occurred in 68% of mixed and 43% of noncalcified plaques. The odds of detecting noncalcified plaque in CT independently increased by 56% (95% CI: 47%-77%, P < 0.0001) with every 0.1 mm increase in maximum intimal thickness as measured by IVUS. Detection rate for noncalcified plaques was poor for plaques <1 mm (36%) but excellent for plaques >1 mm maximal intimal thickness (90%). Conclusion: Reader agreement and diagnostic accuracy for the detection of coronary atherosclerotic plaque vary with plaque composition. Intimal thickness independently predicts detection of noncalcified plaque by CT with excellent sensitivity for >1 mm thick plaques. C1 [van der Giessen, Alina G.; Toepker, Michael H.; Donelly, Patrick M.; Bamberg, Fabian; Schlett, Christopher L.; Raffle, Christopher; Irlbeck, Thomas; Maurovich-Horvat, Pal; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02144 USA. [van der Giessen, Alina G.; Toepker, Michael H.; Donelly, Patrick M.; Bamberg, Fabian; Schlett, Christopher L.; Raffle, Christopher; Irlbeck, Thomas; Lee, Hang; Maurovich-Horvat, Pal; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02144 USA. [van der Giessen, Alina G.; Gijsen, Frank J. H.; Wentzel, Jolanda J.] Erasmus MC, Dept Cardiol, Rotterdam, Netherlands. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02144 USA. [van Walsum, Theo] Erasmus MC, Biomed Imaging Grp Rotterdam, Dept Radiol, Rotterdam, Netherlands. [van Walsum, Theo] Erasmus MC, Biomed Imaging Grp Rotterdam, Dept Med Informat, Rotterdam, Netherlands. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02144 USA. EM uhoffmann@partners.org OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU Austrian Science Fund FWF [J 2803] NR 34 TC 26 Z9 27 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD NOV PY 2010 VL 45 IS 11 BP 693 EP 701 DI 10.1097/RLI.0b013e3181e0a541 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 658SL UT WOS:000282509600001 PM 20479650 ER PT J AU Osborn, EA Jaffer, FA AF Osborn, Eric A. Jaffer, Farouc A. TI The Year in Molecular Imaging SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; heart failure; molecular imaging; myocardial infarction; thrombosis ID POSITRON-EMISSION-TOMOGRAPHY; RABBIT ATHEROSCLEROTIC PLAQUES; CARDIAC MAGNETIC-RESONANCE; ACUTE CORONARY SYNDROMES; IN-VIVO; STEM-CELLS; MYOCARDIAL-INFARCTION; CONTRAST AGENT; MATRIX METALLOPROTEINASES; ACTIVE INFLAMMATION AB Molecular imaging aims to enable personalized medicine via imaging specific molecular and cellular targets that are relevant to the diagnosis and treatment of disease By providing in vivo readouts of biological detail, molecular imaging complements traditional anatomical imaging modalities to allow 1) visualization of important disease-modulating molecules and cells in vivo, 2) serial investigations to image evolutionary changes in disease attributes, and 3) evaluation of the in vivo molecular effects of biotherapeutics The added information garnered by molecular imaging can improve risk assessment and prognosticative studies this is of particular benefit in the management of cardiovascular disease (CVD) (J Am Coll Cardiol Img 2010,3 1181-95) (C) 2010 by the American College of Cardiology Foundation C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiol, Sch Med, Boston, MA 02215 USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Cardiol Div, Boston, MA USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Jaffer, FA (reprint author), MGH Cardiovasc Res Ctr, 185 Cambridge St,Simches Res Bldg 3206, Boston, MA 02114 USA. OI Jaffer, Farouc/0000-0001-7980-384X FU Howard Hughes Medical Institute; American Heart Association [0830352N]; National Institutes of Health [RO1 HL 108229] FX This work was supported by a Howard Hughes Medical Institute Early Career Award American Heart Association Scientist Development Grant #0830352N and National Institutes of Health grant RO1 HL 108229 NR 56 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD NOV PY 2010 VL 3 IS 11 BP 1181 EP 1195 DI 10.1016/j.jcmg.2010.09.009 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 683UL UT WOS:000284501900012 PM 21071007 ER PT J AU Kadakia, MB Desai, NR Alexander, KP Chen, AY Foody, JM Cannon, CP Wiviott, SD Scirica, BM AF Kadakia, Mitul B. Desai, Nihar R. Alexander, Karen P. Chen, Anita Y. Foody, JoAnne M. Cannon, Christopher P. Wiviott, Stephen D. Scirica, Benjamin M. CA Natl Cardiovasc Data Registry TI Use of Anticoagulant Agents and Risk of Bleeding Among Patients Admitted With Myocardial Infarction SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE anticoagulants; bleeding; heparin; myocardial infarction; registries ID ACUTE CORONARY SYNDROMES; UNFRACTIONATED HEPARIN; INVASIVE STRATEGY; RANDOMIZED-TRIAL; UNSTABLE ANGINA; ENOXAPARIN; INTERVENTION; BIVALIRUDIN; FONDAPARINUX; OUTCOMES AB Objectives The aim of this study was to evaluate anticoagulant use patterns and bleeding risk in a contemporary population of patients with acute coronary syndrome. Background Current practice guidelines support the use of unfractionated heparin, low molecular weight heparin, bivalirudin, or fondaparinux in non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Little is known about how these agents are selected in clinical practice. Methods Between January 2007 and June 2009, data were captured for 72,699 patients with NSTEMI and 48,943 patients with STEMI at 360 U.S. hospitals for the NCDR ACTION Registry-GWTG (National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines). Patients were categorized based on anticoagulant strategy selected during hospitalization and their CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of ACC/AHA [American College of Cardiology/American Heart Association] Guidelines) bleeding risk category. Results At least 1 anticoagulant was administered to 66,279 patients (91.2%) with NSTEMI and 46,149 patients (94.3%) with STEW. Among STEMI patients, unfractionated heparin was most commonly used (66%), followed by bivalirudin (14%) and low molecular weight heparin (8%). In NSTEMI patients, unfractionated heparin was also the most commonly used anticoagulant (42%), followed by low molecular weight heparin (27%) and then bivalirudin (13%). There were significant differences in anticoagulant use by age, risk factors, concomitant medications, and invasive care. There was a 5-fold difference in the rate of bleeding between patients in the lowest and highest CRUSADE bleeding risk groups, which was consistently observed in most anticoagulant groups. Conclusions There is a wide variability in the use of anticoagulant regimens with significant differences according to baseline characteristics and concomitant therapies. Major bleeding is common, though a great degree of the variability in the rate of bleeding is largely based on differences in baseline characteristics, comorbidities, and invasive treatment strategies, rather than specific anticoagulant regimens. (J Am Coll Cardiol Intv 2010;3:1166-77) (C) 2010 by the American College of Cardiology Foundation C1 [Kadakia, Mitul B.; Desai, Nihar R.; Foody, JoAnne M.; Cannon, Christopher P.; Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Kadakia, Mitul B.; Desai, Nihar R.; Foody, JoAnne M.; Cannon, Christopher P.; Wiviott, Stephen D.; Scirica, Benjamin M.] Harvard Univ, Sch Med, Boston, MA USA. [Kadakia, Mitul B.; Desai, Nihar R.; Cannon, Christopher P.; Wiviott, Stephen D.; Scirica, Benjamin M.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Alexander, Karen P.; Chen, Anita Y.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Alexander, Karen P.; Chen, Anita Y.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org FU Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; Genentech; Schering-Plough Corporation; Bristol-Myers Squibb; Merck; Pfizer; Sanofi-Aventis; Accumetrics; AstraZeneca; GlaxoSmithKline; Intekrin Therapeutics; Takeda; Daiichi Sankyo; Eli Lilly; Schering-Plough; Cogentus; Novartis; CV Therapeutics; ohnson Johnson; Bayer HealthcareMichael Lemer Foundation FX From the 'TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; dagger Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; and double dagger Duke Clinical Research, Institute and Division of Cardiology, Duke University Medical Center, Durham, North Carolina. The NCDR ACTION Registry-GWTG is administered by the American College of Cardiology Foundation (ACCF) and sponsored by Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Genentech, and Schering-Plough Corporation, who provide material support for the operation of the data collection and infrastructure. The sponsors had no additional role in this project including the selection of topic, analysis of data, decision to publish, or approval of the manuscript before publication. Dr. Foody reports receiving consulting fees from Bristol-Myers Squibb, Merck, Pfizer, and Sanofi-Aventis. Dr. Cannon reports receiving research grants from Accumetrics, AstraZeneca, GlaxoSmithKline, Intekrin Therapeutics, Merck, and Takeda; he is a clinical adviser for and holds equity in Automedics Medical Systems; he is on the Advisory Board (but funds donated to charity) for Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam; and he received honorarium for development of independent educational symposia: Pfizer, AstraZeneca. Dr. Wiviott reports receiving honoraria for educational presentations from Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Schering-Plough, Merck, and The Medicines Company, consulting fees from AstraZeneca, Bristol-Myers Squibb, and Sanofi-Aventis; and research grant support from Daiichi Sankyo, Eli Lilly, and Schering-Plough. Dr. Scirica has received honoraria for educational presentations from CV Therapeutics, Merck, Novartis, and Schering-Plough; consulting fees from AstraZeneca, Cogentus, and Novartis; and received research grant support from AstraZeneca, Bristol-Myers Squibb, CV Therapeutics, Merck, Daiichi Sankyo, Novartis, Johnson & Johnson, and Bayer Healthcare, as well as an unrestricted research grant from the Michael Lemer Foundation. All other authors have reported that they have no relationships to disclose. NR 20 TC 45 Z9 47 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD NOV PY 2010 VL 3 IS 11 BP 1166 EP 1177 DI 10.1016/j.jcin.2010.08.015 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 686DR UT WOS:000284677500010 PM 21087753 ER PT J AU Tien, PC Choi, AI Zolopa, AR Benson, C Tracy, R Scherzer, R Bacchetti, P Shlipak, M Grunfeld, C AF Tien, Phyllis C. Choi, Andy I. Zolopa, Andrew R. Benson, Constance Tracy, Russell Scherzer, Rebecca Bacchetti, Peter Shlipak, Michael Grunfeld, Carl TI Inflammation and Mortality in HIV-Infected Adults: Analysis of the FRAM Study Cohort SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; inflammation; C-reactive protein; fibrinogen; mortality ID HUMAN-IMMUNODEFICIENCY-VIRUS; C-REACTIVE PROTEIN; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION; FAT REDISTRIBUTION; METABOLIC-CHANGE; DEATH; ASSOCIATION; SURVIVAL AB Objective: To determine the association of inflammatory markers, fibrinogen, and C-reactive protein (CRP), with 5-year mortality risk. Methods: Vital status was ascertained in 922 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. Multivariable logistic regression estimated odds ratios after adjustment for demographic, cardiovascular, and HIV-related factors. Results: Over a 5-year period, HIV-infected participants with fibrinogen levels in the highest tertile (>406 mg/dL) had 2.6-fold higher adjusted odds of death than those with fibrinogen in the lowest tertile (<319 mg/dL). Those with high CRP (>3 mg/L) had 2.7-fold higher adjusted odds of death than those with CRP <1 mg/L. When stratified by CD4 count category, fibrinogen (as a linear variable) remained independently associated [odds ratio (95% confidence intervals)] per 100 mg/dL increase in fibrinogen: 1.93 (1.57 to 2.37); 1.43 (1.14 to 1.79); 1.43 (1.14 to 1.81); and 1.30 (1.04 to 1.63) for CD4 <200, 200-350, >350 to 500, and >500 cells per microliter, respectively. Higher CRP also remained associated with higher odds of death overall and within each CD4 subgroup. Conclusions: Fibrinogen and CRP are strong and independent predictors of mortality in HIV-infected adults. Our findings suggest that even in those with relatively preserved CD4 counts >500 cells per microliter, inflammation remains an important risk factor for mortality. Further investigation should determine whether interventions to reduce inflammation might decrease mortality risk in HIV-infected individuals. C1 [Tien, Phyllis C.] Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, San Francisco, CA 94121 USA. [Tien, Phyllis C.; Choi, Andy I.; Scherzer, Rebecca; Shlipak, Michael; Grunfeld, Carl] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Zolopa, Andrew R.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Benson, Constance] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Tracy, Russell] Univ Vermont, Dept Pathol & Biochem, Colchester, VT USA. [Bacchetti, Peter] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. RP Tien, PC (reprint author), Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, 111W,4150 Clement St, San Francisco, CA 94121 USA. EM ptien@ucsf.edu FU National Institutes of Health (NIH) [R01-DK57508, HL74814, HL53359, K23-AI66943, DK080645]; NIH center [M01-RR00036, RR00051, RR00052, RR00054, RR00083, RR0636, RR00865, UL1 RR024131] FX Supported by National Institutes of Health (NIH) grants R01-DK57508, HL74814, and HL53359; K23-AI66943 and DK080645, and NIH center grants M01-RR00036, RR00051, RR00052, RR00054, RR00083, RR0636, RR00865, and UL1 RR024131. The funding agency had no role in the collection or analysis of the data. NR 26 TC 126 Z9 128 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2010 VL 55 IS 3 BP 316 EP 322 DI 10.1097/QAI.0b013e3181e66216 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 675RE UT WOS:000283847400007 PM 20581689 ER PT J AU Miller, JW AF Miller, Joan W. TI Treatment of Age-Related Macular Degeneration: Beyond VEGF SO JAPANESE JOURNAL OF OPHTHALMOLOGY LA English DT Review DE age-related macular degeneration; anti-VEGF therapies; apoptosis; Bruch membrane; genetic associations ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; INTRAVITREAL TRIAMCINOLONE ACETONIDE; COMBINED PHOTODYNAMIC THERAPY; FACTOR-H POLYMORPHISM; RETINAL-DETACHMENT; EXPERIMENTAL-MODEL; BRUCHS MEMBRANE; CLINICAL-TRIAL; VERTEPORFIN; GENE AB Current therapy for age-related macular degeneration (AMD) shows a dramatic change from clinical practice a decade ago. While the first pharmacologic treatment, verteporfin photodynamic therapy (PDT) slowed disease progression, newer anti-vascular epithelial growth factor (VEGF) therapies have also shown vision improvement in many patients. Combination therapies (PDT + steroid + anti-VEGF) have shown some promise, particularly in certain classes of disease. Genetic studies have identified common gene variants in the complement factor H gene that confers susceptibility to AMD, and treatments targeting the complement pathway are being explored. Another area of research is directed at the components of Bruch membrane; studies of changes in the elastic fibers and collagen within Bruch may yield drug targets for prevention and halting of disease progression. Finally, studies in photoreceptor apoptosis have identified the role of cytokines, such as monocyte chemotactic protein 1, tumor necrosis factor a, and interleukin 1 beta, associated with photoreceptor cell death and should be pursued as potential therapies to improve vision outcomes in neovascular AMD. Today's research into the biology of AMD will lead us to better treatment and perhaps even preventive measures in the decades ahead. Jpn J Ophthalmol 2010;54:523-528 (C) Japanese Ophthalmological Society 2010 C1 [Miller, Joan W.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Miller, Joan W.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Miller, JW (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM ophthalmology@meei.harvard.edu NR 51 TC 15 Z9 15 U1 0 U2 7 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0021-5155 J9 JPN J OPHTHALMOL JI Jpn. J. Ophthalmol. PD NOV PY 2010 VL 54 IS 6 BP 523 EP 528 DI 10.1007/s10384-010-0863-4 PG 6 WC Ophthalmology SC Ophthalmology GA 709VK UT WOS:000286469300001 PM 21191711 ER PT J AU Hale, JE Bonilla, FA Pai, SY Gerstel-Thompson, JL Notarangelo, LD Eaton, RB Comeau, AM AF Hale, Jaime E. Bonilla, Francisco A. Pai, Sung-Yun Gerstel-Thompson, Jacalyn L. Notarangelo, Luigi D. Eaton, Roger B. Comeau, Anne Marie TI Identification of an infant with severe combined-immunodeficiency bynewborn screening SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 [Hale, Jaime E.; Gerstel-Thompson, Jacalyn L.; Eaton, Roger B.; Comeau, Anne Marie] Univ Massachusetts, Sch Med, New England Newborn Screening Program, Boston, MA 02125 USA. [Bonilla, Francisco A.; Notarangelo, Luigi D.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Pai, Sung-Yun] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Eaton, Roger B.; Comeau, Anne Marie] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. RP Hale, JE (reprint author), Univ Massachusetts, Sch Med, New England Newborn Screening Program, Boston, MA 02125 USA. EM anne.comeau@umassmed.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU NCEH CDC HHS [IV01-EH000362-01] NR 5 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2010 VL 126 IS 5 BP 1073 EP 1074 DI 10.1016/j.jaci.2010.08.043 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 674HB UT WOS:000283727100027 PM 20933257 ER PT J AU Jartti, T Ruuskanen, O Mansbach, JM Vuorinen, T Camargo, CA AF Jartti, Tuomas Ruuskanen, Olli Mansbach, Jonathan M. Vuorinen, Tytti Camargo, Carlos A., Jr. TI Low serum 25-hydroxyvitamin D levels are associated with increased risk of viral coinfections in wheezing children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID RESPIRATORY SYNCYTIAL VIRUS; VITAMIN-D; HUMAN BOCAVIRUS; PREDNISOLONE; RHINOVIRUS; INFECTION; EFFICACY; AGE C1 [Jartti, Tuomas; Ruuskanen, Olli] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. [Mansbach, Jonathan M.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Vuorinen, Tytti] Univ Turku, Dept Virol, Turku, Finland. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. RP Jartti, T (reprint author), Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. EM tuomas.jartti@utu.fi FU NIAID NIH HHS [K23 AI077801, K23 AI-77801] NR 18 TC 33 Z9 36 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2010 VL 126 IS 5 BP 1074 EP U269 DI 10.1016/j.jaci.2010.09.004 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 674HB UT WOS:000283727100028 PM 21050947 ER PT J AU Mijailovich, SM Stojanovic, B Kojic, M Liang, A Wedeen, VJ Gilbert, RJ AF Mijailovich, Srboljub M. Stojanovic, Boban Kojic, Milos Liang, Alvin Wedeen, Van J. Gilbert, Richard J. TI Derivation of a finite-element model of lingual deformation during swallowing from the mechanics of mesoscale myofiber tracts obtained by MRI SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE multiscale model; diffusion tensor imaging tractography; Hill's three-element model; muscle mechanics ID BOVINE TONGUE; 3-DIMENSIONAL MYOARCHITECTURE; HYDROSTATIC SKELETON; FIBER ARCHITECTURE; MUSCLE-CONTRACTION; IN-VIVO; DIFFUSION; TISSUE; MOVEMENT; BIOMECHANICS AB Mijailovich SM, Stojanovic B, Kojic M, Liang A, Wedeen VJ, Gilbert RJ. Derivation of a finite-element model of lingual deformation during swallowing from the mechanics of mesoscale myofiber tracts obtained by MRI. J Appl Physiol 109: 1500-1514, 2010. First published August 5, 2010; doi: 10.1152/japplphysiol.00493.2010.-To demonstrate the relationship between lingual myoarchitecture and mechanics during swallowing, we performed a finite-element (FE) simulation of lingual deformation employing mesh aligned with the vector coordinates of myofiber tracts obtained by diffusion tensor imaging with tractography in humans. Material properties of individual elements were depicted in terms of Hill's three-component phenomenological model, assuming that the FE mesh was composed of anisotropic muscle and isotropic connective tissue. Moreover, the mechanical model accounted for elastic constraints by passive and active elements from the superior and inferior directions and the effect of out-of-plane muscles and connective tissue. Passive bolus effects were negligible. Myofiber tract activation was simulated over 500 ms in 1-ms steps following lingual tip association with the hard palate and incorporated specifically the accommodative and propulsive phases of the swallow. Examining the displacement field, active and passive muscle stress, elemental stretch, and strain rate relative to changes of global shape, we demonstrate that lingual reconfiguration during these swallow phases is characterized by (in sequence) the following: 1) lingual tip elevation and shortening in the anterior-posterior direction; 2) inferior displacement related to hyoglossus contraction at its inferior-most position; and 3) dominant clockwise rotation related to regional contraction of the genioglossus and contraction of the hyoglossus following anterior displacement. These simulations demonstrate that lingual deformation during the indicated phases of swallowing requires temporally patterned activation of intrinsic and extrinsic muscles and delineate a method to ascertain the mechanics of normal and pathological swallowing. C1 [Mijailovich, Srboljub M.; Kojic, Milos] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Mijailovich, Srboljub M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Stojanovic, Boban; Kojic, Milos] Univ Kragujevac, Res & Dev Ctr Bioengn, Kragujevac, Serbia. [Stojanovic, Boban] Univ Kragujevac, Fac Sci, Kragujevac, Serbia. [Kojic, Milos] Univ Texas Hlth Sci Ctr, Dept Nanomed & Biomed Engn, Houston, TX USA. [Liang, Alvin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Liang, Alvin] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Wedeen, Van J.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Mijailovich, Srboljub M.; Gilbert, Richard J.] Caritas St Elizabeths Med Ctr, Dept Med, Boston, MA USA. RP Mijailovich, SM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Rm 1010D, Boston, MA 02115 USA. EM smijailo@hsph.harvard.edu OI Mijailovich, Srboljub/0000-0003-1498-308X FU National Institutes of Health [R01 AR048776, R01 DC005604]; National Administration Grant [NNJ06HE06A]; Ministry of Science and Technological Development of Serbia [10-144028] FX This work was supported in part by National Institutes of Health Grants R01 AR048776 (S. M. Mijailovich); R01 DC005604 (R. J. Gilbert); National Administration Grant NNJ06HE06A (M. Kojic) and Ministry of Science and Technological Development of Serbia Grant 10-144028 (M. Kojic). NR 49 TC 8 Z9 8 U1 1 U2 9 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 NOV PY 2010 VL 109 IS 5 BP 1500 EP 1514 DI 10.1152/japplphysiol.00493.2010 PG 15 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 695BQ UT WOS:000285346000028 PM 20689096 ER PT J AU Joshi, G Petty, C Wozniak, J Henin, A Fried, R Galdo, M Kotarski, M Walls, S Biederman, J AF Joshi, Gagan Petty, Carter Wozniak, Janet Henin, Aude Fried, Ronna Galdo, Maribel Kotarski, Meghan Walls, Sarah Biederman, Joseph TI The Heavy Burden of Psychiatric Comorbidity in Youth with Autism Spectrum Disorders: A Large Comparative Study of a Psychiatrically Referred Population SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Psychiatric comorbidity; Children and adolescents ID PERVASIVE DEVELOPMENTAL DISORDERS; OBSESSIVE-COMPULSIVE DISORDER; SCHOOL-AGE-CHILDREN; ASPERGER-SYNDROME; INTELLECTUAL DISABILITY; RESONANCE SPECTROSCOPY; SCHIZOID PERSONALITY; MENTAL-RETARDATION; EMOTIONAL-PROBLEMS; ANXIETY SYMPTOMS AB The objective of the study was to systematically examine patterns of psychiatric comorbidity in referred youth with autism spectrum disorders (ASD) including autistic disorder and pervasive developmental disorder not otherwise specified. Consecutively referred children and adolescents to a pediatric psychopharmacology program were assessed with structured diagnostic interview and measures of psychosocial functioning. Comparisons were made between those youth satisfying diagnostic criteria for ASD and age and sex matched youth without ASD referred to the same clinical program. 9.3% (217/2323) of the referred youth (age range: 3-17 years) met DSM-III-R criteria for ASD. ASD youth suffered from significantly higher number of comorbid disorders than comparisons (6.4 +/- 2.7 vs. 5.2 +/- 2.9; p < 0.001). Ninety-five percent of the youth with ASD had three or more comorbid psychiatric disorders and 74% had five or more comorbid disorders. ASD youth were also more functionally impaired and required extra-assistance in school and therapeutic interventions at higher rates than age and sex matched non-ASD referred youth. Youth with ASD have high levels of psychiatric comorbidity and dysfunction comparable to the referred population of youth without ASD. These findings emphasize the heavy burden of psychiatric comorbidity afflicting youth with ASD and may be important targets for intervention. C1 [Joshi, Gagan; Petty, Carter; Wozniak, Janet; Henin, Aude; Fried, Ronna; Galdo, Maribel; Kotarski, Meghan; Walls, Sarah; Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Dept, Boston, MA 02114 USA. [Joshi, Gagan; Petty, Carter; Wozniak, Janet; Henin, Aude; Fried, Ronna; Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Joshi, G (reprint author), 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM gaganjoshi@hotmail.com NR 64 TC 83 Z9 83 U1 3 U2 28 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD NOV PY 2010 VL 40 IS 11 BP 1361 EP 1370 DI 10.1007/s10803-010-0996-9 PG 10 WC Psychology, Developmental SC Psychology GA 673AP UT WOS:000283630800006 PM 20309621 ER PT J AU Chen, D Lei, L Lu, CX Galaleldeen, A Hart, PJ Zhong, GM AF Chen, Ding Lei, Lei Lu, Chunxue Galaleldeen, Ahmad Hart, P. John Zhong, Guangming TI Characterization of Pgp3, a Chlamydia trachomatis Plasmid-Encoded Immunodominant Antigen SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; HUMAN-ANTIBODY RESPONSES; OUTER-MEMBRANE PROTEIN; SECRETED PROTEASE; INFECTED CELLS; INHIBITION; ACTIVATION; DIFFERENTIATION; IDENTIFICATION; PURIFICATION AB Human antibody recognition of Chlamydia trachomatis plasmid-encoded Pgp3 protein is dependent on the native conformation of Pgp3. The structural basis for the conformation dependence and the function of Pgp3 remain unknown. Here, we report that Pgp3 trimerization is required for the recognition of Pgp3 by human antibodies. In a native polyacrylamide gel, Pgp3 purified from a bacterial expression system migrated as stable trimers that were dissociated into monomers only by treatment with urea or sodium dodecyl sulfate (SDS) but not nonionic detergents. Human antibodies recognized trimeric but not monomeric Pgp3, suggesting that Pgp3 is presented to the human immune system as trimers during C. trachomatis infection. The endogenous Pgp3 secreted into the chlamydial outer membrane complex or host cell cytosol is always trimerized. Intact Pgp3 trimers were eluted from the outer membrane complex by a combination of nonionic detergents with reducing agents but not by the presence of either alone. These observations have provided important information for further understanding the role of Pgp3 in chlamydial pathogenesis and potentially optimizing Pgp3 as a subunit vaccine candidate antigen. C1 [Chen, Ding; Lei, Lei; Lu, Chunxue; Zhong, Guangming] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Galaleldeen, Ahmad; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, P. John] US Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Zhong, GM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Zhongg@UTHSCSA.EDU RI Lei, Lei/I-3002-2013 FU U.S. National Institutes of Health; Robert A. Welch Foundation [AQ-1399]; Office of the Vice President for Research at the University of Texas Health Science Center FX This work was supported in part by grants (to G. Zhong) from the U.S. National Institutes of Health and from the Robert A. Welch Foundation (grant AQ-1399 to P. J. Hart). Support for the Center for Analytical Ultracentrifugation of Macromolecular Assemblies by the Office of the Vice President for Research at the University of Texas Health Science Center is also gratefully acknowledged. NR 47 TC 11 Z9 17 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2010 VL 192 IS 22 BP 6017 EP 6024 DI 10.1128/JB.00847-10 PG 8 WC Microbiology SC Microbiology GA 672BZ UT WOS:000283559300018 PM 20851898 ER PT J AU Kane, BJ Younan, G Helm, D Dastouri, P Prentice-Mott, H Irimia, D Chan, RK Toner, M Orgill, DP AF Kane, Bartholomew J. Younan, George Helm, Douglas Dastouri, Pouya Prentice-Mott, Harrison Irimia, Daniel Chan, Rodney K. Toner, Mehmet Orgill, Dennis P. TI Controlled induction of distributed microdeformation in wounded tissue via a microchamber array dressing SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE microfabrication; microfluidic devices; negative pressure wound therapy; micromechanical forces; wound healing ID VACUUM-ASSISTED CLOSURE; DISTRACTION OSTEOGENESIS; EXTRACELLULAR-MATRIX; CELL-PROLIFERATION; THERAPY; MECHANOTRANSDUCTION; FOUNDATION; MECHANISMS; CHALLENGES; EXPANSION AB Mechanical stimuli are known to play an important role in determining the structure and function of living cells and tissues. Recent studies have highlighted the role of mechanical signals in mammalian dermal wound healing. However, the biological link between mechanical stimulation of wounded tissue and the subsequent cellular response has not been fully determined. The capacity for researchers to study this link is partially limited by the lack of instrumentation capable of applying controlled mechanical stimuli to wounded tissue. The studies outlined here tested the hypothesis that it was possible to control the magnitude of induced wound tissue deformation using a microfabricated dressing composed of an array of open-faced, hexagonally shaped microchambers rendered in a patch of silicone rubber. By connecting the dressing to a single vacuum source, the underlying wounded tissue was drawn up into each of the microchambers, thereby inducing tissue deformation. For these studies, the dressings were applied to full-thickness murine dermal wounds with 200 mmHg vacuum for 12 h. These studies demonstrated that the dressing was capable of inducing wound tissue deformation with values ranging from 11 to 29%. Through statistical analysis, the magnitude of the induced deformation was shown to be a function of both microchamber height and width. These results demonstrated that the dressing was capable of controlling the amount of deformation imparted in the underlying tissue. By allowing the application of mechanical stimulation with varying intensities, such a dressing will enable the performance of sophisticated mechanobiology studies in dermal wound healing. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 95A: 333-340, 2010. C1 [Younan, George; Helm, Douglas; Dastouri, Pouya; Chan, Rodney K.; Orgill, Dennis P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. [Kane, Bartholomew J.] Univ Virginia Hlth Syst, Dept Surg, Div Pediat Surg, Charlottesville, VA 22908 USA. [Prentice-Mott, Harrison] Massachusetts Gen Hosp, Ctr Engn Med, BioMEMS Resource Ctr, Boston, MA 02114 USA. [Irimia, Daniel; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Irimia, Daniel; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Orgill, DP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. EM dorgill@partners.org OI Orgill, Dennis/0000-0002-8279-7310; Younan, George/0000-0001-8502-4850; Irimia, Daniel/0000-0001-7347-2082 FU National Institutes of Health [UL1RR 025758-01, P41 EB002503] FX Contract grant sponsor: National Institutes of Health; contract grant numbers: UL1RR 025758-01, P41 EB002503 NR 31 TC 4 Z9 4 U1 0 U2 13 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD NOV PY 2010 VL 95A IS 2 BP 333 EP 340 DI 10.1002/jbm.a.32840 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 660TF UT WOS:000282666600001 PM 20607869 ER PT J AU Wijelath, E Kohler, TR Murray, J Namekata, M Yagi, M Sobel, M AF Wijelath, Errol Kohler, Ted R. Murray, Jacqueline Namekata, Mayumi Yagi, Mayumi Sobel, Michael TI Enhancement of capillary and cellular ingrowth in ePTFE implants with a proangiogenic recombinant construct derived from fibronectin SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE expanded polytetrafluoroethylene; fibronectin; neovascularization; vascular endothelial growth factor; prostheses and implants; rats ID POLYTETRAFLUOROETHYLENE ARTERIAL GRAFTS; BIOLOGICAL-ACTIVITY; POROUS IMPLANTS; VASCULAR GRAFTS; ADIPOSE-TISSUE; SMALL-CALIBER; POROSITY; NEOVASCULARIZATION; GROWTH; VEGF AB Based on our discoveries of a unique, synergistic interplay between vascular endothelial growth factor (VEGF) and specific domains of the matrix protein fibronectin (FN), we used recombinant technology to create a new protein construct derived from the cell-binding and VEGF-binding domains of FN. We wished to test the hypothesis that this prototype recombinant FN (rFN) protein would enhance cellular and capillary ingrowth in vivo into expanded polytetrafluoroethylene (ePTFE) implants. ePTFE disks of high porosity (60 micron internodal distance) were embedded with fibrin gel and heparin, with/without mixtures of VEGF and rFN and were implanted subcutaneously in rats. Control implants embedded with fibrin glue and heparin alone showed an average of 8.5% (+/- 0.51% standard error mean (SEM)) cellular ingrowth. The addition of either VEGF or rFN caused a mod-est but significant increase in cellular ingrowth (12.7 +/- 1% and 11.8 +/- 0.98%, respectively, p < 0.004). However, the combination of rFN/VEGF/heparin dramatically increased cellular ingrowth (27.6 +/- 1.62%, p < 0.001), compared with all other treatments. Quantification of capillary ingrowth yielded the same pattern. These results suggest that the incorporation of such biological modulators into cardiovascular implants could offer new strategies for the design of a ready-made small diameter prosthetic graft with enhanced capacity for neovascularization and endothelialization. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 95A: 641-648, 2010. C1 [Wijelath, Errol; Kohler, Ted R.; Murray, Jacqueline; Namekata, Mayumi; Yagi, Mayumi; Sobel, Michael] Univ Washington, Sch Med, Dept Surg, Div Vasc Surg,VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Wijelath, E (reprint author), Univ Washington, Sch Med, Dept Surg, Div Vasc Surg,VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM errolw@u.washington.edu FU NHLBI, National Institutes of Health [R01 HL079182]; Research Service of the Department of Veterans Affairs FX Contract grant sponsor: NHLBI, National Institutes of Health; contract grant number: R01 HL079182; Contract grant sponsor: Research Service of the Department of Veterans Affairs NR 26 TC 2 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD NOV PY 2010 VL 95A IS 2 BP 641 EP 648 DI 10.1002/jbm.a.32871 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 660TF UT WOS:000282666600033 PM 20725965 ER PT J AU Zhu, SM Zhu, ED Provot, S Gori, F AF Zhu, Shimei Zhu, Eric D. Provot, Sylvain Gori, Francesca TI Wdr5 Is Required for Chick Skeletal Development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE WDR5; RCAS; shRNA; ENDOCHONDRAL; BONE; FORMATION; CHICKEN; LIMB ID REPLICATION-COMPETENT RETROVIRUSES; VERTEBRATE LIMB DEVELOPMENT; WD-40 REPEAT PROTEIN; OSTEOBLAST DIFFERENTIATION; BONE-DEVELOPMENT; CHONDROCYTE DIFFERENTIATION; GENE-EXPRESSION; TRANSCRIPTION FACTORS; GROWTH-PLATE; MODEL SYSTEM AB Wdr5 a bone morphogenetic protein 2 (BMP 2)-induced protein belonging to the family of the WD repeat proteins is expressed in proliferating and hypertrophic chondrocytes of the growth plate and in osteoblasts Although previous studies have provided insight into the mechanisms by which Wdr5 affects chondrocyte and osteoblast differentiation, whether Wdr5 is required in vivo for endochondral bone development has not been addressed In this study using an avian replication competent retrovirus (RCAS) system delivering Wdr5 short hairpin (sh) RNA to silence Wdr5 in the developing limb we report that reduction of Wdr5 levels delays endochondral bone development and consequently results in shortening of the skeletal elements Shortening of the skeletal elements was due to impaired chondrocyte maturation evidenced by a significant reduction of Runx2, type X collagen, and osteopontin expression A decrease in Runx2 type collagen I and ostepontin expression in osteoblasts and a subsequent defect in mineralized bone was observed as well when Wdr5 levels were reduced Most important retroviral misexpression of Runx2 rescued the phenotype induced by Wdr5 shRNA These findings suggest that during limb development Wdr5 is required for endochondral bone formation and that Wdr5 influences this process at least in part by regulating Runx2 expression (C) 2010 American Society for Bone and Mineral Research C1 [Zhu, Shimei; Zhu, Eric D.; Gori, Francesca] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Provot, Sylvain] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. RP Gori, F (reprint author), 50 Blossom St, Boston, MA 02114 USA. FU National Institutes of Health [DK 076093] FX We thank Dr Marie Demay for helpful discussion This work was supported by Grant DK 076093 to FG from the National Institutes of Health NR 57 TC 2 Z9 3 U1 1 U2 4 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 NOV PY 2010 VL 25 IS 11 BP 2504 EP 2514 DI 10.1002/jbmr.144 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 679BD UT WOS:000284133500025 PM 20533303 ER PT J AU Butler, KL Goverman, J Ma, H Fischman, A Yu, YM Bilodeau, M Rad, AM Bonab, AA Tompkins, RG Fagan, SP AF Butler, Kathryn L. Goverman, Jeremy Ma, Harry Fischman, Alan Yu, Yong-Ming Bilodeau, Maryelizabeth Rad, Ali M. Bonab, Ali A. Tompkins, Ronald G. Fagan, Shawn P. TI Stem Cells and Burns: Review and Therapeutic Implications SO JOURNAL OF BURN CARE & RESEARCH LA English DT Review ID ADIPOSE-DERIVED STEM; CULTURED EPITHELIAL AUTOGRAFT; ENDOTHELIAL PROGENITOR CELLS; THERMAL-INJURY; IN-VITRO; REGENERATIVE MEDICINE; WOUND EXCISION; SKIN; TISSUE; DIFFERENTIATION AB Despite significant advances in burn resuscitation and wound care over the past 30 years, morbidity and mortality from thermal injury remain high. Limited donor skin in severely burned patients hinders effective wound excision and closure, leading to infectious complications and prolonged hospitalizations. Even with large-volume fluid resuscitation, the systemic inflammatory response syndrome compromises end-organ perfusion in burn patients, with resultant multiorgan failure. Stem cells, which enhance wound healing and counteract systemic inflammation, now offer potential therapies for these challenges. Through a review of the literature, this article seeks to illustrate applications of stem cell therapy to burn care and to highlight promising areas of research. (J Burn Care Res 2010; 31: 874-881) C1 [Fagan, Shawn P.] Massachusetts Gen Hosp, Dept Burn Surg, Sumner Redstone Burn Ctr, Boston, MA 02114 USA. [Goverman, Jeremy; Fischman, Alan; Yu, Yong-Ming; Rad, Ali M.; Bonab, Ali A.; Tompkins, Ronald G.; Fagan, Shawn P.] Shriners Hosp Children, Boston, MA USA. RP Fagan, SP (reprint author), Massachusetts Gen Hosp, Dept Burn Surg, Sumner Redstone Burn Ctr, 55 Fruit St, Boston, MA 02114 USA. NR 99 TC 18 Z9 19 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD NOV-DEC PY 2010 VL 31 IS 6 BP 874 EP 881 DI 10.1097/BCR.0b013e3181f9353a PG 8 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 677LH UT WOS:000283993400003 PM 20859216 ER PT J AU Prelack, K Yu, YM Dylewski, M Lydon, M Sheridan, RL Tompkins, RG AF Prelack, Kathrina Yu, Yong Ming Dylewski, Maggie Lydon, Martha Sheridan, Robert L. Tompkins, Ronald G. TI The Contribution of Muscle to Whole-Body Protein Turnover Throughout the Course of Burn Injury in Children SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID CATABOLISM; 3-METHYLHISTIDINE; CLOSURE AB The physiologic response to trauma results in the efflux of large amounts of amino acids from skeletal muscle. This is extreme in large burn injuries. Protein kinetic studies, although useful in determining the rates of protein synthesis and breakdown, do not provide information about muscle loss. This study determined the contribution of muscle protein to whole-body protein breakdown in children throughout their course of burn injury. Children aged 0 to 18 years with initial burn size >= 30% TBSA underwent (15)N glycine and 3 methylhistidine (3MH) analysis during three phases of care: A, early acute; B, wound closure; and C, convalescence. Muscle protein breakdown was estimated using a factor of 4.2 mu mol 3MH per 1 g of mixed protein. Twenty-two patients with a mean of 54.5 +/- 20.1% TBSA burn were studied. Protein balance did not change remarkably and remained positive by 2 g/kg during hospitalization. However, muscle protein breakdown dropped from 1.1 to 0.6 g/kg with wound closure (P < .0001), representing a decrease in the contribution of muscle protein to whole-body protein breakdown from 20 to 7%. Ten patients returned for a third measurement after discharge. Although protein turnover was high, muscle breakdown was consistent with 3MH values reported in healthy children. Serial determination of 3MH excretion is a simple way to track muscle catabolism throughout burn injury. Our data suggest that despite accelerated protein turnover, muscle catabolism significantly decreases with wound closure and begins to normalize around discharge. In convalescence, 3MH excretion is comparable with normal children. (J Burn Care Res 2010; 31: 942-948) C1 [Prelack, Kathrina; Yu, Yong Ming; Dylewski, Maggie; Lydon, Martha; Sheridan, Robert L.; Tompkins, Ronald G.] Shriners Hosp Children, Boston, MA 02114 USA. [Prelack, Kathrina; Yu, Yong Ming; Sheridan, Robert L.; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Prelack, K (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-15] NR 17 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD NOV-DEC PY 2010 VL 31 IS 6 BP 942 EP 948 DI 10.1097/BCR.0b013e3181f938e1 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 677LH UT WOS:000283993400012 PM 21105320 ER PT J AU Yeh, GY McCarthy, EP Wayne, PM Stevenson, LW Wood, MJ Forman, DE Davis, RB Phillips, RS AF Yeh, G. Y. McCarthy, E. P. Wayne, P. M. Stevenson, L. W. Wood, M. J. Forman, D. E. Davis, R. B. Phillips, R. S. TI Tai Chi Exercise Improves Quality of Life in Patients With Chronic Stable Heart Failure in a Randomized Controlled Trial SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 [Yeh, G. Y.; McCarthy, E. P.; Wayne, P. M.; Davis, R. B.; Phillips, R. S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gen Med & Primary Care,Osher Res Ctr, Boston, MA 02215 USA. [Yeh, G. Y.; Wayne, P. M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Wood, M. J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 8 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD NOV PY 2010 VL 16 IS 11 BP 911 EP 911 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680PT UT WOS:000284247600010 ER PT J AU Shahian, DM AF Shahian, David M. TI Public Reporting of Cardiac Surgery Outcomes-What Do We Know, What Can We Expect? SO JOURNAL OF CARDIAC SURGERY LA English DT Editorial Material ID NEW-YORK-STATE; BYPASS GRAFT-SURGERY; RISK-ADJUSTED OUTCOMES; QUALITY IMPROVEMENT; CORONARY INTERVENTION; VETERANS-AFFAIRS; MARKET SHARE; MORTALITY; CARE; PERFORMANCE C1 [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 39 TC 1 Z9 1 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 NOV PY 2010 VL 25 IS 6 BP 710 EP 712 DI 10.1111/j.1540-8191.2010.01147.x PG 3 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 678YY UT WOS:000284121100030 PM 21070355 ER PT J AU Riley, BE Kaiser, SE Shaler, TA Ng, ACY Hara, T Hipp, MS Lage, K Xavier, RJ Ryu, KY Taguchi, K Yamamoto, M Tanaka, K Mizushima, N Komatsu, M Kopito, RR AF Riley, Brigit E. Kaiser, Stephen E. Shaler, Thomas A. Ng, Aylwin C. Y. Hara, Taichi Hipp, Mark S. Lage, Kasper Xavier, Ramnik J. Ryu, Kwon Yul Taguchi, Keiko Yamamoto, Masayuki Tanaka, Keiji Mizushima, Noboru Komatsu, Masaaki Kopito, Ron R. TI Ubiquitin accumulation in autophagy-deficient mice is dependent on the Nrf2-mediated stress response pathway: a potential role for protein aggregation in autophagic substrate selection SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR NRF2; RIBOSOME ENTRY SITES; RAT-LIVER LYSOSOMES; ANTIOXIDANT RESPONSE; NEURODEGENERATIVE DISEASE; OXIDATIVE STRESS; MOLECULAR-MECHANISMS; HUNTINGTONS-DISEASE; TRANSLATION INITIATION; FLUORESCENT PROTEINS AB Genetic ablation of autophagy in mice leads to liver and brain degeneration accompanied by the appearance of ubiquitin (Lib) inclusions, which has been considered to support the hypothesis that ubiquitination serves as a cis-acting signal for selective autophagy We show that tissue-specific disruption of the essential autophagy genes Atg5 and Atg7 leads to the accumulation of all detectable Ub-Ub topologies, arguing against the hypothesis that any particular Ub linkage serves as a specific autophagy signal The increase in Ub conjugates in Atg7(-/-) liver and brain is completely suppressed by simultaneous knockout of either p62 or Nrf2 We exploit a novel assay for selective autophagy in cell culture, which shows that inactivation of Atg5 leads to the selective accumulation of aggregation prone proteins, and this does not correlate with an increase in substrate ubiquitination We propose that protein oligomerization drives autophagic substrate selection and that the accumulation of poly Ub chains in autophagy deficient circumstances is an indirect consequence of activation of Nrf2-dependent stress response pathways C1 [Riley, Brigit E.; Kaiser, Stephen E.; Hipp, Mark S.; Kopito, Ron R.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Shaler, Thomas A.] Stanford Res Inst, Menlo Pk, CA 94025 USA. [Ng, Aylwin C. Y.; Xavier, Ramnik J.] Massachusetts Gen Hosp, MassGen Hosp Children, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Lage, Kasper] Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Surg Res Labs, Boston, MA 02114 USA. [Ng, Aylwin C. Y.; Lage, Kasper; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hara, Taichi; Mizushima, Noboru] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Bunkyo Ku, Tokyo 1138519, Japan. [Ng, Aylwin C. Y.; Lage, Kasper; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA. [Lage, Kasper] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Ryu, Kwon Yul] Univ Seoul, Dept Life Sci, Seoul 130743, South Korea. [Taguchi, Keiko; Yamamoto, Masayuki] Tohoku Univ, Grad Sch Med, Dept Med Biochem, Aoba Ku, Sendai, Miyagi 9808575, Japan. [Taguchi, Keiko; Yamamoto, Masayuki] Tohoku Univ, Grad Sch Med, Exploratory Res Adv Technol Japan Sci & Technol A, Aoba Ku, Sendai, Miyagi 9808575, Japan. [Tanaka, Keiji; Komatsu, Masaaki] Tokyo Metropolitan Inst Med Sci, Lab Frontier Sci, Bunkyo Ku, Tokyo 1138613, Japan. RP Riley, BE (reprint author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA. RI Yamamoto, Masayuki/A-4873-2010; Mizushima, Noboru/C-3635-2009 OI Mizushima, Noboru/0000-0002-6258-6444 FU Hereditary Disease Foundation; Crohn s and Colitis Foundation of America; Huntington s Disease Society of America Cure Huntington s Disease Forskningsradet for Sundhed og Sygdom; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Neurological Disease and Stroke FX This work was supported by a fellowship award from the Hereditary Disease Foundation (to B E Riley) a fellowship award from the Crohn s and Colitis Foundation of America (to A C Y Ng) and grants from the Huntington s Disease Society of America Cure Huntington s Disease Forskningsradet for Sundhed og Sygdom (to K Lage) Eunice Kennedy Shriver National Institute of Child Health and Human Development (to K Loge) and National Institute of Neurological Disease and Stroke (to R R Kopito and R J Xavier) NR 99 TC 79 Z9 79 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 1 PY 2010 VL 191 IS 3 BP 537 EP 552 DI 10.1083/jcb.201005012 PG 16 WC Cell Biology SC Cell Biology GA 679BZ UT WOS:000284135700012 PM 21041446 ER PT J AU Kuhn, EN Wu, SM AF Kuhn, Elizabeth N. Wu, Sean M. TI Origin of Cardiac Progenitor Cells in the Developing and Postnatal Heart SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID EMBRYONIC STEM-CELLS; ADULT MAMMALIAN CARDIOMYOCYTES; SMOOTH-MUSCLE; EPICARDIAL PROGENITORS; MOUSE HEART; MESP1; DIFFERENTIATION; PROLIFERATION; MULTIPOTENT; REGENERATION AB The mammalian heart lacks the capacity to replace the large numbers of cardiomyocytes lost due to cardiac injury. Several different cell-based routes to myocardial regeneration have been explored, including transplantation of cardiac progenitors and cardiomyocytes into injured myocardium. As seen with cell-based therapies in other solid organ systems, inherent limitations, such as host immune response, cell death and long-term graft instability have hampered meaningful cardiac regeneration. An understanding of the cell biology of cardiac progenitors, including their developmental origin, lineage markers, renewal pathways, differentiation triggers, microenvironmental niche, and mechanisms of homing and migration to the site of injury, will enable further refinement of therapeutic strategies to enhance clinically meaningful cardiac repair. J. Cell. Physiol. 225: 321-325, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Kuhn, Elizabeth N.; Wu, Sean M.] Cardiovasc Res Ctr, Cambridge, MA USA. [Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA. [Wu, Sean M.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Wu, SM (reprint author), Room 3224,Simches Bldg,185 Cambridge St, Boston, MA 02114 USA. EM smwu@partners.org FU NHLBI NIH HHS [K08 HL081086, U01 HL099776]; NIH HHS [DP2 OD004411] NR 57 TC 10 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 2010 VL 225 IS 2 BP 321 EP 325 DI 10.1002/jcp.22281 PG 5 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 664ZS UT WOS:000283003400007 PM 20568226 ER PT J AU Heber, D Greenway, FL Kaplan, LM Livingston, E Salvador, J Still, C AF Heber, David Greenway, Frank L. Kaplan, Lee M. Livingston, Edward Salvador, Javier Still, Christopher TI Endocrine and Nutritional Management of the Post-Bariatric Surgery Patient: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID Y GASTRIC BYPASS; FATTY LIVER-DISEASE; VERTICAL BANDED GASTROPLASTY; TYPE-2 DIABETES-MELLITUS; MORBIDLY OBESE-PATIENTS; METABOLIC BONE-DISEASE; INDUCED WEIGHT-LOSS; PLASMA GHRELIN LEVELS; VITAMIN-D DEPLETION; BODY-MASS INDEX AB Objective: We sought to provide guidelines for the nutritional and endocrine management of adults after bariatric surgery, including those with diabetes mellitus. The focus is on the immediate postoperative period and long-term management to prevent complications, weight regain, and progression of obesity-associated comorbidities. The treatment of specific disorders is only summarized. Participants: The Task Force was composed of a chair, five additional experts, a methodologist, and a medical writer. It received no corporate funding or remuneration. Conclusions: Bariatric surgery is not a guarantee of successful weight loss and maintenance. Increasingly, patients regain weight, especially those undergoing restrictive surgeries such as laparoscopic banding rather than malabsorptive surgeries such as Roux-en-Y bypass. Active nutritional patient education and clinical management to prevent and detect nutritional deficiencies are recommended for all patients undergoing bariatric surgery. Management of potential nutritional deficiencies is particularly important for patients undergoing malabsorptive procedures, and strategies should be employed to compensate for food intolerance in patients who have had a malabsorptive procedure to reduce the risk for clinically important nutritional deficiencies. To enhance the transition to life after bariatric surgery and to prevent weight regain and nutritional complications, all patients should receive care from a multidisciplinary team including an experienced primary care physician, endocrinologist, or gastroenterologist and consider enrolling postoperatively in a comprehensive program for nutrition and lifestyle management. Future research should address the effectiveness of intensive postoperative nutritional and endocrine care in reducing morbidity and mortality from obesity-associated chronic diseases. (J Clin Endocrinol Metab 95: 4823-4843, 2010) C1 [Heber, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Greenway, Frank L.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Livingston, Edward] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Salvador, Javier] Univ Navarra Clin, Pamplona, Spain. [Still, Christopher] Geisinger Med Ctr, Danville, PA 17822 USA. RP Heber, D (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. EM govt-prof@endo-society.org FU American Gastroenterological Association Institute; European Society of Endocrinology FX Cosponsoring associations include the American Gastroenterological Association Institute, and European Society of Endocrinology. NR 255 TC 140 Z9 153 U1 2 U2 15 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 NOV PY 2010 VL 95 IS 11 BP 4823 EP 4843 DI 10.1210/jc.2009-2128 PG 21 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 675QB UT WOS:000283844400020 PM 21051578 ER PT J AU Fazeli, PK Lawson, EA Prabhakaran, R Miller, KK Donoho, DA Clemmons, DR Herzog, DB Misra, M Klibanski, A AF Fazeli, Pouneh K. Lawson, Elizabeth A. Prabhakaran, Rajani Miller, Karen K. Donoho, Daniel A. Clemmons, David R. Herzog, David B. Misra, Madhusmita Klibanski, Anne TI Effects of Recombinant Human Growth Hormone in Anorexia Nervosa: A Randomized, Placebo-Controlled Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FACTOR-I; GH TREATMENT; CARDIOVASCULAR RISK; ADOLESCENT GIRLS; LIPID-METABOLISM; BODY-COMPOSITION; BONE METABOLISM; DOUBLE-BLIND; IGF-I; INSULIN AB Context: Anorexia nervosa (AN), a state of chronic nutritional deprivation, is characterized by GH resistance with elevated GH levels and decreased levels of IGF-I. The effects of supraphysiological recombinant human GH (rhGH) on GH resistance in AN are not currently known. Objective: The aim was to investigate whether supraphysiological rhGH increases IGF-I levels in AN. Design and Setting: We conducted a randomized, placebo-controlled study in a Clinical Research Center. Patients: We studied 21 women with AN, 10(mean age, 28 +/- 2.1 yr) treated with rhGH and 11(mean age, 29.2 +/- 2.6 yr) treated with placebo. Interventions: rhGH (mean maximum daily dose, 1.4 +/- 0.12 mg/d) or placebo was administered to patients for 12 wk. Main Outcome Measures: IGF-I, N-terminal propeptide of type 1 procollagen, type I collagen C-telopeptide, glucose, and insulin levels were measured at wk 0, 1, 2, 3, 4, 8, and 12; C-terminal propeptide of type 1 procollagen, leptin, and free fatty acid levels were measured at wk 0 and 12. Body composition, including total fat and lean mass, was measured by dual-energy x-ray absorptiometry at wk 0 and 12. Results: IGF-I levels did not differ between the groups at baseline or after treatment (median after 12 wk-rhGH, 124 ng/ml, interquartile range, 94.5, 170.3; vs. placebo, 85.5 ng/ml, interquartile range, 62, 139; P = 0.3). Similarly, changes in glucose, insulin, free fatty acids, and bone markers did not differ between the groups. Total fat mass and percentage fat mass (rhGH, -2.5 +/- 0.6%, vs. placebo, 2.2 +/- 1.1%; P = 0.004) decreased significantly in the rhGH group compared to placebo despite comparable weight. Conclusions: Supraphysiological rhGH administration decreases fat mass in AN without increasing IGF-I levels, supporting the role of GH as a mediator of lipolysis independent of IGF-I. (J Clin Endocrinol Metab 95: 4889-4897, 2010) C1 [Fazeli, Pouneh K.; Lawson, Elizabeth A.; Prabhakaran, Rajani; Miller, Karen K.; Donoho, Daniel A.; Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Herzog, David B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Clemmons, David R.] Univ N Carolina, Dept Med, Div Endocrinol, Chapel Hill, NC 27599 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM aklibanski@partners.org FU Genentech; National Center for Research Resources [UL1 RR025758-01]; National Institutes of Health [M01-RR-01066, T32 DK007028]; Pfizer FX The project described was supported by an investigator-initiated grant from Genentech; Grant UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resources; and National Institutes of Health Grants M01-RR-01066 and T32 DK007028. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.; Disclosure Summary: P.K.F., E.A.L., R.P., K.K.M., D.A.D., D.R.C., and D.B.H. have nothing to declare. M.M. will be a future principal investigator for an investigator-initiated grant funded by Genentech. A.K. is a principal investigator for investigator-initiated grants funded by Genentech and Pfizer. NR 38 TC 35 Z9 36 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 NOV PY 2010 VL 95 IS 11 BP 4889 EP 4897 DI 10.1210/jc.2010-0493 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 675QB UT WOS:000283844400032 PM 20668047 ER PT J AU Baker, AM Haeri, S Camargo, CA Espinola, JA Stuebe, AM AF Baker, Arthur M. Haeri, Sina Camargo, Carlos A., Jr. Espinola, Janice A. Stuebe, Alison M. TI A Nested Case-Control Study of Midgestation Vitamin D Deficiency and Risk of Severe Preeclampsia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NULLIPAROUS WOMEN; D SUPPLEMENTATION; ECLAMPSIA; CALCIUM; 25-HYDROXYVITAMIN-D; METABOLISM; PREGNANCY; DELIVERY; COHORT; BIRTHS AB Context: Vitamin D may be important in the pathogenesis of severe preeclampsia. Given the few effective preventive strategies for severe preeclampsia, studies establishing this link are needed so that effective interventions can be developed. Objective: Our objective was to assess whether midgestation vitamin D deficiency is associated with development of severe preeclampsia. Design and Setting: We conducted a nested case-control study of pregnant women who had previously given blood for routine genetic multiple marker screening and subsequently delivered at a tertiary hospital between January 2004 and November 2008. Patients: Participants included women with singleton pregnancies in the absence of any chronic medical illnesses. From an overall cohort of 3992 women, 51 cases of severe preeclampsia were matched by race/ethnicity with 204 women delivering at term with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. Main Outcome Measure: The main outcome was severe preeclampsia. Results: Midgestation maternal 25(OH)D concentration was lower in women who subsequently developed severe preeclampsia compared with controls [median (interquartile range), 75 (47-107) nmol/liter vs. 98 (68-113) nmol/liter; P = 0.01]. Midgestation maternal 25(OH)D of less than 50 nmol/liter was associated with an almost 4-fold odds of severe preeclampsia (unadjusted odds ratio, 3.63; 95% confidence interval, 1.52-8.65) compared with midgestation levels of at least 75 nmol/liter. Adjustment for known confounders strengthened the observed association (adjusted odds ratio, 5.41; 95% confidence interval, 2.02-14.52). Conclusion: Maternal midgestation vitamin D deficiency was associated with increased risk of severe preeclampsia. Vitamin D deficiency may be a modifiable risk factor for severe preeclampsia. (J Clin Endocrinol Metab 95: 5105-5109, 2010) C1 [Baker, Arthur M.; Haeri, Sina; Stuebe, Alison M.] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chapel Hill, NC 27599 USA. [Camargo, Carlos A., Jr.; Espinola, Janice A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Ctr Receptor Activat Res D, Boston, MA 02114 USA. RP Baker, AM (reprint author), Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, 3010 Old Clin Bldg,CB 7516, Chapel Hill, NC 27599 USA. EM abaker2@med.unc.edu FU National Institutes of Health [5K12HD050113-04]; Massachusetts General Hospital Center for D-Receptor Activation Research FX This work was supported by the National Institutes of Health Grant 5K12HD050113-04 (to A. M. S.) and the Massachusetts General Hospital Center for D-Receptor Activation Research (to C.A.C.). NR 30 TC 107 Z9 111 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2010 VL 95 IS 11 BP 5105 EP 5109 DI 10.1210/jc.2010-0996 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 675QB UT WOS:000283844400059 PM 20719829 ER PT J AU Ortqvist, E Brooks-Worrell, B Lynch, K Radtke, J Bekris, LM Kockum, I Agardh, CD Cilio, CM Lethagen, AL Persson, B Lernmark, A Reichow, J Oak, S Palmer, JP Hampe, CS AF Ortqvist, E. Brooks-Worrell, B. Lynch, K. Radtke, J. Bekris, L. M. Kockum, I. Agardh, C. -D. Cilio, C. M. Lethagen, A. L. Persson, B. Lernmark, A. Reichow, J. Oak, S. Palmer, J. P. Hampe, C. S. TI Changes in GAD65Ab-Specific Antiidiotypic Antibody Levels Correlate with Changes in C-Peptide Levels and Progression to Islet Cell Autoimmunity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; JUVENILE DIABETES-MELLITUS; DNA ANTIBODIES; DISEASE-ACTIVITY; T-CELLS; ONSET; AUTOANTIBODIES; GAD65; DECARBOXYLASE; EPITOPE AB Context: The previously reported absence of 65-kDa glutamate decarboxylase antibody (GAD65Ab)-specific antiidiotypic antibodies (anti-Id) in type 1 diabetes (T1D) patients at clinical onset could be due to an inability to mount an antibody response to GAD65Ab or a longitudinal decline in anti-Id levels. Objective and Design: We investigated anti-Id levels in longitudinal samples obtained from T1D patients (n = 41) (clinical diagnosis- 12 months), and latent autoimmune diabetes in adults (LADA) patients (n = 32) who received alum-formulated human recombinant GAD65 (baseline -12 months). We also determined anti-Id levels in a small cohort of Type 2 diabetes patients during their development of autoimmune T cell responses. Results: At clinical onset T1D patients presented no or low anti-Id levels. However, 22/41 T1D patients showed >= 50% increase in GAD65Ab-specific anti-Id levels during follow-up; peaking at 3 (n = 1), 6 (n = 10), 9 (n = 10), or 12 (n = 1) months. Increasing anti-Id levels marked patients who experienced a temporary increase in C-peptide levels. Anti-Id levels correlated significantly with glycated hemoglobin and C-peptide levels at 6 and 9 months (P values ranged from < 0.001 to < 0.05). In LADA patients receiving placebo, anti-Id levels declined in seven of nine patients, whereas four of five patients receiving 20 mu g alum-formulated human recombinant GAD65 showed increasing anti-Id levels. Changes in anti-Id and C-peptide levels closely correlated (P < 0.0001). The significant decline in anti-Id levels (P = 0.03) in T2D patients developing T cell autoimmune responses supports our hypothesis that declining anti-Id levels are associated with developing islet autoimmunity. Conclusions: The close association between GAD65Ab-specific anti-Id levels and beta-cell function may provide a novel marker for the progression of autoimmune diabetes. (J Clin Endocrinol Metab 95: E310-E318, 2010) C1 [Reichow, J.; Palmer, J. P.; Hampe, C. S.] Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98109 USA. [Ortqvist, E.; Persson, B.] Karolinska Inst, Dept Woman & Child Hlth, SE-17177 Stockholm, Sweden. [Kockum, I.] Karolinska Inst, Dept Mol Med, SE-17177 Stockholm, Sweden. [Lynch, K.] Univ S Florida, Dept Pediat, Pediat Epidemiol Ctr, Tampa, FL 33620 USA. [Agardh, C. -D.; Cilio, C. M.; Lethagen, A. L.; Lernmark, A.] Lund Univ, Dept Clin Sci, Univ Hosp, SE-20502 Malmo, Sweden. [Reichow, J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Inst Biomed & Clin Res, Seattle, WA 98108 USA. RP Hampe, CS (reprint author), Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, SLU S-276,815 Mercer St, Seattle, WA 98109 USA. EM champe@u.washington.edu FU National Institutes of Health [DK26190, DK17047]; Swedish Diabetes Foundation; Swedish Diabetes Association; Swedish Child Diabetes Foundation; Jerring Foundation; Foundation of Queen Silvia's Jubilee Fund for Research on Children and Handicaps; American Diabetes Association; Medical Research Service of the Department of Veterans Affairs FX The study was performed as independent research sponsored by the National Institutes of Health (DK26190 and DK17047), the Swedish Diabetes Foundation, Swedish Diabetes Association, Swedish Child Diabetes Foundation, the Jerring Foundation, the Foundation of Queen Silvia's Jubilee Fund for Research on Children and Handicaps, and a Basic Science Award from the American Diabetes Association to (C.S.H.). The study also received support through the Medical Research Service of the Department of Veterans Affairs. NR 43 TC 4 Z9 6 U1 0 U2 3 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 NOV PY 2010 VL 95 IS 11 BP E310 EP E318 DI 10.1210/jc.2010-0785 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 675QB UT WOS:000283844400004 PM 20685858 ER PT J AU Ma, QF AF Ma, Qiufu TI Labeled lines meet and talk: population coding of somatic sensations SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID SPINOTHALAMIC TRACT NEURONS; THERMAL GRILL ILLUSION; SENSORY NEURONS; PAIN MECHANISMS; VANILLOID RECEPTOR-1; SCRATCHING BEHAVIOR; CHANNEL EXPRESSION; ITCH SENSATION; COLD SENSATION; NERVE BLOCK AB The somatic sensory system responds to stimuli of distinct modalities, including touch, pain, itch, and temperature sensitivity. In the past century, great progress has been made in understanding the coding of these sensory modalities. From this work, two major features have emerged. First, there are specific neuronal circuits or labeled lines transmitting specific sensory information from the skin to the brain. Second, the generation of specific sensations often involves crosstalk among distinct labeled lines. These features suggest that population coding is the mechanism underlying somatic sensation. C1 [Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM Qiufu_Ma@dfci.harvard.edu FU National Institute of Dental and Craniofacial Research (NIDCR) [R01DE018025]; National Institute of Neurological Disorders and Stroke (NINDS) [P01NS047572, R01NS047710] FX The author thanks Joachim Scholz for critically reading the manuscript as well as his laboratory colleagues, particularly Fu-Chia Yang and Taralyn Tan, for reading and discussions. Q. Ma is supported by NIH grants from the National Institute of Dental and Craniofacial Research (NIDCR; R01DE018025) and the National Institute of Neurological Disorders and Stroke (NINDS; P01NS047572 and R01NS047710). NR 106 TC 59 Z9 61 U1 0 U2 14 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 NOV PY 2010 VL 120 IS 11 BP 3773 EP 3778 DI 10.1172/JCI43426 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 672XU UT WOS:000283621800006 PM 21041959 ER PT J AU Vinciguerra, P Godinho, SA Parmar, K Pellman, D D'Andrea, AD AF Vinciguerra, Patrizia Godinho, Susana A. Parmar, Kalindi Pellman, David D'Andrea, Alan D. TI Cytokinesis failure occurs in Fanconi anemia pathway-deficient murine and human bone marrow hematopoietic cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CROSS-LINK REPAIR; BLOOMS SYNDROME; ABNORMAL CYTOKINESIS; TARGETED DISRUPTION; ANAPHASE BRIDGES; NUCLEAR-COMPLEX; C GENE; MICE; CHECKPOINT; APOPTOSIS AB Fanconi anemia (FA) is a genomic instability disorder characterized by bone marrow failure and cancer predisposition. FA is caused by mutations in any one of several genes that encode proteins cooperating in a repair pathway and is required for cellular resistance to DNA crosslinking agents. Recent studies suggest that the FA pathway may also play a role in mitosis, since FANCD2 and FANCI, the 2 key FA proteins, are localized to the extremities of ultrafine DNA bridges (UFBs), which link sister chromatids during cell division. However, whether FA proteins regulate cell division remains unclear. Here we have shown that FA pathway-deficient cells display an increased number of UFBs compared with FA pathway-proficient cells. The UFBs were coated by BLM (the RecQ helicase mutated in Bloom syndrome) in early mitosis. In contrast, the FA protein FANCM was recruited to the UFBs at a later stage. The increased number of bridges in FA pathway-deficient cells correlated with a higher rate of cytokinesis failure resulting in binucleated cells. Binucleated cells were also detectable in primary murine FA pathway-deficient hematopoietic stem cells (HSCs) and bone marrow stromal cells from human patients with FA. Based on these observations, we suggest that cytokinesis failure followed by apoptosis may contribute to bone marrow failure in patients with FA. C1 [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Godinho, Susana A.; Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst,Childrens Hosp, Howard Hughes Med Inst,Dept Pediat Oncol,Dept Cel, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Alan_dandrea@dfci.harvard.edu FU NIH [R01DK43889, R01HL52725, P01CA092584]; Swiss Foundation; Swiss National Science Foundation [PASMA3-119584] FX We would like to thank Erich A. Nigg for the anti-PICH antibody and AndrewJ. Deans and Stephen C. West for the FANCM siRNAmir and FANCMWT or FANCMK117R corrected HEK293 cells. We thank members of the D'Andrea and Pellman laboratories for helpful discussions and Kanchan Mirchandani and Fabio Martinon for critically reading the manuscript. We also thank Lisa Moreau, Kaya Zhu, and Abigail Hamilton for technical help. This work was supported by NIH grants R01DK43889, R01HL52725, and P01CA092584 to A.D. D'Andrea. P. Vinciguerra was supported by a fellowship from the Swiss Foundation for grants in biology and medicine and by Swiss National Science Foundation grant PASMA3-119584. D. Pellman is an Howard Hughes Medical Institute Investigator. NR 53 TC 55 Z9 55 U1 1 U2 2 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 NOV PY 2010 VL 120 IS 11 BP 3834 EP 3842 DI 10.1172/JCI43391 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 672XU UT WOS:000283621800018 PM 20921626 ER PT J AU Flutter, B Edwards, N Fallah-Arani, F Henderson, S Chai, JG Sivakumaran, S Ghorashian, S Bennett, CL Freeman, GJ Sykes, M Chakraverty, R AF Flutter, Barry Edwards, Noha Fallah-Arani, Farnaz Henderson, Stephen Chai, Jian-Guo Sivakumaran, Shivajanani Ghorashian, Sara Bennett, Clare L. Freeman, Gordon J. Sykes, Megan Chakraverty, Ronjon TI Nonhematopoietic antigen blocks memory programming of alloreactive CD8(+) T cells and drives their eventual exhaustion in mouse models of bone marrow transplantation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GRAFT-VERSUS-HOST; DONOR LYMPHOCYTE INFUSION; CHRONIC VIRAL-INFECTION; CHRONIC MYELOID-LEUKEMIA; TOTAL-BODY IRRADIATION; PRESENTING CELLS; STEM-CELLS; ADOPTIVE IMMUNOTHERAPY; CONDITIONING REGIMEN; LEUKOCYTE INFUSIONS AB Allogeneic blood or BM transplantation (BMT) is the most commonly applied form of adoptive cellular therapy for cancer. In this context, the ability of donor T cells to respond to recipient antigens is coopted to generate graft-versus-tumor (GVT) responses. The major reason for treatment failure is tumor recurrence, which is linked to the eventual loss of functional, host-specific CTLs. In this study, we have explored the role of recipient antigen expression by nonhematopoietic cells in the failure to sustain effective CTL immunity. Using clinically relevant models, we found that nonhematopoietic antigen severely disrupts the formation of donor CD8(+) T cell memory at 2 distinct levels that operate in the early and late phases of the response. First, initial and direct encounters between donor CD8+ T cells and nonhematopoietic cells blocked the programming of memory precursors essential for establishing recall immunity. Second, surviving CD8+ T cells became functionally exhausted with heightened expression of the coinhibitory receptor programmed death-1 (PD-1). These 2 factors acted together to induce even more profound failure in long-term immunosurveillance. Crucially, the functions of exhausted CD8+ T cells could be partially restored by late in vivo blockade of the interaction between PD-1 and its ligand, PD-L1, without induction of graft-versus-host disease, suggestive of a potential clinical strategy to prevent or treat relapse following allogeneic BMT. C1 [Flutter, Barry; Edwards, Noha; Fallah-Arani, Farnaz; Sivakumaran, Shivajanani; Ghorashian, Sara; Bennett, Clare L.; Chakraverty, Ronjon] UCL, Transplantat Immunol Grp, Dept Haematol, London NW3 2PF, England. [Chai, Jian-Guo] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Immunol, London, England. [Henderson, Stephen] Univ London Imperial Coll Sci Technol & Med, Canc Res UK Viral Oncol Grp, London, England. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sykes, Megan] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY USA. RP Chakraverty, R (reprint author), UCL, Transplantat Immunol Grp, Dept Haematol, Rowland Hill St, London NW3 2PF, England. EM r.chakraverty@medsch.ucl.ac.uk RI bennett, clare/J-5249-2013; OI bennett, clare/0000-0001-9146-2347; Henderson, Stephen/0000-0002-9032-3828 FU Leukaemia and Lymphoma Research, United Kingdom; NIH [PO1 CA111519, RO1 CA79989, 5HSSN266200500030C, PO1 AI56299]; Multiple Myeloma Foundation FX G.J. Freeman has patents in the PD-1/PD-L1 pathway and receives royalty payments.; This work was supported by Leukaemia and Lymphoma Research, United Kingdom; by NIH grants PO1 CA111519, RO1 CA79989, 5HSSN266200500030C, and PO1 AI56299; and by a Senior Research Award from the Multiple Myeloma Foundation. We thank Marcel van den Brink, Hans Stauss, and Bernd Arnold for their helpful reviews of the manuscript. We also thank Konstantinos Giannopoulos for technical assistance. NR 75 TC 27 Z9 27 U1 1 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2010 VL 120 IS 11 BP 3855 EP 3868 DI 10.1172/JCI41446 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 672XU UT WOS:000283621800020 PM 20978352 ER PT J AU Titanji, K Velu, V Chennareddi, L Vijay-Kumar, M Gewirtz, AT Freeman, GJ Amara, RR AF Titanji, Kehmia Velu, Vijayakumar Chennareddi, Lakshmi Vijay-Kumar, Matam Gewirtz, Andrew T. Freeman, Gordon J. Amara, Rama R. TI Acute depletion of activated memory B cells involves the PD-1 pathway in rapidly progressing SIV-infected macaques SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; CD8(+) T-CELLS; HIV-1 INFECTION; DISEASE PROGRESSION; LYMPHOCYTE DYSFUNCTIONS; ANTIRETROVIRAL THERAPY; PROGRAMMED DEATH-1; PROSPECTIVE COHORT; IMMUNE ACTIVATION; EXPRESSION AB Rapid progression to AIDS is a significant problem, especially in developing countries, where the majority of HIV-infected individuals reside. As rapid disease progression is also frequently observed in SIV-infected macaques, they represent a valuable tool to investigate the pathogenesis of this condition in humans. Here, we have shown that pathogenic Sly infection in rhesus macaques resulted in a rapid depletion (as early as week 2) of activated memory B (CD21(-)CD27(+); mB(Act)) cells that was strongly associated with rapid disease progression. This depletion was progressive and sustained in rapid progressors, but less severe and transient in typical progressors. Because of the rapid and sustained depletion of mB(Act) cells, rapid progressors failed to develop SIV-specific Ab responses, showed a decline in non-SIV-specific Ab titers, and succumbed faster to intestinal bacterial infections. Depletion of mBAct cells was strongly associated with preferential depletion of mB(Act) cells expressing programmed death-1 (PD-1), and in vitro blockade of PD-1 improved their survival. Furthermore, in vivo PD-1 blockade in SIV-infected macaques enhanced Ab responses to non-SIV as well as SIV Ags. Our results identify depletion of mB(Act) cells as a very early predictor of rapid disease progression in pathogenic SW infection and suggest an important role for the PD-1 pathway in depletion of mBAct cells and impaired humoral immune responses in SIV-infected macaques. C1 [Titanji, Kehmia; Velu, Vijayakumar; Chennareddi, Lakshmi; Amara, Rama R.] Emory Univ, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30329 USA. [Titanji, Kehmia; Velu, Vijayakumar; Chennareddi, Lakshmi; Amara, Rama R.] Emory Univ, Sch Med, Dept Microbiol & Immunol, Emory Vaccine Ctr, Atlanta, GA 30329 USA. [Vijay-Kumar, Matam; Gewirtz, Andrew T.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30329 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA USA. RP Amara, RR (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, 954 Gatewood Rd, Atlanta, GA 30329 USA. EM ramara@emory.edu OI Velu, Vijayakumar/0000-0003-4238-1924 FU NIH/National Institute of Allergy and Infectious Diseases [R01 AI057029, R01 AI074471, R01 AI071852]; Yerkes National Primate Research Center [P51 RR00165]; Emory CFAR [P30 AI050409, R01 AI074417, P01 AI08080192] FX G.J. Freeman has patents and receives patent royalties on the PD-1 pathway.; We thank A. Grakoui, H. Hon, and H. Radziewicz for the Huh 7.5 and Huh7.5.PD-L1 cell lines and R. Ahmed for critical input throughout the study. We are grateful to the veterinary staff at the Yerkes Division of Research Resources for their support and H. Drake-Perrow for administrative support. We also thank the Emory CFAR virology core for viral RNA measurements. This work was supported by NIH/National Institute of Allergy and Infectious Diseases grants R01 AI057029, R01 AI074471, and R01 AI071852 to R.R. Amara; Yerkes National Primate Research Center base grant P51 RR00165; and Emory CFAR grants P30 AI050409, R01 AI074417, and P01 AI08080192 to G.J. Freeman. NR 51 TC 62 Z9 66 U1 2 U2 11 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 NOV PY 2010 VL 120 IS 11 BP 3878 EP 3890 DI 10.1172/JCI43271 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 672XU UT WOS:000283621800022 PM 20972331 ER PT J AU Vicent, S Chen, R Sayles, LC Lin, CW Walker, RG Gillespie, AK Subramanian, A Hinkle, G Yang, XP Saif, S Root, DE Huff, V Hahn, WC Sweet-Cordero, EA AF Vicent, Silvestre Chen, Ron Sayles, Leanne C. Lin, Chenwei Walker, Randal G. Gillespie, Anna K. Subramanian, Aravind Hinkle, Gregory Yang, Xiaoping Saif, Sakina Root, David E. Huff, Vicki Hahn, William C. Sweet-Cordero, E. Alejandro TI Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ROUND-CELL TUMOR; GENE-EXPRESSION; HUMAN CANCER; LUNG-CANCER; PREMATURE SENESCENCE; RNA INTERFERENCE; K-RAS; TRANSGENIC MICE; SUPPRESSOR; PROTEIN AB KRAS is one of the most frequently mutated human oncogenes. In some settings, oncogenic KRAS can trigger cellular senescence, whereas in others it produces hyperproliferation. Elucidating the mechanisms regulating these 2 drastically distinct outcomes would help identify novel therapeutic approaches in RAS-driven cancers. Using a combination of functional genomics and mouse genetics, we identified a role for the transcription factor Wilms tumor 1 (WT1) as a critical regulator of senescence and proliferation downstream of oncogenic KRAS signaling. Deletion or suppression of Wtl led to senescence of mouse primary cells expressing physiological levels of oncogenic Kras but had no effect on wild-type cells, and Wt1 loss decreased tumor burden in a mouse model of Kras-driven lung cancer. In human lung cancer cell lines dependent on oncogenic KRAS, WT1 loss decreased proliferation and induced senescence. Furthermore, WT1 inactivation defined a gene expression signature that was prognostic of survival only in lung cancer patients exhibiting evidence of oncogenic KRAS activation. These findings reveal an unexpected role for WT1 as a key regulator of the genetic network of oncogenic KRAS and provide important insight into the mechanisms that regulate proliferation or senescence in response to oncogenic signals. C1 [Vicent, Silvestre; Chen, Ron; Sayles, Leanne C.; Lin, Chenwei; Walker, Randal G.; Gillespie, Anna K.; Sweet-Cordero, E. Alejandro] Stanford Univ, Dept Pediat, Sch Med, Canc Biol Program, Stanford, CA 94305 USA. [Walker, Randal G.] CardioDx, Palo Alto, CA USA. [Subramanian, Aravind; Hinkle, Gregory; Yang, Xiaoping; Saif, Sakina; Root, David E.; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Huff, Vicki] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sweet-Cordero, EA (reprint author), 269 Campus Dr CCSR 1215B, Stanford, CA 94305 USA. EM ascor@stanford.edu OI Vicent, Silvestre/0000-0002-9457-6881 FU Fundacion Alfonso Martin Escudero; Tobacco-Related Disease Research Program of California (TRDRP); NIH; National Cancer Institute [I-K08CA98096-01, 1R01CA138256-01, R33 CA128625]; Sidney Kimmel Foundation; Rita Allen Foundation; Joan's Legacy Foundation; Harold Amos Medical Faculty Development Program; Starr Cancer Consortium [I1-A11] FX We thank Sheila Stewart for providing us with the pLKO.1s vector. We thank Julien Sage, Steve Artandi, Laura Attardi, Kevin Haigis, Erica Jackson, and all the members of the Sweet-Cordero lab for helpful discussions. We thank the Stanford High-Throughput Biosciences Center and David Solow-Cordero for assistance in the execution of the pooled shRNA screen. We thank the members of the RNAi Platform at the Broad Institute and The RNAi Consortium (TRC) for advice and technical support. S. Vicent was supported by fellowships from the Fundacion Alfonso Martin Escudero and the Tobacco-Related Disease Research Program of California (TRDRP). This work was supported in part by the NIH and the National Cancer Institute (I-K08CA98096-01 and 1R01CA138256-01 to E.A. Sweet-Cordero). E.A. Sweet-Cordero was also supported by grants from the Sidney Kimmel Foundation, the Rita Allen Foundation, the Joan's Legacy Foundation, and the Harold Amos Medical Faculty Development Program. W.C. Hahn was supported in part by the National Cancer Institute (R33 CA128625) and the Starr Cancer Consortium (I1-A11). NR 61 TC 63 Z9 68 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2010 VL 120 IS 11 BP 3940 EP 3952 DI 10.1172/JCI44165 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 672XU UT WOS:000283621800028 PM 20972333 ER PT J AU Dentice, M Marsili, A Ambrosio, R Guardiola, O Sibilio, A Paik, JH Minchiotti, G DePinho, RA Fenzi, G Larsen, PR Salvatore, D AF Dentice, Monica Marsili, Alessandro Ambrosio, Raffaele Guardiola, Ombretta Sibilio, Annarita Paik, Ji-Hye Minchiotti, Gabriella DePinho, Ronald A. Fenzi, Gianfranco Larsen, P. Reed Salvatore, Domenico TI The FoxO3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TYPE-2 IODOTHYRONINE DEIODINASE; STEM-CELL FUNCTION; SKELETAL-MUSCLE; THYROID-HORMONE; SATELLITE CELLS; MYOD GENE; MOLECULAR REGULATION; ACTIVATION; EXPRESSION; DIFFERENTIATION AB The active thyroid hormone 3,5,3' triiodothyronine (T3) is a major regulator of skeletal muscle function. The deiodinase family of enzymes controls the tissue-specific activation and inactivation of the prohorrnone thyroxine (T4). Here we show that type 2 deiodinase (D2) is essential for normal mouse myogenesis and muscle regeneration. Indeed, D2-mediated increases in T3 were essential for the enhanced transcription of myogenic differentiation 1 (MyoD) and for execution of the myogenic program. Conversely, the expression of T3-dependent genes was reduced and after injury regeneration markedly delayed in muscles of mice null for the gene encoding D2 (Dio2), despite normal circulating T3 concentrations. Forkhead box 03 (Fox03) was identified as a key molecule inducing D2 expression and thereby increasing intracellular T3 production. Accordingly, Fox03-depleted primary myoblasts also had a differentiation deficit that could be rescued by high levels of T3. In conclusion, the Fox03/D2 pathway selectively enhances intracellular active thyroid hormone concentrations in muscle, providing a striking example of how a circulating hormone can be tissue-specifically activated to influence development locally. C1 [Dentice, Monica; Sibilio, Annarita; Fenzi, Gianfranco; Salvatore, Domenico] Univ Naples Federico 2, Dept Mol & Clin Endocrinol & Oncol, I-80131 Naples, Italy. [Marsili, Alessandro; Larsen, P. Reed] Brigham & Womens Hosp, Thyroid Sect, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med Oncol, Belfer Inst Appl Canc Sci, Boston, MA USA. [Ambrosio, Raffaele] IRCCS Fdn SDN, Naples, Italy. [Guardiola, Ombretta; Minchiotti, Gabriella] CNR, Stem Cell Fate Lab, Inst Genet & Biophys A Buzzati Traverso, I-80125 Naples, Italy. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Salvatore, Domenico] CEINGE Biotecnol Avanzate ScarI, Naples, Italy. RP Salvatore, D (reprint author), Univ Naples Federico 2, Dept Mol & Clin Endocrinol & Oncol, Via S Pansini 5, I-80131 Naples, Italy. EM domsalva@unina.it RI Salvatore, Domenico/D-4881-2013; OI SALVATORE, DOMENICO/0000-0002-4556-7620 FU Associazione Italiana per la Ricerca sul Cancro (AIRC); Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR); Telethon [GGP08120]; NIH [DK044128] FX We are grateful to C. Cepko, A. Wagers, and D.D. Moore for their critical reading of the manuscript and to J. Harney and M. Mulcahey for technical support. This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) to D. Salvatore; an MFAG grant from the AIRC to M. Dentice; AIRC and Telethon grant GGP08120 to G. Minchiotti; and NIH grant DK044128 to P.R. Larsen. NR 52 TC 50 Z9 54 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2010 VL 120 IS 11 BP 4021 EP 4030 DI 10.1172/JCI43670 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 672XU UT WOS:000283621800034 PM 20978344 ER PT J AU Xia, ZQ Chen-Plotkin, A Schmahmann, JD AF Xia, Zongqi Chen-Plotkin, Alice Schmahmann, Jeremy D. TI Hypertrophic pachymeningitis and cerebral venous sinus thrombosis in inflammatory bowel disease SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Cerebral venous sinus thrombosis; Hypertrophic pachymeningitis; Inflammatory bowel disease; Intracranial hypertension; Neuroimmunology AB Hypertrophic pachymeningitis is rarely observed in inflammatory bowel disease. We report a woman with ulcerative colitis whose biopsy-confirmed hypertrophic pachymeningitis was complicated by cerebral venous sinus thrombosis and intracranial hypertension and required ventriculostomy and steroid therapy. This report highlights the challenges of the diagnosis and management of hypertrophic pachymeningitis from an unusual primary cause. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Xia, Zongqi] Brigham & Womens Hosp, Div Neurol, Boston, MA 02115 USA. [Chen-Plotkin, Alice] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Chen-Plotkin, Alice] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Xia, Zongqi; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Xia, Zongqi] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Xia, ZQ (reprint author), Brigham & Womens Hosp, Div Neurol, Boston, MA 02115 USA. EM zxia1@partners.org FU NIH [AI074549-02, K08 AG033101]; Burroughs Wellcome Fund Career Award for Medical Scientists; Birmingham Foundation FX We thank the patient and her family. Dr Xia is supported by NIH (AI074549-02). Chen-Plotkin is supported by a Burroughs Wellcome Fund Career Award for Medical Scientists and NIH (K08 AG033101). Schmahmann is supported in part by the Birmingham Foundation. NR 6 TC 6 Z9 7 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD NOV PY 2010 VL 17 IS 11 BP 1454 EP 1456 DI 10.1016/j.jocn.2010.04.019 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 705JF UT WOS:000286124000028 PM 20727771 ER PT J AU deIpolyi, A Auguste, KI Yang, I Tihan, T Parsa, AT AF deIpolyi, Amy Auguste, Kurtis I. Yang, Isaac Tihan, Tarik Parsa, Andrew T. TI Occipital ganglioglioma in an older adult SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Adult; Occipital ganglioglioma; Seizure ID LOBE EPILEPSY; ABNORMALITIES; EXPERIENCE; LESIONS; TUMORS AB Gangliogliomas are rare benign tumors of the central nervous system that typically involve the temporal lobe in younger patients. We present a 63-year-old man with an unusual occipital ganglioma with new seizures resolving after resection. A search of the literature revealed only three reports of occipital ganglioma in adults over 30 years old. Therefore, ganglioglioma of the occipital lobe in older patients is rare, but is a diagnostic consideration. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Auguste, Kurtis I.; Yang, Isaac; Tihan, Tarik; Parsa, Andrew T.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Auguste, Kurtis I.; Yang, Isaac; Tihan, Tarik; Parsa, Andrew T.] Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. [deIpolyi, Amy] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [deIpolyi, Amy] Harvard Univ, Sch Med, Boston, MA USA. RP Parsa, AT (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,Room M779, San Francisco, CA 94143 USA. EM parsaa@neurosurg.ucsf.edu OI Deipolyi, Amy/0000-0003-3144-386X NR 21 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD NOV PY 2010 VL 17 IS 11 BP 1459 EP 1461 DI 10.1016/j.jocn.2010.04.018 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 705JF UT WOS:000286124000030 PM 20727766 ER PT J AU Ingle, JN Schaid, DJ Goss, PE Liu, M Mushiroda, T Chapman, JAW Kubo, M Jenkins, GD Batzler, A Shepherd, L Pater, J Wang, LW Ellis, MJ Stearns, V Rohrer, DC Goetz, MP Pritchard, KI Flockhart, DA Nakamura, Y Weinshilboum, RM AF Ingle, James N. Schaid, Daniel J. Goss, Paul E. Liu, Mohan Mushiroda, Taisei Chapman, Judy-Anne W. Kubo, Michiaki Jenkins, Gregory D. Batzler, Anthony Shepherd, Lois Pater, Joseph Wang, Liewei Ellis, Matthew J. Stearns, Vered Rohrer, Daniel C. Goetz, Matthew P. Pritchard, Kathleen I. Flockhart, David A. Nakamura, Yusuke Weinshilboum, Richard M. TI Genome-Wide Associations and Functional Genomic Studies of Musculoskeletal Adverse Events in Women Receiving Aromatase Inhibitors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID STAGE BREAST-CANCER; EXTENDED ADJUVANT THERAPY; POSTMENOPAUSAL WOMEN; POPULATION SUBSTRUCTURE; RANDOMIZED-TRIAL; TAMOXIFEN; ANASTROZOLE; SYMPTOMS; ARNO-95; TCL1 AB Purpose We performed a case-control genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with musculoskeletal adverse events (MS-AEs) in women treated with aromatase inhibitors (AIs) for early breast cancer. Patients and Methods A nested case-control design was used to select patients enrolled onto the MA. 27 phase III trial comparing anastrozole with exemestane. Cases were matched to two controls and were defined as patients with grade 3 or 4 MS-AEs (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0) or those who discontinued treatment for any grade of MS-AE within the first 2 years. Genotyping was performed with the Illumina Human610-Quad BeadChip. Results The GWAS included 293 cases and 585 controls. A total of 551,358 SNPs were analyzed, followed by imputation and fine mapping of a region of interest on chromosome 14. Four SNPs on chromosome 14 had the lowest P values (2.23E-06 to 6.67E-07). T-cell leukemia 1A (TCL1A) was the gene closest (926-7000 bp) to the four SNPs. Functional genomic studies revealed that one of these SNPs (rs11849538) created an estrogen response element and that TCL1A expression was estrogen dependent, was associated with the variant SNP genotypes in estradiol-treated lymphoblastoid cells transfected with estrogen receptor alpha and was directly related to interleukin 17 receptor A (IL17RA) expression. Conclusion This GWAS identified SNPs associated with MS-AEs in women treated with AIs and with a gene (TCL1A) which, in turn, was related to a cytokine (IL17). These findings provide a focus for further research to identify patients at risk for MS-AEs and to explore the mechanisms for these adverse events. C1 [Ingle, James N.] Mayo Clin, Rochester, MN 55905 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RIKEN Ctr Genom Med, Tokyo, Japan. Univ Toronto, Sunnybrook Odette Reg Canc Ctr, Toronto, ON, Canada. Washington Univ, St Louis, MO USA. Indiana Univ, Indianapolis, IN 46204 USA. Johns Hopkins Sch Med, Baltimore, MD USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. RP Ingle, JN (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM ingle.james@mayo.edu RI Mushiroda, Taisei/E-3022-2010; Kubo, Michiaki/N-7947-2015; Pritchard, Kathleen/I-2184-2014 OI Pritchard, Kathleen/0000-0003-0758-9666 FU National Institutes of Health (NIH) [U01GM61388, U01GM63173, P50CA116201, U10CA77202]; Canadian Cancer Society [CCS 015469]; Japanese Ministry of Education, Culture, Sports, Science and Technology; Breast Cancer Research Foundation, New York, NY; NIH Pharmacogenomics Research Network-RIKEN Center for Genomic Medicine Global Alliance FX Supported in part by National Institutes of Health (NIH) Grants No. U01GM61388, U01GM63173, P50CA116201, and U10CA77202; by Grant No. CCS 015469 from the Canadian Cancer Society; and by the Biobank Japan Project funded by the Japanese Ministry of Education, Culture, Sports, Science and Technology; the Breast Cancer Research Foundation, New York, NY; and the NIH Pharmacogenomics Research Network-RIKEN Center for Genomic Medicine Global Alliance, Pfizer supported the clinical trial from which the patients in this study were obtained. NR 30 TC 111 Z9 112 U1 0 U2 14 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 NOV 1 PY 2010 VL 28 IS 31 BP 4674 EP 4682 DI 10.1200/JCO.2010.28.5064 PG 9 WC Oncology SC Oncology GA 672LQ UT WOS:000283585200019 PM 20876420 ER PT J AU Arico, M Schrappe, M Hunger, SP Carroll, WL Conter, V Galimberti, S Manabe, A Saha, V Baruchel, A Vettenranta, K Horibe, K Benoit, Y Pieters, R Escherich, G Silverman, LB Pui, CH Valsecchi, MG AF Arico, Maurizio Schrappe, Martin Hunger, Stephen P. Carroll, William L. Conter, Valentino Galimberti, Stefania Manabe, Atsushi Saha, Vaskar Baruchel, Andre Vettenranta, Kim Horibe, Keizo Benoit, Yves Pieters, Rob Escherich, Gabriele Silverman, Lewis B. Pui, Ching-Hon Valsecchi, Maria Grazia TI Clinical Outcome of Children With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated Between 1995 and 2005 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MINIMAL RESIDUAL DISEASE; CHILDHOOD; TRIALS; THERAPY; BFM AB Purpose In a previous analysis of 326 children with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL) treated between 1986 and 1996, hematopoietic stem-cell transplantation from HLA-matched related donors, but not from unrelated donors, offered a superior outcome than chemotherapy alone. To evaluate the impact of recent improvements in chemotherapy and transplantation, we performed a similar analysis on patients treated in the following decade. Patients and Methods We analyzed 610 patients with Ph-positive ALL treated between 1995 and 2005 without tyrosine kinase inhibitor therapy. The median follow-up duration was 6.3 years. Results Complete remission was achieved in 89% of patients. The 7-year event-free survival and overall survival rates were superior in the present cohort compared with the previous cohort (32.0% +/- 2.0% v 25.0% +/- 3.0, respectively, P = .007; and 44.9% +/- 2.2% v 36.0% +/- 3.0%, respectively, P = .017). Compared with chemotherapy alone, transplantation with matched related donors or unrelated donors in first remission (325 patients) showed an advantage with increasing follow-up, suggesting greater protection against late relapses (hazard ratio at 5 years, 0.37; P < .001). In the multivariate Cox regression analysis accounting for treatment (transplantation v no transplantation), age, leukocyte count, and early response had independent impact on treatment outcome. Conclusion Clinical outcome of children and adolescents with Ph-positive ALL has improved with advances in transplantation and chemotherapy. Transplantations with matched related donors and unrelated donors were equivalent and offered better disease control compared with chemotherapy alone. Age, leukocyte count, and early treatment response were independent prognostic indicators. The results of this study will serve as a historical reference to evaluate the therapeutic impact of tyrosine kinase inhibitors on the outcome of Ph-positive ALL. J Clin Oncol 28: 4755-4761. (C) 2010 by American Society of Clinical Oncology C1 [Arico, Maurizio] Azienda Osped Univ Meyer, Dept Pediat Hematol Oncol, I-50139 Florence, Italy. Pediat Osped Riuniti Bergamo, Bergamo, Italy. Univ Milano Bicocca, Monza, Italy. Univ Med Ctr Schleswig Holstein, Kiel, Germany. Univ Hamburg, Hamburg, Germany. Childrens Hosp, Aurora, CO USA. Univ Colorado, Sch Med, Aurora, CO USA. NYU, Inst Canc, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Coll Med, Memphis, TN 38163 USA. St Lukes Int Hosp, Tokyo, Japan. Natl Hosp Org, Nagoya Med Ctr, Clin Res Ctr, Nagoya, Aichi, Japan. Univ Manchester, Manchester Acad Hlth Sci Ctr, Canc Res United Kingdom Childrens Canc Grp, Manchester, Lancs, England. Hop Robert Debre, AP HP, F-75019 Paris, France. Univ Paris Diderot, Paris, France. Univ Tampere, FIN-33101 Tampere, Finland. Ghent Univ Hosp, B-9000 Ghent, Belgium. Erasmus MC Sophia Childrens Hosp, Rotterdam, Netherlands. Dutch Childhood Oncol Grp, The Hague, Netherlands. RP Arico, M (reprint author), Azienda Osped Univ Meyer, Dept Pediat Hematol Oncol, Viale Pieraccini 24, I-50139 Florence, Italy. EM m.arico@meyer.it RI galimberti, stefania/H-2594-2012; OI Saha, Vaskar/0000-0002-2916-9649 FU NCI NIH HHS [P30 CA021765, R01 CA086011, U10 CA098543, U24 CA114766]; Associazione Italiana per la Ricerca sul Cancro NR 32 TC 80 Z9 91 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2010 VL 28 IS 31 BP 4755 EP 4761 DI 10.1200/JCO.2010.30.1325 PG 7 WC Oncology SC Oncology GA 672LQ UT WOS:000283585200029 PM 20876426 ER PT J AU Fiorentino, L Martin, JL AF Fiorentino, Lavinia Martin, Jennifer L. TI Awake at 4 a.m.: Treatment of Insomnia With Early Morning Awakenings Among Older Adults SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE insomnia; circadian rhythms; advanced sleep phase syndrome; aging; cognitive-behavioral therapy; light therapy ID SLEEP DISORDERS; INTERVENTIONS; METAANALYSIS; EFFICACY AB Insomnia is a common problem among older adults. In particular, older adults experience insomnia coupled with early morning awakenings due to an interaction between age-related changes in circadian rhythm timing coupled with behavior changes that contribute to sustained poor sleep. Cognitive behavioral therapy for insomnia (CBT-I), at times coupled with circadian interventions (e.g., timed light exposure), are likely to be most successful in optimizing sleep quality. In delivering CBT-I to older adults, modifications are sometimes necessary to accommodate for medical problems, lifestyle, social factors, and patient preferences. Addition of circadian interventions can ameliorate the negative effects of inappropriately timed sleep as well. These treatment methods can be highly effective and benefits can be long-standing. A case example is used to illustrate these points. (C) 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66:1161-1174, 2010. C1 [Fiorentino, Lavinia; Martin, Jennifer L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Martin, JL (reprint author), VA Greater Los Angeles Healthcare Syst Geriatr Re, Educ & Clin Ctr 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU NIA NIH HHS [K23 AG028452, K23 AG028452-03, R01 AG026364]; NIMH NIH HHS [T32 MH019925, T32 MH019925-10, T32 MH 019925-1] NR 12 TC 2 Z9 3 U1 1 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD NOV PY 2010 VL 66 IS 11 BP 1161 EP 1174 DI 10.1002/jclp.20734 PG 14 WC Psychology, Clinical SC Psychology GA 679TF UT WOS:000284183000004 PM 20845423 ER PT J AU Gehrman, PR Harb, GC AF Gehrman, Philip R. Harb, Gerlinde C. TI Treatment of Nightmares in the Context of Posttraumatic Stress Disorder SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE nightmares; sleep; PTSD; cognitive-behavioral therapy; REM; prazosin; imagery rehearsal ID SLEEP DISTURBANCE; COMBAT VETERANS; PRAZOSIN; SYMPTOMS; THERAPY; TRIAL; PTSD AB Nightmares are a common feature of posttraumatic stress disorder (PTSD) and are frequently resistant to treatment. Two emerging treatments for nightmares are pharmacotherapy with prazosin and psychotherapy using imagery rehearsal (IR). A case illustration demonstrates the application of these treatments with a client suffering from chronic, severe PTSD. The case illustrates the use of these strategies for managing PTSD-related nightmares, as well as the novel approach of scheduled awakenings following relapse. (C) 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66:1185-1194, 2010. C1 [Gehrman, Philip R.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Gehrman, Philip R.; Harb, Gerlinde C.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Gehrman, PR (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,Suite 670, Philadelphia, PA 19104 USA. EM gehrman@exchange.upenn.edu NR 17 TC 10 Z9 10 U1 1 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD NOV PY 2010 VL 66 IS 11 BP 1185 EP 1194 DI 10.1002/jclp.20730 PG 10 WC Psychology, Clinical SC Psychology GA 679TF UT WOS:000284183000006 PM 20865767 ER PT J AU Hayes, SM Baena, E Truong, TK Cabeza, R AF Hayes, Scott M. Baena, Elsa Truong, Trong-Kha Cabeza, Roberto TI Neural Mechanisms of Context Effects on Face Recognition: Automatic Binding and Context Shift Decrements SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID MEDIAL TEMPORAL-LOBE; EVENT-RELATED FMRI; PARAHIPPOCAMPAL CORTEX; EPISODIC MEMORY; ENVIRONMENTAL CONTEXT; OBJECT RECOGNITION; SPATIAL LOCATION; FUNCTIONAL MRI; OLDER ADULTS; RETRIEVAL AB Although people do not normally try to remember associations between faces and physical contexts, these associations are established automatically, as indicated by the difficulty of recognizing familiar faces in different contexts ("butcher-on-the-bus" phenomenon). The present fMRI study investigated the automatic binding of faces and scenes. In the face-face (F-F) condition, faces were presented alone during both encoding and retrieval, whereas in the face/scene-face (FS-F) condition, they were presented overlaid on scenes during encoding but alone during retrieval (context change). Although participants were instructed to focus only on the faces during both encoding and retrieval, recognition performance was worse in the FS-F than in the F-F condition ("context shift decrement" [CSD]), confirming automatic face-scene binding during encoding. This binding was mediated by the hippocampus as indicated by greater subsequent memory effects (remembered > forgotten) in this region for the FS-F than the F-F condition. Scene memory was mediated by right parahippocampal cortex, which was reactivated during successful retrieval when the faces were associated with a scene during encoding (FS-F condition). Analyses using the CSD as a regressor yielded a clear hemispheric asymmetry in medial temporal lobe activity during encoding: Left hippocampal and parahippocampal activity was associated with a smaller CSD, indicating more flexible memory representations immune to context changes, whereas right hippocampal/rhinal activity was associated with a larger CSD, indicating less flexible representations sensitive to context change. Taken together, the results clarify the neural mechanisms of context effects on face recognition. C1 [Truong, Trong-Kha; Cabeza, Roberto] Duke Univ, Med Ctr, Durham, NC USA. [Baena, Elsa] Univ Arizona, Tucson, AZ USA. RP Hayes, SM (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr 151A, 150 S Huntington Ave, Boston, MA 02130 USA. EM scott.hayes@va.gov RI Truong, Trong-Kha/S-3089-2016 OI Truong, Trong-Kha/0000-0003-2699-1554 FU National Institutes of Health; National Institute on Aging (NIA) [R01 AG019731, R01 AG23770, F32 AG029738]; National Institute of Neurological Disorders and Stroke (NINDS) [PPG NS 41328, R01 NS 50329]; DOD FX This work was supported by the National Institutes of Health, the National Institute on Aging (NIA) [grant numbers R01 AG019731 and R01 AG23770 awarded to R. C. and grant number F32 AG029738 awarded to S. M. H.] and the National Institute of Neurological Disorders and Stroke (NINDS) [grant numbers PPG NS 41328 and R01 NS 50329 awarded to Allen Song]. E. B. was supported by funding from the National Institutes of Health awarded to Duke University's Post-baccalaureate Research Education Program (PREP).; We thank Allen Song for providing technical assistance with MRI data acquisition, James Kragel for assistance with data preprocessing and analysis, and Odera Umeano for assistance with data collection. Portions of the research in this article use the FERET database of facial images collected under the FERET program, sponsored by the DOD Counterdrug Technology Development Program Office, as well as face images provided by the Computer Vision Library, University of Ljubljana, Slovenia (www.lrv.fri.uni-lj.si/facedb.html; and Solina et al., 2003). We also thank the anonymous reviewers for helpful comments on the manuscript. NR 60 TC 13 Z9 14 U1 0 U2 2 PU M I T PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD NOV PY 2010 VL 22 IS 11 BP 2541 EP 2554 DI 10.1162/jocn.2009.21379 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 626OW UT WOS:000279976300012 PM 19925208 ER PT J AU Palmer, CA Kent, R Loo, CY Hughes, CV Stutius, E Pradhan, N Dahlan, M Kanasi, E Vasquez, SSA Tanner, ACR AF Palmer, C. A. Kent, R., Jr. Loo, C. Y. Hughes, C. V. Stutius, E. Pradhan, N. Dahlan, M. Kanasi, E. Vasquez, S. S. Arevalo Tanner, A. C. R. TI Diet and Caries-associated Bacteria in Severe Early Childhood Caries SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE childhood caries; food frequency; cariogenicity; S. mutans; Bifidobacteria ID DENTAL-CARIES; STREPTOCOCCUS-MUTANS; CHILDREN; FOOD; BIFIDOBACTERIA; ADULTS; AGE; PCR AB Frequent consumption of cariogenic foods and bacterial infection are risk factors for early childhood caries (ECC). This study hypothesized that a short diet survey focused on frequency of foods, categorized by putative cariogenicity, would differentiate severe ECC (S-ECC) from caries-free children. Children's diets were obtained by survey and plaque bacteria detected by PCR from 72 S-ECC and 38 caries-free children. S-ECC children had higher scores for between-meal juice (p < 0.01), solid-retentive foods (p < 0.001), eating frequency (p < 0.005), and estimated food cariogenicity (p < 0.0001) than caries-free children. S-ECC children with lesion recurrence ate fewer putative caries-protective foods than children without new lesions. Streptococcus mutans (p < 0.005), Streptococcus sobrinus (p < 0.005), and Bifidobacteria (p < 0.0001) were associated with S-ECC, and S. mutans with S. sobrinus was associated with lesion recurrence (p < 0.05). S. mutans-positive children had higher food cariogenicity scores. Food frequency, putative cariogenicity, and S. mutans were associated with S-ECC individually and in combination. C1 [Kanasi, E.; Tanner, A. C. R.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Kent, R., Jr.] Forsyth Inst, Dept Biostat, Boston, MA 02115 USA. [Loo, C. Y.; Pradhan, N.] Tufts Univ, Sch Dent Med, Dept Pediat Dent, Boston, MA 02111 USA. [Palmer, C. A.] Tufts Univ, Sch Dent Med, Dept Publ Hlth & Community Serv, Boston, MA 02111 USA. [Hughes, C. V.; Dahlan, M.] Boston Univ, Goldman Sch Dent Med, Dept Pediat Dent, Boston, MA 02118 USA. [Kent, R., Jr.; Kanasi, E.] Harvard Univ, Harvard Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. [Tanner, A. C. R.] Harvard Univ, Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Tanner, ACR (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM annetanner@forsyth.org RI Hughes, Christopher/E-1438-2014 FU National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD [DE-015847, DE-007327]; Umea University, Sweden; Tufts University School of Dental Medicine, Boston, MA FX We thank Rachel Montgomery, Benita Demirza, and Ronnie Kraus for recruiting and coding diet data, Natalia Chalmers and Pernilla Lif Holgerson for oversight of the PCR assays, and Ingegerd Johansson and Dominick DePaola for reviewing the manuscript. This investigation was supported by USPHS grants DE-015847 and DE-007327 from the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, by a Medical Faculty PhD grant, Umea University, Sweden, and by an intern fellowship from Tufts University School of Dental Medicine, Boston, MA. NR 28 TC 47 Z9 51 U1 1 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2010 VL 89 IS 11 BP 1224 EP 1229 DI 10.1177/0022034510376543 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 669PS UT WOS:000283363300009 PM 20858780 ER PT J AU Bell, JF Johnson, ML Myers, K Patrick, DL AF Bell, Janice F. Johnson, M. Laura Myers, Kathleen Patrick, Donald L. TI Primary Health Care Quality in a National Sample of Children and Youth with Mental Health Impairment SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE quality of care; mental health impairment; Medical Expenditures Panel Survey; children; adolescents ID MEDICAL HOME; PSYCHIATRIC-DISORDERS; UNMET NEED; CENTERED CARE; SERVICES; ADOLESCENTS; DEPRESSION; PERFORMANCE; PREVALENCE; BARRIERS AB Objective: To examine the general pediatric health care quality experiences of children and youth with mental health impairment. Methods: We conducted a cross-sectional analysis of 2006 Medical Expenditures Panel Survey data for children and youth aged 5 to 17 years (n = 7263). Mental health impairment was defined using the recommended cut-point (score >= 16) on the parent version of the Columbia Impairment Scale. Health care quality was measured with the Consumer Assessment of Healthcare Providers and Systems including parent ratings in 3 domains: provider communication, getting needed care, and getting care quickly. Logistic regression was used to test associations between mental health impairment and dichotomized Consumer Assessment of Healthcare Providers and Systems measures (poor vs good quality) adjusted for demographic characteristics, health insurance, and socioeconomic status. Analysis was conducted with Stata, Version 10.1 SE, and all estimates accounted for the Medical Expenditures Panel Survey complex sampling design. Results: In multivariable analysis, health care experiences of children with mental health impairment (versus those without) were consistently rated less favorably by parents, with greater odds of inferior quality of care ratings in all domains: getting needed care (odds ratio [OR] = 2.35), getting care quickly (OR = 1.41), physician communication (OR = 1.72), and overall health care quality (OR = 1.63). Conclusions: Further research is needed to identify specific aspects of care that families find problematic in relation to the organization and delivery of care within each quality domain. Interventions are needed to improve service systems for children and youth with mental health impairment, especially to support access to needed care. C1 [Bell, Janice F.] Univ Washington, Dept Hlth Serv, Maternal & Child Hlth Program, Seattle, WA 98195 USA. [Bell, Janice F.; Patrick, Donald L.] Seattle Qual Life Grp, Dept Hlth Serv, Seattle, WA USA. [Johnson, M. Laura] Vet Affairs Puget Sound Hlth Care Syst, NW Ctr Excellence Hlth Serv Res & Dev, Seattle, WA USA. [Myers, Kathleen] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Myers, Kathleen] Childrens Hosp, Med Ctr, Seattle, WA USA. RP Bell, JF (reprint author), Univ Washington, Dept Hlth Serv, Maternal & Child Hlth Program, Box 357230, Seattle, WA 98195 USA. EM jfbell@u.washington.edu NR 51 TC 4 Z9 4 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD NOV-DEC PY 2010 VL 31 IS 9 BP 694 EP 704 DI 10.1097/DBP.0b013e3181f17b09 PG 11 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 675NV UT WOS:000283838300002 PM 21057254 ER PT J AU Just, AC Adibi, JJ Rundle, AG Calafat, AM Camann, D Hauser, R Silva, MJ Whyatt, RM AF Just, Allan C. Adibi, Jennifer J. Rundle, Andrew G. Calafat, Antonia M. Camann, Davide. Hauser, Russ Silva, Manori J. Whyatt, Robin M. TI Urinary and air phthalate concentrations and self-reported use of personal care products among minority pregnant women in New York city SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE DEP; DnBP; human biomonitoring; personal care products ID COSMETIC PRODUCTS; CONSUMER PRODUCTS; EXPOSURE; METABOLITES; HUMANS; INGREDIENTS; POPULATION; OUTCOMES; SAMPLES; HEALTH AB Diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) are used extensively in personal care products, including fragrances (DEP) and nail polish (DnBP). Between May 2003 and July 2006, we gathered questionnaire data on the use of seven product categories (deodorant, perfume, hair spray, hair gel, nail polish/polish remover, liquid soap/body wash, and lotion/mist) over 48 h during the third trimester of pregnancy from 186 inner-city women. A 48-h personal air sample was collected and analyzed for DEP and DnBP; a maternal spot urine sample was collected and analyzed for their monoester metabolites, monoethyl phthalate (MEP) and mono-n-butyl phthalate (MnBP), respectively. In all, 97% of air samples and 84% of urine samples were collected within +/- 2 days of the questionnaire. During the 48 h, 41% of women reported perfume use and 10% reported nail polish/polish remover use. In adjusted analyses, no association was seen between nail product use and air DnBP or urine MnBP concentrations. Women reporting perfume use had 2.3 times higher (95% CI 1.6, 3.3) urinary MEP concentrations. Personal air DEP increased by 7% for each 25% increase in a composite indicator of the six other product categories (P<0.05), but was not associated with perfume use. Air DEP was correlated with urine MEP concentrations only among non-perfume users (r = 0.51, P<0.001). Results suggest that perfume use is a significant source of DEP exposure. Journal of Exposure Science and Environmental Epidemiology (2010) 20, 625-633; doi:10.1038/jes.2010.13; published online 31 March 2010 C1 [Just, Allan C.; Rundle, Andrew G.; Whyatt, Robin M.] Columbia Univ, Mailman Sch Publ Hlth, Columbia Ctr Childrens Environm Hlth, New York, NY 10032 USA. [Adibi, Jennifer J.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Calafat, Antonia M.; Silva, Manori J.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Camann, Davide.] SW Res Inst, San Antonio, TX USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA USA. RP Just, AC (reprint author), Columbia Univ, Joseph L Mailman Sch Publ Hlth, Dept Environm Hlth Sci, 60 Haven Ave,B-109, New York, NY 10032 USA. EM acj2109@columbia.edu RI Rundle, Andrew/A-5282-2009; Adibi, Jennifer/I-8077-2016; OI Rundle, Andrew/0000-0003-0211-7707; Adibi, Jennifer/0000-0001-6562-8315; Just, Allan/0000-0003-4312-5957 FU National Institutes of Environmental Health Sciences (NIEHS) [R01 ES013543, R01 ES014393, R01 ES008977]; [P01 ES09600/EPA RD-8321] FX The authors gratefully acknowledge the contributions of many staff and participants at the Columbia Center for Children's Environmental Health and the technical assistance of Ella Samandar, James Preau, Jack Reidy, and others at the Centers for Disease Control and Prevention (CDC) in measuring the urinary concentrations of phthalate metabolites. This work was supported by Grants R01 ES013543, R01 ES014393, and R01 ES008977 from the National Institutes of Environmental Health Sciences (NIEHS), as well as P01 ES09600/EPA RD-8321. Doctoral training support for ACJ came from T32 ES07322 and TL1 RR024158. NR 28 TC 42 Z9 44 U1 1 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD NOV-DEC PY 2010 VL 20 IS 7 BP 625 EP 633 DI 10.1038/jes.2010.13 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 667CO UT WOS:000283170400009 PM 20354564 ER PT J AU Finley, EP Baker, M Pugh, MJ Peterson, A AF Finley, Erin P. Baker, Monty Pugh, Mary Jo Peterson, Alan TI Patterns and Perceptions of Intimate Partner Violence Committed by Returning Veterans with Post-Traumatic Stress Disorder SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Partner violence; Veterans; PTSD; Patterns of abuse; Trauma ID MENTAL-HEALTH PROBLEMS; PERITRAUMATIC DISSOCIATION; MILITARY VETERANS; VIETNAM VETERANS; COMBAT VETERANS; TRAUMA; IRAQ; WAR; AFGHANISTAN; SLEEP AB Data from a recent mixed-methods study conducted among Veterans of Iraq and Afghanistan diagnosed with Post-Traumatic Stress Disorder (PTSD) raise important questions regarding the occurrence of Intimate Partner Violence (IPV) in this population. Three case studies illustrate two main findings. First, Veterans and family members participating in the study described three patterns of partner violence-violence committed in anger; dissociative violence; and parasomniac/hypnopompic violence-suggesting that distinct patterns of IPV may emerge in relation to PTSD symptoms. Second, participants' descriptions suggest that common ideas about PTSD and war-related suffering can play an important role in influencing how Veterans and their partners respond to episodes of partner violence. It is important for those providing care to PTSD-diagnosed Veterans and their partners to understand when and how partner violence may occur, and how both parties may perceive and respond to it, in order to aid in developing appropriate plans for coping and safety-seeking. C1 [Finley, Erin P.] S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, VERDICT Res Unit 1IC6, San Antonio, TX 78229 USA. [Peterson, Alan] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Behav Med, STRONG STAR Multidisciplinary PTSD Res Consortium, San Antonio, TX 78229 USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, Dept Med Geriatr & Gerontol, San Antonio, TX 78229 USA. [Finley, Erin P.] Univ Texas Hlth Sci Ctr San Antonio, Div Clin Epidemiol, Dept Med, San Antonio, TX 78229 USA. [Finley, Erin P.; Pugh, Mary Jo] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX 78229 USA. RP Finley, EP (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, VERDICT Res Unit 1IC6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM finleye@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763; Finley, Erin/0000-0003-4497-7721 NR 39 TC 18 Z9 18 U1 4 U2 20 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD NOV PY 2010 VL 25 IS 8 BP 737 EP 743 DI 10.1007/s10896-010-9331-7 PG 7 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 679SR UT WOS:000284181600004 ER PT J AU Gordon, WJ Polansky, JM Boscardin, WJ Fung, KZ Steinman, MA AF Gordon, William J. Polansky, Jesse M. Boscardin, W. John Fung, Kathy Z. Steinman, Michael A. TI Coronary Risk Assessment by Point-Based vs. Equation-Based Framingham Models: Significant Implications for Clinical Care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med DE risk assessment; cholesterol; heart diseases; practice guidelines as topic; prognosis ID ISCHEMIC-HEART-DISEASE; TREATMENT PANEL-III; CARDIOVASCULAR RISK; PRIMARY PREVENTION; CHOLESTEROL; GUIDELINES; PREDICTION; STATINS; SCORE; RECLASSIFICATION AB BACKGROUND: US cholesterol guidelines use original and simplified versions of the Framingham model to estimate future coronary risk and thereby classify patients into risk groups with different treatment strategies. We sought to compare risk estimates and risk group classification generated by the original, complex Framingham model and the simplified, point-based version. METHODS: We assessed 2,543 subjects age 20-79 from the 2001-2006 National Health and Nutrition Examination Surveys (NHANES) for whom Adult Treatment Panel III (ATP-III) guidelines recommend formal risk stratification. For each subject, we calculated the 10-year risk of major coronary events using the original and point-based Framingham models, and then compared differences in these risk estimates and whether these differences would place subjects into different ATP-III risk groups (<10% risk, 10-20% risk. or >20% risk). Using standard procedures, all analyses were adjusted for survey weights, clustering, and stratification to make our results nationally representative. RESULTS: Among 39 million eligible adults, the original Framingham model categorized 71% of subjects as having "moderate" risk (<10% risk of a major coronary event in the next 10 years), 22% as having "moderately high" (10-20%) risk, and 7% as having "high" (>20%) risk. Estimates of coronary risk by the original and point-based models often differed substantially. The point-based system classified 15% of adults (5.7 million) into different risk groups than the original model, with 10% (3.9 million) misclassified into higher risk groups and 5% (1.8 million) into lower risk groups, for a net impact of classifying 2.1 million adults into higher risk groups. These risk group misclassifications would impact guideline-recommended drug treatment strategies for 25-46% of affected subjects. Patterns of misclassifications varied significantly by gender. age. and underlying CHD risk. CONCLUSIONS: Compared to the original Framingham model, the point-based version misclassifies millions of Americans into risk groups for which guidelines recommend different treatment strategies. C1 [Fung, Kathy Z.; Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Gordon, William J.] Weill Cornell Med Coll, New York, NY USA. [Gordon, William J.; Steinman, Michael A.] Med Student Training Aging Res Program, San Francisco, CA USA. [Polansky, Jesse M.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Boscardin, W. John; Fung, Kathy Z.; Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU NIA NIH HHS [K23 AG030999, K23-AG030999] NR 38 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2010 VL 25 IS 11 BP 1145 EP 1151 DI 10.1007/s11606-010-1454-2 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 672YN UT WOS:000283624000005 PM 20824362 ER PT J AU Ananthakrishnan, AN Hoffmann, RG Saeian, K AF Ananthakrishnan, Ashwin N. Hoffmann, Raymond G. Saeian, Kia TI Higher Physician Density is Associated with Lower Incidence of Late-stage Colorectal Cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colon cancer; colorectal cancer; physician supply; screening; incidence; physician density ID PRIMARY-CARE PHYSICIANS; SERVICES TASK-FORCE; FECAL OCCULT BLOOD; COLON-CANCER; SCREENING COLONOSCOPY; SOCIOECONOMIC-STATUS; FAMILY PHYSICIANS; UNITED-STATES; POPULATION; US AB INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer in the United States and a leading cause of cancer related mortality. Routine screening decreases incidence and mortality; however rates of screening remain low. Physician recommendation is a key determinant of screening rates; thus, physician availability may also influence CRC incidence and mortality. METHODS: Data on CRC incidence and stage at diagnosis was obtained for each county in Pennsylvania from the Pennsylvania cancer registry. Physician density (per 100,000 population) was calculated for each county using physician counts from the American Medical Association. Pearson correlation coefficients and linear regression models were used to examine the association between physician density and CRC incidence and outcomes. RESULTS: Primary care physician density (Pearson's correlation coefficient: -0.25, p=0.05) and gastroenterologist density (correlation coefficient -0.25, p=0.04) inversely correlated with county-level incidence of late-stage CRC. However, this association was seen only in non-metropolitan counties or those with low population density. On linear regression, non-metropolitan counties which had a high density of gastroenterologists had an incidence of late-stage CRC that was lower by 4/100,000 (reduction of 14%). Low population density counties had lower incidence of late-stage CRC by 5/100,000 (reduction of 17%) when they had at least 3.3 gastroenterologists/100,000 population compared to counties with a lower gastroenterologist-per-population ratio. Gastroenterologist density did not correlate with reduced late-stage CRC incidence prior to institution of Medicare coverage for colonoscopy for routine CRC screening. CONCLUSION: Higher gastroenterologist or PCP density is associated with 14-17% lower incidence of late-stage CRC in non-metropolitan counties or those with low population density. Efforts at increasing physician supply should target these underserved areas. C1 [Ananthakrishnan, Ashwin N.; Saeian, Kia] Med Coll Wisconsin, Div Gastroenterol & Hepatol, Milwaukee, WI 53226 USA. [Hoffmann, Raymond G.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 165 Cambridge St, Boston, MA 02114 USA. EM aananthakrishnan@partners.org NR 45 TC 20 Z9 20 U1 1 U2 3 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 NOV PY 2010 VL 25 IS 11 BP 1164 EP 1171 DI 10.1007/s11606-010-1457-z PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 672YN UT WOS:000283624000008 PM 20658268 ER PT J AU Percac-Lima, S Aldrich, LS Gamba, GB Bearse, AM Atlas, SJ AF Percac-Lima, Sonja Aldrich, Leslie S. Gamba, Gloria B. Bearse, Adriana M. Atlas, Steven J. TI Barriers to Follow-Up of an Abnormal Pap Smear in Latina Women Referred for Colposcopy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colposeopy; Latino; health disparities; patient navigation ID INCOME MINORITY WOMEN; CERVICAL-CANCER; PAPANICOLAOU SMEARS; EDUCATIONAL BROCHURES; UNDERSERVED WOMEN; HISPANIC WOMEN; HPV VACCINE; ADHERENCE; KNOWLEDGE; RISK AB BACKGROUND: Lower rates of follow-up after an abnormal Pap smear in racial and ethnic minorities may contribute to the higher incidence and mortality rates of cervical cancer seen in these groups. OBJECTIVE: To identify patient-perceived barriers to follow-up after an abnormal Pap smear result among Latina women. DESIGN, PARTICIPANTS AND APPROACH: Qualitative, semi-structured, one-on-one interviews were conducted with patients from an academic hospital-affiliated urban community health center. Three groups of women were interviewed: new colposcopy clinic patients, patients who had previous colposcopies and patients enrolled in the health center's patient navigator program. Open-ended questions explored their knowledge, beliefs and experiences with colposcopy. Content analysis of transcripts was performed using established qualitative techinques. RESULTS: Of 40 Latina women recruited, 75% spoke only Spanish. The average age was 31.5 (range 18-55). Personal and system barriers identified were categorized into four themes: (1) anxiety/fear of procedure and diagnosis; (2) scheduling/availability of appointments interfering with work and/or child care: (3) inadequate communication about appointments, including lack of explanation regarding diagnosis, procedure and results; and (4) pain. New patients more commonly reported problems with scheduling and communication. Followup patients were more concerned about pain, and navigated women most often reported fear of results but had fewer concerns about inadequate communication. CONCLUSION: Anxiety/fear was the most common personal barrier, while difficulty scheduling appointments and inadequate communication were the major systems barriers identified in these Latina women. Interventions to lower these barriers to colposcopy among Latina women may increase adherence to follow-up of abnormal Pap smears. C1 [Percac-Lima, Sonja; Gamba, Gloria B.] Massachusetts Gen Hosp, Chelsea HealthCare Cter, Chelsea, MA 02150 USA. [Percac-Lima, Sonja; Aldrich, Leslie S.; Gamba, Gloria B.; Bearse, Adriana M.] Massachusetts Gen Hosp, Ctr Community Hlth Improvement, Boston, MA 02114 USA. [Percac-Lima, Sonja; Atlas, Steven J.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Percac-Lima, Sonja; Atlas, Steven J.] Harvard Univ, Sch Med, Boston, MA USA. RP Percac-Lima, S (reprint author), Massachusetts Gen Hosp, Chelsea HealthCare Cter, 151 Everett Ave, Chelsea, MA 02150 USA. EM spercaclima@partners.org FU Gillette Corporation; MGH Center for Community Health Improvement; Agency for Healthcare Research and Quality [1R18 HS019161-01] FX The study was funded by a grant from Gillette Corporation to the MGH Chelsea Cervical Outreach Program and the MGH Center for Community Health Improvement. Drs. Percac-Lima and Atlas were supported in part by a grant from the Agency for Healthcare Research and Quality (1R18 HS019161-01). NR 38 TC 23 Z9 24 U1 1 U2 8 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 NOV PY 2010 VL 25 IS 11 BP 1198 EP 1204 DI 10.1007/s11606-010-1450-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 672YN UT WOS:000283624000013 PM 20652647 ER PT J AU Rosman, AS Korsten, MA AF Rosman, Alan S. Korsten, Mark A. TI Effect of Verification Bias on the Sensitivity of Fecal Occult Blood Testing: a Meta-Analysis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE fecal occult blood; guaiac; colorectal cancer; summary receiver operating characteristic curve: meta-analysis ID DIAGNOSTIC-TEST ACCURACY; AVERAGE-RISK POPULATION; COLORECTAL-CANCER; SYSTEMATIC REVIEWS; PROSPECTIVE MULTICENTER; SYMPTOMATIC PATIENTS; IMMUNOCHEMICAL TEST; HEMOCCULT TEST; TOTAL COLONOSCOPY; AMERICAN-COLLEGE AB OBJECTIVES: There is controversy regarding the sensitivity of fecal occult blood tests (FOBT) for detecting colorectal cancer. Many of the published studies failed to correct for verification bias which may have increased the sensitivity. METHODS: A meta-analysis of published studies evaluating the sensitivity and specificity of chemical-based FOBT for colorectal cancer was performed. Studies were included if both cancer and control subjects underwent confirmatory testing. We also included studies that attempted to correct for verification bias by either performing colonoscopy on all subjects regardless of the FOBT result or by using longitudinal follow-up. We then compared the sensitivity, specificity, and other diagnostic characteristics of the studies that attempted to correct for verification (n=10) vs. those that did not correct for this bias (n=19). RESULTS: The pooled sensitivity of guaiac-based FOBT for colorectal cancer of studies without verification bias was significantly lower than those studies with this bias [0.36 (95% CI 0.25-0.47) vs. 0.70 (95% CI 0.60-0.80), p=0.0011. The pooled specificity of the studies without verification bias was higher [0.96 (95% CI 0.94-0.97) vs. 0.88 (95% CI 0.84-0.91), p<0.005]. There was no significant difference in the area under the summary receiver operating characteristic curves. More sensitive chemical-based FOBT methods (e.g., Hemoccult (R) SENSA (R)) had a higher sensitivity but a lower specificity than standard guaiac methods. CONCLUSIONS: The sensitivity of guaiac-based FOBT for colorectal cancer has been overestimated as a result of verification bias. This test may not be sensitive enough to serve as an effective screening option for colorectal cancer. C1 [Rosman, Alan S.; Korsten, Mark A.] James J Peters Vet Affairs Med Ctr, Gastroenterol Sect, Bronx, NY 10468 USA. [Rosman, Alan S.; Korsten, Mark A.] James J Peters Vet Affairs Med Ctr, Program Med, Bronx, NY 10468 USA. [Rosman, Alan S.; Korsten, Mark A.] Mt Sinai Sch Med NYU, New York, NY USA. RP Rosman, AS (reprint author), James J Peters Vet Affairs Med Ctr, Gastroenterol Sect, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Alan.Rosman@VA.Gov FU Department of Veterans Affairs FX Funding Source: Department of Veterans Affairs. NR 74 TC 12 Z9 12 U1 0 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 NOV PY 2010 VL 25 IS 11 BP 1211 EP 1221 DI 10.1007/s11606-010-1375-0 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 672YN UT WOS:000283624000015 PM 20499198 ER PT J AU Widera, E Chang, A Chen, HL AF Widera, Eric Chang, Anna Chen, Helen L. TI Presenteeism: A Public Health Hazard SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE presenteeism; infection control; norovirus; long-term care; outbreak ID SICKNESS PRESENTEEISM; CARE WORKERS; INFLUENZA VACCINE; OUTBREAK; INFECTION; NOROVIRUS; IMPACT; STAFF; COST; GASTROENTERITIS AB "Presenteeism" occurs when an employee goes to work despite a medical illness that will prevent him or her from fully functioning at work. This problem has been well studied in the business and social science literature, and carries increased importance in the health care setting due to the risk of infectious disease transmission in vulnerable patient populations. In this manuscript, we discuss an outbreak of viral gastroenteritis in a long-term care facility and the role presenteeism played in disease transmission and extension of the outbreak. We use existing literature to point out the hazards of presenteeism in the health care sector. We will also discuss factors that may be involved in the decision to work while ill and propose policy changes that may reduce the incidence of presenteeism in health care organizations. C1 [Widera, Eric] VA Med Ctr 181G, San Francisco, CA 94121 USA. [Widera, Eric; Chang, Anna; Chen, Helen L.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Widera, Eric; Chang, Anna] San Francisco VA Med Ctr, San Francisco, CA USA. [Chen, Helen L.] Ctr Elders Independence, Oakland, CA USA. RP Widera, E (reprint author), VA Med Ctr 181G, 4150 Clement St, San Francisco, CA 94121 USA. EM Eric.Widera@ucsf.edu FU Health Resources and Services Administration FX Dr. Widera has received funding support from a Geriatrics Academic Career Award from the Health Resources and Services Administration. Dr. Chen has received funding support from a Geriatrics Education Center Grant from the Health Resources and Services Administration. NR 40 TC 34 Z9 38 U1 3 U2 23 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 NOV PY 2010 VL 25 IS 11 BP 1244 EP 1247 DI 10.1007/s11606-010-1422-x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 672YN UT WOS:000283624000021 PM 20549378 ER PT J AU Ring, D AF Ring, David TI Commentary: The World Health Organization's International Classification of Functioning, Disability and Health: Invaluable Framework, Questionable Research Tool SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkee Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkee Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 2 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 2010 VL 35A IS 11 BP 1806 EP 1806 DI 10.1016/j.jhsa.2010.07.025 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 677XZ UT WOS:000284031400010 PM 21050963 ER PT J AU Osborn, CY Amico, KR Fisher, WA Egede, LE Fisher, JD AF Osborn, Chandra Y. Amico, K. Rivet Fisher, William A. Egede, Leonard E. Fisher, Jeffrey D. TI An Information-Motivation-Behavioral Skills Analysis of Diet and Exercise Behavior in Puerto Ricans with Diabetes SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE behavior; diabetes; glycemic control; Information-Motivation-Behavioral Skills (IMB) model; Puerto Rican ID AIDS-PREVENTIVE BEHAVIOR; PHYSICAL-ACTIVITY; ANTIRETROVIRAL THERAPY; GLYCEMIC CONTROL; HEALTH-BEHAVIOR; RISK BEHAVIOR; MODEL; INTERVENTION; CARE; ADHERENCE AB Frameworks are needed to inform diabetes self-care programs for diverse populations. We tested the Information-Motivation-Behavioral Skills (IMB) model in a sample of Puerto Ricans with Type 2 diabetes (N = 118). Structural equation models evaluated model fit and interrelations between IMB constructs. For diet behavior, information and motivation related to behavioral skills (r = 0.19, p < .05 and r = 0.39, p < .01, respectively); behavioral skills related to behavior (r = 0.42, p < .01 and r = 0.32, p < .05); and behavior related to glycemic control (r = -0.26, p < .05). For exercise, personal motivation related to behavioral skills (r = 0.53, p < .001), and behavioral skills related to behavior (r = 0.45, p < .001). The IMB model could inform interventions targeting these behaviors in diabetes. C1 [Osborn, Chandra Y.] Vanderbilt Univ, Sch Med, Vanderbilt Ctr Hlth Serv Res, Div Gen Internal Med & Publ Hlth, Nashville, TN 37232 USA. [Amico, K. Rivet; Fisher, Jeffrey D.] Univ Connecticut, Ctr Hlth Intervent & Prevent, Storrs, CT 06269 USA. [Fisher, William A.] Univ Western Ontario, Dept Psychol, London, ON N6A 3K7, Canada. [Fisher, William A.] Univ Western Ontario, Dept Obstet & Gynecol, London, ON N6A 3K7, Canada. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Osborn, CY (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Ctr Hlth Serv Res, Div Gen Internal Med & Publ Hlth, 1215 21st Ave S,Suite 6000,MCE N Tower, Nashville, TN 37232 USA. EM chandra.osborn@vanderbilt.edu FU NIDDK NIH HHS [F31 DK067022-01, P60 DK020593-30S2, P60 DK020593, F31 DK067022-02, F31 DK067022] NR 48 TC 13 Z9 13 U1 5 U2 16 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD NOV PY 2010 VL 15 IS 8 BP 1201 EP 1213 DI 10.1177/1359105310364173 PG 13 WC Psychology, Clinical SC Psychology GA 675RG UT WOS:000283847600008 PM 20453056 ER PT J AU Warshaw, AL AF Warshaw, Andrew L. TI Distal pancreatectomy with preservation of the spleen SO JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES LA English DT Article DE Distal pancreatectomy; Splenic preservation; Splenectomy ID SPLENIC ARTERY; CHRONIC-PANCREATITIS; PRESERVING PANCREATECTOMY; SPLENECTOMY; VEIN; MORTALITY; CIRCULATION; RESECTION; EXCISION; RISK AB Distal pancreatectomy (resection of the pancreatic body and tail) can be performed with or without preservation of the spleen. Splenic preservation has the advantages of fewer postoperative complications such as abscesses in the resection bed, shorter length of hospitalization, and avoidance of the long-term risk of post-splenectomy sepsis related to encapsulated bacteria. Two techniques can be used to save the spleen: either by dissecting out the splenic artery and vein with division of the arterial and venous branches between the pancreas and the splenic artery and vein; or by resecting the splenic artery and vein along with the pancreas but with careful preservation of the vascular collaterals in the splenic hilum, which allows the spleen to survive on the short gastric vessels (Warshaw technique). The latter method has been shown to be associated with a shorter operation, less blood loss, and a shorter hospitalization. In general the Warshaw technique is easier, especially for laparoscopic pancreatectomy. The subsequent appearance of enlarged gastric veins (varices) is to be expected as a consequence of loss of the splenic vein but has not led to bleeding from these natural collaterals during long-term follow up. C1 [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Warshaw, Andrew L.] Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT506, Boston, MA 02114 USA. EM awarshaw@partners.org NR 23 TC 42 Z9 49 U1 0 U2 6 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1868-6974 J9 J HEPATO-BIL-PAN SCI JI J. Hepato-Biliary-Pancreat. Sci. PD NOV PY 2010 VL 17 IS 6 BP 808 EP 812 DI 10.1007/s00534-009-0226-z PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 642TJ UT WOS:000281241000013 PM 19882099 ER PT J AU Lee, HH Meyer, EH Goya, S Pichavant, M Kim, HY Bu, X Umetsu, SE Jones, JC Savage, PB Iwakura, Y Casasnovas, JM Kaplan, G Freeman, GJ DeKruyff, RH Umetsu, DT AF Lee, Hyun-Hee Meyer, Everett H. Goya, Sho Pichavant, Muriel Kim, Hye Young Bu, Xia Umetsu, Sarah E. Jones, Jennifer C. Savage, Paul B. Iwakura, Yoichiro Casasnovas, Jose M. Kaplan, Gerardo Freeman, Gordon J. DeKruyff, Rosemarie H. Umetsu, Dale T. TI Apoptotic Cells Activate NKT Cells through T Cell Ig-Like Mucin-Like-1 Resulting in Airway Hyperreactivity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEPATITIS-A VIRUS; MUCIN-DOMAIN; KOREAN POPULATION; ALLERGIC DISEASES; EXON-4 VARIATIONS; EPITHELIAL-CELLS; DENDRITIC CELLS; TIM-1 GENE; PHOSPHATIDYLSERINE; ASTHMA AB T cell Ig-like mucin-like-1 (TIM-1) is an important asthma susceptibility gene, but the immunological mechanisms by which TIM-1 functions remain uncertain. TIM-1 is also a receptor for phosphatidylserine (PtdSer), an important marker of cells undergoing programmed cell death, or apoptosis. We now demonstrate that NKT cells constitutively express TIM-1 and become activated by apoptotic cells expressing PtdSer. TIM-1 recognition of PtdSer induced NKT cell activation, proliferation, and cytokine production. Moreover, the induction of apoptosis in airway epithelial cells activated pulmonary NKT cells and unexpectedly resulted in airway hyperreactivity, a cardinal feature of asthma, in an NKT cell-dependent and TIM-1-dependent fashion. These results suggest that TIM-1 serves as a pattern recognition receptor on NKT cells that senses PtdSer on apoptotic cells as a damage-associated molecular pattern. Furthermore, these results provide evidence for a novel innate pathway that results in airway hyperreactivity and may help to explain how TIM-1 and NKT cells regulate asthma. The Journal of Immunology, 2010, 185: 5225-5235. C1 [Lee, Hyun-Hee; Pichavant, Muriel; Kim, Hye Young; Umetsu, Sarah E.; DeKruyff, Rosemarie H.; Umetsu, Dale T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Karp Labs,Div Immunol & Allergy,Dept Pediat, Boston, MA 02115 USA. [Bu, Xia; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bu, Xia; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Meyer, Everett H.; Jones, Jennifer C.] Stanford Univ, Stanford, CA 94305 USA. [Goya, Sho] Osaka Univ, Grad Sch Med, Dept Resp Med Allergy & Rheumat Dis, Suita, Osaka 5650871, Japan. [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo, Japan. [Savage, Paul B.] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. [Casasnovas, Jose M.] Consejo Super Invest Cient, Ctr Nacl Biotecnol, Madrid 28049, Spain. [Kaplan, Gerardo] US FDA, Ctr Biol Res & Evaluat, Bethesda, MD 20892 USA. RP Umetsu, DT (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Karp Labs,Div Immunol & Allergy,Dept Pediat, Room 10127,1 Blackfan Circle, Boston, MA 02115 USA. EM dale.umetsu@childrens.harvard.edu RI Iwakura, Yoichiro/E-5457-2011; Casasnovas, Jose/L-6299-2014; Jones, Jennifer/C-8691-2015 OI Iwakura, Yoichiro/0000-0002-9934-5775; Casasnovas, Jose/0000-0002-2873-6410; Jones, Jennifer/0000-0002-9488-7719 FU National Institutes of Health [R01HL62348, RO1AI02632, PO1AI05546]; American Lung Association; Bunning Food Allergy Project; Harvard Digestive Diseases Center Imaging Core [DK-034854] FX This work was supported by National Institutes of Health Grants R01HL62348, RO1AI02632, and PO1AI05546; by a fellowship from the American Lung Association; by an award from the Bunning Food Allergy Project; and by Harvard Digestive Diseases Center Imaging Core Grant B, DK-034854. NR 69 TC 37 Z9 41 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 NOV 1 PY 2010 VL 185 IS 9 BP 5225 EP 5235 DI 10.4049/jimmunol.1001116 PG 11 WC Immunology SC Immunology GA 668DL UT WOS:000283248700036 PM 20889552 ER PT J AU Chen, M Lam, BK Luster, AD Zarini, S Murphy, RC Bair, AM Soberman, RJ Lee, DM AF Chen, Mei Lam, Bing K. Luster, Andrew D. Zarini, Simona Murphy, Robert C. Bair, Angela M. Soberman, Roy J. Lee, David M. TI Joint Tissues Amplify Inflammation and Alter Their Invasive Behavior via Leukotriene B-4 in Experimental Inflammatory Arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-ENDOTHELIAL CELLS; RHEUMATOID-ARTHRITIS; TRANSCELLULAR BIOSYNTHESIS; CYSTEINYL LEUKOTRIENES; MAST-CELLS; IN-VIVO; 5-LIPOXYGENASE-ACTIVATING PROTEIN; SYNOVIAL FIBROBLASTS; HUMAN-ERYTHROCYTES; A(4) HYDROLASE AB Mechanisms by which mesenchymal-derived tissue lineages participate in amplifying and perpetuating synovial inflammation in arthritis have been relatively underinvestigated and are therefore poorly understood. Elucidating these processes is likely to provide new insights into the pathogenesis of multiple diseases. Leukotriene B-4 (LTB4) is a potent proinflammatory lipid mediator that initiates and amplifies synovial inflammation in the K/BxN model of arthritis. We sought to elucidate mechanisms by which mesenchymal-derived fibroblast-like synoviocytes (FLSs) perpetuate synovial inflammation. We focused on the abilities of FLSs to contribute to LTB4 synthesis and to respond to LTB4 within the joint. Using a series of bone marrow chimeras generated from 5-lipoxygenase(-/-) and leukotriene A(4) (LTA(4)) hydrolase(-/-) mice, we demonstrate that FLSs generate sufficient levels of LTB4 production through transcellular metabolism in K/BxN serum-induced arthritis to drive inflammatory arthritis. FLSs-which comprise the predominant lineage populating the synovial lining-are competent to metabolize exogenous LTA(4) into LTB4 ex vivo. Stimulation of FLSs with TNF increased their capacity to generate LTB4 3-fold without inducing the expression of LTA(4) hydrolase protein. Moreover, LTB4 (acting via LTB4 receptor 1) was found to modulate the migratory and invasive activity of FLSs in vitro and also promote joint erosion by pannus tissue in vivo. Our results identify novel roles for FLSs and LTB4 in joints, placing LTB4 regulation of FLS biology at the center of a previously unrecognized amplification loop for synovial inflammation and tissue pathology. The Journal of Immunology, 2010, 185: 5503-5511. C1 [Chen, Mei; Lam, Bing K.; Lee, David M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Chen, Mei; Lam, Bing K.; Lee, David M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Charlestown, MA 02129 USA. [Bair, Angela M.; Soberman, Roy J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit,Dept Med, Charlestown, MA 02129 USA. [Zarini, Simona; Murphy, Robert C.] Univ Colorado Denver, Dept Pharmacol, Aurora, CO 80045 USA. [Zarini, Simona; Murphy, Robert C.] Hlth Sci Ctr, Aurora, CO 80045 USA. RP Lee, DM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, 1 Jimmy Fund Way,Smith Bldg, Boston, MA 02115 USA. EM dlee@rics.bwh.harvard.edu FU National Arthritis Research Foundation; National Institutes of Health [P01-AI-065858-01, R01 AI-068871, R01 DK74821, R01 AI-050892]; Cogan Family Foundation FX This work was supported by grants from the National Arthritis Research Foundation (to M.C.), National Institutes of Health (P01-AI-065858-01 to D.M.L., R01 AI-068871 to R.J.S. and A.M.B., R01 DK74821 to R.J.S., and R01 AI-050892 to A.D.L.), and the Cogan Family Foundation (to D.M.L.). NR 64 TC 11 Z9 11 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2010 VL 185 IS 9 BP 5503 EP 5511 DI 10.4049/jimmunol.1001258 PG 9 WC Immunology SC Immunology GA 668DL UT WOS:000283248700064 PM 20876351 ER PT J AU Gardet, A Benita, Y Li, C Sands, BE Ballester, I Stevens, C Korzenik, JR Rioux, JD Daly, MJ Xavier, RJ Podolsky, DK AF Gardet, Agnes Benita, Yair Li, Chun Sands, Bruce E. Ballester, Isabel Stevens, Christine Korzenik, Joshua R. Rioux, John D. Daly, Mark J. Xavier, Ramnik J. Podolsky, Daniel K. TI LRRK2 Is Involved in the IFN-gamma Response and Host Response to Pathogens SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; SEVERE CROHNS-DISEASE; PARKINSONS-DISEASE; INTERFERON-GAMMA; KINASE-ACTIVITY; INTESTINAL-MUCOSA; EXPRESSION; MUTATIONS; CELLS AB LRRK2 was previously identified as a defective gene in Parkinson's disease, and it is also located in a risk region for Crohn's disease. In this study, we aim to determine whether LRRK2 could be involved in immune responses. We show that LRRK2 expression is enriched in human immune cells. LRRK2 is an IFN-gamma target gene, and its expression increased in intestinal tissues upon Crohn's disease inflammation. In inflamed intestinal tissues, LRRK2 is detected in the lamina propria macrophages, B-lymphocytes, and CD103-positive dendritic cells. Furthermore, LRRK2 expression enhances NF-kappa B-dependent transcription, suggesting its role in immune response signaling. Endogenous LRRK2 rapidly translocates near bacterial membranes, and knockdown of LRRK2 interferes with reactive oxygen species production during phagocytosis and bacterial killing. These observations indicate that LRRK2 is an IFN-gamma target gene, and it might be involved in signaling pathways relevant to Crohn's disease pathogenesis. The Journal of Immunology, 2010, 185: 5577-5585. C1 [Podolsky, Daniel K.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Gardet, Agnes; Benita, Yair; Li, Chun; Sands, Bruce E.; Ballester, Isabel; Korzenik, Joshua R.; Xavier, Ramnik J.; Podolsky, Daniel K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Gardet, Agnes; Benita, Yair; Li, Chun; Sands, Bruce E.; Ballester, Isabel; Korzenik, Joshua R.; Xavier, Ramnik J.; Podolsky, Daniel K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Benita, Yair; Li, Chun; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Stevens, Christine; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Stevens, Christine; Daly, Mark J.; Xavier, Ramnik J.] MIT, Broad Inst, Cambridge, MA 02141 USA. [Stevens, Christine; Daly, Mark J.] Harvard Univ, Cambridge, MA 02141 USA. [Rioux, John D.] Univ Montreal, Montreal, PQ, Canada. [Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. RP Podolsky, DK (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM xavier@molbio.mgh.harvard.edu; daniel.podolsky@utsouthwestern.edu RI Benita, Yair/E-3094-2012; Rioux, John/A-9599-2015 OI Rioux, John/0000-0001-7560-8326 FU National Institutes of Health [AI062773, DK83756, DK060049, DK043351]; La Fondation pour la Recherche Medicale; Crohn's and Colitis Foundation of America FX This work was supported by National Institutes of Health Grants AI062773 and DK83756 (to R.J.X.) and DK060049 and DK043351 (to D.K.P.). A.G. was supported by fellowships from La Fondation pour la Recherche Medicale and the Crohn's and Colitis Foundation of America. NR 44 TC 105 Z9 105 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2010 VL 185 IS 9 BP 5577 EP 5585 DI 10.4049/jimmunol.1000548 PG 9 WC Immunology SC Immunology GA 668DL UT WOS:000283248700072 PM 20921534 ER PT J AU Wiernik, PH Dutcher, JP Yao, XP Venkatraj, U Falkson, CI Rowe, JM Cassileth, PA AF Wiernik, Peter H. Dutcher, Janice P. Yao, Xiapan Venkatraj, Usha Falkson, Carla I. Rowe, Jacob M. Cassileth, Peter A. TI Phase II Study of Interleukin-4 in Indolent B-cell Non-Hodgkin Lymphoma and B-cell Chronic Lymphocytic Leukemia: A Study of the Eastern Cooperative Oncology Group (E5Y92) SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE interleukin-4; interleukin-6; low-grade lymphoma; chronic lymphocytic leukemia ID RECOMBINANT HUMAN INTERLEUKIN-4; IL-4; THERAPY; TRIAL; TOXICITY; CANCER AB Recombinant interleukin (IL)-4, 5 mu g/kg thrice weekly for 3 weeks followed by a 2-week rest period (1 cycle) was administered to 32 eligible previously treated B-cell chronic lymphocytic leukemia (7 patients) or low-grade B-cell lymphoma patients (25 patients). Two cycles were given before response was evaluated. IL-6 serum levels were evaluated before therapy in all patients and at 12 weeks on study in 7 patients. None of the chronic lymphocytic leukemia patients responded. A partial response was observed in 3 lymphoma patients of 1.2, 3.0, and 3.5 months' duration and stable disease (median 1.5mo) was observed in another 7 lymphoma patients. The median survival from registration on study was 29.7 months with 7 patients alive at the time of analysis for a median follow-up of 72.8 months. Toxicity was generally mild with no grade 4 nonhematologic toxicity observed. Recombinant IL-4 treatment was well tolerated in this study but had minimal antitumor activity. C1 [Wiernik, Peter H.; Dutcher, Janice P.; Venkatraj, Usha] New York Med Coll, Valhalla, NY 10595 USA. [Wiernik, Peter H.; Dutcher, Janice P.; Yao, Xiapan; Venkatraj, Usha; Falkson, Carla I.; Rowe, Jacob M.; Cassileth, Peter A.] Eastern Cooperat Grp, Cambridge, England. [Yao, Xiapan] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Falkson, Carla I.] Univ Alabama, Birmingham, AL USA. [Cassileth, Peter A.] Univ Miami, Sylvester Canc Ctr, Miami, FL USA. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. RP Dutcher, JP (reprint author), Montefiore Med Ctr N Div, Ctr Canc, 600 E 233rd St, Bronx, NY 10466 USA. EM Jpd4401@aol.com FU National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA14958, CA17145]; Department of Health and Human Services FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA14958, and CA17145 from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 20 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2010 VL 33 IS 9 BP 1006 EP 1009 DI 10.1097/CJI.0b013e3181f5dfc5 PG 4 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 671HS UT WOS:000283492300010 PM 20948435 ER PT J AU Lederman, MM Alter, G Daskalakis, DC Rodriguez, B Sieg, SF Hardy, G Cho, M Anthony, D Harding, C Weinberg, A Silverman, RH Douek, DC Margolis, L Goldstein, DB Carrington, M Goedert, JJ AF Lederman, Michael M. Alter, Galit Daskalakis, Demetre C. Rodriguez, Benigno Sieg, Scott F. Hardy, Gareth Cho, Michael Anthony, Donald Harding, Clifford Weinberg, Aaron Silverman, Robert H. Douek, Daniel C. Margolis, Leonid Goldstein, David B. Carrington, Mary Goedert, James J. TI Determinants of Protection among HIV-Exposed Seronegative Persons: An Overview SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Symposium on Natural Immunity to HIV CY NOV 15-17, 2009 CL Winnipeg, CANADA ID SIMIAN IMMUNODEFICIENCY VIRUS; KENYAN SEX WORKERS; DISEASE PROGRESSION; TYPE-1 INFECTION; T-CELLS; VAGINAL TRANSMISSION; GENETIC-VARIATION; BOOSTING REGIMEN; RESISTANCE; SUSCEPTIBILITY AB Both clinical experience and a growing medical literature indicate that some persons who have been exposed to human immunodeficiency virus (HIV) infection remain uninfected. Although in some instances this may represent good fortune, cohorts of uninfected persons have been reported who are considered at high risk for infection. In these cohorts a variety of characteristics have been proposed as mediating protection, but to date only the 32-base pair deletion in the chemokine (C-C motif) receptor 5 gene, which results in complete failure of cell surface expression of this coreceptor, has been associated with high-level protection from HIV infection. With this in mind, there are probably many other factors that may individually or in combination provide some level of protection from acquisition of HIV infection. Because some of these factors are probably incompletely protective or inconsistently active, identifying them with confidence will be difficult. Nonetheless, clarifying the determinants of protection against HIV infection is a high priority that will require careful selection of high-risk uninfected cohorts, who should undergo targeted studies of plausible mediators and broad screening for unexpected determinants of protection. C1 [Lederman, Michael M.; Rodriguez, Benigno; Sieg, Scott F.; Hardy, Gareth; Anthony, Donald; Harding, Clifford] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, Ctr AIDS Res, Cleveland, OH 44106 USA. [Weinberg, Aaron] Case Western Reserve Univ, Sch Dent, Cleveland, OH 44106 USA. [Silverman, Robert H.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA. [Alter, Galit] Harvard Univ, Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02115 USA. [Daskalakis, Demetre C.] NYU, Sch Med, Div Infect Dis & Immunol, New York, NY USA. [Cho, Michael] Iowa State Univ, Coll Vet Med, Ames, IA USA. [Douek, Daniel C.] Natl Inst Allergy Immunol & Infect Dis, Human Immunol Sect, Vaccine Res Ctr, Bethesda, MD USA. [Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, NIH, Bethesda, MD 20892 USA. [Carrington, Mary] NCI, Expt Immunol Lab, SAIC Frederick, NIH, Frederick, MD 21701 USA. [Goldstein, David B.] Duke Univ, Inst Genome Sci & Policy, Ctr Human Genome Variat, Durham, NC USA. RP Lederman, MM (reprint author), Case Western Reserve Univ, 2061 Cornell Rd, Cleveland, OH 44106 USA. EM MXL6@case.edu RI Rodriguez, Benigno/C-3365-2009 OI Rodriguez, Benigno/0000-0001-9736-7957 FU Center for AIDS Research at Case Western Reserve University, University Hospitals / Case Medical Center [AI -36219]; Bill and Melinda Gates Foundation; University of Manitoba FX Center for AIDS Research at Case Western Reserve University, University Hospitals / Case Medical Center (grant AI -36219).; This article is part of a supplement entitled "Natural Immunity to HIV-1 Infection," sponsored by the Bill and Melinda Gates Foundation and the University of Manitoba. NR 54 TC 29 Z9 30 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2010 VL 202 SU 3 BP S333 EP S338 DI 10.1086/655967 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 656VK UT WOS:000282369000003 PM 20887220 ER PT J AU Chi, WY Enshell-Seijffers, D Morgan, BA AF Chi, Woo Y. Enshell-Seijffers, David Morgan, Bruce A. TI De Novo Production of Dermal Papilla Cells during the Anagen Phase of the Hair Cycle SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID CYTOKINETIC DYNAMICS; FOLLICLE MESENCHYME; GROWTH-CONTROL; PLASTICITY; INDUCTION; MATRIX; VOLUME C1 [Chi, Woo Y.; Enshell-Seijffers, David; Morgan, Bruce A.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Chi, Woo Y.; Enshell-Seijffers, David; Morgan, Bruce A.] Massachusetts Gen Hosp, Cutaneous Biol Res Dept, Boston, MA 02114 USA. RP Chi, WY (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu OI Enshell-Seijffers, David/0000-0002-8228-2659 FU NIAMS NIH HHS [5R01AR055256, 5T32AR007098-35, R01 AR052339, R01 AR052339-03, T32 AR007098, 5R01AR052339, R01 AR055256-03, R01 AR055256] NR 14 TC 23 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2010 VL 130 IS 11 BP 2664 EP 2666 DI 10.1038/jid.2010.176 PG 3 WC Dermatology SC Dermatology GA 664MC UT WOS:000282963600020 PM 20574444 ER PT J AU Zorzi, P Aplin, AC Smith, KD Nicosia, RF AF Zorzi, Penelope Aplin, Alfred C. Smith, Kelly D. Nicosia, Roberto F. TI The rat aorta contains resident mononuclear phagocytes with proliferative capacity and proangiogenic properties SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE M-CSF; GM-CSF; IL-4; MHC II; dendritic cells; aortic ring; collagen ID MULTINUCLEATED GIANT-CELLS; ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; MACROPHAGE ACCUMULATION; INFLAMMATORY CYTOKINES; VESSEL FORMATION; DENDRITIC CELLS; ADIPOSE-TISSUE; IN-VITRO; ANGIOGENESIS AB Angiogenesis in the aortic ring model is preceded by activation of the immune system and impaired by ablation of adventitial macrophages. Treatment of aortic cultures with M-CSF induced extensive periaortic outgrowth of CD45(+) CD68(+) mononuclear cells with ultrastructural features of macrophages and DCs. Periaortic lysis of collagen caused many CD45(+) CD68(+) cells to attach to the bottom of the culture dish. Lifting the collagen gels left behind patches of CD45(+) CD68(+) cells, which focally organized into branching cords. These cells also expressed CD14, CD169, F4/80, and alpha-SMA but not CD31, vWF, desmin, or CD163. DNA synthesis studies showed that M-CSF-stimulated cells were actively proliferating. Aortic patch cells showed phagocytic properties and responded to IL-4 and GM-CSF by expressing MHC II, differentiating into DCs, and forming multinucleated giant cells. They also stimulated angiogenesis and VEGF production in aortic ring cultures. This study demonstrates that the rat aorta contains a distinct subset of immature immunocytes capable of proliferating, differentiating into macrophages and DCs, and stimulating angiogenesis. Isolation of these cells in patches from M-CSF-stimulated aortic rings provides a reproducible system to study the biology and angiogenic role of the resident immune system of the aortic wall. J. Leukoc. Biol. 88: 1051-1059; 2010. C1 [Nicosia, Roberto F.] Vet Adm Puget Sound Hlth Care syst, Pathol & Lab Med Serv, Seattle, WA USA. [Zorzi, Penelope; Aplin, Alfred C.; Smith, Kelly D.; Nicosia, Roberto F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv S 113, 1660 S Columbian Way, Seattle, WA 98108 USA. EM roberto.nicosia@va.gov FU National Heart Lung and Blood Institute [HL-52585]; Department of Veterans Affairs Medical Research Services FX This study was supported by the National Heart Lung and Blood Institute grant HL-52585 and a Merit Review grant from the Department of Veterans Affairs Medical Research Services. We gratefully acknowledge Ms. Debbie Jones for her excellent technical assistance with the electron microscopy studies. NR 41 TC 12 Z9 12 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2010 VL 88 IS 5 BP 1051 EP 1059 DI 10.1189/jlb.0310178 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 692YG UT WOS:000285191200024 PM 20628067 ER PT J AU Guella, I Asselta, R Ardissino, D Merlini, PA Peyvandi, F Kathiresan, S Mannucci, PM Tubaro, M Duga, S AF Guella, Ilaria Asselta, Rosanna Ardissino, Diego Merlini, Pier Angelica Peyvandi, Flora Kathiresan, Sekar Mannucci, Pier Mannuccio Tubaro, Marco Duga, Stefano TI Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population SO JOURNAL OF LIPID RESEARCH LA English DT Article DE proprotein-convertase subtilisin-kexin type 9 genetic variants; low density lipoprotein; association study ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; SEQUENCE VARIATIONS; ARTERY-DISEASE; LIPID LEVELS; ASSOCIATION; HAPLOTYPE; GENOME; SUSCEPTIBILITY; METAANALYSIS AB The R46L variant in the proprotein-convertase subtilisin-kexin type 9 (PCSK9) gene was associated with reduced levels of LDL and total cholesterol and with a lower risk of coronary artery disease. We investigated the association of R46L with myocardial infarction (MI) in 1,880 Italian patients with premature MI and 1,880 controls. A trend toward a protective effect of the L46 allele was observed [ odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.49-1.13; P = 0.17], although the association with MI was not significant. This is probably due to the combined effect of the low frequency of R46L among Italians and of the young age of the analyzed cohort for whom the impact of coronary atherosclerosis is less important. This hypothesis was indirectly confirmed by the significant association found after including 1,056 additional older controls (OR = 0.67, 95% CI = 0.46-0.97; P = 0.036). LDL cholesterol was significantly lower in L46 carriers (116.2 +/- 34.7 mg/dl) than in noncarriers (137.4 +/- 47.3 mg/dl; P = 0.00022); a similar reduction was observed for total cholesterol (191.7 +/- 37.7 vs. 211.7 +/- 49 mg/dl; P = 0.00019). Analysis of 23 additional polymorphisms in the PCSK9 region identified another single nucleotide polymorphism (SNP) (rs11206510) associated with cholesterol levels. We confirmed that the L46 allele not only decreases LDL cholesterol but also protects against MI. Moreover, we replicated the association of total and LDL cholesterol with the SNP rs11206510.-Guella, I., R. Asselta, D. Ardissino, P. A. Merlini, F. Peyvandi, S. Kathiresan, P. M. Mannucci, M. Tubaro, and S. Duga. Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population. J. Lipid Res. 2010. 51: 3342-3349. C1 [Guella, Ilaria; Asselta, Rosanna; Duga, Stefano] Univ Milan, Dipartimento Biol & Genet Sci Med, Milan, Italy. [Ardissino, Diego] Azienda Osped Univ Parma, Dipartimento Cardiopolmonare, Unita Operat Cardiol, Parma, Italy. [Merlini, Pier Angelica] Osped Niguarda Ca Granda, Dipartimento Cardiol, Milan, Italy. [Peyvandi, Flora; Mannucci, Pier Mannuccio] Univ Milan, IRCCS Fdn Ca Granda Osped Maggiore, Dipartimento Med & Specialita Med, Ctr Emofilia & Trombosi A Bianchi Bonomi, Milan, Italy. [Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Tubaro, Marco] Osped San Filippo Neri, Div Cardiol, Rome, Italy. Broad Inst, Cambridge, MA USA. RP Duga, S (reprint author), Univ Milan, Dipartimento Biol & Genet Sci Med, Milan, Italy. EM stefano.duga@unimi.it RI Mannucci, Pier/C-3102-2014; Duga, Stefano/F-8173-2014; OI Asselta, Rosanna/0000-0001-5351-0619; Peyvandi, Flora/0000-0001-7423-9864; Duga, Stefano/0000-0003-3457-1410 FU IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena FX This study was supported by "Progetto a concorso" for the years 2009/2010 from "IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena" to R.A. NR 33 TC 22 Z9 23 U1 1 U2 9 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 NOV PY 2010 VL 51 IS 11 BP 3342 EP 3349 DI 10.1194/jlr.M010009 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 662LG UT WOS:000282808200027 PM 20699424 ER PT J AU Cheung, JS Fan, SJ Gao, DS Chow, AM Man, K Wu, EX AF Cheung, Jerry S. Fan, Shu Juan Gao, Darwin S. Chow, April M. Man, Kwan Wu, Ed X. TI Diffusion Tensor Imaging of Liver Fibrosis in an Experimental Model SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE diffusion tensor imaging; diffusion-weighted imaging; liver fibrosis; liver cirrhosis; apparent diffusion coefficient; fractional anisotropy; MRI; CCl(4) ID CHRONIC HEPATITIS-C; ECHO-PLANAR MR; ISCHEMIA-REPERFUSION INJURY; MAGNETIC-RESONANCE; HEPATOCELLULAR-CARCINOMA; WEIGHTED MRI; CARBON-TETRACHLORIDE; ADC MEASUREMENTS; CIRRHOSIS; LESIONS AB Purpose: To characterize changes in diffusion properties of liver using diffusion tensor imaging (DTI) in an experimental model of liver fibrosis. Materials and Methods: Liver fibrosis was induced in Sprague-Dawley rats (n = 12) by repetitive dosing of carbon tetrachloride (CCl(4)). The animals were examined with a respiratory-gated single-shot spin-echo echo-planar DTI protocol at 7 T before, 2 weeks after, and 4 weeks after CCl(4) insult. Apparent diffusion coefficient (ADC), directional diffusivities (ADC(/) (/) and ADC(perpendicular to)), and fractional anisotropy (FA) were measured. Liver histology was performed with hematoxylin-eosin staining and Masson's trichrome staining. Results: Significant decrease (P < 0.01) in ADC was found at 2 weeks (0.86 +/- 0.09 x 10(-3) mm(2)/s) and 4 weeks (0.74 +/- 0.09 x 10(-3) mm(2)/s) following CCl(4) insult, as compared with that before insult (0.97 +/- 0.08 x 10(-3) mm(2)/s). Meanwhile, FA at 2 weeks (0.18 +/- 0.03) after CCl(4) insult was significantly lower (P < 0.01) than that before insult (0.26 +/- 0.05), and subsequently normalized at 4 weeks (0.26 +/- 0.07) after the insult. Histology showed collagen deposition, presence of intracellular fat vacuoles, and cell necrosis/apoptosis in livers with CCl(4) insult. Conclusion: DTI detected the progressive changes in water diffusivities and diffusion anisotropy of liver tissue in this liver fibrosis model. ADC and FA are potentially valuable in detecting liver fibrosis at early stages and monitoring its progression. Future human studies are warranted to further verify the applicability of DTI in characterizing liver fibrosis and to determine its role in clinical settings. C1 [Cheung, Jerry S.; Fan, Shu Juan; Gao, Darwin S.; Chow, April M.; Wu, Ed X.] Univ Hong Kong, Dept Elect & Elect Engn, Lab Biomed Imaging & Signal Proc, Pokfulam, Hong Kong, Peoples R China. [Cheung, Jerry S.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Cheung, Jerry S.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Man, Kwan] Univ Hong Kong, Dept Surg, Pokfulam, Hong Kong, Peoples R China. [Wu, Ed X.] Univ Hong Kong, Dept Anat, Pokfulam, Hong Kong, Peoples R China. RP Wu, EX (reprint author), Univ Hong Kong, Dept Elect & Elect Engn, Lab Biomed Imaging & Signal Proc, Pokfulam, Hong Kong, Peoples R China. EM ewu@eee.hku.hk FU Hong Kong Grant Council [GRF HKU7808/09M] FX Contract grant sponsor: Hong Kong Grant Council: Contract grant number: GRF HKU7808/09M. NR 66 TC 24 Z9 30 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2010 VL 32 IS 5 BP 1141 EP 1148 DI 10.1002/jmri.22367 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 679VZ UT WOS:000284190200017 PM 21031520 ER PT J AU Andronesi, OC Mintzopoulos, D Psychogios, N Kesarwani, M He, JX Yasuhara, S Dai, G Rahme, LG Tzika, AA AF Andronesi, Ovidiu C. Mintzopoulos, Dionyssios Psychogios, Nikolaos Kesarwani, Meenu He, Jianxin Yasuhara, Shingo Dai, George Rahme, Laurence G. Tzika, Aria A. TI Combined Off-Resonance Imaging and T2 Relaxation in the Rotating Frame for Positive Contrast MR Imaging of Infection in a Murine Burn Model SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE positive contrast; transverse relaxation in the rotating frame (T(2p)); superparamagnetic iron-oxide (USPIO); burn; infection; macrophages ID SPIN-LATTICE RELAXATION; WATER SUPPRESSION IRON; LABELED STEM-CELLS; IN-VIVO; HUMAN BRAIN; SUPERPARAMAGNETIC PARTICLES; INVERSION-RECOVERY; ADIABATIC PULSES; OXIDE PARTICLES; FIELD-STRENGTH AB Purpose: To develop novel magnetic resonance (MR) imaging methods to monitor accumulation of macrophages in inflammation and infection. Positive-contrast MR imaging provides an alternative to negative-contrast MRI, exploiting the chemical shift induced by ultra-small superparamagnetic iron-oxide (USPIO) nanoparticles to nearby water molecules. We introduce a novel combination of off-resonance (ORI) positive-contrast MRI and T(2p) relaxation in the rotating frame (ORI-T(2p)) for positive-contrast MR imaging of USPIO. Materials and Methods: We tested ORI-T(2p) in phantoms and imaged in vivo the accumulation of USPIO-labeled macrophages at the infection site in a mouse model of burn trauma and infection with Pseudomonas aeruginosa (PA). PA infection is clinically important. The USPIO nanoparticlies were injected directly in the animals in solution, and macrophage labeling occurred in vivo in the animal model. Results: We observed a significant difference between ORI-T(2p) and OM, which leads us to suggest that ORI-T(2p) is more sensitive in detecting USPIO signal. To this end, the ORI-T(2p) positive contrast method may prove to be of higher utility in future research. Conclusion: Our results may have direct implications in the longitudinal monitoring of infection, and open perspectives for testing novel anti-infective compounds. C1 [Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Psychogios, Nikolaos; Tzika, Aria A.] Massachusetts Gen Hosp, Dept Surg, NMR Surg Lab, Boston, MA 02114 USA. [Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Psychogios, Nikolaos; Kesarwani, Meenu; He, Jianxin; Rahme, Laurence G.] Harvard Univ, Sch Med, Shriners Burn Inst, Boston, MA 02114 USA. [Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Psychogios, Nikolaos; Dai, George; Tzika, Aria A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Boston, MA 02115 USA. [Andronesi, Ovidiu C.] Univ Babes Bolyai, Dept Clin Psychol, R-3400 Cluj Napoca, Romania. [Kesarwani, Meenu; He, Jianxin; Rahme, Laurence G.] Massachusetts Gen Hosp, Dept Surg, Mol Surg Lab, Boston, MA 02114 USA. [Yasuhara, Shingo] Massachusetts Gen Hosp, Dept Anesthesiol, Shriners Burn Inst, Boston, MA 02114 USA. [Yasuhara, Shingo] Massachusetts Gen Hosp, Dept Crit Care, Shriners Burn Inst, Boston, MA 02114 USA. RP Tzika, AA (reprint author), Massachusetts Gen Hosp, Dept Surg, NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@partners.org RI Psychogios, Nikolaos/B-6867-2011; OI Psychogios, Nikolaos/0000-0002-2747-6012 FU NIH/NIAID [R01AI063433]; Shriners Hospitals [8893] FX Contract grant sponsor: NIH/NIAID; Contract grant number: R01AI063433; Contract grant sponsor: Shriners Hospitals; Contract grant number: 8893. NR 61 TC 6 Z9 7 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2010 VL 32 IS 5 BP 1172 EP 1183 DI 10.1002/jmri.22349 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 679VZ UT WOS:000284190200021 PM 21031524 ER PT J AU Staropoli, JF Xin, WN Sims, KB AF Staropoli, John F. Xin, Winnie Sims, Katherine B. TI Co-segregation of Norrie disease and idiopathic pulmonary hypertension in a family with a microdeletion of the NDP region at Xp11.3-p11.4 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID AFFECTING MONOAMINE-OXIDASE; X-CHROMOSOME; PRENATAL-DIAGNOSIS; SUDDEN-DEATH; DELETION; GENE; SUSCEPTIBILITY; MUTATIONS; PATIENT; AMINE AB Introduction Norrie disease is a rare X-linked congenital retinal vasculopathy that may be accompanied by sensorineural deafness, mental retardation, and other neurological deficits. Here we present a family in which Norrie disease co-segregated with either early-onset idiopathic pulmonary hypertension or sudden death preceded by a period of progressive dyspnea. Neither Norrie disease, nor its atypical variants described to date, have been associated with this extended clinical phenotype. Methods and Results Molecular analysis of the Norrie disease gene (NDP) and adjacent loci was performed by multiplex ligation-dependent probe amplification and comparative genomic hybridisation. Affected males in this family showed an inherited hemizygous deletion restricted to NDP and two immediately telomeric genes, monoamine oxidase-B (MAO-B) and monoamine oxidase-A (MAO-A), which encode closely related enzymes that metabolize biogenic amines including serotonin, dopamine, and norepinephrine. Sequencing of the deletion junction showed an unusual pattern in which a region of microhomology flanked intervening genomic sequence. Conclusion Because abnormalities of biogenic amines, particularly serotonin, have been implicated in the pathophysiology of pulmonary hypertension, we propose that presumed MAO deficiency in these patients may represent a novel risk factor for pulmonary hypertension, particularly forms with very early onset. Fine-mapping of other microdeletions at this locus may provide insights into additional mechanisms for nonrecurrent genomic rearrangements at this and other chromosomal loci. C1 [Staropoli, John F.; Xin, Winnie; Sims, Katherine B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Neurogenet DNA Diagnost Lab, Boston, MA 02114 USA. [Staropoli, John F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Xin, Winnie; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sims, KB (reprint author), MGH Neurogenet DNA Diagnost Lab, Simches Res Bldg,5-300,185 Cambridge St,Room 5238, Boston, MA 02114 USA. EM ksims@partners.org NR 29 TC 4 Z9 5 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 2010 VL 47 IS 11 BP 786 EP 790 DI 10.1136/jmg.2010.079301 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 683XN UT WOS:000284511700014 PM 20679667 ER PT J AU Sabath, DE Bender, MA Kentsis, A Pitchford, K Yi, H Greisman, HA AF Sabath, D. E. Bender, M. A. Kentsis, A. Pitchford, K. Yi, H. Greisman, H. A. TI Identification of Globin Gene Deletions Using a Custom Microarray and Comparative Genomic Hybridization SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 18-20, 2010 CL San Jose, CA SP Assoc Mol Pathol C1 [Sabath, D. E.; Bender, M. A.; Pitchford, K.; Yi, H.; Greisman, H. A.] Univ Washington, Seattle, WA 98195 USA. [Kentsis, A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2010 VL 12 IS 6 BP 860 EP 860 PG 1 WC Pathology SC Pathology GA 677FE UT WOS:000283973700032 ER PT J AU Ogino, S Baba, Y Fuchs, C Huttenhower, C AF Ogino, S. Baba, Y. Fuchs, C. Huttenhower, C. TI LINE 1 Extreme Hypomethylator A New Distinct Molecular Subtype of Colorectal Cancer Identified in a Database of 869 Tumors SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 18-20, 2010 CL San Jose, CA SP Assoc Mol Pathol C1 [Ogino, S.; Fuchs, C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Huttenhower, C.] HSPH, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2010 VL 12 IS 6 BP 897 EP 897 PG 1 WC Pathology SC Pathology GA 677FE UT WOS:000283973700191 ER PT J AU Ogino, S Baba, Y Fuchs, C AF Ogino, S. Baba, Y. Fuchs, C. TI IGF2 DMR0 Methylation Pyrosequencing Overcomes Weakness of Conventional LOI Assay and Shows That IGF2 DMR0 Hypomethylation in Colorectal Cancer Predicts Poor Prognosis SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 18-20, 2010 CL San Jose, CA SP Assoc Mol Pathol C1 [Ogino, S.; Fuchs, C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2010 VL 12 IS 6 BP 897 EP 897 PG 1 WC Pathology SC Pathology GA 677FE UT WOS:000283973700192 ER PT J AU Su, ZL Santagata, DD Duke, M Hutchinson, K Borger, DR Chung, CH Massion, PP Jones, CLV Iafrate, A Pao, W AF Su, Z. L. Santagata, D. Dias Duke, M. Hutchinson, K. Borger, D. R. Chung, C. H. Massion, P. P. Jones, C. L. Vnencak Iafrate, A. Pao, W. TI A Platform for Rapid Detection of Multiple Oncogenic Mutations with Relevance to Targeted Therapy in Non Small Cell Lung Cancer SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 18-20, 2010 CL San Jose, CA SP Assoc Mol Pathol C1 [Su, Z. L.; Duke, M.; Hutchinson, K.; Chung, C. H.; Massion, P. P.; Jones, C. L. Vnencak; Pao, W.] Vanderbilt Univ, Nashville, TN USA. [Santagata, D. Dias; Borger, D. R.; Iafrate, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2010 VL 12 IS 6 BP 899 EP 899 PG 1 WC Pathology SC Pathology GA 677FE UT WOS:000283973700200 ER PT J AU Peereboom, DM Supko, JG Carson, KA Batchelor, T Phuphanich, S Lesser, G Mikkelson, T Fisher, J Desideri, S He, XY Grossman, SA AF Peereboom, David M. Supko, Jeffrey G. Carson, Kathryn A. Batchelor, Tracy Phuphanich, Surasak Lesser, Glenn Mikkelson, Tom Fisher, Joy Desideri, Serena He, Xiaoying Grossman, Stuart A. CA NABTT Consortium TI A phase I/II trial and pharmacokinetic study of ixabepilone in adult patients with recurrent high-grade gliomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Ixabepilone; Recurrent gliomas; Chemotherapy; Phase II ID MICROTUBULE-STABILIZING AGENTS; BRAIN-TUMOR CONSORTIUM; EPOTHILONE-B ANALOG; MALIGNANT GLIOMA; ANTIEPILEPTIC DRUGS; HUMAN HEPATOCYTES; GLIOBLASTOMA-MULTIFORME; CYP3A4 EXPRESSION; SOLID TUMORS; I TRIAL AB Ixabepilone is an epothilone, a novel class of non-taxane microtubule stabilizing agents. A phase I/II and pharmacokinetic trial of ixabepilone was conducted in patients with recurrent high-grade gliomas. Adult patients received ixabepilone as a 1-h infusion daily for 5 days every 3 weeks. A modified continual reassessment method was used to escalate doses, beginning at 5.0 mg/m(2), in patients stratified by use or non-use of enzyme inducing antiepileptic drugs (EIAED). In the phase I study, the maximum tolerated dose (MTD) and pharmacokinetics of ixabepilone were determined for each group. The phase II study used a two-stage design to evaluate response rate. Secondary endpoints were survival and 6-month progression free survival. In the phase I trial, 38 patients (median age 54 years) were enrolled. The MTD was 6.8 mg/m(2) for patients not taking EIAEDs and 9.6 mg/m(2) for those taking EIAEDs. The dose limiting toxicities in both groups were hematologic. Twenty-three patients (median age 54 years) were enrolled in the first stage of the phase II trial. No objective responses were observed. Median overall survival was 5.8 (95% CI, 5.0-8.6) months and 6-month PFS rate was 4% (95% CI, 0-22%). The overall mean total body clearance for ixabepilone was significantly higher (P = 0.003) in patients receiving EIAEDs (36 +/- A 11 l/h/m(2)) than those not (24 +/- A 9.2 l/h/m(2)). Patients on EIAEDs had a substantially higher MTD likely due to induction of cytochrome P450. Ixabepilone had no activity in patients with recurrent high-grade gliomas. C1 [Fisher, Joy; Desideri, Serena; Grossman, Stuart A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Peereboom, David M.] Cleveland Clin, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. [Supko, Jeffrey G.; Batchelor, Tracy; He, Xiaoying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Carson, Kathryn A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Phuphanich, Surasak] Cedar Sinai Med Ctr, Los Angeles, CA USA. [Lesser, Glenn] Wake Forest Univ, Winston Salem, NC 27109 USA. [Mikkelson, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. RP Fisher, J (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Canc Res Bldg 2,Room 1M15,1550 Orleans St, Baltimore, MD 21231 USA. EM jfisher@jhmi.edu FU National Cancer Institute [CA62475]; National Center for Research Resources [UL1 RR 025005] FX This study was performed by the New Approaches to Brain Tumor Therapy CNS Consortium, Baltimore, MD, USA, and supported in part by National Cancer Institute UO1 Grant CA62475 (NABTT Central Office). Kathryn A. Carson's work on the manuscript was supported by National Center for Research Resources grant UL1 RR 025005. We are grateful to Kimberly Busby for her support of this clinical trial development and manuscript. NR 39 TC 9 Z9 9 U1 1 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 NOV PY 2010 VL 100 IS 2 BP 261 EP 268 DI 10.1007/s11060-010-0190-0 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 682BP UT WOS:000284373800014 PM 20449631 ER PT J AU Lima, MA Bernal-Cano, F Clifford, DB Gandhi, RT Koralnik, IJ AF Lima, M. A. Bernal-Cano, F. Clifford, D. B. Gandhi, R. T. Koralnik, I. J. TI Clinical outcome of long-term survivors of progressive multifocal leukoencephalopathy SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; ERA AB Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the polyomavirus JC (JCV) in immunosuppressed people. There is no cure for PML but 1-year survival has increased from 10% to 50% in HIV-infected individuals treated with highly active antiretroviral therapy. We describe herein the clinical outcome of 24 PML patients whose survival exceeded 5 years, with a mean follow-up of 94.2 months (range, 60-188 months). Of all patients, only two were females including one who had non-Hodgkin's lymphoma and was HIV negative. All 23 HIV-positive patients received highly active antiretroviral therapy, and additional experimental therapies were not associated with a better clinical outcome. Marked neurological improvement occurred in 4/24 (17%) of patients, while 11/24 (46%) had partial improvement and 9/24 (37%) remained stable. By the end of the period of observation, 8/24 (33%) of patients had no significant disability despite persistent symptoms (modified Rankin disability scale (MRDS) =1), 6/24 (25%) had slight disability and were living independently (MRDS=2), 5/24 (21%) were moderately disabled, requiring some help during activities of daily living (MRDS=3) and 5/24 (21%) had moderately severe disability, requiring constant help or institutionalisation (MRDS=4). Patients with cerebellar lesions tended to have a worse clinical outcome. MRI showed leukomalacia with ventricular enlargement secondary to destruction of the white matter at the site of previous PML lesions, and focal areas of subcortical atrophy with preservation of the cortical ribbon. Of 20 patients tested, 19(95%) had detectable CD8+ cytotoxic T-lymphocytes against JCV in their blood. In absence of a specific treatment, immunotherapies aiming at boosting the cellular immune response against JCV may improve the prognosis of PML. C1 [Lima, M. A.; Bernal-Cano, F.; Koralnik, I. J.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Lima, M. A.; Bernal-Cano, F.; Koralnik, I. J.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Gandhi, R. T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02138 USA. [Lima, M. A.] Fundacao Oswaldo Cruz, Neuroinfect & HTLV Lab, Rio De Janeiro, Brazil. [Bernal-Cano, F.] Hosp San Ignacio, Div Infect Dis, Bogota, Colombia. [Clifford, D. B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Clifford, D. B.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Koralnik, IJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, E CLS 1005,330 Brookline, Boston, MA 02215 USA. EM ikoralni@bidmc.harvard.edu FU Public Health Service Grant [R01 NS/AI 041198 NS 047029, K24 NS 060950]; NIH FX This work was supported in part by Public Health Service Grants R01 NS/AI 041198 NS 047029, and K24 NS 060950 to IJK.; Other Funders: NIH. NR 19 TC 28 Z9 28 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 2010 VL 81 IS 11 BP 1288 EP 1291 DI 10.1136/jnnp.2009.179002 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 669ML UT WOS:000283354800240 PM 20710013 ER PT J AU Freeman, DK Eddington, DK Rizzo, JF Fried, SI AF Freeman, Daniel K. Eddington, Donald K. Rizzo, Joseph F., III Fried, Shelley I. TI Selective Activation of Neuronal Targets With Sinusoidal Electric Stimulation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RETINAL GANGLION-CELLS; DEEP BRAIN-STIMULATION; TIGER SALAMANDER RETINA; BIPOLAR CELLS; PARKINSONS-DISEASE; CALCIUM CURRENTS; CORTICAL-NEURONS; PROSTHESIS; CHANNELS; MICROSTIMULATION AB Freeman DK, Eddington DK, Rizzo JF, Fried SI. Selective activation of neuronal targets with sinusoidal electric stimulation. J Neurophysiol 104: 2778-2791, 2010. First published September 1, 2010; doi:10.1152/jn.00551.2010. Electric stimulation of the CNS is being evaluated as a treatment modality for a variety of neurological, psychiatric, and sensory disorders. Despite considerable success in some applications, existing stimulation techniques offer little control over which cell types or neuronal substructures are activated by stimulation. The ability to more precisely control neuronal activation would likely improve the clinical outcomes associated with these applications. Here, we show that specific frequencies of sinusoidal stimulation can be used to preferentially activate certain retinal cell types: photoreceptors are activated at 5 Hz, bipolar cells at 25 Hz, and ganglion cells at 100 Hz. In addition, low-frequency stimulation (<= 25 Hz) did not activate passing axons but still elicited robust synaptically mediated responses in ganglion cells; therefore, elicited neural activity is confined to within a focal region around the stimulating electrode. Our results suggest that sinusoidal stimulation provides significantly improved control over elicited neural activity relative to conventional pulsatile stimulation. C1 [Freeman, Daniel K.; Fried, Shelley I.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Eddington, Donald K.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Freeman, Daniel K.; Rizzo, Joseph F., III; Fried, Shelley I.] Boston Vet Adm Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA USA. [Eddington, Donald K.] MIT, Cambridge, MA 02139 USA. [Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Dept NeuroOphthalmol, Boston, MA 02114 USA. RP Fried, SI (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 50 Blossom St,Rm 429, Boston, MA 02114 USA. EM fried.shelley@mgh.harvard.edu FU VA Healthcare System [CDA-1]; National Eye Institute [R01 EY-019967-01] FX This work was funded in part by the VA Healthcare System-Career Development Award (CDA-1) to D. Freeman, Center Grant (Center for Innovative Visual Rehabilitation) to J. Rizzo, and National Eye Institute Grant (R01 EY-019967-01) to S. Fried. NR 58 TC 50 Z9 50 U1 1 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2010 VL 104 IS 5 BP 2778 EP 2791 DI 10.1152/jn.00551.2010 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 695SD UT WOS:000285392000042 PM 20810683 ER PT J AU Papadaki, ME Troulis, MJ Glowacki, J Kaban, LB AF Papadaki, Maria E. Troulis, Maria J. Glowacki, Julie Kaban, Leonard B. TI A Minipig Model of Maxillary Distraction Osteogenesis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID CLEFT-LIP; BONE; CHILDREN; LATENCY; MIDFACE; DEVICE; PALATE AB Purpose: To establish a porcine model for maxillary distraction osteogenesis and to document the sequence of bone formation in the zone of advancement. Materials and Methods: Female Yucatan minipigs (n = 9) in the mixed dentition stage underwent modified Le Fort I osteotomy through a vestibular incision under general anesthesia. A unidirectional, semiburied Le Fort I distraction device was fixed across the osteotomy. The distraction protocol was 0-day latency, 1-mm/d rate for 12 days, and 24 days of fixation. Maxillary specimens (n = 9) were harvested and divided in half at the end of distraction (n = 6 sides), midfixation (n = 6), and the end of fixation (n = 6). Clinical stability, volume, and radiographic density across the zone of advancement were graded on semiquantitative scales. Specimens were stained with hematoxylin and eosin and examined with light microscopy. Results: Animals tolerated the operation, the distraction and fixation periods. There were no infections and no devices failed. At the end of the distraction period, bone trabeculae were present at the periphery and fibrous tissues, and vessels, preosteoblasts, and osteoblasts were present in the center of the zone of advancement. Islands of chondrocyte-like cells appeared in 1 specimen each at midfixation and the end of fixation. At the end of fixation, clinical stability and radiographic density were graded 3/3 and bone formation was complete across the advancement zone in all specimens. Conclusion: A model for Le Fort I distraction osteogenesis was established. Intramembranous bone formation was the predominant mechanism of healing in the zone of advancement. Latency was not necessary for bone formation in this minipig model. (c) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:2783-2791, 2010 C1 [Papadaki, Maria E.] Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Troulis, Maria J.] Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Residency Training Program, Boston, MA 02114 USA. [Glowacki, Julie] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Papadaki, ME (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Warren 1201,MGH, Boston, MA 02114 USA. EM mpapadaki@partners.org FU MGH Department of Oral and Maxillofacial Education and Research Fund; Hanson Foundation (Boston, MA); AO/ASIF Foundation (Berne, Switzerland) [03-K69] FX The research was funded by the MGH Department of Oral and Maxillofacial Education and Research Fund, the Hanson Foundation (Boston, MA), and a grant from the AO/ASIF Foundation (Berne, Switzerland; 03-K69). Technical support was provided by Synthes CMF (West Chester, PA). NR 26 TC 15 Z9 15 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2010 VL 68 IS 11 BP 2783 EP 2791 DI 10.1016/j.joms.2010.06.179 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 677EH UT WOS:000283971400019 PM 20971370 ER PT J AU Susarla, SM Abramson, ZR Dodson, TB Kaban, LB AF Susarla, Srinivas M. Abramson, Zachary R. Dodson, Thomas B. Kaban, Leonard B. TI Cephalometric Measurement of Upper Airway Length Correlates With the Presence and Severity of Obstructive Sleep Apnea SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MAXILLOMANDIBULAR ADVANCEMENT; SURGERY AB Purpose: The purpose of this study was to measure upper airway length (UAL) on lateral cephalograms and to assess its relationship with the presence and severity of obstructive sleep apnea (OSA). Materials and Methods: Using a case-control study design, the investigators enrolled a sample of cases defined as adult subjects with OSA and controls who were adult patients with skeletal Class II malocclusions. The primary predictor variable was UAL Other variables were demographic and cephalometric parameters. The respiratory disturbance index (RDI) was used to measure disease severity in cases. Bivariate analyses were computed to evaluate the associations between predictor and outcome variables. Multiple regression analyses were used to provide adjusted measures of association, controlling for the effects of confounders/effect modifiers. Diagnostic test characteristics were computed for threshold airway lengths. P <= .05 was considered statistically significant. Results: The sample consisted of 96 cases with OSA (76 males) and 56 controls without OSA (36 males). OSA subjects were older, were predominately male, and had higher body mass indexes and longer and narrower airways (P < .05). After controlling for confounding variables, UALs >= 72 mm for males and 62 nun for females were significantly associated with the presence of OSA (P = .03). The sensitivity and specificity of UAL as a diagnostic test for OSA were >= 0.8. UAL was strongly correlated with RDI (disease severity) in males (r = 0.72, P < .01) and moderately correlated with RDI in females (r = 0.52, P < .01). Conclusion: Increased upper airway length was correlated with the presence and severity of OSA in this sample of adult patients. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:2846-2855, 2010 C1 [Susarla, Srinivas M.; Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Susarla, Srinivas M.; Abramson, Zachary R.; Dodson, Thomas B.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Boston, MA 02114 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. EM ssusarla1@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Massachusetts General Hospital Department of Oral and Maxillofacial Surgery; Center for Applied Clinical Investigation and OMS Foundation; AO/Synthes Research Fellowship in Pediatric Oral and Maxillofacial Surgery FX Supported by the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund (S.M.S., Z.R.A.), Center for Applied Clinical Investigation and OMS Foundation Clinical Investigation Fellowship (S.M.S.), and the AO/Synthes Research Fellowship in Pediatric Oral and Maxillofacial Surgery (Z.R.A.). NR 21 TC 29 Z9 32 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2010 VL 68 IS 11 BP 2846 EP 2855 DI 10.1016/j.joms.2010.06.196 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 677EH UT WOS:000283971400026 PM 20869147 ER PT J AU O'Toole, RV Riche, K Cannada, LK Hennessy, M Sciadini, MF Shi, LL Woodford, M Harris, MB AF O'Toole, Robert V. Riche, Kevin Cannada, Lisa K. Hennessy, Michael Sciadini, Marcus F. Shi, Lewis L. Woodford, Mathew Harris, Mitchel B. TI Analysis of Postoperative Knee Sepsis After Retrograde Nail Insertion of Open Femoral Shaft Fractures SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE retrograde nailing; open femoral shaft fractures; septic arthritis; septic knee; infection ID HETEROTOPIC OSSIFICATION; IPSILATERAL FRACTURES; FEMUR; ANTEGRADE; DIAPHYSEAL; INFECTION; FIXATION AB Objectives: Retrograde nailing of open femoral fractures has presumed increased risk of knee sepsis. Our hypothesis was that the incidence of secondary knee infection after retrograde nailing of open femoral fractures is low. Design: Retrospective, multicenter. Setting: Four Level I trauma centers. Patients and Methods: A retrospective review of prospective trauma registries and fracture databases identified all open femoral fractures treated with retrograde intramedullary nailing from January 1, 2003, through February 15, 2007. Patients with ballistic injuries and those with less than 1 month follow up were excluded. Ninety-three open femoral fractures were identified in 90 patients. We defined a septic knee as a knee with infection that required reoperation with arthrotomy or arthroscopy. Infections at an open fracture site were defined as those treated with local irrigation and debridement and intravenously and/or orally administered antibiotics. Intervention: Open femoral shaft fractures treated with a retrograde approach. Main Outcome Measurements: Occurrence of an ipsilateral postoperative septic knee. Results: One acute septic knee was identified (1.1%; 95% confidence interval, 0.0%-3.2%) noted at time of repeat irrigation and debridement of a massive degloving wound that left no skin coverage over the knee. We also observed one late knee sepsis 2.5 years after the index procedure occurring after quadricepsplasty. The nail had been removed 1.5 years before surgery, so we did not include that case in our knee sepsis rate. Two additional infections at the open wound site did not involve the knee. Conclusions: Previous publications have argued that retrograde nailing of open femoral fractures provides a potential conduit for knee infection. Our data show that risk of a septic knee as a direct result of retrograde nailing of an open femoral fracture is relatively low (1.1%; 95% confidence interval, 0.0%-3.2%). To our knowledge, this is the first case series to document the relative safety associated with retrograde nailing of open femoral fractures. C1 [O'Toole, Robert V.; Sciadini, Marcus F.; Woodford, Mathew] Univ Maryland, Sch Med, R Adams Cowley Shock Trauma Ctr, Dept Orthopaed, Baltimore, MD 21201 USA. [Riche, Kevin; Shi, Lewis L.; Harris, Mitchel B.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. [Cannada, Lisa K.] St Louis Univ Hosp, St Louis, MO USA. [Cannada, Lisa K.; Hennessy, Michael] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP O'Toole, RV (reprint author), Univ Maryland, Sch Med, R Adams Cowley Shock Trauma Ctr, Dept Orthopaed, 22 S Greene St,T3R62, Baltimore, MD 21201 USA. EM rvo3@yahoo.com FU Smith Nephew; Stryker; Synthes; DePuy; Orthopaedic Trauma Association; Zimmer; Foundation for Orthopedic Trauma; Southeastern Fracture Symposium; Parkland Medical Center; Southwestern Medical Center at the University of Texas; Medtronic FX Respective department of each author has received grant from Smith & Nephew (R.V.O., L. K. C., and M. F. S.), Stryker (R.V.O. and M. F. S.), Synthes (R.V.O., M. H., M. F. S., and M. B. S.), DePuy (R.V.O., M. F. S., and M. B. S), Orthopaedic Trauma Association (L. K. C.), Zimmer, Foundation for Orthopedic Trauma (L. K. C.), Southeastern Fracture Symposium (L. K. C.), Parkland Medical Center (M. H.), Southwestern Medical Center at the University of Texas (M. H.), and Medtronic (M.B.H.). NR 45 TC 8 Z9 8 U1 0 U2 3 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 NOV PY 2010 VL 24 IS 11 BP 677 EP 682 DI 10.1097/BOT.0b013e3181cec32c PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 664MU UT WOS:000282966300009 PM 20881635 ER PT J AU Shugarman, LR Goebel, JR Lanto, A Asch, SM Sherbourne, CD Lee, ML Rubenstein, LV Wen, L Meredith, L Lorenz, KA AF Shugarman, Lisa R. Goebel, Joy R. Lanto, Andy Asch, Steven M. Sherbourne, Cathy D. Lee, Martin L. Rubenstein, Lisa V. Wen, Li Meredith, Lisa Lorenz, Karl A. TI Nursing Staff, Patient, and Environmental Factors Associated with Accurate Pain Assessment SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Pain measurement; veterans; outpatients ID CANCER PAIN; NURSES ASSESSMENT; PRIMARY-CARE; REPRESENTATIVE SAMPLE; ANXIETY DISORDERS; DECISION-MAKING; MANAGEMENT; QUESTIONNAIRE; DEPRESSION; IMPAIRMENT AB Context Although pain ranks highly among reasons for seeking care, routine pain assessment is often inaccurate Objectives This study evaluated factors associated with nurses (e g, registered) and other nursing support staff (e g, licensed vocational nurses and health technicians) discordance with patients in estimates of pain in a health system where routine pain screening using a 0-10 numeric rating scale (NRS) is mandated Methods This was a cross-sectional, visit-based, cohort study that included surveys of clinic outpatients (n = 465) and nursing staff (n = 94) who screened for pain as part of routine vital sign measurement during intake These data were supplemented by chart review We compared patient pain levels documented by the nursing staff (N-NRS) with those reported by the patient during the study survey (S-NRS) Results Pain underestimation (N-NRS < S-NRS) occurred in 25% and overestimation (N-NRS > S-NRS) in 7% of the cases Nursing staff used informal pain-screening techniques that did not follow established NRS protocols in half of the encounters Pain underestimation was positively associated with more years of nursing staff work experience and patient anxiety or post-traumatic stress disorder and negatively associated with better patient-reported health status Pain overestimation was positively associated with nursing staffs use of the full NRS protocol and with a distracting environment in which patient vitals were taken Conclusion Despite a long-standing mandate, pain-screening implementation falls short, and informal screening is common J Pain Symptom Manage 2010,40 723-733 (C) 2010 US Cancer Pain Relief Committee Published by Elsevier Inc All rights reserved C1 [Lanto, Andy; Asch, Steven M.; Lee, Martin L.; Rubenstein, Lisa V.; Lorenz, Karl A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Asch, Steven M.; Rubenstein, Lisa V.; Lorenz, Karl A.] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. [Wen, Li] Vet Adm Long Beach Healthcare Syst, Long Beach, CA USA. [Goebel, Joy R.] Calif State Univ Long Beach, Sch Nursing, Dept Nursing, Long Beach, CA 90840 USA. [Shugarman, Lisa R.; Asch, Steven M.; Sherbourne, Cathy D.; Rubenstein, Lisa V.; Meredith, Lisa; Lorenz, Karl A.] RAND Corp, Santa Monica, CA USA. RP Lorenz, KA (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Code 111 G, Los Angeles, CA 90073 USA. FU Veterans Administration [IIR-030150] FX Dr Karl Lorenz was supported by a VA HSR&D Career Development Award This study was funded by The Veterans Administration (IIR-030150) The funder was not involved in the conduct of the study or development of the submission The authors declare no conflicts of interest NR 45 TC 11 Z9 12 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2010 VL 40 IS 5 BP 723 EP 733 DI 10.1016/j.jpainsymman.2010.02.024 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 686BI UT WOS:000284671400009 PM 20692807 ER PT J AU Fine, PG Messina, J Xie, F Rathmell, J AF Fine, Perry G. Messina, John Xie, Fang Rathmell, James TI Long-Term Safety and Tolerability of Fentanyl Buccal Tablet for the Treatment of Breakthrough Pain in Opioid-Tolerant Patients with Chronic Pain An 18-Month Study SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Fentanyl buccal tablet; opioid; long-term safety ID CHRONIC NONCANCER PAIN; CLINICAL-PRACTICE GUIDELINE; AMERICAN ACADEMY; TREATED PATIENTS; DOUBLE-BLIND; BACK-PAIN; PREVALENCE; EFFICACY; PRESCRIPTIONS; RELEASE AB Context Breakthrough pain (BTP) is highly prevalent in patients with chronic cancer and noncancer pain, commonly requiring treatment with short-acting or rapid-onset opioids. This is the first report of an analysis of long-term safety from combined clinical trials of a rapid-onset transmucosal formulation of fentanyl, the fentanyl buccal tablet (FBT). Objectives This long-term (18-month), open-label study assessed the safety and tolerability of FBT for the treatment of BTP in a large cohort (n = 646) of opioid-tolerant patients receiving around-the-clock (ATC) opioids for persistant noncancer pain. Methods This was a long-term, multicenter, open-label safety study that accepted patients naive to FBT (new patients) as well as rollover patients from one of two previous short-term, randomized, placebo-controlled studies involving opioid-tolerant adults with chronic noncancer pain. All patients gave written informed consent, and the study was conducted according to Good Clinical Practice and with Independent Ethics Committee or Institutional Review Board approval. Results During maintenance treatment, 70 of 646 patients (11%) discontinued because of adverse events (AEs), 69 of 646 (11%) because of withdrawn consent, and 57 of 646 (9%) because of noncompliance. A total of 571 of 646 patients (88%) had one or more AEs; most were mild to moderate in intensity and typical of AEs associated with opioid use in a noncancer chronic pain population. Serious AEs were seen in 118 of 646 patients (18%); most were considered by the investigators to be unrelated or unlikely to be related to FBT. There were six deaths (three myocardial infarction, two cardiac arrest, and one pneumonia) that were considered by investigators to be unrelated or unlikely to be related to FBT. There were two reports of accidental overdose contained within nine reports of nonfatal overdose (FBT and/or ATC and/or other medications). Four patients had AEs of abuse or drug dependence, two in association with FBT. Drug withdrawal syndrome occurred in 23 patients after discontinuation of FBT alone or in combination with other opioids. Secondary assessments showed that average pain ratings, as assessed by the Brief Pain Inventory, remained relatively stable throughout the study and that consistent improvements were noted in functional measures. Conclusion FBT was generally safe and well tolerated, with self-reported functional improvement observed in most of the opioid-tolerant patients with BTP in association with chronic noncancer pain. (C) 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Fine, Perry G.] Univ Utah, Dept Anesthesiol, Pain Management Ctr, Salt Lake City, UT 84109 USA. [Messina, John; Xie, Fang] Cephalon Inc, Frazer, PA USA. [Rathmell, James] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Fine, PG (reprint author), Univ Utah, Dept Anesthesiol, Pain Management Ctr, Suite 200,615 Arapeen Dr, Salt Lake City, UT 84109 USA. NR 29 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2010 VL 40 IS 5 BP 747 EP 760 DI 10.1016/j.jpainsymman.2010.02.009 PG 14 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 686BI UT WOS:000284671400011 PM 20594801 ER PT J AU Anderson, WG Goldstein, NE AF Anderson, Wendy G. Goldstein, Nathan E. TI Update in Hospice and Palliative Care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID ADVANCED CANCER; ASSOCIATION; DIALYSIS; DEATH C1 [Anderson, Wendy G.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Anderson, Wendy G.] Univ Calif San Francisco, Palliat Care Program, San Francisco, CA 94143 USA. [Goldstein, Nathan E.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, Bronx, NY USA. RP Anderson, WG (reprint author), Univ Calif San Francisco, Div Hosp Med, 521 Parnassus Ave,Box 0903, San Francisco, CA 94143 USA. EM anderson.wg@gmail.com FU University of California San Francisco Clinical and Translational Science Institute by National Institutes of Health [5KL2 RR024130-04]; National Institute of Aging [K23 AG025933] FX Dr. Anderson was supported by the University of California San Francisco Clinical and Translational Science Institute Career Development Program, which is supported by National Institutes of Health grant number 5KL2 RR024130-04. Dr. Goldstein was supported by a Mentored Patient-Oriented Research Career Development Award from the National Institute of Aging (K23 AG025933). Drs. Anderson and Goldstein presented these articles for the State of the Science Plenary Session at the Annual Assembly of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association on March 6, 2010 in Boston, Massachusetts. NR 16 TC 1 Z9 1 U1 1 U2 1 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 NOV PY 2010 VL 13 IS 11 BP 1305 EP 1310 DI 10.1089/jpm.2010.0253 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 682JD UT WOS:000284397000002 ER PT J AU Carlson, MDA Bradley, EH Du, QL Morrison, RS AF Carlson, Melissa D. A. Bradley, Elizabeth H. Du, Qingling Morrison, R. Sean TI Geographic Access to Hospice in the United States SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID FOR-PROFIT; CARE; NONPROFIT; HOSPITALS; PATTERNS; CANCER; LIFE; HOME AB Background: Despite a 41% increase in the number of hospices since 2000, more than 60% of Americans die without hospice care. Given that hospice care is predominantly home based, proximity to a hospice is important in ensuring access to hospice services. We estimated the proportion of the population living in communities within 30 and 60 minutes driving time of a hospice. Methods: We conducted a cross-sectional study of geographic access to U. S. hospices using the 2008 Medicare Provider of Services data, U. S. Census data, and ArcGIS software. We used multivariate logistic regression to identify gaps in hospice availability by community characteristics. Results: As of 2008, 88% of the population lived in communities within 30 minutes and 98% lived in communities within 60 minutes of a hospice. Mean time to the nearest hospice was 15 minutes and the range was 0 to 403 minutes. Community characteristics independently associated with greater geographic access to hospice included higher population density, higher median income, higher educational attainment, higher percentage of black residents, and the state not having a Certificate of Need policy. The percentage of each state's population living in communities more than 30 minutes from a hospice ranged from 0% to 48%. Conclusions: Recent growth in the hospice industry has resulted in widespread geographic access to hospice care in the United States, although state and community level variation exists. Future research regarding variation and disparities in hospice use should focus on barriers other than geographic proximity to a hospice. C1 [Carlson, Melissa D. A.; Du, Qingling; Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Bradley, Elizabeth H.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Carlson, MDA (reprint author), Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM melissa.carlson@mssm.edu FU National Institute of Nursing Research [1K99NR010495-01]; Patrick and Catherine Weldon Donaghue Medical Research Foundation [02-102]; National Institute on Aging [K24 AG022345] FX Funding sources: Brookdale Leadership in Aging Fellowship, National Institute of Nursing Research Career Development Award (1K99NR010495-01); Patrick and Catherine Weldon Donaghue Medical Research Foundation Investigator Award (Grant #02-102); National Institute on Aging Mid-Career Investigator Award in Patient Oriented Research (K24 AG022345). NR 30 TC 26 Z9 26 U1 3 U2 11 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 NOV PY 2010 VL 13 IS 11 BP 1331 EP 1338 DI 10.1089/jpm.2010.0209 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 682JD UT WOS:000284397000007 PM 20979524 ER PT J AU Jackson, V Arnold, RM AF Jackson, Vicki Arnold, Robert M. TI A Model of Mosaic Mentoring SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Jackson, Vicki] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jackson, V (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM VJackson@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD NOV PY 2010 VL 13 IS 11 BP 1371 EP 1371 DI 10.1089/jpm.2010.9764 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 682JD UT WOS:000284397000013 PM 21091021 ER PT J AU Katavetin, P Cheunsuchon, P Grant, E Boepple, PA Hedley-Whyte, ET Misra, M Levitsky, LL AF Katavetin, Paravee Cheunsuchon, Pornsuk Grant, Ellen Boepple, Paul A. Hedley-Whyte, E. Tessa Misra, Madhusmita Levitsky, Lynne L. TI Rathke's Cleft Cysts in Children and Adolescents: Association with Female Puberty SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE Rathke cleft cyst; pituitary; headaches; adolescents; visual deficits; hypopituitarism; estrogen; progesterone ID ENDOTHELIAL GROWTH-FACTOR; ESTROGEN-RECEPTOR; PATHOLOGICAL FEATURES; CLINICAL-FEATURES; HUMAN PITUITARY; RAT PITUITARY; EXPRESSION; MANAGEMENT; ADENOMAS; OUTCOMES AB There are few pediatric data regarding manifestations and outcomes of Rathke's cleft cysts (RCC). We retrospectively reviewed 13 cases treated at Massachusetts General Hospital over 10 years. Age at presentation was 12-17 years, except for one 7-year-old who presented with sexual precocity. There was a female preponderance [11 females, 2 males, p=0.01], and all were pubertal at diagnosis. Common features at presentation were headaches (11/13), endocrine abnormalities (5/13) and visual disturbances (2/13). Four patients underwent transsphenoidal surgery. Symptoms improved in all but one, in whom headaches persisted. Recurrent growth in one patient was treated successfully by excision. For conservatively treated patients, cyst size was unchanged over follow-up (6 months-5 years). Female preponderance and pubertal presentation suggest a possible link between sex hormones and RCC pathogenesis. Although estrogen and progesterone receptor immunostaining was negative in the cyst lining, estrogen receptor immunostaining was positive in adjacent pituitary cells. Further investigations regarding this issue are warranted. C1 [Katavetin, Paravee; Boepple, Paul A.; Misra, Madhusmita; Levitsky, Lynne L.] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. [Katavetin, Paravee; Grant, Ellen; Boepple, Paul A.; Misra, Madhusmita; Levitsky, Lynne L.] Harvard Univ, Sch Med, Boston, MA USA. [Cheunsuchon, Pornsuk; Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Grant, Ellen] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. EM llevitsky@partners.org RI Cheunsuchon, Pornsuk/O-7915-2015 OI Cheunsuchon, Pornsuk/0000-0001-8851-3553 NR 21 TC 2 Z9 2 U1 0 U2 1 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0334-018X EI 2191-0251 J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD NOV PY 2010 VL 23 IS 11 BP 1175 EP 1180 DI 10.1515/jpem.2010.184 PG 6 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 697RH UT WOS:000285533000012 PM 21284332 ER PT J AU Gupta, P Goyal, S Grant, PE Fawaz, R Lok, J Yager, P Sharma, A Sassower, K Noviski, N Browning, M Sahai, I AF Gupta, Punkaj Goyal, Sunali Grant, P. Ellen Fawaz, Rima Lok, Josephine Yager, Phoebe Sharma, Amita Sassower, Kenneth Noviski, Natan Browning, Marsha Sahai, Inderneel TI Acute Liver Failure and Reversible Leukoencephalopthy in a Pediatric Patient With Homocystinuria SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID BETA-SYNTHASE DEFICIENCY; HYDROGEN-PEROXIDE; AMINO-ACIDS; HOMOCYSTEINE; METHIONINE C1 [Gupta, Punkaj] Arkansas Childrens Hosp, Dept Cardiol, Little Rock, AR 72202 USA. [Goyal, Sunali] Univ Arkansas Med Sci, Dept Ophthalmol, Little Rock, AR 72205 USA. [Grant, P. Ellen] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Fawaz, Rima] Childrens Hosp, Dept Gastroenterol & Nutr, Boston, MA 02115 USA. [Lok, Josephine; Yager, Phoebe; Noviski, Natan] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Crit Care Med, Boston, MA 02114 USA. [Sharma, Amita] Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. [Sassower, Kenneth] Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA. [Browning, Marsha] Massachusetts Gen Hosp, Neurogenet Lab Biochem, Boston, MA 02114 USA. RP Gupta, P (reprint author), Arkansas Childrens Hosp, Dept Cardiol, 800 Marshall St,Slot 512-3, Little Rock, AR 72202 USA. EM pgupta2@uams.edu NR 18 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2010 VL 51 IS 5 BP 668 EP 671 DI 10.1097/MPG.0b013e3181eb7a1f PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 671UM UT WOS:000283536900023 PM 20871414 ER PT J AU Aftandilian, CC Friedmann, AM AF Aftandilian, Catherine C. Friedmann, Alison M. TI Burkitt Lymphoma With Pancreatic Involvement SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE Burkitt lymphoma; non-Hodgkin lymphoma; unusual sites; pancreatic lymphoma; pediatrics ID NON-HODGKINS-LYMPHOMA; 1ST MANIFESTATION; CHILDHOOD; SECONDARY AB A 10-year-old boy was referred to our clinic for tonsillectomy and was found to have a large mass within his oropharynx. Intraoperative biopsies confirmed Burkitt lymphoma. Further imaging and biopsy revealed pancreatic involvement. He was treated with multiagent chemotherapy. He remains disease-free 6 years later. Review of the literature demonstrates other cases of non-Hodgkin lymphoma with pancreatic involvement with good outcomes. Pancreatic involvement is a relatively rare occurrence in childhood lymphoma. C1 [Aftandilian, Catherine C.; Friedmann, Alison M.] Massachusetts Gen Hosp Children, Boston, MA USA. RP Friedmann, AM (reprint author), Massachusetts Gen Hosp, Yawkey 8B,55 Fruit St, Boston, MA 02114 USA. EM afriedmann@partners.org NR 15 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV PY 2010 VL 32 IS 8 BP E338 EP E340 DI 10.1097/MPH.0b013e3181ed1178 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 671VA UT WOS:000283538300021 PM 20930650 ER PT J AU Vesco, AT Anderson, BJ Laffel, LMB Dolan, LM Ingerski, LM Hood, KK AF Vesco, Anthony T. Anderson, Barbara J. Laffel, Lori M. B. Dolan, Lawrence M. Ingerski, Lisa M. Hood, Korey K. TI Responsibility Sharing between Adolescents with Type 1 Diabetes and Their Caregivers: Importance of Adolescent Perceptions on Diabetes Management and Control SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE adolescents; family; glycemic control; responsibility sharing; type 1 diabetes ID METABOLIC-CONTROL; GLYCEMIC CONTROL; HEALTH-STATUS; ADHERENCE; CHILDREN; FAMILY; MELLITUS; OUTCOMES; ASSOCIATION; INVOLVEMENT AB Objective To analyze associations between factor scores for caregiver responsibility for direct and indirect diabetes management tasks with glycemic control and blood glucose monitoring (BGM) frequency. Methods Two hundred and sixty one adolescents with type 1 diabetes and their caregivers completed the Diabetes Family Responsibility Questionnaire (DFRQ). Data on diabetes management (e.g., BGM frequency) and glycemic control (e.g., A1c values) were obtained. Results Confirmatory factor analysis of the DFRQ revealed two factors-direct and indirect management tasks. Multivariate analyses demonstrated that adolescent perception of greater responsibility sharing with caregivers on direct management tasks was significantly associated with higher BGM frequency. Conclusions Adolescents who perceive greater caregiver responsibility, particularly around direct management tasks, engage in better diabetes management. Implications of these findings include designing interventions that encourage and sustain caregiver responsibility through adolescence and make explicit the contribution of caregivers. C1 [Vesco, Anthony T.; Ingerski, Lisa M.; Hood, Korey K.] Cincinnati Childrens Hosp, Med Ctr, Ctr Promot Treatment Adherence & Self Management, Div Behav Med & Clin Psychol, Cincinnati, OH 45229 USA. [Anderson, Barbara J.] Texas Childrens Hosp, Dept Pediat, Baylor Coll Med, Houston, TX 77030 USA. [Laffel, Lori M. B.] Harvard Univ, Sch Med, Pediat Adolescent & Youth Adult Sect, Joslin Diabet Ctr, Cambridge, MA 02138 USA. [Dolan, Lawrence M.] Cincinnati Childrens Hosp, Med Ctr, Ctr Diabet, Div Endocrinol, Cincinnati, OH 45229 USA. [Dolan, Lawrence M.; Hood, Korey K.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45221 USA. RP Hood, KK (reprint author), Cincinnati Childrens Hosp, Med Ctr, Ctr Promot Treatment Adherence & Self Management, Div Behav Med & Clin Psychol, MLC 7039,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM korey.hood@cchmc.org FU NICHD NIH HHS [N01 HD003364]; NIDDK NIH HHS [K23 DK073340] NR 29 TC 15 Z9 15 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD NOV-DEC PY 2010 VL 35 IS 10 BP 1168 EP 1177 DI 10.1093/jpepsy/jsq038 PG 10 WC Psychology, Developmental SC Psychology GA 666MI UT WOS:000283119100012 PM 20444852 ER PT J AU Laffel, L AF Laffel, Lori TI Exercise: It Isn't Just Child's Play When it Comes to Managing Type 1 Diabetes SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID NOCTURNAL HYPOGLYCEMIA; ADOLESCENTS; IMPACT C1 Harvard Univ, Sch Med, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect,Joslin Diabet Ctr, Boston, MA 02215 USA. RP Laffel, L (reprint author), Harvard Univ, Sch Med, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect,Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2010 VL 157 IS 5 BP 701 EP 703 DI 10.1016/j.jpeds.2010.07.061 PG 4 WC Pediatrics SC Pediatrics GA 665OS UT WOS:000283045900004 PM 20850760 ER PT J AU Mehta, M Mansfield, T VanderVeen, DK AF Mehta, M. Mansfield, T. VanderVeen, D. K. TI Effect of topical anesthesia and age on pain scores during retinopathy of prematurity screening SO JOURNAL OF PERINATOLOGY LA English DT Article DE retinopathy of prematurity; screening; topical anesthesia; Premature Infant Pain Profile; PIPP ID EYE EXAMINATIONS; PRETERM; INFANTS; STRESS; TRIAL; VALIDATION; ANALGESIA; CHILDREN; NEWBORN; PROFILE AB Objective: The efficacy of topical anesthesia during retinopathy of prematurity (ROP) screening has been a controversial issue. To determine the efficacy of proparacaine eye drops (0.5%), we compared the Premature Infant Pain Profile (PIPP) scores in 40 preterm infants undergoing ROP screening. Study Design: Prospective randomized double masked cross-over clinical trial. The study was conducted in the neonatal intensive units for infants undergoing routine ROP screening exams. Baseline PIPP scores and post-examination PIPP scores at 1 and 5 min were compared for: (1) those receiving saline vs proparacaine eye drops (2) first ROP screening vs second ROP screening, regardless of the type of eye drops used. Wilcoxon signed-ranks test was used to pair pain scores. Result: Forty preterm infants were included in the study. Mean gestational age (GA) at first and second examinations was 33.3 and 35.3 weeks, respectively. Proparacaine use significantly lowered mean PIPP scores (P=0.027) and delta scores (P=0.013) at 1 min after examination, but there was no difference at 5 min after examination. Second examinations showed significantly lower mean PIPP scores after examination (1 min (P=0.003) and 5 min (P=0.025)), regardless of the type of drop used. Conclusion: Proparacaine eye drops offer significant relief of pain that is apparently short lived. Significantly lower PIPP scores at second ROP examinations suggested that infants of older GA may have a greater ability to tolerate ROP screening. We recommend the use of proparacaine eye drops for the short term, immediate relief of pain during ROP screening in preterm infants of lesser GA. Journal of Perinatology (2010) 30, 731-735; doi:10.1038/jp.2010.36; published online 18 March 2010 C1 [VanderVeen, D. K.] Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. [Mehta, M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP VanderVeen, DK (reprint author), Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. EM deborah.vanderveen@childrens.harvard.edu NR 24 TC 11 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD NOV PY 2010 VL 30 IS 11 BP 731 EP 735 DI 10.1038/jp.2010.36 PG 5 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 672KY UT WOS:000283583100006 PM 20237484 ER PT J AU Pierre, JM AF Pierre, Joseph M. TI The Borders of Mental Disorder in Psychiatry and the DSM: Past, Present, and Future SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE Diagnostic and Statistical Manual of Mental Disorders (DSM); DSM-5; diagnosis; normality; spectrum; categorical diagnosis; dimensional diagnosis; personality disorders; neuroethics; neuroenhancement ID NATIONAL COMORBIDITY SURVEY; HARMFUL DYSFUNCTION ANALYSIS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED-TRIAL; BIPOLAR DISORDER; PERSONALITY-DISORDERS; DIAGNOSTIC CRITERIA; LIFETIME PREVALENCE; COGNITIVE DEFICITS; SURVEY REPLICATION AB Over the past 60 years, the Diagnostic and Statistical Manual of Mental Disorders (DSM) has evolved from early efforts to collect statistical information to a modern compendium of mental disorders that can be reliably diagnosed, but have not been validated. Throughout this history, DSM architects have struggled with the seemingly fundamental, but complex question of how to define a mental disorder. Current proposals indicate that a spectrum model of mental illness will be embraced in DSM-5, prompting renewed concern and debate about pathologizing normal existence. While a spectrum view of mental illness may reflect biologic reality and help pave the path towards validated models of psychiatric disorder, diagnostic expansion does have important practical implications and could give rise to problems in clinical work and society at large, including the further sanctioning of a shift from psychiatric treatment to neuroenhancement. Debates about what should or should not be considered a mental illness in DSM-5 are likely to remain unresolved and, in the future, must be framed according to contextual utility. Diagnosis and thresholds of pathology are ultimately value-based so that careful analysis and perhaps even different definitions of disorder may be required to guide decision-making in research, clinical work, and public policy. (Journal of Psychiatric Practice 2010;16:375-386) C1 [Pierre, Joseph M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Pierre, Joseph M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Pierre, JM (reprint author), 11301 Wilshire Blvd,Bldg 210,Room 15, Los Angeles, CA 90073 USA. EM joseph.pierre2@va.gov NR 117 TC 7 Z9 7 U1 4 U2 18 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 NOV PY 2010 VL 16 IS 6 BP 375 EP 386 DI 10.1097/01.pra.0000390756.37754.68 PG 12 WC Psychiatry SC Psychiatry GA 685CC UT WOS:000284601000002 PM 21107142 ER PT J AU Ball, SW Gilman, SE Mick, E Fitzmaurice, G Ganz, ML Seidman, LJ Buka, SL AF Ball, Sarah W. Gilman, Stephen E. Mick, Eric Fitzmaurice, Garrett Ganz, Michael L. Seidman, Larry J. Buka, Stephen L. TI Revisiting the association between maternal smoking during pregnancy and ADHD SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE ADHD; Maternal smoking; Pregnancy; Etiology; Epidemiology ID DEFICIT HYPERACTIVITY DISORDER; NICOTINE EXPOSURE; CONDUCT PROBLEMS; ALCOHOL-USE; RISK-FACTOR; CHILDREN; SYMPTOMS; RATS; LIFE AB Objective Studies examining the relationship between maternal smoking during pregnancy and the development of Attention Deficit Hyperactivity Disorder (ADHD) among offspring have yielded mixed results with some studies suggesting a strong association and others finding no association These studies have varied in quality of design and measures The purpose of this study was to evaluate the association between maternal smoking during pregnancy and offspring ADHD using detailed prospective smoking data and subsequent follow-up data from the Collaborative Perinatal Project (CPP) Method Maternal smoking status was collected throughout pregnancy during the original CPP study Offspring were followed-up in early adulthood and questioned about ADHD symptoms and diagnosis Logistic regression was used to model the association between maternal smoking during pregnancy and ADHD Linear and logistic regression were used to examine clinical characteristics and remission rates associated with ADHD in relation to maternal smoking Results No association was found between maternal smoking during pregnancy and offspring ADHD Further no differences in age of onset number of symptoms or likelihood of remission were found among ADHD subjects with and without a history of maternal smoking during pregnancy Conclusions These findings do not support the hypothesis that maternal smoking during pregnancy is causally related to ADHD Ongoing research should continue to strive to identify those environmental or genetic factors that may enhance the impact of maternal smoking on ADHD or that may be associated more clearly with the development and potential prevention of ADHD (C) 2010 Elsevier Ltd All rights reserved C1 [Ball, Sarah W.] ABT Associates Inc, Cambridge, MA 02138 USA. [Ball, Sarah W.; Gilman, Stephen E.; Ganz, Michael L.; Buka, Stephen L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.; Buka, Stephen L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fitzmaurice, Garrett] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ganz, Michael L.] Abt Bio Pharma Solut Inc, Lexington, MA USA. [Mick, Eric] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Commonwealth Res Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. RP Ball, SW (reprint author), ABT Associates Inc, 55 Wheeler St, Cambridge, MA 02138 USA. RI Buka, Stephen/H-7335-2014; Gilman, Stephen/E-7632-2010; OI Buka, Stephen/0000-0002-8578-9308; Gilman, Stephen/0000-0002-8331-6419; Ganz, Michael/0000-0002-9702-2999; Mick, Eric/0000-0001-8505-8145 FU MCHB (Maternal and Child Health Bureau) [2T76MC00001] FX This work was supported in part by a grant from MCHB (Maternal and Child Health Bureau) Grant # 2T76MC00001 (SWB) MCHB had no further role in the study design analysis and interpretation of the data in the writing of the report and in the decision to submit the paper for publication NR 37 TC 13 Z9 13 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV PY 2010 VL 44 IS 15 BP 1058 EP 1062 DI 10.1016/j.jpsychires.2010.03.009 PG 5 WC Psychiatry SC Psychiatry GA 684RJ UT WOS:000284566700010 PM 20413131 ER PT J AU Perez-Rodriguez, MM Weinstein, S New, AS Bevilacqua, L Yuan, QP Zhou, ZF Hodgkinson, C Goodman, M Koenigsberg, HW Goldman, D Siever, LJ AF Perez-Rodriguez, M. Mercedes Weinstein, Shauna New, Antonia S. Bevilacqua, Laura Yuan, Qiaoping Zhou, Zhifeng Hodgkinson, Colin Goodman, Marianne Koenigsberg, Harold W. Goldman, David Siever, Larry J. TI Tryptophan-hydroxylase 2 haplotype association with borderline personality disorder and aggression in a sample of patients with personality disorders and healthy controls SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Borderline personality disorder; TPH2; Suicidal behavior; Affective instability; Impulsive aggression ID CENTRAL SEROTONERGIC FUNCTION; ISOFORM TPH2 GENE; IMPULSIVE-AGGRESSION; PROLACTIN RESPONSE; D-FENFLURAMINE; CEREBROSPINAL-FLUID; VIOLENT OFFENDERS; MAJOR DEPRESSION; TRANSMISSION DISEQUILIBRIUM; POLYMORPHIC VARIANTS AB Background There is a decreased serotonergic function in impulsive aggression and borderline personality disorder (BPD) and genetic association studies suggest a role of serotonergic genes in impulsive aggression and BPD Only one study has analyzed the association between the tryptophan-hydroxylase 2 (TPH2) gene and BPD A TPH2 "risk" haplotype has been described that is associated with anxiety depression and suicidal behavior Methods We assessed the relationship between the previously identified risk" haplotype at the TPH2 locus and BPD diagnosis impulsive aggression affective lability and suicidal/parasuicidal behaviors in a well-characterized clinical sample of 103 healthy controls (HCs) and 251 patients with personality disorders (109 with BPD) A logistic regression including measures of depression affective lability and aggression scores in predicting risk" haplotype was conducted Results The prevalence of the "risk" haplotype was significantly higher in patients with BPD compared to HCs Those with the "risk" haplotype have higher aggression and affect lability scores and more suicidal/parasuicidal behaviors than those without it In the logistic regression model affect lability was the only significant predictor and it correctly classified 83 1% of the subjects as risk or non-risk haplotype carriers Conclusions We found an association between the previously described TPH2 risk haplotype and BPD diagnosis affective lability suicidal/parasuicidal behavior and aggression scores (C) 2010 Elsevier Ltd All rights reserved C1 [Perez-Rodriguez, M. Mercedes; Weinstein, Shauna; New, Antonia S.; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Weinstein, Shauna; New, Antonia S.; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.] James J Peters Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr, Bronx, NY 10468 USA. [Bevilacqua, Laura; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Siever, LJ (reprint author), James J Peters Vet Adm Med Ctr, 3rd Floor,Room 3B,20 130 W Kingsbridge Rd, Bronx, NY 10468 USA. RI Perez Rodriguez, Maria/B-9410-2013; Goldman, David/F-9772-2010 OI Perez Rodriguez, Maria/0000-0001-5137-1993; Goldman, David/0000-0002-1724-5405 FU National Institute of Mental Health [MH56140, MH63875]; Veterans Affairs [7609-028, 9001-03-0051]; Veterans Affairs VISN 3 Mental Illness Research Education & Clinical Center; National Center for Research Resources (NCRR) [MO1-RR-00071] FX This research was supported by Grants MH56140 & MH63875 from the National Institute of Mental Health to Larry J Siever by a Veterans Affairs Merit Review Grant (7609-028) to Larry J Siever and by the Veterans Affairs VISN 3 Mental Illness Research Education & Clinical Center; This publication was made possible by Grant Number MO1-RR-00071 from the National Center for Research Resources (NCRR) a component of the National Institutes of Health (NIH) Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH; This work was supported in part by a VA Merit award to Dr New (9001-03-0051) New (PI)- Intermediate Phenotypes for Borderline Personality Disorder and a VA Career Development Award to Dr Goodman NR 78 TC 30 Z9 34 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV PY 2010 VL 44 IS 15 BP 1075 EP 1081 DI 10.1016/j.jpsychires.2010.03.014 PG 7 WC Psychiatry SC Psychiatry GA 684RJ UT WOS:000284566700013 PM 20451217 ER PT J AU Chen, DC Xiu, MH Liu, H Zhang, BS Wang, Y Kosten, TR Zhang, XY AF Chen, Da Chun Xiu, Mei Hong Liu, Hong Zhang, Ben Shu Wang, Yu Kosten, Thomas R. Zhang, Xiang Yang TI Reduced status of plasma total antioxidant capacity in schizophrenia with tardive dyskinesia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Letter C1 [Zhang, Xiang Yang] Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Chen, Da Chun; Xiu, Mei Hong; Zhang, Xiang Yang] Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing, Peoples R China. [Liu, Hong; Zhang, Ben Shu; Wang, Yu] TianJin Med Univ, Dept Neurol, Tianjin, Peoples R China. RP Zhang, XY (reprint author), Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV PY 2010 VL 44 IS 15 BP 1111 EP 1112 DI 10.1016/j.jpsychires.2010.03.008 PG 2 WC Psychiatry SC Psychiatry GA 684RJ UT WOS:000284566700019 PM 20398909 ER PT J AU Singh, JA Mahowald, ML Noorbaloochi, S AF Singh, Jasvinder A. Mahowald, Maren L. Noorbaloochi, Siamak TI Intraarticular Botulinum Toxin A for Refractory Painful Total Knee Arthroplasty: A Randomized Controlled Trial SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE TOTAL KNEE ARTHROPLASTY; INTRAARTICULAR; BOTULINUM TOXIN A; RANDOMIZED CONTROLLED TRIAL; PAIN; FUNCTION ID DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; NEUROPATHIC PAIN; OUTCOME MEASURES; CLINICAL-TRIAL; SUBSTANCE-P; RAT BLADDER; JOINT PAIN; OSTEOARTHRITIS; INJECTIONS AB Objective. To assess short-term efficacy of single intraarticular botulinum toxin (IA-BoNT/A) injection in patients with chronically painful total knee arthroplasty (TKA) in a randomized, placebo-controlled, triple-blind study. Methods. Patients with chronic TKA pain (pain > 6 on 0-10 scale and > 6 months post-TKA) evaluated in and referred from orthopedic surgery clinics were recruited. The primary outcome, proportion of patients with clinically meaningful decrease of at least 2 points on 0-10 visual analog scale (VAS) for pain, was compared between treatment groups at 2 months using comparison of proportions test and for all efficacy timepoints (2, 3, and 4 months) using generalized estimating equations (GEE). Secondary outcomes of global assessment, function, and quality of life were compared using GEE, duration of pain relief by t-test, and adverse events by chi-square test. Results. In total, 54 patients with 60 painful TKA were randomized, with main analyses restricted to one TKA per patient (49 TKA in 49 patients). Mean age was 67 years, 84% were men, and mean duration of TKA pain was 4.5 years. A significantly greater proportion of patients (71%) in the IA-BoNT/A group compared to IA-placebo (35%) achieved clinically meaningful reduction in VAS pain at 2 months (p = 0.028) and at all efficacy timepoints (p = 0.019). Duration of meaningful pain relief was significantly greater after IA-BoNT/A, 39.6 days (SD 50.4) compared to IA-placebo, 15.7 days (SD 22.6; p = 0.045). Statistically significantly better scores were seen in IA-BoNT/A vs IA-placebo for all efficacy timepoints for the following outcomes: "very much improved" on physician global assessment of change (p = 0.003); Western Ontario McMaster Osteoarthritis Index physical function (p = 0.026), stiffness (p = 0.004), and total scores (p = 0.024); and Short-Form 36 pain subscale score (p = 0.049). Number of total and serious adverse events was similar between groups, with no patients in either group with new objective motor or sensory deficits during followup. Conclusion. In this single-center randomized trial, single IA-BoNT/A injection provided clinically meaningful short-term improvements in pain, global assessment, and function in patients with chronic painful TKA. A multicenter trial is needed to confirm these findings. (First Release September I 2010; J Rheumatol 2010;37:2377-86; doi:10.3899/jrheum.100336) C1 [Singh, Jasvinder A.; Mahowald, Maren L.] Univ Minnesota, Vet Affairs Med Ctr, Rheumatol Sect, Med Serv, Minneapolis, MN USA. Univ Minnesota, Vet Affairs Med Ctr, Div Rheumatol, Dept Med, Minneapolis, MN USA. Univ Minnesota, Vet Affairs Med Ctr, Dept Med, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Hlth Sci Res, Rochester, MN USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped, Rochester, MN USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, MN USA. [Singh, Jasvinder A.] Univ Alabama, Fac Off Tower 805B, Birmingham, AL 35294 USA. RP Singh, JA (reprint author), Univ Alabama, Fac Off Tower 805B, 510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com RI teng, yj/C-4440-2011; OI singh, jasvinder/0000-0003-3485-0006 FU NIH CTSA [1 KL2 RR024151-01]; Arthritis Foundation North Central Chapter Grant; University of Minnesota Academic Health Center; Minnesota Medical Foundation; Allergan Pharmaceuticals, Irvine, CA FX Supported by the NIH CTSA Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Thanslational Research), Arthritis Foundation North Central Chapter Grant, University of Minnesota Academic Health Center Seed Grant, and Minnesota Medical Foundation Grant. Dr. Singh and Dr Mahowald have received research and travel grants from Allergan Pharmaceuticals, Irvine, CA, for other research projects. Dr. Mahowald served as a consultant to Allergan Pharmaceuticals. NR 57 TC 17 Z9 18 U1 1 U2 5 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 NOV PY 2010 VL 37 IS 11 BP 2377 EP 2386 DI 10.3899/jrheum.100336 PG 10 WC Rheumatology SC Rheumatology GA 681HL UT WOS:000284301900030 PM 20810509 ER PT J AU Schytz, HW Hansson, A Phillip, D Seib, J Boas, DA Iversen, HK Ashina, M AF Schytz, Henrik W. Hansson, Andreas Phillip, Dorte Seib, Juliette Boas, David A. Iversen, Helle K. Ashina, Messoud TI Spontaneous Low-Frequency Oscillations in Cerebral Vessels: Applications in Carotid Artery Disease and Ischemic Stroke SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Cerebral autoregulation; low frequency oscillations; stroke; carotid artery disease; transcranial Doppler; near-infrared spectroscopy ID BLOOD-FLOW VELOCITY; NEAR-INFRARED SPECTROSCOPY; DYNAMIC AUTOREGULATION; SPECTRAL-ANALYSIS; HEART-RATE; SPONTANEOUS FLUCTUATIONS; PRESSURE-AUTOREGULATION; PHASE RELATIONSHIP; AUTO-REGULATION; PIAL VESSELS AB The etiology behind and physiological significance of spontaneous oscillations in the low-frequency spectrum in both systemic and cerebral vessels remain unknown. Experimental studies have proposed that spontaneous oscillations in cerebral blood flow reflect impaired cerebral autoregulation (CA). Analysis of CA by measurement of spontaneous oscillations in the low-frequency spectrum in cerebral vessels might be a useful tool for assessing risk and investigating different treatment strategies in carotid artery disease (CAD) and stroke. We reviewed studies exploring spontaneous oscillations in the low-frequency spectrum in patients with CAD and ischemic stroke, conditions known to involve impaired CA. Several studies have reported changes in oscillations after CAD and stroke after surgery and over time compared with healthy controls. Phase shift in the frequency domain and correlation coefficients in the time domain are the most frequently used parameters for analyzing spontaneous oscillations in systemic and cerebral vessels. At present, there is no gold standard for analyzing spontaneous oscillations in the low-frequency spectrum, and simplistic models of CA have failed to predict or explain the spontaneous oscillation changes found in CAD and stroke studies. Near-infrared spectroscopy is suggested as a future complementary tool for assessing changes affecting the cortical arterial system. C1 [Schytz, Henrik W.; Hansson, Andreas; Phillip, Dorte; Ashina, Messoud] Univ Copenhagen, Danish Headache Ctr, Glostrup, Denmark. [Iversen, Helle K.] Univ Copenhagen, Glostrup Hosp, Stroke Unit, Dept Neurol,Fac Hlth Sci, Glostrup, Denmark. [Seib, Juliette; Boas, David A.] Harvard Univ, Photon Migrat Imaging Lab, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA USA. RP Schytz, HW (reprint author), Univ Copenhagen, Danish Headache Ctr, DK-2600 Copenhagen, Denmark. EM henrikschytz@dadlnet.com OI Schytz, Henrik Winther/0000-0002-6262-2986; Iversen, Helle Klingenberg/0000-0002-5880-6352 FU NCRR NIH HHS [P41 RR014075] NR 89 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD NOV-DEC PY 2010 VL 19 IS 6 BP 465 EP 474 DI 10.1016/j.jstrokecerebrovasdis.2010.06.001 PG 10 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 686CH UT WOS:000284673900008 PM 20864356 ER PT J AU Raval, MV Bilimoria, KY Bentrem, DJ Stewart, AK Ko, CY Reynolds, M Wayne, JD AF Raval, Mehul V. Bilimoria, Karl Y. Bentrem, David J. Stewart, Andrew K. Ko, Clifford Y. Reynolds, Marleta Wayne, Jeffrey D. TI Use of Sentinel Lymph Node Biopsy for Melanoma in Children and Adolescents SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE melanoma; sentinel lymph node biopsy; pediatric oncology; pediatric surgery; National Cancer Data Base ID CANCER-DATA-BASE; UNITED-STATES; PEDIATRIC MELANOMA; MELANOCYTIC LESIONS; MALIGNANT-MELANOMA; SINGLE-INSTITUTION; POPULATION; EPIDEMIOLOGY; EXPERIENCE; SURVIVAL AB Background: Though sentinel lymph node biopsy (SLNB) is an integral component of melanoma staging, little is known about its use in children Methods: Patients (0-18 years) with melanoma diagnosed from 2003 to 2007 in the National Cancer Data Base were assessed Logistic regression models were used to identify clinicopathologic, socioeconomic, and hospital factors associated with SLNB use and lymph node metastases (LNM) Results: 01 671 children, 68 7% underwent SLNB SLNB utilization rates were 39 9% for T1a patients and 87 6% for T1b-T3 patients T1b-T3 patients were more likely to undergo SLNB if they were older (OR 4 86 95% Cl 1 88-12 59) or cared for at Children's hospitals (OR 2 43 95% CI 1 09-5 40) T1b-T3 patients were less likely to undergo SLNB if uninsured (OR 0 25 95% CI 0 08-0 76) Of those with SLNB, 1 I 8 (25 6%) had pathologically confirmed LNM Patients were more likely to have LNM if younger (OR 3 19 95% Cl 1 20-8 51) or having higher T stage. (OR 10 38 95% CI 4 59-23 47) Conclusions: SI,NB use for children with melanoma was associated with clinicopathologic. socioeconomic, and hospital factors Younger patients have a higher likelihood of LNM but are the least likely to undergo SLNB Though overall adherence appears high. there remains an opportunity for improved care for children with melanoma J. Surg Oncol 2010,102 634-639 (C) 2010 Wiley-Liss, Inc C1 [Raval, Mehul V.; Bilimoria, Karl Y.; Stewart, Andrew K.; Ko, Clifford Y.] Amer Coll Surg, Canc Programs, Div Res & Optimal Patient Care, Chicago, IL USA. [Raval, Mehul V.; Reynolds, Marleta] Childrens Mem Hosp, Div Pediat Surg, Chicago, IL 60614 USA. [Raval, Mehul V.; Bilimoria, Karl Y.; Bentrem, David J.; Wayne, Jeffrey D.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Div Gastrointestinal & Oncol Surg, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Raval, MV (reprint author), 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. OI Raval, Mehul/0000-0002-1527-2661 FU John Gray Research Fellowship; Daniel F and Ada L Rice Foundation; Northwestern University; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service; American College of Surgeons, Commission on Cancer; American Cancer Society FX M V R participates in the American College of Surgeons Clinical Scholars in Residence Program M V R is supported by the John Gray Research Fellowship and the Daniel F and Ada L Rice Foundation. K Y B is supported by a Priority Grant from Northwestern University D J B is supported by a Career Development Award from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service The National Cancer Data Base is supported by the American College of Surgeons, Commission on Cancer, and the American Cancer Society NR 43 TC 3 Z9 3 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD NOV 1 PY 2010 VL 102 IS 6 BP 634 EP 639 DI 10.1002/jso.21683 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 674OZ UT WOS:000283758300018 PM 20721965 ER PT J AU Konstantinidis, IT Warshaw, AL Deshpande, V Sahani, D Berger, D Fernandez-Del Castillo, C Ferrone, CR AF Konstantinidis, Ioannis T. Warshaw, Andrew L. Deshpande, Vikram Sahani, Dushyant Berger, David Fernandez-Del Castillo, Carlos Ferrone, Cristina R. TI Cholesterol Crystal Embolization Presenting as Either Solid or Cystic Pancreatic Lesion SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE cholesterol emboli; pancreas; mass ID EMBOLISM; MIMICKING; CARCINOMA; SYSTEM; COMMON; COLON AB Cholesterol crystal embolization (CCE) can result in end-organ ischemia Retrospective review of clinicopathologic data The first patient was anticoagulated with coumadin for chronic atrial fibrillation and presented subacutely with a solid mass The second patient suffered from coronary artery disease post-angioplasty/stenting and presented with acute pancreatitis and pancreatic cystification CCE should be considered in patients with significant vascular disease. arrhythmias or vascular manipulation who present with a pancreatic mass J Sung Oncol 2010.102 706-708 (C) 2010 Wiley-Liss. Inc C1 [Konstantinidis, Ioannis T.; Warshaw, Andrew L.; Berger, David; Fernandez-Del Castillo, Carlos; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sahani, Dushyant] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Wang Ambulatory Care Ctr 460,15 Parkman St, Boston, MA 02114 USA. FU Institute for Pancreatic Cancer Research, Boston FX Grant sponsor Andrew L Warshaw, MD Institute for Pancreatic Cancer Research, Boston NR 20 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD NOV 1 PY 2010 VL 102 IS 6 BP 706 EP 708 DI 10.1002/jso.21521 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 674OZ UT WOS:000283758300029 PM 20976733 ER PT J AU O'Gorman, DE Colburn, HS Shera, CA AF O'Gorman, David E. Colburn, H. Steven Shera, Christopher A. TI Auditory sensitivity may require dynamically unstable spike generators: Evidence from a model of electrical stimulation SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID DESYNCHRONIZING PULSE TRAINS; COCHLEAR IMPLANTS; SPEECH RECOGNITION; NERVE FIBERS; NOISE; ENHANCEMENT; INFORMATION; RESPONSES; TIME AB The response of the auditory nerve to electrical stimulation is highly sensitive to small modulations (<0.5%). This report demonstrates that dynamical instability (i.e., a positive Lyapunov exponent) can account for this sensitivity in a modified FitzHugh-Nagumo model of spike generation, so long as the input noise is not too large. This finding suggests both that spike generator instability is necessary to account for auditory nerve sensitivity and that the amplitude of physiological noise, such as that produced by the random behavior of voltage-gated sodium channels, is small. Based on these results with direct electrical stimulation, it is hypothesized that spike generator instability may be the mechanism that reconciles high sensitivity with the cross-fiber independence observed under acoustic stimulation. (C) 2010 Acoustical Society of America C1 [O'Gorman, David E.; Colburn, H. Steven] Boston Univ, Dept Biomed Engn, Hearing Res Ctr, Boston, MA 02115 USA. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP O'Gorman, DE (reprint author), Boston Univ, Dept Biomed Engn, Hearing Res Ctr, Boston, MA 02115 USA. EM ogorman@bu.edu; colburn@bu.edu; shera@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC000100] NR 28 TC 1 Z9 1 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 2010 VL 128 IS 5 BP EL300 EP EL305 DI 10.1121/1.3469765 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 685GT UT WOS:000284617900016 PM 21110542 ER PT J AU Jalovec, KE AF Jalovec, Kathryn Eckstein TI Whatever It Takes: Geoffrey Canada's Quest to Change Harlem and America SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Jalovec, Kathryn Eckstein] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jalovec, KE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kjalovec@partners.org NR 1 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2010 VL 49 IS 11 BP 1174 EP 1175 DI 10.1016/j.jaac.2010.09.002 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 674NX UT WOS:000283755000011 ER PT J AU Lemos, BD Storer, BE Iyer, JG Phillips, JL Bichakjian, CK Fang, LC Johnson, TM Liegeois-Kwon, NJ Otley, CC Paulson, KG Ross, MI Yu, SS Zeitouni, NC Byrd, DR Sondak, VK Gershenwald, JE Sober, AJ Nghiem, P AF Lemos, Bianca D. Storer, Barry E. Iyer, Jayasri G. Phillips, Jerri Linn Bichakjian, Christopher K. Fang, L. Christine Johnson, Timothy M. Liegeois-Kwon, Nanette J. Otley, Clark C. Paulson, Kelly G. Ross, Merrick I. Yu, Siegrid S. Zeitouni, Nathalie C. Byrd, David R. Sondak, Vernon K. Gershenwald, Jeffrey E. Sober, Arthur J. Nghiem, Paul TI Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: Analysis of 5823 cases as the basis of the first consensus staging system SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE clinical staging; Merkel cell carcinoma; neuroendocrine carcinoma of the skin; pathologic staging; prognosis; sentinel lymph node biopsy; staging ID UNITED-STATES; MANAGEMENT; FEATURES AB Background: The management of Merkel cell carcinoma (MCC) has been complicated by a lack of detailed prognostic data and by the presence of conflicting staging systems. Objective: We sought to determine the prognostic significance of tumor size, clinical versus pathologic nodal evaluation, and extent of disease at presentation and thereby derive the first consensus staging/prognostic system for MCC. Methods: A total of 5823 prospectively enrolled MCC cases from the National Cancer Data Base had follow-up data (median 64 months) and were used for prognostic analyses. Results: At 5 years, overall survival was 40% and relative survival (compared with age- and sex-matched population data) was 54%. Among all MCC cases, 66% presented with local, 27% with nodal, and 7% with distant metastatic disease. For cases presenting with local disease only, smaller tumor size was associated with better survival (stage 1, <= 2 cm, 66% relative survival at 5 years; stage II, >2 cm, 51%; P < .0001). Patients with clinically local-only disease and pathologically proven negative nodes had better outcome (76% at 5 years) than those who only underwent clinical nodal evaluation (59%, P < .0001). Limitations:The National Cancer Data Base does not capture disease-specific survival. Overall survival for patients with MCC was therefore used to calculate relative survival based on matched population data. Conclusion: Although the majority (68%) of patients with MCC in this nationwide cohort did not undergo pathologic nodal evaluation, this procedure may be indicated in many cases as it improves prognostic accuracy and has important treatment implications for those found to have microscopic nodal involvement. Am Acad Dermatol 2010;63:751-61.) C1 [Lemos, Bianca D.; Iyer, Jayasri G.; Paulson, Kelly G.; Nghiem, Paul] Univ Washington, Dept Med Dermatol, Seattle, WA 98195 USA. [Fang, L. Christine] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. [Byrd, David R.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Storer, Barry E.; Nghiem, Paul] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Phillips, Jerri Linn] Amer Coll Surg, Commiss Canc, Chicago, IL USA. [Bichakjian, Christopher K.; Johnson, Timothy M.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. [Ross, Merrick I.; Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Liegeois-Kwon, Nanette J.] Johns Hopkins Med, Baltimore, MD USA. [Otley, Clark C.] Mayo Clin, Dept Dermatol, Rochester, MN USA. [Sondak, Vernon K.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Sondak, Vernon K.] Univ S Florida, Tampa, FL USA. [Yu, Siegrid S.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Zeitouni, Nathalie C.] SUNY Buffalo, Roswell Pk Canc Inst, Buffalo, NY 14260 USA. [Sober, Arthur J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Byrd, David R.; Nghiem, Paul] Seattle Canc Care Alliance, Seattle, WA USA. RP Nghiem, P (reprint author), 815 Mercer St,Brotman 242, Seattle, WA 98109 USA. EM pnghiem@uw.edu RI Nghiem, Paul/A-9210-2011; Paulson, Kelly/E-5761-2010; OI Nghiem, Paul/0000-0003-2784-963X; Paulson, Kelly/0000-0002-0033-3708; Lemos, Bianca/0000-0002-2222-0499 FU National Institutes of Health (NIH) [K02-AR50993, K24-CA139052]; American Cancer Society (ACS) [RSG-08-115-01-CCE]; Schering Pharmaceutical, Kenilworth, NJ; David & Rosalind Bloom Endowment for MCC Research; University of Washington FX Supported by National Institutes of Health (NIH) K02-AR50993; American Cancer Society (ACS) RSG-08-115-01-CCE; ACS Jerry Wachter Merkel Cell Carcinoma (MCC) Fund; NIH K24-CA139052; an unrestricted educational grant from Schering Pharmaceutical, Kenilworth, NJ; the David & Rosalind Bloom Endowment for MCC Research; and the University of Washington MCC Patient Gift Fund. NR 26 TC 172 Z9 174 U1 2 U2 9 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 NOV PY 2010 VL 63 IS 5 BP 751 EP 761 DI 10.1016/j.jaad.2010.02.056 PG 11 WC Dermatology SC Dermatology GA 675EP UT WOS:000283809300002 PM 20646783 ER PT J AU Patti, JA AF Patti, John A. TI Entitlement, Complacency, and Inertia: Obstacles to Progress, Impediments to Survival SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2010 VL 7 IS 11 BP 825 EP 825 DI 10.1016/j.jacr.2010.09.010 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SU UT WOS:000208363300001 PM 21040858 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI Untitled SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter ID DENTAL PROCEDURES; ARTHROPLASTY C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 2010 VL 141 IS 11 BP 1295 EP 1296 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 680OK UT WOS:000284244100002 PM 21037183 ER PT J AU Alley, DE Koster, A Mackey, D Cawthon, P Ferrucci, L Simonsick, EM Yu, BB Hardy, S Goodpaster, B Sarkisian, C Houston, DK Kritchevsky, SB Cummings, S Lee, JS Tylavsky, FA Newman, A Harris, T AF Alley, Dawn E. Koster, Annemarie Mackey, Dawn Cawthon, Peggy Ferrucci, Luigi Simonsick, Eleanor M. Yu, Binbing Hardy, Susan Goodpaster, Bret Sarkisian, Catherine Houston, Denise K. Kritchevsky, Stephen B. Cummings, Steven Lee, Jung-Sun Tylavsky, Frances A. Newman, Anne Harris, Tamara CA Hlth Aging & Body Composition Stud TI Hospitalization and Change in Body Composition and Strength in a Population-Based Cohort of Older Persons SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE lean mass; weight loss; function; hospitalization; strength ID BED REST; WEIGHT CHANGE; MUSCLE MASS; ADULTS; FRAILTY; HEALTH; WOMEN; DISABILITY; MORTALITY; RECOVERY AB OBJECTIVES: To examine the association between hospitalization and annual changes in body composition and strength in older adults. DESIGN: Cohort study. SETTING: Clinic examinations in Pittsburgh, Pennsylvania, or Memphis, Tennessee. PARTICIPANTS: Well-functioning adults aged 70 to 79 who participated in the Health, Aging and Body Composition Study. MEASUREMENTS: Hospitalizations were reported at annual clinic visits and in semiannual phone interviews. In the event of death or reported hospitalization, hospitalizations were adjudicated according to medical record review. Dual X-ray absorptiometry (DXA) assessments of total, lean, and fat mass were conducted in six annual examinations, and measures of knee extensor strength were conducted in two annual examinations. RESULTS: DXA assessments followed 2,309 hospitalizations. In men and women, hospitalization in the previous year was associated with greater declines in total mass (- 0.76 and -0.81 kg, respectively), fat mass (-0.41 and -0.54 kg), and lean mass (-0.33 and -0.25 kg) (P < .001 for all) than in nonhospitalized participants, after adjustment for demographics and baseline values. Hospitalization was associated with strength declines in men (-4.02 Nm, P = .046) but not in women. Relationships were similar after adjusting for health behaviors and chronic conditions, although the association between hospitalization and strength was attenuated. Associations increased with number of days hospitalized; hospitalizations totaling 8 days or more in the previous year were associated with significantly greater loss of total, lean, and fat mass and loss of strength in both sexes than in nonhospitalized participants. CONCLUSION: Hospitalization is associated with significant changes in body composition and strength in older persons. These effects appear particularly important in persons hospitalized for 8 or more days per year. J Am Geriatr Soc 58:2085-2091, 2010. C1 [Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Koster, Annemarie; Yu, Binbing; Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Mackey, Dawn; Cawthon, Peggy; Cummings, Steven] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Ferrucci, Luigi; Simonsick, Eleanor M.] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA. [Hardy, Susan; Goodpaster, Bret; Newman, Anne] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Newman, Anne] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. [Sarkisian, Catherine] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Lee, Jung-Sun] Univ Georgia, Coll Publ Hlth, Athens, GA 30602 USA. [Tylavsky, Frances A.] Univ Tennessee, Dept Epidemiol, Memphis, TN USA. RP Alley, DE (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. EM dalley@epi.umaryland.edu RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institutes of Health, National Institute on Aging (NIA); Organized Research Center on Aging at the University of Maryland, Baltimore; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-2106] FX D. Houston received a speaker honorarium from Abbott Nutrition Health Institute. All other authors have no financial disclosure to report. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (NIA) and by the Organized Research Center on Aging at the University of Maryland, Baltimore. The Health ABC Study is funded under NIA Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-2106. NR 25 TC 22 Z9 23 U1 4 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC 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 NOV PY 2010 VL 58 IS 11 BP 2085 EP 2091 DI 10.1111/j.1532-5415.2010.03144.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 676WT UT WOS:000283950100005 PM 21054288 ER PT J AU Hwang, U Richardson, LD Harris, B Morrison, RS AF Hwang, Ula Richardson, Lynne D. Harris, Ben Morrison, R. Sean TI The Quality of Emergency Department Pain Care for Older Adult Patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE emergency department; pain; quality of care; geriatrics ID ELDERLY-PATIENTS; MEDICAL-RECORD; CANCER PAIN; MANAGEMENT; ANALGESIA; DEMENTIA; FRACTURE AB OBJECTIVES: To determine whether there are differences in emergency department (ED) pain assessment and treatment for older and younger adults. DESIGN: Retrospective observational cohort. SETTING: Urban, academic tertiary care ED during July and December 2005. PARTICIPANTS: Adult patients with conditions warranting ED pain care. MEASUREMENTS: Age, Charlson comorbidity score, number of prior medications, sex, race and ethnicity, triage severity, degree of pain, treating clinician, and final ED diagnosis. Pain care process measures were pain assessment and treatment and time of activities. RESULTS: One thousand thirty-one ED visits met inclusion criteria; 92% of these had a documented pain assessment. Of those reporting pain, 41% had follow-up pain assessments, and 59% received analgesic medication (58% of these as opioids, 24% as nonsteroidal anti-inflammatory drugs (NSAIDs)). In adjusted analyses, there were no differences according to age in pain assessment and receiving any analgesic. Older patients (65-84) were less likely than younger patients (18-64) to receive opioid analgesics for moderate to severe (odds ratio (OR) 50.44, 95% confidence interval (CI) 50.22-0.88) and were more likely to more likely to receive NSAIDs for mild pain (OR = 3.72, 95% CI = 0.97-14.24). Older adults had a lower reduction of initial to final recorded pain scores (P = .002). CONCLUSION: There appear to be differences in acute ED pain care for older and younger adults. Lower overall reduction of pain scores and less opioid use for the treatment of painful conditions in older patients highlight disparities of concern. Future studies should determine whether these differences represent inadequate ED pain care. J Am Geriatr Soc 58:2122-2128, 2010. C1 [Hwang, Ula; Richardson, Lynne D.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Hwang, Ula; Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hwang, Ula; Morrison, R. Sean] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Harris, Ben] Univ Illinois, Dept Emergency Med, Advocate Christ Med Ctr, Oak Lawn, IL USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. EM ula.hwang@mountsinai.org FU National Institute on Aging [K24 AG022345]; Jahnigen Career Development Award FX Ula Hwang was a recipient of a Jahnigen Career Development Award administered by the American Geriatrics Society. R. Sean Morrison is a recipient of a Mid-Career Investigator Award in Patient-Oriented Research (K24 AG022345) from the National Institute on Aging. NR 31 TC 33 Z9 33 U1 3 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC 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 NOV PY 2010 VL 58 IS 11 BP 2122 EP 2128 DI 10.1111/j.1532-5415.2010.03152.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 676WT UT WOS:000283950100010 PM 21054293 ER PT J AU Espinoza, SE Jung, I Hazuda, H AF Espinoza, Sara E. Jung, Inkyung Hazuda, Helen TI Lower Frailty Incidence in Older Mexican Americans than in Older European Americans: The San Antonio Longitudinal Study of Aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE frailty; ethnic differences; older adults ID MINI-MENTAL-STATE; WOMENS HEALTH; ADULTS; ASSOCIATION; PHENOTYPE; MORTALITY; PARADOX; INDEX; ADL AB OBJECTIVES: To directly compare frailty incidence of older Mexican American (MA) and European American (EA) adults. DESIGN: Longitudinal, observational cohort study. SETTING: Socioeconomically diverse neighborhoods in San Antonio, Texas. PARTICIPANTS: Three hundred one older MA and 305 older EA adults in the San Antonio Longitudinal Study of Aging (SALSA) who were nonfrail at baseline. MEASUREMENTS: Frailty was assessed at baseline, and three follow-ups conducted over an average of 9.9 years using well-established criteria from the Cardiovascular Health Study. Covariates were baseline age, sex, socioeconomic status (SES), prefrailty status, diabetes mellitus, and comorbidity. The adjusted ethnic odds (MA vs EA) of incident frailty were estimated using generalized estimating equations. RESULTS: There was no ethnic difference in the unadjusted incidence of frailty over the three follow-up examinations (odds ratio (OR) 50.97, 95% confidence interval (CI) 50.62-1.52), even though baseline SES was significantly lower in MAs than EAs. After covariate adjustment, the odds of incident frailty were significantly lower for MAs than EAs (OR = 0.40, 95% CI = 0.23-0.72). Other significant predictors of frailty in the adjusted model were prefrailty (present vs absent OR = 3.19, 95% CI = 1.86-5.47), education (1-year increment OR = 0.89, 95% CI = 0.83-0.96), and income (1-year increment OR = 0.88, 95% CI = 0.79-2.04). CONCLUSION: These findings lend support to the Hispanic Paradox and suggest that MAs who live to older ages are less likely than similarly aged EAs to become frail. Further research is needed to identify the underlying biological and social mechanisms that explain this finding to enhance the development of interventions for the prevention and treatment of this clinical geriatric syndrome. J Am Geriatr Soc 58:2142-2148, 2010. C1 [Espinoza, Sara E.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Espinoza, Sara E.; Hazuda, Helen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Jung, Inkyung] Yonsei Univ, Coll Med, Dept Biostat, Seoul, South Korea. [Espinoza, Sara E.; Hazuda, Helen] S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Espinoza, SE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Div Geriatr Gerontol & Palliat Med, 7703 Floyd Curl Dr,Mail Code 7875, San Antonio, TX 78229 USA. EM espinozas2@uthscsa.edu FU National Institute on Aging [R01-AG10444, R01-AG16518]; National Center for Research Resources (NCRR) [M01-RR01345, KL2 RR025766] FX Research support was received from National Institute on Aging Grants R01-AG10444 and R01-AG16518 and National Center for Research Resources (NCRR) Grant M01-RR01345. This work was also supported by Clinical and Translational Science Awards Award KL2 RR025766 from NCRR. NR 29 TC 18 Z9 21 U1 3 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC 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 NOV PY 2010 VL 58 IS 11 BP 2142 EP 2148 DI 10.1111/j.1532-5415.2010.03153.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 676WT UT WOS:000283950100013 PM 21054295 ER PT J AU Al-Aly, Z Zeringue, A Fu, J Rauchman, MI McDonald, JR El-Achkar, TM Balasubramanian, S Nurutdinova, D Xian, H Stroupe, K Abbott, KC Eisen, S AF Al-Aly, Ziyad Zeringue, Angelique Fu, John Rauchman, Michael I. McDonald, Jay R. El-Achkar, Tarek M. Balasubramanian, Sumitra Nurutdinova, Diaria Xian, Hong Stroupe, Kevin Abbott, Kevin C. Eisen, Seth TI Rate of Kidney Function Decline Associates with Mortality SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; NONTRADITIONAL RISK-FACTORS; CORONARY-HEART-DISEASE; REVERSE EPIDEMIOLOGY; RENAL-DISEASE; UNITED-STATES; CARDIOVASCULAR OUTCOMES; VASCULAR CALCIFICATION; DIABETES-MELLITUS; SERUM CREATININE AB The effect of rate of decline of kidney function on risk for death is not well understood Using the Department of Veterans Affairs national databases, we retrospectively studied a cohort of 4171 patients who had rheumatoid arthritis and early stage 3 chronic kidney disease (CKD, estimated GFR 45 to 60 ml/min) and followed them longitudinally to characterize predictors of disease progression and the effect of rate of kidney function decline on mortality After a median of 2 6 years, 1604 (38%) maintained stable kidney function, 426 (10%), 1147 (28%), and 994 (24%) experienced mild moderate, and severe progression of CKD, respectively (defined as estimated GFR decline of 0 to 1, 1 to 4, and >4 ml/min per yr) Peripheral artery disease predicted moderate progression of CKD progression Black race, hypertension, diabetes, cardiovascular disease, and peripheral artery disease predicted severe progression of CKD After a median of 5 7 years, patients with severe progression had a significantly increased risk for mortality (hazard ratio 1 54 95% confidence interval 1 30 to 1 82) compared with those with mild progression, patients with moderate progression exhibited a similar trend (hazard ratio 1 10 95% confidence interval 0 98 to 1 30) Our results demonstrate an independent and graded association between the rate of kidney function decline and mortality Incorporating the rate of decline into the definition of CKD may transform a static definition into a dynamic one that more accurately describes the potential consequences of the disease for an individual C1 [Al-Aly, Ziyad; Rauchman, Michael I.; El-Achkar, Tarek M.] St Louis Vet Affairs Med Ctr, Div Nephrol, St Louis, MO 63106 USA. [Al-Aly, Ziyad; Zeringue, Angelique; Fu, John; McDonald, Jay R.; Balasubramanian, Sumitra; Nurutdinova, Diaria; Xian, Hong; Eisen, Seth] St Louis Vet Affairs Clin Res & Epidemiol Ctr, St Louis, MO USA. [Fu, John] St Louis Univ, Div Biostat, Sch Publ Hlth, St Louis, MO 63103 USA. [McDonald, Jay R.; Nurutdinova, Diaria] Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA. [Stroupe, Kevin] Edward Hines Vet Affairs Med Ctr, Ctr Management Complex Chron Care, Hines, IL USA. [Abbott, Kevin C.] Walter Reed Army Med Ctr, Div Nephrol, Washington, DC 20307 USA. [Eisen, Seth] US Dept Vet Affairs, Washington, DC USA. RP Al-Aly, Z (reprint author), St Louis Vet Affairs Med Ctr, Div Nephrol, 915 N Grand Blvd,111B JC, St Louis, MO 63106 USA. RI Zeringue, Angelique/I-1755-2012; Al-Aly, Ziyad/S-4439-2016; OI Al-Aly, Ziyad/0000-0002-2600-0434; Abbott, Kevin/0000-0003-2111-7112 FU Department of Veterans Affairs [VISN 15] FX This work was funded by a Department of Veterans Affairs VISN 15 Career Development Award to Ziyad Al-Aly, M D NR 48 TC 85 Z9 86 U1 1 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2010 VL 21 IS 11 BP 1961 EP 1969 DI 10.1681/ASN.2009121210 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 689ZL UT WOS:000284969500020 PM 20947634 ER PT J AU Kan, IP Larocque, KF Lafleche, G Coslett, HB Verfaellie, M AF Kan, Irene P. Larocque, Karen F. Lafleche, Ginette Coslett, H. Branch Verfaellie, Mieke TI Memory monitoring failure in confabulation Evidence from the semantic illusion paradigm SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Anterior communicating artery aneurysm; Memory disorders; Neuropsychology; Cognition Frontal lobe; Recognition ID STRATEGIC RETRIEVAL; FALSE RECOGNITION; PREFRONTAL CORTEX; AMNESIA; LESIONS; MECHANISMS; RECOLLECTION; HYPOTHESIS; RECALL; SELF AB Several prominent models of confabulation characterize the syndrome as a failure in controlled aspects of memory retrieval, such as pre-retrieval cue specification and post-retrieval monitoring These models have been generated primarily in the context of studies of autobiographical memory retrieval Less research has focused on the existence and mechanisms of semantic confabulation We examined whether confabulation extends to the semantic domain and if so whether it could be understood as a monitoring failure We focus on post-retrieval monitoring by using a verification task that minimizes cue specification demands We used the semantic illusion paradigm that elicits erroneous endorsement of misleading statements (e g Two animals of each kind were brought onto the Ark by Moses before the great flood') even in controls despite their knowing the correct answer (e g, Noah) Monitoring demands were manipulated by varying semantic overlap between target and foils, ranging from high semantic overlap to unrelated We found that semantic overlap modulated the magnitude of semantic illusion in all groups Compared to controls both confabulators and non-confabulators had greater difficulty monitoring semantically related foils however, elevated endorsement of unrelated foils was unique to confabulators We interpret our findings in the context of a two-process model of post-retrieval monitoring (JINS 2010, 16 1006-1017) C1 [Kan, Irene P.] Villanova Univ, Dept Psychol, Villanova, PA 19085 USA. [Kan, Irene P.; Larocque, Karen F.; Lafleche, Ginette; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kan, Irene P.; Larocque, Karen F.; Lafleche, Ginette; Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA. [Coslett, H. Branch] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Kan, IP (reprint author), Villanova Univ, Dept Psychol, 800 Lancaster Ave, Villanova, PA 19085 USA. OI Verfaellie, Mieke/0000-0001-5535-4584; LaRocque, Karen/0000-0002-6058-2706 FU Office of Research and Development Medical Research Service Department of Veterans Affairs FX This research was supported by the Office of Research and Development Medical Research Service Department of Veterans Affairs (awarded to M V) We thank Olufunsho Faseyitan and Dr David Schnyer for assistance with lesion reconstructions Thanks are also due to Dr Marianna Stark for assistance with patient recruitment Lisa Peterson for assistance with data collection and two anonymous reviewers for their insightful comments on an earlier draft of this manuscript We are especially indebted to all the patients and controls who participated in this research NR 50 TC 8 Z9 8 U1 1 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD NOV PY 2010 VL 16 IS 6 BP 1006 EP 1017 DI 10.1017/S1355617710000536 PG 12 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 690RL UT WOS:000285023200008 PM 20630119 ER PT J AU Victor, TL Boone, KB Kulick, AD AF Victor, Tara L. Boone, Kyle B. Kulick, Alexis D. TI My head hurts just thinking about it SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Letter ID EXAGGERATION C1 [Victor, Tara L.] Calif State Univ Dominguez Hills, Dept Psychol, Carson, CA 90747 USA. [Victor, Tara L.; Boone, Kyle B.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Boone, Kyle B.] Alliant Int Univ, Calif Sch Forens Studies, Alhambra, CA USA. [Victor, Tara L.; Kulick, Alexis D.] Greater Los Angeles Vet Healthcare Syst, Dept Phys Med & Rehabil, Los Angeles, CA USA. RP Victor, TL (reprint author), Calif State Univ Dominguez Hills, Dept Psychol, 1000 E Victoria St,SBS G305, Carson, CA 90747 USA. NR 6 TC 3 Z9 3 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD NOV PY 2010 VL 16 IS 6 BP 1151 EP 1152 DI 10.1017/S1355617710000858 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 690RL UT WOS:000285023200023 PM 20673382 ER PT J AU LaCroix, AZ Powles, T Osborne, CK Wolter, K Thompson, JR Thompson, DD Allred, DC Armstrong, R Cummings, SR Eastell, R Ensrud, KE Goss, P Lee, A Neven, P Reid, DM Curto, M Vukicevic, S AF LaCroix, Andrea Z. Powles, Trevor Osborne, C. Kent Wolter, Kevin Thompson, John R. Thompson, David D. Allred, D. Craig Armstrong, Roisin Cummings, Steve R. Eastell, Richard Ensrud, Kristine E. Goss, Paul Lee, Andrew Neven, Patrick Reid, David M. Curto, Madelyn Vukicevic, Slobodan CA PEARL Investigators TI Breast Cancer Incidence in the Randomized PEARL Trial of Lasofoxifene in Postmenopausal Osteoporotic Women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PREVENTION TRIAL; FOLLOW-UP; TAMOXIFEN; RALOXIFENE; RISK; OUTCOMES; INTERVENTION; EVENTS; NSABP; IBIS AB Background Currently available selective estrogen receptor modulators reduce the risk of breast cancer, but they are not widely used. In the Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene (PEARL) trial, lasofoxifene was shown to reduce the risk of estrogen receptor-positive (ER+) breast cancer, nonvertebral and vertebral fractures, coronary artery disease, and stroke, but the effects on total breast cancer (invasive and ductal carcinoma in situ, ER+ and estrogen receptor-negative [ER-]) and ER+ invasive breast cancer are unknown. Methods Postmenopausal women (n = 8556) aged 59-80 years with low bone density and normal mammograms were randomly assigned to two doses of lasofoxifene (0.25 and 0.5 mg) or placebo. The primary endpoints of the PEARL trial were incidence of ER+ breast cancer and nonvertebral fractures at 5 years. A nested case-control study of 49 incident breast cancer case patients and 156 unaffected control subjects from the PEARL trial was performed to evaluate treatment effects on risk of total and ER+ invasive breast cancer by baseline serum estradiol and sex hormone-binding globulin levels using logistic regression models. Cox proportional hazards models were used to evaluate risk of total breast cancer and ER+ invasive breast cancer using intention-to-treat analysis. All statistical tests were two-sided. Results Breast cancer was confirmed in 49 women. Compared with placebo, 0.5 mg of lasofoxifene statistically significantly reduced the risk of total breast cancer by 79% (hazard ratio = 0.21; 95% confidence interval [CI] = 0.08 to 0.55) and ER+ invasive breast cancer by 83% (hazard ratio = 0.17; 95% CI = 0.05 to 0.57). The effects of 0.5 mg of lasofoxifene on total breast cancer were similar regardless of Gail score, whereas the effects were markedly stronger for women with baseline estradiol levels greater than the median (odds ratio = 0.11; 95% CI = 0.02 to 0.51) vs those with levels less than the median (odds ratio = 0.78; 95% CI = 0.16 to 3.79; P(interaction) = .04). Conclusion A 0.5-mg dose of lasofoxifene appears to reduce the risks of both total and ER+ invasive breast cancer in postmenopausal women with osteoporosis. C1 [LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Osborne, C. Kent] Baylor Coll Med, Baylor Canc Ctr, Houston, TX 77030 USA. [Osborne, C. Kent] Breast Ctr, Houston, TX USA. [Powles, Trevor] Parkside Oncol Clin, London, England. [Allred, D. Craig] Washington Univ, Sch Med, Div Anat & Mol Pathol, St Louis, MO USA. [Wolter, Kevin; Thompson, John R.; Thompson, David D.; Armstrong, Roisin; Lee, Andrew; Curto, Madelyn] Pfizer Global Res & Dev, New London, CT USA. [Cummings, Steve R.] Calif Pacific Med Ctr, San Francisco Coordinating Ctr, Res Inst, San Francisco, CA USA. [Cummings, Steve R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eastell, Richard] Univ Sheffield, Acad Unit Bone Metab, Sheffield, S Yorkshire, England. [Ensrud, Kristine E.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ensrud, Kristine E.] VA Med Ctr, Minneapolis, MN USA. [Goss, Paul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Breast Canc Res, Boston, MA USA. [Neven, Patrick] Univ Leuven, Univ Hosp Gasthuisberg, Div Gynecol Oncol, Dept Obstet & Gynecol, Louvain, Belgium. [Reid, David M.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland. [Vukicevic, Slobodan] Univ Zagreb, Sch Med, Lab Mineralized Tissue, Zagreb 41001, Croatia. RP LaCroix, AZ (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, POB 19024,M3-A410,1100 Fairview Ave N, Seattle, WA 98109 USA. EM alacroix@whi.org RI Eastell, Richard/G-5851-2011 OI Eastell, Richard/0000-0002-0323-3366 FU Pfizer Inc. FX This study was funded by Pfizer Inc and editorial assistance was provided by Annie Neild, PhD, of PAREXEL and was funded by Pfizer Inc. NR 27 TC 57 Z9 60 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV PY 2010 VL 102 IS 22 BP 1706 EP 1715 DI 10.1093/jnci/djq415 PG 10 WC Oncology SC Oncology GA 682VW UT WOS:000284432100009 PM 21051656 ER PT J AU Annunziata, CM Birrer, MJ AF Annunziata, Christina M. Birrer, Michael J. TI Re: CD157 in Ovarian Carcinoma: How Does It Help Us? Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Annunziata, Christina M.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV PY 2010 VL 102 IS 22 BP 1741 EP U79 DI 10.1093/jnci/djq395 PG 2 WC Oncology SC Oncology GA 682VW UT WOS:000284432100013 ER PT J AU Tuttle, RM Ball, DW Byrd, D Dilawari, RA Doherty, GM Duh, QY Ehya, H Farrar, WB Haddad, RI Kandeel, F Kloos, RT Kopp, P Lamonica, DM Loree, TR Lydiatt, WM McCaffrey, JC Olson, JA Parks, L Ridge, JA Shah, JP Sherman, SI Sturgeon, C Waguespack, SG Wang, TN Wirth, LJ AF Tuttle, R. Michael Ball, Douglas W. Byrd, David Dilawari, Raza A. Doherty, Gerard M. Duh, Quan Yang Ehya, Hormoz Farrar, William B. Haddad, Robert I. Kandeel, Fouad Kloos, Richard T. Kopp, Peter Lamonica, Dominick M. Loree, Thom R. Lydiatt, William M. McCaffrey, Judith C. Olson, John A., Jr. Parks, Lee Ridge, John A. Shah, Jatin P. Sherman, Steven I. Sturgeon, Cord Waguespack, Steven G. Wang, Thomas N. Wirth, Lori J. TI Thyroid Carcinoma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines thyroid gland cancer malignancy tumor anaplastic thyroid cancer follicular cancer; Hurthle cell carcinoma papillary thyroid cancer medullary thyroid cancer thyroidectomy radioactive ID RECOMBINANT HUMAN THYROTROPIN; SERUM THYROGLOBULIN MEASUREMENT; INITIAL SURGICAL-MANAGEMENT; NEEDLE-ASPIRATION-CYTOLOGY; PROGNOSTIC SCORING SYSTEM; RECEPTOR MESSENGER-RNA; LYMPH-NODE METASTASIS; HIGH-RISK PAPILLARY; PHASE-II TRIAL; UNITED-STATES C1 [Tuttle, R. Michael; Shah, Jatin P.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Byrd, David] Univ Washington, Seattle, WA 98195 USA. [Dilawari, Raza A.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Doherty, Gerard M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Ehya, Hormoz; Ridge, John A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Farrar, William B.; Kloos, Richard T.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Kopp, Peter; Sturgeon, Cord] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Lamonica, Dominick M.; Loree, Thom R.] Roswell Pk Canc Inst, Buffalo, NY USA. [Lydiatt, William M.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Parks, Lee] Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA. [Sherman, Steven I.; Waguespack, Steven G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wang, Thomas N.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Wirth, Lori J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Tuttle, RM (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. OI Sherman, Steven/0000-0002-3079-5153; Shah, Jatin/0000-0002-6444-6592 NR 217 TC 97 Z9 104 U1 1 U2 12 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2010 VL 8 IS 11 BP 1228 EP + PG 27 WC Oncology SC Oncology GA 681HP UT WOS:000284302300002 PM 21081783 ER PT J AU Ettinger, DS Akerley, W Bepler, G Blum, MG Chang, A Cheney, RT Chineac, LR Amico, TAD Demmy, TL Govindan, R Grannis, FW Jahan, T Johnson, DH Kessinger, A Komaki, R Kong, FM Kris, MG Krug, LM Le, QT Lennes, IT Martins, R Malley, JO Osarogiagbon, RU Otterson, GA Patel, JD Pisters, KM Reckamp, K Riely, GJ Rohren, E Swanson, SJ Wood, DE Yang, SC AF Ettinger, David S. Akerley, Wallace Bepler, Gerold Blum, Matthew G. Chang, Andrew Cheney, Richard T. Chineac, Lucian R. Amico, Thomas A. D. Demmy, Todd L. Govindan, Ramaswamy Grannis, Frederic W., Jr. Jahan, Thierry Johnson, David H. Kessinger, Anne Komaki, Ritsuko Kong, Feng-Ming Kris, Mark G. Krug, Lee M. Le, Quynh Thu Lennes, Inga T. Martins, Renato Malley, Janis O. Osarogiagbon, Raymond U. Otterson, Gregory A. Patel, Jyoti D. Pisters, Katherine M. Reckamp, Karen Riely, Gregory J. Rohren, Eric Swanson, Scott J. Wood, Douglas E. Yang, Stephen C. TI Thymic Malignancies SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines thymoma thymic carcinoma mediastinal tumor ID ADJUVANT RADIATION-THERAPY; PRIMARY MEDIASTINAL TUMORS; STAGE-II THYMOMA; EPITHELIAL TUMORS; MULTIDISCIPLINARY APPROACH; ADOC CHEMOTHERAPY; INTERGROUP TRIAL; INVASIVE THYMOMA; FOLLOW-UP; PHASE-II C1 [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bepler, Gerold] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Blum, Matthew G.; Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Chang, Andrew; Kong, Feng-Ming] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cheney, Richard T.; Demmy, Todd L.] Roswell Pk Canc Inst, Roswell, GA USA. [Amico, Thomas A. D.] Duke Comprehens Canc Ctr, Durham, NC USA. [Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Jahan, Thierry] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Johnson, David H.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Kessinger, Anne] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Komaki, Ritsuko; Rohren, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Kris, Mark G.; Krug, Lee M.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Le, Quynh Thu] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Lennes, Inga T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Martins, Renato; Wood, Douglas E.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Malley, Janis O.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA. [Osarogiagbon, Raymond U.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. OI Chang, Andrew/0000-0001-9506-0425; Reckamp, Karen/0000-0002-9213-0325 NR 46 TC 7 Z9 7 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2010 VL 8 IS 11 BP 1302 EP 1315 PG 14 WC Oncology SC Oncology GA 681HP UT WOS:000284302300005 PM 21081786 ER PT J AU Jetzfellner, T Rosenthal, A Buehler, A Dima, A Englmeier, KH Ntziachristos, V Razansky, D AF Jetzfellner, Thomas Rosenthal, Amir Buehler, Andreas Dima, Alexander Englmeier, Karl-Hans Ntziachristos, Vasilis Razansky, Daniel TI Optoacoustic tomography with varying illumination and non-uniform detection patterns SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID PHOTOACOUSTIC MICROSCOPY; IN-VIVO AB Quantification of tissue morphology and biomarker distribution by means of optoacoustic tomography is an important and longstanding challenge, mainly caused by the complex heterogeneous structure of biological tissues as well as the lack of accurate and robust reconstruction algorithms. The recently introduced model-based inversion approaches were shown to mitigate some of reconstruction artifacts associated with the commonly used back-projection schemes, while providing an excellent platform for obtaining quantified maps of optical energy deposition in experimental configurations of various complexity. In this work, we introduce a weighted model-based approach, capable of overcoming reconstruction challenges caused by per-projection variations of object's illumination and other partial illumination effects. The universal weighting procedure is equally shown to reduce reconstruction artifacts associated with other experimental imperfections, such as non-uniform transducer sensitivity fields. Significant improvements in image fidelity and quantification are show-cased both numerically and experimentally on tissue phantoms and mice. (C) 2010 Optical Society of America C1 [Jetzfellner, Thomas; Rosenthal, Amir; Buehler, Andreas; Dima, Alexander; Englmeier, Karl-Hans; Ntziachristos, Vasilis; Razansky, Daniel] Tech Univ Munich, IBMI, D-85764 Neuherberg, Germany. [Jetzfellner, Thomas; Rosenthal, Amir; Buehler, Andreas; Dima, Alexander; Englmeier, Karl-Hans; Ntziachristos, Vasilis; Razansky, Daniel] Helmholtz Ctr Munich, D-85764 Neuherberg, Germany. [Rosenthal, Amir] Massachusetts Gen Hosp, Cardiovasc Res Ctr CVRC, Boston, MA 02115 USA. [Rosenthal, Amir] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. [Rosenthal, Amir] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Razansky, D (reprint author), Tech Univ Munich, IBMI, Ingolstaedter Landstr 1, D-85764 Neuherberg, Germany. EM dr@tum.de RI Rosenthal, Amir/C-8650-2014; OI Englmeier, Karl-Hans/0000-0001-6028-5392; Buhler, Andreas/0000-0002-6402-8585; Razansky, Daniel/0000-0001-8676-0964 FU German Research Foundation (DFG) [RA 1848/1]; European Research Council FX D. Razansky acknowledges support from the German Research Foundation (DFG) Research Grant (RA 1848/1). V. Ntziachristos acknowledges support from the European Research Council through an Advanced Investigator Award. NR 26 TC 14 Z9 14 U1 1 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD NOV PY 2010 VL 27 IS 11 BP 2488 EP 2495 PG 8 WC Optics SC Optics GA 674GC UT WOS:000283723400043 PM 21045914 ER PT J AU Shahian, DM Edwards, F Grover, FL Jacobs, JP Wright, CD Prager, RL Rich, JB Mack, MJ Mathisen, DJ AF Shahian, David M. Edwards, Fred Grover, Fred L. Jacobs, Jeffrey P. Wright, Cameron D. Prager, Richard L. Rich, Jeffrey B. Mack, Michael J. Mathisen, Douglas J. TI The Society of Thoracic Surgeons National Adult Cardiac Database: A continuing commitment to excellence SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Review ID CONGENITAL HEART-DISEASE; BYPASS-GRAFTING SURGERY; ADMINISTRATIVE DATABASES; QUALITY MEASUREMENT; CABG SURGERY; MORTALITY; VARIABILITY; GUIDELINES; MEDICARE; VALIDITY C1 [Shahian, David M.; Wright, Cameron D.; Mathisen, Douglas J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Edwards, Fred] Univ Florida, Div Cardiothorac Surg, Jacksonville, FL USA. [Grover, Fred L.] Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA. [Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA. [Prager, Richard L.] Univ Michigan, Ctr Hlth, Div Adult Cardiac Surg, Ann Arbor, MI 48109 USA. [Rich, Jeffrey B.] Midatlantic Cardiothorac Surg, Norfolk, VA USA. [Mack, Michael J.] Cardiothorac Surg Associates N Texas, Dallas, TX USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 28 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 2010 VL 140 IS 5 BP 955 EP 959 DI 10.1016/j.jtcvs.2010.09.004 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 665TE UT WOS:000283057600013 PM 20951246 ER PT J AU Hoganson, DM Anderson, JL Weinberg, EF Swart, EJ Orrick, BK Borenstein, JT Vacanti, JP AF Hoganson, David M. Anderson, Jennifer L. Weinberg, Eli F. Swart, Eric J. Orrick, Brian K. Borenstein, Jeffrey T. Vacanti, Joseph P. TI Branched vascular network architecture: A new approach to lung assist device technology SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID ARTIFICIAL LUNG; MICROCHANNEL TECHNOLOGIES; RESPIRATORY SUPPORT; OXYGENATOR; CHANNELS; TRANSPLANTATION; PROTOTYPE; REMOVAL; BRIDGE; CO2 AB Objective: A lung assist device would serve an important clinical need as a bridge to transplant or destination therapy for patients with end-stage lung disease. A new lung assist device has been developed that incorporates a branched network of vascular channels adjacent to a gas chamber, separated by a thin, gas-permeable membrane. This study investigated 2 potential gas exchange membranes within this new architecture. Methods: Oxygen and carbon dioxide exchange within the device was tested in vitro using 3 gas-permeable membranes. Two of the membranes, silicone only and silicone-coated microporous polymer, were plasma impermeable. The third, a microporous polymer, was used as a control. Gas exchange testing was done using anticoagulated porcine blood over a range of flow rates. Results: Oxygen and carbon dioxide transfer was demonstrated in the device and increased nearly linearly from 0.6 to 8.0 mL/min blood flow for all of the membranes. There was no significant difference in the gas transfer between the silicone and the silicone-coated microporous polymer membranes. The transfer of oxygen and carbon dioxide in the device was similar to existing hollow fiber oxygenators controlling for surface area. Conclusions: The silicone and silicone-coated microporous polymer membranes both show promise as gas-permeable membranes in a new lung assist device design. Further optimization of the device by improving the membranes and reducing the channel diameter in the vascular network will improve gas transfer. The current device may be scaled up to function as an adult lung assist device. (J Thorac Cardiovasc Surg 2010;140:990-5) C1 [Hoganson, David M.; Anderson, Jennifer L.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Ctr Regenerat Med, Dept Surg, Boston, MA 02114 USA. [Weinberg, Eli F.; Swart, Eric J.; Orrick, Brian K.; Borenstein, Jeffrey T.] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Dept Surg, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org OI Hoganson, David/0000-0002-8141-7793 FU National Institutes of Health [F32 DK076349-01] FX National Institutes of Health (F32 DK076349-01, DMH). NR 23 TC 17 Z9 17 U1 0 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 2010 VL 140 IS 5 BP 990 EP 995 DI 10.1016/j.jtcvs.2010.02.062 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 665TE UT WOS:000283057600019 PM 20591445 ER PT J AU Thrall, JH AF Thrall, James H. TI What Will Radiology Look Like Twenty-five Years From Now? SO JOURNAL OF THORACIC IMAGING LA English DT Editorial Material C1 [Thrall, James H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD NOV PY 2010 VL 25 IS 4 BP 268 EP 269 DI 10.1097/RTI.0b013e3181f740f1 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 674DZ UT WOS:000283715600014 PM 21042064 ER PT J AU Chung, JH Sharma, A Mino-Kenudson, M Lanuti, M Shepard, JAO Digumarthy, SR AF Chung, Jonathan H. Sharma, Amita Mino-Kenudson, Mari Lanuti, Michael Shepard, Jo-Anne O. Digumarthy, Subba R. TI Amyloidosis Presenting as Pulmonary Infarcts A Case Report SO JOURNAL OF THORACIC IMAGING LA English DT Article DE amyloidosis; pulmonary infarct; halo sign ID EXPERIENCE; SPECTRUM AB Amyloidosis is a multisystem disease characterized by extracellular deposition of complex protein-polysaccharide in a beta-pleated configuration. The imaging features in the thorax are well described and are traditionally divided into tracheobronchial, nodular parenchymal, and diffuse alveolar septal subtypes. We describe an unusual case of pulmonary amyloidosis presenting with hemoptysis as a result of pulmonary infarcts related to vascular deposition. With this case, we show that amyloidosis should be considered (along with embolic disease) when vascular insults (infarcts) are seen in multiple vascular territories. C1 [Chung, Jonathan H.; Sharma, Amita; Shepard, Jo-Anne O.; Digumarthy, Subba R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lanuti, Michael] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Digumarthy, SR (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM sdigumarthy@partners.org NR 10 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD NOV PY 2010 VL 25 IS 4 BP W138 EP W140 DI 10.1097/RTI.0b013e3181ced01a PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 674DZ UT WOS:000283715600012 PM 20634764 ER PT J AU LaRocque, RC Rao, SR Tsibris, A Lawton, T Barry, MA Marano, N Brunette, G Yanni, E Ryan, ET AF LaRocque, Regina C. Rao, Sowmya R. Tsibris, Athe Lawton, Thomas Barry, M. Anita Marano, Nina Brunette, Gary Yanni, Emad Ryan, Edward T. TI Pre-travel Health Advice-Seeking Behavior Among US International Travelers Departing From Boston Logan International Airport SO JOURNAL OF TRAVEL MEDICINE LA English DT Article ID ATTITUDES; KNOWLEDGE AB Background. Globally mobile populations are at higher risk of acquiring geographically restricted infections and may play a role in the international spread of infectious diseases. Despite this, data about sources of health information used by international travelers are limited. Methods. We surveyed 1,254 travelers embarking from Boston Logan International Airport regarding sources of health information. We focused our analysis on travelers to low or low-middle income (LLMI) countries, as defined by the World Bank 2009 World Development Report. Results. A total of 476 survey respondents were traveling to LLMI countries. Compared with travelers to upper-middle or high income (UMHI) countries, travelers to LLMI countries were younger, more likely to be foreign-born, and more frequently reported visiting family as the purpose of their trip. Prior to their trips, 46% of these travelers did not pursue health information of any type. In a multivariate analysis, being foreign-born, traveling alone, traveling for less than 14 days, and traveling for vacation each predicted a higher odds of not pursuing health information among travelers to LLMI countries. The most commonly cited reason for not pursuing health information was a lack of concern about health problems related to the trip. Among travelers to LLMI countries who did pursue health information, the internet was the most common source, followed by primary care practitioners. Less than a third of travelers to LLMI countries who sought health information visited a travel medicine specialist. Conclusions. In our study, 46% of travelers to LLMI countries did not seek health advice prior to their trip, largely due to a lack of concern about health issues related to travel. Among travelers who sought medical advice, the internet and primary care providers were the most common sources of information. These results suggest the need for health outreach and education programs targeted at travelers and primary care practitioners. C1 [LaRocque, Regina C.; Tsibris, Athe; Lawton, Thomas; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [LaRocque, Regina C.; Rao, Sowmya R.; Tsibris, Athe; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Barry, M. Anita] Boston Publ Hlth Commiss, Boston, MA USA. [Marano, Nina; Brunette, Gary; Yanni, Emad] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 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 FU US Centers for Disease Control and Prevention [U19CI000514] FX This work was supported by funding from the US Centers for Disease Control and Prevention (U19CI000514). We thank the staff of Boston Logan International Airport, particularly Chief Robert Donahue, Robert Callahan, Catherine Obert, Brad Martin, David Ishihara, and Dr James Watkins, CDC quarantine officer, for their assistance with this project. We also thank Jana Eisenstein, Jennifer Kendall, Robert Citorik, Erica Sennott, and Richelle Charles for their assistance with administering the airport surveys. We thank Ricky Morse and Peter Lazar for their assistance with data management. We are grateful to Dr Emilia Koumans for a critical review of the manuscript. NR 10 TC 44 Z9 44 U1 2 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1195-1982 J9 J TRAVEL MED JI J. Travel Med. PD NOV-DEC PY 2010 VL 17 IS 6 BP 387 EP 391 DI 10.1111/j.1708-8305.2010.00457.x PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 677IN UT WOS:000283982900005 PM 21050318 ER PT J AU Karaosmanoglu, AD Blake, M AF Karaosmanoglu, A. Devrim Blake, Michael TI Hamartomatous Polyp of the Gallbladder With an Associated Choledochal Cyst SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article AB Ahamartomatous polyp is an extremely rare polypoidal lesion of the gallbladder, with the first case having been reported in 1998.(1) To the best of our knowledge, fewer than 10 hamartomatous gallbladder polyps have been reported in patients with Peutz-Jeghers syndrome (PJS). The largest series evaluating extraintestinal polyps in patients with PJS revealed 3 patients with a gallbladder polyp among 72 patients with 1 pathologically proven hamartomatous polyp.(2) Hamartomatous gallbladder polyps are thus rare in patients with PJS, and as mentioned before, to the best of our knowledge, it has not been reported before in a patient without PJS. Another interesting finding in this case was the association of a type 1 choledochal cyst with the hamartomatous gallbladder polyp. C1 [Karaosmanoglu, A. Devrim; Blake, Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Karaosmanoglu, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 2, Boston, MA 02114 USA. EM alidevrim76@yahoo.com RI Karaosmanoglu, Ali/D-8624-2015 OI Karaosmanoglu, Ali/0000-0003-0027-9593 NR 8 TC 0 Z9 0 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 2010 VL 29 IS 11 BP 1663 EP 1666 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 685ZP UT WOS:000284666900018 PM 20966480 ER PT J AU Walker, TG Kalva, SP Yeddula, K Wicky, S Kundu, S Drescher, P d'Othee, BJ Rose, SC Cardella, JF AF Walker, T. Gregory Kalva, Sanjeeva P. Yeddula, Kalpana Wicky, Stephan Kundu, Sanjoy Drescher, Peter d'Othee, B. Janne Rose, Steven C. Cardella, John F. TI Clinical Practice Guidelines for Endovascular Abdominal Aortic Aneurysm Repair: Written by the Standards of Practice Committee for the Society of Interventional Radiology and Endorsed by the Cardiovascular and Interventional Radiological Society of Europe and the Canadian Interventional Radiology Association SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID ILIAC ARTERY EMBOLIZATION; STENT-GRAFT INFECTION; RANDOMIZED CONTROLLED-TRIAL; INTERMEDIATE FOLLOW-UP; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; CONTRAST-ENHANCED ULTRASOUND; COLOR DUPLEX ULTRASONOGRAPHY; INFERIOR MESENTERIC-ARTERY; SINGLE-CENTER EXPERIENCE; VASCULAR-SURGERY DEVICE C1 [Walker, T. Gregory; Kalva, Sanjeeva P.; Yeddula, Kalpana; Wicky, Stephan] Massachusetts Gen Hosp, Dept Radiol, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Kundu, Sanjoy] Scarborough Gen Hosp, Dept Med Imaging, Toronto, ON, Canada. [Drescher, Peter] W Allis Mem Hosp, Dept Intervent Radiol, Milwaukee, WI USA. [d'Othee, B. Janne] Univ Maryland, Med Ctr, Dept Radiol, Div Intervent Radiol, Baltimore, MD 21201 USA. [Rose, Steven C.] Univ Calif San Diego, Med Ctr, Dept Radiol, San Diego, CA 92103 USA. [Cardella, John F.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA. RP Walker, TG (reprint author), Care of Katsarelis D, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. RI Janne d'Othee, Bertrand/E-8467-2010 NR 224 TC 34 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2010 VL 21 IS 11 BP 1632 EP 1655 DI 10.1016/j.jvir.2010.07.008 PG 24 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 680OL UT WOS:000284244200002 PM 20884242 ER PT J AU Honeyborne, I Codoner, FM Leslie, A Tudor-Williams, G Luzzi, G Ndung'u, T Walker, BD Goulder, PJ Prado, JG AF Honeyborne, Isobella Codoner, Francisco M. Leslie, Alasdair Tudor-Williams, Gareth Luzzi, Graz Ndung'u, Thumbi Walker, Bruce D. Goulder, Philip J. Prado, Julia G. TI HLA-Cw*03-Restricted CD8(+) T-Cell Responses Targeting the HIV-1 Gag Major Homology Region Drive Virus Immune Escape and Fitness Constraints Compensated for by Intracodon Variation SO JOURNAL OF VIROLOGY LA English DT Article ID HLA-C; LYMPHOCYTE ESCAPE; TYPE-1 INFECTION; VIRAL LOAD; EPITOPE; MUTATIONS; REPLICATION; PROTEINS; SEQUENCE; ASSOCIATIONS AB The potential importance of HLA-C-restricted CD8(+) cytotoxic T lymphocytes (CTL) in HIV infection remains undetermined. We studied the dominant HLA-Cw*03-restricted CTL response to YVDRFFKTL296-304 (YL9), within the conserved major homology region (MHR) of the Gag protein, in 80 HLA-Cw*03-positive individuals with chronic HIV infection to better define the efficacy of the YL9 HLA-C-restricted response. The HLA-Cw*03 allele is strongly associated with HIV sequence changes from Thr-303 to Val, Ile, or Ala at position 8 within the YL9 epitope (P = 1.62 x 10(-10)). In vitro studies revealed that introduction of the changes T303I and T303A into the YL9 epitope both significantly reduced CTL recognition and substantially reduced the viral replicative capacity. However, subsequent selection of the Val-303 variant, via intracodon variation from Ile-303 (I303V) or Ala-303 (A303V), restored both viral fitness and CTL recognition, as supported by our in vivo data. These results illustrate that HLA-C-restricted CTL responses are capable of driving viral immune escape within Gag, but in contrast to what was previously described for HLA-B-restricted Gag escape mutants, the common Cw*03-Gag-303V variant selected resulted in no detectable benefit to the host. C1 [Codoner, Francisco M.; Prado, Julia G.] Hosp Badalona Germans Trias & Pujol, AIDS Res Inst IrsiCaixa, Badalona 08916, Spain. [Honeyborne, Isobella; Leslie, Alasdair; Goulder, Philip J.; Prado, Julia G.] Peter Medawar Bldg Pathogen Res, Dept Paediat, Oxford OX1 3SY, England. [Tudor-Williams, Gareth] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Dept Paediat, London W2 1NY, England. [Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip J.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa. [Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip J.] Massachusetts Inst Technol & Harvard, Ragon Inst Massachusetts Gen Hosp, Boston, MA 02129 USA. [Luzzi, Graz] Wycombe Hosp, Dept Genitourinary Med, High Wycombe, Bucks, England. RP Prado, JG (reprint author), Hosp Badalona Germans Trias & Pujol, AIDS Res Inst IrsiCaixa, Crta Canyet SN, Badalona 08916, Spain. EM jgarciaprado@irsicaixa.es OI Ndung'u, Thumbi/0000-0003-2962-3992 FU Doris Duke Charitable Foundation [2001 1031]; Wellcome Trust; Bristol Myers Squibb Secure the Future [RES 16/01]; FIS-ISCIII (Spanish Government) [CP09/00279]; European Commission [238885] FX This project was funded by the Doris Duke Charitable Foundation (2001 1031 to P.J.G.), the Wellcome Trust (P.J.G.), and Bristol Myers Squibb Secure the Future (RES 16/01 to P.J.G.). J.G.P. holds a Miguel Servet Contract (CP09/00279) funded by FIS-ISCIII (Spanish Government). F.M.C. was supported by Marie Curie European Reintegration Grant number 238885 from European Commission Framework Program 7. T.N. holds the South African Department of Science and Technology/National Research Foundation Chair in Systems Biology of HIV/AIDS. NR 45 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2010 VL 84 IS 21 BP 11279 EP 11288 DI 10.1128/JVI.01144-10 PG 10 WC Virology SC Virology GA 660LE UT WOS:000282643400033 PM 20739527 ER PT J AU Brockman, MA Brumme, ZL Brumme, CJ Miura, T Sela, J Rosato, PC Kadie, CM Carlson, JM Markle, TJ Streeck, H Kelleher, AD Markowitz, M Jessen, H Rosenberg, E Altfeld, M Harrigan, PR Heckerman, D Walker, BD Allen, TM AF Brockman, Mark A. Brumme, Zabrina L. Brumme, Chanson J. Miura, Toshiyuki Sela, Jennifer Rosato, Pamela C. Kadie, Carl M. Carlson, Jonathan M. Markle, Tristan J. Streeck, Hendrik Kelleher, Anthony D. Markowitz, Martin Jessen, Heiko Rosenberg, Eric Altfeld, Marcus Harrigan, P. Richard Heckerman, David Walker, Bruce D. Allen, Todd M. TI Early Selection in Gag by Protective HLA Alleles Contributes to Reduced HIV-1 Replication Capacity That May Be Largely Compensated for in Chronic Infection SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; CELLULAR IMMUNE-RESPONSES; ESCAPE MUTATIONS; VIRAL LOAD; ELITE CONTROLLERS; TYPE-1 INFECTION; CLEAVAGE SITES; EPITOPE; VIREMIA AB Mutations that allow escape from CD8 T-cell responses are common in HIV-1 and may attenuate pathogenesis by reducing viral fitness. While this has been demonstrated for individual cases, a systematic investigation of the consequence of HLA class I-mediated selection on HIV-1 in vitro replication capacity (RC) has not been undertaken. We examined this question by generating recombinant viruses expressing plasma HIV-1 RNA-derived Gag-Protease sequences from 66 acute/early and 803 chronic untreated subtype B-infected individuals in an NL4-3 background and measuring their RCs using a green fluorescent protein (GFP) reporter CD4 T-cell assay. In acute/early infection, viruses derived from individuals expressing the protective alleles HLA-B*57, -B*5801, and/or -B*13 displayed significantly lower RCs than did viruses from individuals lacking these alleles (P < 0.05). Furthermore, acute/early RC inversely correlated with the presence of HLA-B-associated Gag polymorphisms (R = -0.27; P = 0.03), suggesting a cumulative effect of primary escape mutations on fitness during the first months of infection. At the chronic stage of infection, no strong correlations were observed between RC and protective HLA-B alleles or with the presence of HLA-B-associated polymorphisms restricted by protective alleles despite increased statistical power to detect these associations. However, RC correlated positively with the presence of known compensatory mutations in chronic viruses from B*57-expressing individuals harboring the Gag T242N mutation (n = 50; R = 0.36; P = 0.01), suggesting that the rescue of fitness defects occurred through mutations at secondary sites. Additional mutations in Gag that may modulate the impact of the T242N mutation on RC were identified. A modest inverse correlation was observed between RC and CD4 cell count in chronic infection (R = -0.17; P<0.0001), suggesting that Gag-Protease RC could increase over the disease course. Notably, this association was stronger for individuals who expressed B*57, B*58, or B*13 (R = -0.27; P = 0.004). Taken together, these data indicate that certain protective HLA alleles contribute to early defects in HIV-1 fitness through the selection of detrimental mutations in Gag; however, these effects wane as compensatory mutations accumulate in chronic infection. The long-term control of HIV-1 in some persons who express protective alleles suggests that early fitness hits may provide lasting benefits. C1 [Brockman, Mark A.; Brumme, Zabrina L.; Markle, Tristan J.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Brockman, Mark A.; Brumme, Zabrina L.; Brumme, Chanson J.; Harrigan, P. Richard] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Brockman, Mark A.; Brumme, Zabrina L.; Brumme, Chanson J.; Miura, Toshiyuki; Sela, Jennifer; Rosato, Pamela C.; Streeck, Hendrik; Altfeld, Marcus; Walker, Bruce D.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Miura, Toshiyuki] Univ Tokyo, Inst Med, Tokyo, Japan. [Kadie, Carl M.; Carlson, Jonathan M.; Heckerman, David] Microsoft Res, eSci Grp, Los Angeles, CA USA. [Kelleher, Anthony D.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2052, Australia. [Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Rosenberg, Eric; Walker, Bruce D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Altfeld, Marcus; Walker, Bruce D.; Allen, Todd M.] Harvard Univ, Div Aids, Cambridge, MA 02138 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Brockman, MA (reprint author), Simon Fraser Univ, 8888 Univ Dr, Burnaby, BC V5A 1S6, Canada. EM mark_brockman@sfu.ca; tallen2@partners.org RI Allen, Todd/F-5473-2011; OI Brumme, Chanson/0000-0003-2722-5288; Brockman, Mark/0000-0001-6432-1426 FU Canadian Institutes for Health Research (CIHR); National Institutes of Health [AI028568, AI030914, AI074415, AI054178, AI071915]; Howard Hughes Medical Institute; Bill and Melinda Gates Foundation; Harvard University Center for AIDS Research; NSERC; Australian National Health and Medical Research Council; Australian Commonwealth Department of Health and Ageing FX This project was supported by grants from the Canadian Institutes for Health Research (CIHR) (to Z.L.B. and M. A. B.), the National Institutes of Health (grants AI028568, AI030914, AI074415, AI054178, and AI071915) (to B. D. W., T. M. A., M. A., and E. R.), the Howard Hughes Medical Institute, the Bill and Melinda Gates Foundation (to B. D. W. and T. M. A.), and the Harvard University Center for AIDS Research. Z.L.B. is a CIHR New Investigator Award recipient. C.J.B. is supported by an NSERC Julie Payette graduate scholarship. A. D. K. is supported by a program grant and practitioner fellowship from the Australian National Health and Medical Research Council. The NCHECR is supported by the Australian Commonwealth Department of Health and Ageing. NR 66 TC 68 Z9 68 U1 3 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2010 VL 84 IS 22 BP 11937 EP 11949 DI 10.1128/JVI.01086-10 PG 13 WC Virology SC Virology GA 670KM UT WOS:000283420500033 PM 20810731 ER PT J AU Maserejian, NN Parish, S Shifren, JL Huang, LY Gerstenberger, E Rosen, RC AF Maserejian, Nancy Nairi Parish, Sharon Shifren, Jan L. Huang, Liyuan Gerstenberger, Eric Rosen, Raymond C. TI Healthcare Utilization in Women Diagnosed with Hypoactive Sexual Desire Disorder: Interim Baseline Results from the HSDD Registry for Women SO JOURNAL OF WOMENS HEALTH LA English DT Article ID SURGICALLY MENOPAUSAL WOMEN; HELP-SEEKING BEHAVIOR; TESTOSTERONE PATCH; VALIDATION; PREVALENCE; INSTRUMENT; ATTITUDES; DISTRESS; PEOPLE AB Objective: To investigate treatment seeking and utilization of women diagnosed with hypoactive sexual desire disorder (HSDD) in the clinical setting. Methods: We used interim baseline data from the ongoing HSDD Registry for Women (n = 724, enrolled at 27 clinical sites across the United States in 2008-2009). The recent diagnosis of generalized, acquired HSDD was confirmed by clinician's administration of the validated diagnostic Decreased Sexual Desire Screener. Treatment-seeking behavior was categorized as formal (discussion with a healthcare provider or use of off-label prescription treatment for HSDD) or informal/none (over-the-counter products, anonymous media, or no help seeking). Results: Over half (n = 386, 53%) of these women with clinically diagnosed HSDD had not sought formal healthcare for their decreased sexual desire problem. Among formal healthcare seekers, 36% remained untreated, whereas 64% received some form of treatment. The most common treatments reported were nonprescription lubricants or arousal creams (36%) and off-label prescription medications (20%). Women were more likely to have sought formal help if they were married/cohabiting, were postmenopausal, had private health insurance, had >5 current prescription medications, had depression symptoms, had a longer duration of sexual desire problems, or reported that the partner relationship or sense of femininity/sexual self was threatened by HSDD. Conclusions: In these women with HSDD, less than half had sought healthcare, but of those who had sought healthcare, almost two thirds received some form of treatment. Regardless of treatment-seeking behavior, most women had a strong desire to "feel like a normal person again'' regarding sexuality, which was the most common motivating factor for treatment seeking. C1 [Maserejian, Nancy Nairi; Huang, Liyuan; Gerstenberger, Eric; Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA 02472 USA. [Parish, Sharon] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Shifren, Jan L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Maserejian, NN (reprint author), New England Res Inst Inc, 9 Galen St, Watertown, MA 02472 USA. EM nmaserejian@neriscience.com FU Boehringer Ingelheim Pharmaceuticals, Inc.; Proctor and Gamble FX This work was supported by a grant from Boehringer Ingelheim Pharmaceuticals, Inc.; No competing financial interests exist for N.N.M., L.H., and E.G. J.L.S. serves as a research consultant for Boehringer Ingelheim Pharmaceuticals and New England Research Institutes and has received research support from Proctor and Gamble. S.P. serves as a research consultant for Boehringer Ingelheim Pharmaceuticals and New England Research Institutes. R.C.R. is an advisory board member for Boehringer Ingelheim Pharmaceuticals and has served as a consultant/advisor to Eli Lilly, Bayer-Schering Pharma, Sanofi-Aventi, Johnson & Johnson, and Endo Pharmaceuticals. He serves as an investigator for Eli Lilly, Bayer-Schering Pharma, Boehringer Ingelheim Pharmaceuticals, and Endo Pharmaceuticals. NR 28 TC 8 Z9 8 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2010 VL 19 IS 11 BP 2001 EP 2009 DI 10.1089/jwh.2010.2152 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 675SX UT WOS:000283855500009 PM 20929408 ER PT J AU Pisania, A Weir, GC O'Neil, JJ Omer, A Tchipashvili, V Lei, J Colton, CK Bonner-Weir, S AF Pisania, Anna Weir, Gordon C. O'Neil, John J. Omer, Abdulkadir Tchipashvili, Vaja Lei, Ji Colton, Clark K. Bonner-Weir, Susan TI Quantitative analysis of cell composition and purity of human pancreatic islet preparations SO LABORATORY INVESTIGATION LA English DT Article DE beta-cells; cell composition; electron microscopy; human islet preparations; islet purity; light microscopy ID TYPE-2 DIABETES-MELLITUS; BETA-CELL; AUTOMATED-METHOD; A-CELL; B-CELL; TRANSPLANTATION; MORPHOMETRY; PATHOLOGY; CULTURE; GLUCOSE AB Despite improvements in outcomes for human islet transplantation, characterization of islet preparations remains poorly defined. This study used both light microscopy (LM) and electron microscopy (EM) to characterize 33 islet preparations used for clinical transplants. EM allowed an accurate identification and quantification of cell types with measured cell number fractions (mean +/- s.e.m.) of 35.6 +/- 2.1% beta-cells, 12.6 +/- 1.0% non-beta-islet cells (48.3 +/- 2.6% total islet cells), 22.7 +/- 1.5% duct cells, and 25.3 +/- 1.8% acinar cells. Of the islet cells, 73.6 +/- 1.7% were beta-cells. For comparison with the literature, estimates of cell number fraction, cell volume, and extracellular volume were combined to convert number fraction data to volume fractions applicable to cells, islets, and the entire preparation. The mathematical framework for this conversion was developed. By volume, beta-cells were 86.5 +/- 1.1% of the total islet cell volume and 61.2 +/- 0.8% of intact islets (including the extracellular volume), which is similar to that of islets in the pancreas. Our estimates produced 1560 +/- 20 cells in an islet equivalent (volume of 150-mu m diameter sphere), of which 1140 +/- 15 were beta-cells. To test whether LM analysis of the same tissue samples could provide reasonable estimates of purity of the islet preparations, volume fraction of the islet tissue was measured on thin sections available from 27 of the clinical preparations by point counting morphometrics. Islet purity (islet volume fraction) of individual preparations determined by LM and EM analyses correlated linearly with excellent agreement (R(2) = 0.95). However, islet purity by conventional dithizone staining was substantially higher with a 20-30% overestimation. Thus, both EM and LM provide accurate methods to determine the cell composition of human islet preparations and can help us understand many of the discrepancies of islet composition in the literature. Laboratory Investigation (2010) 90, 1661-1675; doi:10.1038/labinvest.2010.124; published online 9 August 2010 C1 [Pisania, Anna; Colton, Clark K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Weir, Gordon C.; Omer, Abdulkadir; Tchipashvili, Vaja; Lei, Ji; Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RP Colton, CK (reprint author), MIT, Dept Chem Engn, Room 66-452,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ckcolton@mit.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU NIH [NCRR ICR U4Z RR 16606, RO1-DK063108]; Joslin Diabetes and Endocrinology Research Center [DERC] [DK36836]; JDRF Center for Islet Transplantation at Harvard Medical School; Diabetes Research and Wellness Foundation FX We thank Christopher Cahill for invaluable technical assistance with both EM and LM. This study was supported by grants from the NIH (NCRR ICR U4Z RR 16606, RO1-DK063108, the Joslin Diabetes and Endocrinology Research Center [DERC] DK36836), the JDRF Center for Islet Transplantation at Harvard Medical School, and the Diabetes Research and Wellness Foundation. NR 37 TC 43 Z9 45 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 2010 VL 90 IS 11 BP 1661 EP 1675 DI 10.1038/labinvest.2010.124 PG 15 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 672MX UT WOS:000283590400012 PM 20697378 ER PT J AU Pisania, A Papas, KK Powers, DE Rappel, MJ Omer, A Bonner-Weir, S Weir, GC Colton, CK AF Pisania, Anna Papas, Klearchos K. Powers, Daryl E. Rappel, Michael J. Omer, Abdulkadir Bonner-Weir, Susan Weir, Gordon C. Colton, Clark K. TI Enumeration of islets by nuclei counting and light microscopic analysis SO LABORATORY INVESTIGATION LA English DT Article DE DTZ staining; islets; islet enumeration; LM; nuclei counting ID DIGITAL IMAGE-ANALYSIS; AUTOMATED-METHOD; PANCREATIC-ISLETS; CULTURED ISLETS; PORCINE ISLETS; CELL GRAFTS; TRANSPLANTATION; LANGERHANS; QUANTITATION; STANDARDIZATION AB Islet enumeration in impure preparations by conventional dithizone staining and visual counting is inaccurate and operator dependent. We examined nuclei counting for measuring the total number of cells in islet preparations, and we combined it with morphological analysis by light microscopy (LM) for estimating the volume fraction of islets in impure preparations. Cells and islets were disrupted with lysis solution and shear, and accuracy of counting successively diluted nuclei suspensions was verified with (1) visual counting in a hemocytometer after staining with crystal violet, and automatic counting by (2) aperture electrical resistance measurement and (3) flow cytometer measurement after staining with 7-aminoactinomycin-D. DNA content averaged 6.5 and 6.9 pg of DNA per cell for rat and human islets, respectively, in agreement with literature estimates. With pure rat islet preparations, precision improved with increasing counts, and samples with about >= 160 islets provided a coefficient of variation of about 6%. Aliquots of human islet preparations were processed for LM analysis by stereological point counting. Total nuclei counts and islet volume fraction from LM analysis were combined to obtain the number of islet equivalents (IEs). Total number of IE by the standard method of dithizone staining/manual counting was overestimated by about 90% compared with LM/nuclei counting for 12 freshly isolated human islet research preparations. Nuclei counting combined with islet volume fraction measurements from LM is a novel method for achieving accurate islet enumeration. Laboratory Investigation (2010) 90, 1676-1686; doi:10.1038/labinvest.2010.125; published online 9 August 2010 C1 [Pisania, Anna; Papas, Klearchos K.; Powers, Daryl E.; Rappel, Michael J.; Colton, Clark K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Omer, Abdulkadir; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RP Colton, CK (reprint author), MIT, Dept Chem Engn, Room 66-452,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ckcolton@mit.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU National Institutes of Health; Juvenile Diabetes Research Foundation Center for Islet Transplantation at Harvard Medical School; Islet Cell Resource (ICR) at Joslin; NIH, Diabetes Research and Wellness Foundation [R01-DK063108-01A1]; Joslin Diabetes and Endocrinology Research Center (DERC), Diabetes Research and Wellness Foundation [DK36836]; [NCRR ICR U4Z 16606]; [NCRR ICR U42 RR0023244-01] FX The beta TC3 cells were a gift from Dr Shimon Efrat (Albert Einstein College of Medicine, Bronx, NY, USA). The INS-1 cells were a gift from Dr Chris Newgard (University of Texas Southwestern Medical Center, Dallas, TX, USA). We thank the Islet Isolation Core at Joslin Diabetes Center (Ji Lei, Vaja Tchipashvilli, Gaurav Chandra, and Vassileios Kostaras) for their help in providing islet preparations as well as Chris Cahill of the Joslin DERC Advanced Microscopy Core for the preparation of the 1-mu m sections. This study was supported by grants from (1) the National Institutes of Health; (2) Juvenile Diabetes Research Foundation Center for Islet Transplantation at Harvard Medical School; (3) Islet Cell Resource (ICR) at Joslin; and (4) The Diabetes Research and Wellness Foundation (Grant numbers: NIH Grants R01-DK063108-01A1, NCRR ICR U4Z 16606, NCRR ICR U42 RR0023244-01; and the Joslin Diabetes and Endocrinology Research Center (DERC), DK36836). NR 53 TC 9 Z9 9 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 2010 VL 90 IS 11 BP 1676 EP 1686 DI 10.1038/labinvest.2010.125 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 672MX UT WOS:000283590400013 PM 20697375 ER PT J AU Merwick, A Albers, GW Amarenco, P Arsava, EM Ay, H Calvet, D Coutts, SB Cucchiara, BL Demchuk, AM Furie, KL Giles, MF Labreuche, J Lavallee, PC Mas, JL Olivot, JM Purroy, F Rothwell, PM Saver, JL Sheehan, OC Stack, JP Walsh, C Kelly, PJ AF Merwick, Aine Albers, Gregory W. Amarenco, Pierre Arsava, Ethem M. Ay, Hakan Calvet, David Coutts, Shelagh B. Cucchiara, Brett L. Demchuk, Andrew M. Furie, Karen L. Giles, Matthew F. Labreuche, Julien Lavallee, Philippa C. Mas, Jean-Louis Olivot, Jean Marc Purroy, Francisco Rothwell, Peter M. Saver, Jeffrey L. Sheehan, Orla C. Stack, John P. Walsh, Cathal Kelly, Peter J. TI Addition of brain and carotid imaging to the ABCD(2) score to identify patients at early risk of stroke after transient ischaemic attack: a multicentre observational study SO LANCET NEUROLOGY LA English DT Article ID MINOR STROKE; TIA PATIENTS; ATRIAL-FIBRILLATION; PREDICTIVE ABILITY; ROC CURVE; STENOSIS; VALIDATION; RECLASSIFICATION; ENDARTERECTOMY; METHODOLOGY AB Background The ABCD(2) score improves stratification of patients with transient ischaemic attack by early stroke risk. We aimed to develop two new versions of the score: one that was based on preclinical information and one that was based on imaging and other secondary care assessments. Methods We analysed pooled data from patients with clinically defined transient ischaemic attack who were investigated while in secondary care. Items that contribute to the ABCD(2) score (age, blood pressure, clinical weakness, duration, and diabetes), other clinical variables, carotid stenosis, and abnormal acute diffusion-weighted imaging (DWI) were recorded and were included in multivariate logistic regression analysis of stroke occurrence at early time intervals after onset of transient ischaemic attack. Scores based on the findings of this analysis were validated in patients with transient ischaemic attack from two independent population-based cohorts. Findings 3886 patients were included in the study: 2654 in the derivation sample and 1232 in the validation sample. We derived the ABCD(3) score (range 0-9 points) by assigning 2 points for dual transient ischaemic attack (an earlier transient ischaemic attack within 7 days of the index event). C statistics (which indicate discrimination better than chance at >0.5) for the ABCD(3) score were 0.78 at 2 days, 0.80 at 7 days, 0.79 at 28 days, and 0.77 at 90 days, compared with C statistics for the ABCD(2) score of 0.71 at 2 days (p=0.083), 0.71 at 7 days (p=0.012), 0.71 at 28 days (p=0.021), and 0.69 at 90 days (p=0.018). We included stenosis of at least 50% on carotid imaging (2 points) and abnormal DWI (2 points) in the ABCD(3)-imaging (ABCD(3)-I) score (0-13 points). C statistics for the ABCD(3)-I score were 0.90 at 2 days (compared with ABCD(2) score p=0.035), 0.92 at 7 days (p=0-001), 0.85 at 28 days (p=0-028), and 0.79 at 90 days (p=0.073). The 90-day net reclassification improvement compared with ABCD(2) was 29.1% for ABCD(3) (p=0.0003) and 39.4% for ABCD(3)-I (p=0.034). In the validation sample, the ABCD(3) and ABCD(3)-I scores predicted early stroke at 7,28, and 90 days. However, discrimination and net reclassification of patients with early stroke were similar with ABCD(3) compared with ABCD(2). Interpretation The ABCD(3)-I score can improve risk stratification after transient ischaemic attack in secondary care settings. However, use of ABCD(3) cannot be recommended without further validation. C1 [Merwick, Aine; Sheehan, Orla C.; Stack, John P.; Kelly, Peter J.] Mater Misericordiae Univ Hosp, Neurovasc Clin Sci Unit, Stroke Serv, Dublin, Ireland. [Merwick, Aine; Sheehan, Orla C.; Stack, John P.; Kelly, Peter J.] Mater Misericordiae Univ Hosp, Dept Neurol, Dublin, Ireland. [Merwick, Aine; Sheehan, Orla C.; Stack, John P.; Kelly, Peter J.] Dublin Acad Med Ctr, Dublin, Ireland. [Albers, Gregory W.; Olivot, Jean Marc] Stanford Univ, Med Ctr, Stanford Stroke Ctr, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Amarenco, Pierre; Labreuche, Julien; Lavallee, Philippa C.] INSERM, U698, Dept Neurol, Paris, France. [Amarenco, Pierre; Labreuche, Julien; Lavallee, Philippa C.] INSERM, U698, Stroke Ctr, Paris, France. [Amarenco, Pierre; Labreuche, Julien; Lavallee, Philippa C.] Paris Diderot Univ, Paris, France. [Amarenco, Pierre; Labreuche, Julien; Lavallee, Philippa C.] Hop Xavier Bichat, Paris, France. [Arsava, Ethem M.; Furie, Karen L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Calvet, David; Mas, Jean-Louis] Paris Descartes Univ, St Anne Hosp, INSERM, Dept Neurol,UMR894, Paris, France. [Coutts, Shelagh B.] Univ Calgary, Foothills Med Ctr, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Coutts, Shelagh B.; Demchuk, Andrew M.] Univ Calgary, Seaman Family MR Res Ctr, Calgary, AB T2N 1N4, Canada. [Cucchiara, Brett L.] Univ Penn, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [Giles, Matthew F.; Rothwell, Peter M.] John Radcliffe Hosp, Stroke Prevent Res Unit, Oxford OX3 9DU, England. [Purroy, Francisco] Univ Hosp Arnau de Vilanova, Dept Neurol, Stroke Unit, Lleida, Spain. [Purroy, Francisco] Univ Lleida, Biomed Res Inst Lleida, Lleida, Spain. [Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Walsh, Cathal] Trinity Coll Dublin, Dept Stat, Dublin, Ireland. RP Kelly, PJ (reprint author), Mater Univ Hosp, UCD DAMC Catherine McAuley Ctr, Neurovasc Clin Sci Unit, 27 Nelson St, Dublin 7, Ireland. EM pjkelly@partners.org RI Purroy, Francisco/D-4538-2009; Arsava, Ethem Murat/I-9197-2013; Merwick, Aine/L-9754-2013; Demchuk, Andrew/E-1103-2012; OI Arsava, Ethem Murat/0000-0002-6527-4139; Merwick, Aine/0000-0001-7533-0117; Demchuk, Andrew/0000-0002-4930-7789; Walsh, Cathal/0000-0001-6599-9562; Saver, Jeffrey/0000-0001-9141-2251; Purroy, Francisco/0000-0002-1808-5968 FU Health Research Board of Ireland; Irish Heart Foundation; Irish National Lottery; Health Research Board; National Institutes of Health [ROI-N5059710]; Canadian Institutes for Health [MOP-118096]; Heart and Stroke Foundation of Alberta, NWT and Nunavut; Canada Foundation for Innovation; Alberta Foundation for Health Research; Canadian Institutes of Health; Respiratory Health and AstraZeneca Canada; Alberta Heritage Foundation; National Institute of Health Research (NIHR); Stroke Association; Medical Research Council; Dunhill Medical Trust; NIHR Biomedical Research Centre, Oxford; Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III: FIS [PIO81398] FX Funding was provided by the Health Research Board of Ireland, Irish Heart Foundation, and Irish National Lottery. AM and OCS are supported by the Health Research Board. HA was supported by National Institutes of Health grant ROI-N5059710. SBC, AMD, and the VISION study were supported by grant funding from: the Canadian Institutes for Health Research (MOP-118096); the Heart and Stroke Foundation of Alberta, NWT and Nunavut; Canada Foundation for Innovation; and Alberta Foundation for Health Research. SBC received the Heart and Stroke Foundation of Canada Distinguished Clinician Scientist award, supported by the Canadian Institutes of Health Research Institute of Circulatory and Respiratory Health and AstraZeneca Canada, and salary support from the Alberta Heritage Foundation for Medical Research. MFG and PMR receive funding from the National Institute of Health Research (NIHR). The Oxford Vascular Study was funded by the Stroke Association, Medical Research Council, Dunhill Medical Trust, and the NIHR Biomedical Research Centre, Oxford. FP was supported by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III: FIS number PIO81398. PJK is the recipient of a Clinician Scientist Award from the Health Research Board of Ireland. We thank the patients who contributed to the research, neurovascular teams and radiologists in participating centres, the Clinical Photography Unit in the Mater University Hospital, and Lorraine Kyne for review of the manuscript. NR 42 TC 134 Z9 149 U1 7 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2010 VL 9 IS 11 BP 1060 EP 1069 DI 10.1016/S1474-4422(10)70240-4 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 680PL UT WOS:000284246800014 PM 20934388 ER PT J AU Richardson, PG AF Richardson, Paul G. TI Towards a better understanding of treatment-related peripheral neuropathy in multiple myeloma SO LANCET ONCOLOGY LA English DT Editorial Material ID BORTEZOMIB C1 Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 8 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2010 VL 11 IS 11 BP 1014 EP 1016 DI 10.1016/S1470-2045(10)70248-5 PG 3 WC Oncology SC Oncology GA 683AP UT WOS:000284444400005 PM 21051016 ER PT J AU D'Amico, AV AF D'Amico, Anthony V. TI Is long-term androgen suppression right for everyone with locally advanced prostate cancer? SO LANCET ONCOLOGY LA English DT Editorial Material C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM adamico@partners.org NR 6 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2010 VL 11 IS 11 BP 1016 EP 1017 DI 10.1016/S1470-2045(10)70235-7 PG 2 WC Oncology SC Oncology GA 683AP UT WOS:000284444400006 PM 20933467 ER PT J AU de Sanjose, S Quint, WGV Alemany, L Geraets, DT Klaustermeier, JE Lloveras, B Tous, S Felix, A Bravo, LE Shin, HR Vallejos, CS de Ruiz, PA Lima, MA Guimera, N Clavero, O Alejo, M Llombart-Bosch, A Cheng-Yang, C Tatti, SA Kasamatsu, E Iljazovic, E Odida, M Prado, R Seoud, M Grce, M Usubutun, A Jain, A Suarez, GAH Lombardi, LE Banjo, A Menendez, C Domingo, EJ Velasco, J Nessa, A Chichareon, SCB Qiao, YL Lerma, E Garland, SM Sasagawa, T Ferrera, A Hammouda, D Mariani, L Pelayo, A Steiner, I Oliva, E Meijer, CJLM Al-Jassar, WF Cruz, E Wright, TC Puras, A Llave, CL Tzardi, M Agorastos, T Garcia-Barriola, V Clavel, C Ordi, J Andujar, M Castellsague, X Sanchez, GI Nowakowski, AM Bornstein, J Munoz, N Bosch, FX AF de Sanjose, Silvia Quint, Wim G. V. Alemany, Laia Geraets, Daan T. Ellen Klaustermeier, Jo Lloveras, Belen Tous, Sara Felix, Ana Eduardo Bravo, Luis Shin, Hai-Rim Vallejos, Carlos S. Alonso de Ruiz, Patricia Lima, Marcus Aurelho Guimera, Nuria Clavero, Omar Alejo, Maria Llombart-Bosch, Antonio Cheng-Yang, Chou Alejandro Tatti, Silvio Kasamatsu, Elena Iljazovic, Ermina Odida, Michael Prado, Rodrigo Seoud, Muhieddine Grce, Magdalena Usubutun, Alp Jain, Asha Hernandez Suarez, Gustavo Adolfo Estuardo Lombardi, Luis Banjo, Aekunbiola Menendez, Clara Javier Domingo, Efren Velasco, Julio Nessa, Ashrafun Chichareon, Saibua C. Bunnag Qiao, You Lin Lerma, Enrique Garland, Suzanne M. Sasagawa, Toshiyuki Ferrera, Annabelle Hammouda, Doudja Mariani, Luciano Pelayo, Adela Steiner, Ivo Oliva, Esther Meijer, Chris J. L. M. Al-Jassar, Waleed Fahad Cruz, Eugenia Wright, Thomas C. Puras, Ana Ladines Llave, Cecilia Tzardi, Maria Agorastos, Theodoros Garcia-Barriola, Victoria Clavel, Christine Ordi, Jaume Andujar, Miguel Castellsague, Xavier Sanchez, Gloria I. Nowakowski, Andrzej Marcin Bornstein, Jacob Munoz, Nubia Xavier Bosch, F. CA Retrospective Int Survey HPV Time Trends Study Grp TI Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study SO LANCET ONCOLOGY LA English DT Article ID HIGH-RISK; INTRAEPITHELIAL NEOPLASIA; UNITED-STATES; LESIONS; WOMEN; CLASSIFICATION; PERSPECTIVE; PREVALENCE; LINE AB Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50.0 years [49.6-50.4], 48.2 years [47.3-49.2], 46.8 years [46.6-48.1], and 55.5 years [54.9-56.1], respectively). Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. C1 [de Sanjose, Silvia; Alemany, Laia; Ellen Klaustermeier, Jo; Lloveras, Belen; Tous, Sara; Guimera, Nuria; Clavero, Omar; Alejo, Maria; Castellsague, Xavier; Munoz, Nubia; Xavier Bosch, F.] Catalan Inst Oncol, Unit Infect & Canc, Canc Epidemiol Res Program, IDIBELL, Barcelona 08907, Spain. [de Sanjose, Silvia; Alemany, Laia; Ellen Klaustermeier, Jo; Castellsague, Xavier] CIBER Epidemiol & Salud Publ, Barcelona, Spain. [Quint, Wim G. V.; Geraets, Daan T.] DDL Diagnost Lab, Voorburg, Netherlands. [Lloveras, Belen] Hosp del Mar, Barcelona, Spain. [Felix, Ana] Inst Portugues Oncol Francisco Gentil, Lisbon, Portugal. [Eduardo Bravo, Luis] Hosp Univ Valle, Cali, Colombia. [Shin, Hai-Rim] Natl Canc Ctr, Seoul, South Korea. [Vallejos, Carlos S.] Inst Nacl Enfermedades Neoplas, Lima, Peru. [Alonso de Ruiz, Patricia] Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Fac Med, Mexico City 04510, DF, Mexico. [Lima, Marcus Aurelho] Hosp Dr Helio Angotti, PATMED, Lab Anat & Patol Citol, Assoc Combate Ao Canc Brasil Cent, Uberaba, Brazil. [Alejo, Maria] Hosp Gen Hosp, Barcelona, Spain. [Llombart-Bosch, Antonio] Univ Valencia, Fac Med, Valencia, Spain. [Cheng-Yang, Chou] Natl Cheng Kung Univ, Coll Med, Taiwan Assoc Gynecol Oncologists, Tainan 70101, Taiwan. [Alejandro Tatti, Silvio] Univ Buenos Aires, Hosp Clin Jose de San Martin, Buenos Aires, DF, Argentina. [Kasamatsu, Elena] Univ Nacl Asuncion, Inst Invest Ciencias Salud, Asuncion, Paraguay. [Iljazovic, Ermina] Univ Clin Ctr Tuzla, Polyclin Lab Diagnost, Tuzla, Bosnia & Herceg. [Odida, Michael] Uganda Makerere Univ, Kampala, Uganda. [Prado, Rodrigo] Univ Chile, Fac Med, Ctr Oncol Prevent, Santiago 7, Chile. [Seoud, Muhieddine] Amer Univ Beirut, Med Ctr, Beirut, Lebanon. [Grce, Magdalena] Rudjer Boskovic Inst, Div Mol Med, Zagreb, Croatia. [Usubutun, Alp] Hacettepe Univ, Sch Med, Dept Pathol, Ankara, Turkey. [Jain, Asha] Canc Prevent & Relief Soc, Raipur, Madhya Pradesh, India. [Hernandez Suarez, Gustavo Adolfo] Inst Nacl Cancerol, Bogota, Colombia. [Estuardo Lombardi, Luis] Hosp Gen San Juan de Dios, Ctr Invest Epidemiol Salud Sexual & Reprod, Guatemala City, Guatemala. [Banjo, Aekunbiola] Lagos Univ Teaching Hosp Idi Araba, Lagos, Nigeria. [Menendez, Clara] Hosp Clin Barcelona, Barcelona Ctr Int Hlth Res, Barcelona, Spain. [Menendez, Clara] Univ Barcelona, Barcelona, Spain. [Menendez, Clara] Manhica Hlth Res Ctr, Barcelona, Spain. [Javier Domingo, Efren] Univ Philippines, Coll Med, Philippine Gen Hosp, Manila, Philippines. [Nessa, Ashrafun] Bangabandhu Sheikh Mujib Med Univ, Dhaka, Bangladesh. [Velasco, Julio] Hosp San Agustin, Aviles, Spain. [Chichareon, Saibua C. Bunnag] Prince Songkla Univ, Fac Med, Hat Yai, Songkhla, Thailand. [Qiao, You Lin] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. [Qiao, You Lin] Union Med Coll, Beijing, Peoples R China. [Lerma, Enrique] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Garland, Suzanne M.] Univ Melbourne, Royal Womens Hosp, Melbourne, Vic, Australia. [Sasagawa, Toshiyuki] Kanazawa Univ Hosp, Kanazawa, Ishikawa, Japan. [Ferrera, Annabelle] Univ Autonoma Honduras, Escuela Microbiol, Tegucigalpa, Honduras. [Hammouda, Doudja] Natl Inst Hlth, Registre Tumeurs Alger, Algiers, Algeria. [Mariani, Luciano] Regina Elena Inst Canc Res, Rome, Italy. [Pelayo, Adela] Clin San Carlos, Madrid, Spain. [Steiner, Ivo] Charles Univ Prague, Fingerland Dept Pathol, Fac Med, Hradec Kralove, Czech Republic. [Steiner, Ivo] Fac Hosp, Hradec Kralove, Czech Republic. [Oliva, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meijer, Chris J. L. M.] Vrije Univ Med Ctr, Amsterdam, Netherlands. [Al-Jassar, Waleed Fahad] Kuwait Univ, Fac Med, Kuwait, Kuwait. [Cruz, Eugenia] Ctr Reg Oncol Coimbra, Inst Portugues Oncol, Coimbra, Portugal. [Wright, Thomas C.] Columbia Univ, New York Presbyterian Hosp, Med Ctr, New York, NY USA. [Puras, Ana] Hosp Virgen del Camino, Pamplona, Spain. [Ladines Llave, Cecilia] Univ Philippines, Cerv Canc Prevent Ctr, Inst Canc, Coll Med,Philippine Gen Hosp, Manila, Philippines. [Tzardi, Maria] Univ Crete, Sch Med, Iraklion, Greece. [Agorastos, Theodoros] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. [Garcia-Barriola, Victoria] Cent Univ Venezuela, Caracas, Venezuela. [Clavel, Christine] Hop Maison Blanche, Ctr Hosp Univ Reims, Lab Pol Bouin, Reims, France. [Ordi, Jaume] CRESIB Hosp Clin, Barcelona, Spain. [Andujar, Miguel] Complejo Hosp Univ Insular Maternoinfantil, Las Palmas Gran Canaria, Spain. [Sanchez, Gloria I.] Univ Antioquia, Medellin, Colombia. [Nowakowski, Andrzej Marcin] Med Univ Lublin, Lublin, Poland. [Bornstein, Jacob] Western Galilee Hosp, Nahariyya, Israel. RP de Sanjose, S (reprint author), Catalan Inst Oncol, Unit Infect & Canc, Canc Epidemiol Res Program, IDIBELL, Gran Via Hosp 199-203, Barcelona 08907, Spain. EM s.sanjose@iconcologia.net RI de Sanjose Llongueras, Silvia/H-6339-2014; Bravo, Luis/K-9882-2014; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012; Qiao, You-Lin/B-4139-2012; Lerma, Enrique/C-8498-2015; Castellsague Pique, Xavier/N-5795-2014; Tous, Sara/G-5052-2015; OI Grce, Magdalena/0000-0001-6178-8418; Felix, Ana/0000-0002-2653-2262; Bravo, Luis/0000-0002-9708-0312; BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Qiao, You-Lin/0000-0001-6380-0871; Castellsague Pique, Xavier/0000-0002-0802-3595; Tous, Sara/0000-0002-5423-7092; Sanchez, Gloria Ines/0000-0001-5992-0475; Usubutun, Alp/0000-0001-9572-7875 FU MSD; Merck; Sanofi Pasteur; GlaxoSmithKline; Qiagen; Roche; GenProbe; Roche Molecular Diagnostics; MSD Internal Steering Committee; GlaxoSmithKline Food and Drug Administration; EMEA; MSD Israel; Marato de TV3 Foundation; EXCEL program; Royal Women's Hospital Melbourne; Instituto de Salud Carlos III [FIS PI030240, FIS PI061246, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, CIBERESP]; Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) [2005SGR 00695, 2009SGR126]; Marato de TV3 Foundation [051530]; GlaxoSmithKline Biologicals FX YLQ has received support for travel to meetings for the study or other purposes (personal) from MSD and GlaxoSmithKline. GAHS has received an independent grant from MSD for epidemiological study related to genital warts in Colombia; and payments from MSD for travel accommodation at the International HPV conference in Canada, 2011. NM has received payment for board membership (personal) from Merck, and for lectures (personal) from Merck and Sanofi Pasteur. AMN has received payment for board membership (personal) and consultancy (personal) from GlaxoSmithKline, and for lectures (personal) from GlaxoSmithKline and MSD. CJLMM has received payment for board membership (institution) from Qiagen until 2009; payment for consultancy from Qiagen (institution); payment for lectures including service on speakers bureaus (institution) from Roche and GlaxoSmithKline; payment for patents (institution) from Qiagen for HPV detection by gp5+/6+; royalties (institution) from Oncomethylome Sciences for a patent on promoter methylation of Technological Support for Strategy, Learning and Change specific marker for cervical intraepithelial neoplasia 2+2005; and travel, accommodations, or meeting expenses (personal) from Qiagen and Roche. TCW has received payment for consultancy (personal) from Merck, GlaxoSmithKline, GenProbe, and Roche Molecular Diagnostics; and for lectures including service on speakers bureaus (personal) from Merck, GlaxoSmithKline, and Roche Molecular Diagnostics. SDS has received payment for consultancy (personal) from Qiagen, and for lectures including service on speakers bureaus (personal) from Qiagen, Sanofi, and GlaxoSmithKline. LA has received support for travel to meetings for the study or other purposes (institutional) from Sanofi Pasteur MSD. NG has received institutional support for occasional travel by GlaxoSmithKline and Merck. FXB has received payment for consultancy (personal) from MSD Internal Steering Committee; payment for expert testimony (personal) from GlaxoSmithKline Food and Drug Administration and EMEA clinical expert; and grants (institution) from GlaxoSmithKline, MSD, and Sanofi Pasteur MSD for epidemiological studies; payment for development of educational presentations (institution) from GlaxoSmithKline; travel, accommodations, and meeting expenses (personal) from GlaxoSmithKline and Sanofi Pasteur MSD. JB has received a grant (institution) from MSD Israel for a research assistant working with the pathology laboratory staff, assisting in the assembly and transport of paraffin blocks; consultancy (personal) payments from MSD Israel; and payment for lectures, including service on speakers bureaus (personal) from GlaxoSmithKline Israel. GIS has received a study grant (institution) from Marato de TV3 Foundation, and grants (institution) from Merck. XC has received a study grant (institution) from Sanofi Pasteur MSD and Merck; consultancy payments from Sanofi Pasteur MSD, and GlaxoSmithKline; grants (institution) from GlaxoSmithKline, Merck, Sanofi Pasteur MS D; and payment for lectures including service on speakers bureaus (personal) from GlaxoSmithKline and Sanofi Pasteur MSD. BL has received payment for lectures including service on speakers bureaus (personal) from Roche and Qiagen. SAT has received payment for lectures including service on speakers bureaus from MSD; and travel, accommodations, or meeting expenses from Merck.; SMG has received board membership from GlaxoSmithKline, Commonwealth Serum Laboratories advisory board for cervical cancer vaccine; payment for development of education presentations from GaxoSmithKline, EXCEL program; grants have been paid to SMG's institute by the Royal Women's Hospital Melbourne. CC has received payment for consultancy from Merck (steering committee about HPV vaccination), expert testimony from Roche, and funding for travel from Sanofi Pasteur, MSD, and GlaxoSmithKline. CLL has received institutional grants from GlaxoSmithKline. The other authors declared no conflicts of interest.; The study has been partly supported by Spanish public grants from the Instituto de Salud Carlos III (grants numbers FIS PI030240, FIS PI061246, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, and CIBERESP), Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR 2005SGR 00695 and 2009SGR126), Marato de TV3 Foundation (051530), and GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck. The contribution of Cristina Rajo in the preparation of the report is recognised. NR 25 TC 695 Z9 713 U1 11 U2 153 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2010 VL 11 IS 11 BP 1048 EP 1056 DI 10.1016/S1470-2045(10)70230-8 PG 9 WC Oncology SC Oncology GA 683AP UT WOS:000284444400018 PM 20952254 ER PT J AU Stelzner, F Stelzner, M AF Stelzner, Friedrich Stelzner, Matthias TI Manometry data support a novel concept of the lower esophageal sphincter system SO LANGENBECKS ARCHIVES OF SURGERY LA English DT Article DE Esophagus; Sphincter; Manometry; Anatomy ID IMPEDANCE CHARACTERISTICS; PARTIAL FUNDOPLICATION; ANTIREFLUX PROCEDURE; MOTOR FUNCTION; ACHALASIA; NISSEN; DISTENSION; DIAPHRAGM; CARDIA; REFLUX AB Purpose Detailed understanding of the functional anatomy of the lower esophageal sphincter (LES) is germane to successful surgical treatment of esophageal disorders. However, a comprehensive concept of the structure-function relationship of the LES is currently lacking. Methods We reviewed published anatomic evidence, medical imaging, and impedance manometry data sets and developed a novel functional concept of the LES. Results Morphologic evidence accumulated over the past three decades indicates that the LES is an anatomic structure that differs markedly from typical ring sphincters of the gastrointestinal tract (e.g., upper esophageal sphincter or anal sphincters). Recent impedance manometry investigations shed new light on the functional anatomy of the LES. These data corroborate a concept of this sphincter as a double-layer, twisted stretch sphincter. This sphincter requires tissue tension for optimal function. Retightening of the longitudinal stretch of the esophagus provides an effective therapy if this tension is lost, e.g., for patients with hiatal hernias. Paralysis of the muscle fibers of this sphincter system results in functional obstruction, and this explains the pathophysiology of "achalasia". Conclusions Based on available data, we propose a novel concept that better explains the structure-function relationship of the LES. Improved knowledge of the biomechanical factors of esophageal disorders can be expected to advance surgical treatment for these diseases. C1 [Stelzner, Friedrich] Univ Klinikum Bonn, Zentrum Chirurg, D-53105 Bonn, Germany. [Stelzner, Friedrich] Univ Bonn, Med Ctr, Dept Surg, D-5300 Bonn, Germany. [Stelzner, Matthias] Univ Calif Los Angeles, Surg Serv, VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Stelzner, Matthias] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. RP Stelzner, F (reprint author), Univ Klinikum Bonn, Zentrum Chirurg, Sigmund Freud Str 25, D-53105 Bonn, Germany. EM Stel33345@aol.com NR 32 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1435-2443 J9 LANGENBECK ARCH SURG JI Langenbecks Arch. Surg. PD NOV PY 2010 VL 395 IS 8 BP 1083 EP 1091 DI 10.1007/s00423-010-0662-x PG 9 WC Surgery SC Surgery GA 679ZW UT WOS:000284200300013 PM 20614132 ER PT J AU Maturo, S Hartnick, CJ AF Maturo, Stephen Hartnick, Christopher J. TI The Vocal Fold Retractor: A Useful Tool for Diagnosis and Treatment of Laryngeal and Tracheal Pathology SO LARYNGOSCOPE LA English DT Editorial Material DE Pediatric airway; vocal fold; laryngeal cleft; glottic web; respiratory papilloma; subglottic stenosis ID CLEFT C1 [Maturo, Stephen; Hartnick, Christopher J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Sch Med, Boston, MA 02114 USA. RP Maturo, S (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM stephen_maturo@meei.harvard.edu NR 7 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2010 VL 120 IS 11 BP 2227 EP 2230 DI 10.1002/lary.21133 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 673FI UT WOS:000283644100018 PM 20938957 ER PT J AU Marzo, SJ Moeller, CW Sharma, N Cunningham, K Jones, KJ Foecking, EM AF Marzo, Sam J. Moeller, Carl W. Sharma, Nijee Cunningham, Kelly Jones, Kathryn J. Foecking, Eileen M. TI Facial Motor Nuclei Cell Loss With Intratemporal Facial Nerve Crush Injuries in Rats SO LARYNGOSCOPE LA English DT Article DE Facial nerve; facial motor nucleus; facial injury; facial crush injury; rat facial nerve ID POOR FUNCTIONAL RECOVERY; QUALITY-OF-LIFE; PERIPHERAL-NERVE; ELECTRICAL-STIMULATION; CONTRIBUTING FACTORS; GONADAL-STEROIDS; ADULT-RAT; REPAIR; MOTONEURONS; TRANSECTION AB Objectives/Hypothesis: Injuries of cranial nerves that are distal to but near the motor nucleus might result in retrograde motoneuron cell death. The hypothesis of this article is that an intratemporal crush injury of the facial nerve in rats can cause facial motor nuclei cell death. Study Design: Prospective, randomized, controlled animal study. Methods: Sprague-Dawley rats were randomly divided into four groups: intratemporal sham, intratemporal crush injury, extratemporal crush injury, and extratemporal sham. The intratemporal (n = 9) and extratemporal crush injury (n = 4) groups underwent a 60-second crush of the nerve at the facial nerve tympanic segment or main facial nerve trunk distal to the stylomastoid foramen, respectively. The intratemporal sham group (n = 4) underwent identical exposure to the intratemporal crush without subsequent injury. Both sham groups and the extratemporal crush group were sacrificed at 4 weeks. The intratemporal crush group was subdivided into 4(n = 4) and 8-week (n = 5) postinjury groups. Brain sections were stained with thionin and facial motor nuclei were counted under magnification. The contralateral uninjured facial motor nucleus was used to compare motor nucleus cell survival. Results: Intratemporal crush injury resulted in increased cell loss at 4 (89.43% +/- 8.57% standard error of mean) and 8 weeks (85.78% +/- 3.15%) after injury compared to sham injury (119.09% +/- 13.35%) (P < .05). No significant change in cell survival was noted between the distal crush (103.29% +/- 6.34%) and sham group (111.71% +/- 3.24%) (P > .05). Conclusions: A rat intratemporal crush injury resulted in approximately 15% facial motor nuclei cell loss compared to an intratemporal sham injury. An extratemporal crush injury did not lead to any significant facial motor nuclei cell loss. This might have future translational implications in humans with intratemporal facial nerve injuries. C1 [Marzo, Sam J.; Moeller, Carl W.; Cunningham, Kelly; Jones, Kathryn J.; Foecking, Eileen M.] Loyola Univ Chicago, Stritch Sch Med, Dept Otolaryngol Head & Neck Surg, Maywood, IL USA. [Sharma, Nijee] Loyola Univ Chicago, Stritch Sch Med, Dept Neurosci, Maywood, IL USA. [Jones, Kathryn J.] Loyola Univ Chicago, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, Maywood, IL USA. [Jones, Kathryn J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res & Dev Serv, Hines, IL 60141 USA. RP Marzo, SJ (reprint author), Loyola Univ Hlth Syst, Div Otol Neurotol & Skull Base Surg, Dept Otolaryngol Head & Neck Surg, 2160 S 1st Ave, Maywood, IL 60153 USA. EM smarzo@lumc.edu FU Loyola Otolaryngology Research Fund [B6175R] FX The work was supported by the VA Pilot Grant (No. B6175R), Loyola Otolaryngology Research Fund. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 50 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2010 VL 120 IS 11 BP 2264 EP 2269 DI 10.1002/lary.21077 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 673FI UT WOS:000283644100024 PM 20830757 ER PT J AU Chan, NPY Ho, SGY Yeung, CK Shek, SYN Chan, HH AF Chan, Nicola P. Y. Ho, Stephanie G. Y. Yeung, Chi K. Shek, Samantha Y. N. Chan, Henry H. TI Fractional Ablative Carbon Dioxide Laser Resurfacing for Skin Rejuvenation and Acne Scars in Asians SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE ablative resurfacing; acne scar; Asian; carbon dioxide; fractional photothermolysis; laser; photorejuvenation; post-inflammatory hyperpigmentation ID CLINICAL-TRIAL; BURN SCAR; DEVICE; PHOTOTHERMOLYSIS; EFFICACY; HYPERPIGMENTATION; COMPLICATIONS; IMPROVEMENT; DISEASES; RISK AB Background and Objectives: Ablative fractional resurfacing (AFR) is a new modality for photorejuvenation and acne scars which combines carbon dioxide (CO2) laser ablation with fractional photothermolysis. The objective is to evaluate the efficacy and side effects of a new fractional CO2 ablative device (Fraxel Re: pair) for skin rejuvenation and acne scars in Asians. Materials and Methods: Nine patients underwent one full-face treatment. The energy levels ranged from 30-70 mJ with coverage between 30% and 45%. Improvement in skin texture, laxity, wrinkles, enlarged pores, overall pigmentation irregularity, and adverse effects were assessed up to 6 months post-treatment. Standardized photographs using the Canfield Visia CR system (R) were assessed by two independent observers. Subjective improvement was assessed by patient questionnaires. Results: Nine Chinese patients (skin types III and IV, mean age 44.8) were included. Statistically significant improvements were seen for skin texture, skin laxity, wrinkles, enlarged pores, and acne scars. The post-inflammatory hyperpigmentation rate was 55.5% and 11.1% at 1 and 6 months post-treatment, respectively. Eighty-six percent of patients were overall satisfied to very satisfied with the treatment. Conclusion: Ablative fractional CO2 laser resurfacing was overall safe and effective for skin rejuvenation and acne scars in Asians. However, in view of the high post-inflammatory rate and the statistically significant but only mild to moderate improvement after a single treatment as observed in this study, there is a need to review the current role of fractional ablative CO2 laser treatment as compared to fractional non-ablative for skin rejuvenation and acne scar treatment in Asians. Lasers Surg. Med. 42:615-623, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Chan, Nicola P. Y.; Ho, Stephanie G. Y.; Yeung, Chi K.; Shek, Samantha Y. N.; Chan, Henry H.] Univ Hong Kong, Dept Med, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Chan, HH (reprint author), Hong Kong Dermatol & Laser Ctr, 13th Floor,16 Ice House St, Hong Kong, Hong Kong, Peoples R China. EM hhlchan@hku.hk RI Yeung, Chi Keung/L-4795-2013; Chan, Henry Hin Lee/L-2267-2013 NR 43 TC 36 Z9 43 U1 1 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD NOV PY 2010 VL 42 IS 9 BP 615 EP 623 DI 10.1002/lsm.20974 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 680DA UT WOS:000284211400002 PM 20976801 ER PT J AU Brown, JR Abramson, J Hochberg, E Mikler, E Dalton, V Werner, L Reynolds, H Thompson, C McDonough, SM Kuang, Y Ritz, J Neuberg, D Freedman, AS AF Brown, J. R. Abramson, J. Hochberg, E. Mikler, E. Dalton, V. Werner, L. Reynolds, H. Thompson, C. McDonough, S. M. Kuang, Y. Ritz, J. Neuberg, D. Freedman, A. S. TI A phase I study of lenalidomide in combination with fludarabine and rituximab in previously untreated CLL/SLL SO LEUKEMIA LA English DT Letter ID CHRONIC LYMPHOCYTIC-LEUKEMIA C1 [Brown, J. R.; Mikler, E.; Dalton, V.; Reynolds, H.; Thompson, C.; McDonough, S. M.; Ritz, J.; Freedman, A. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brown, J. R.; Abramson, J.; Hochberg, E.; Ritz, J.; Freedman, A. S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Abramson, J.; Hochberg, E.] Massachusetts Gen Hosp, Dept Med, Div Oncol, Boston, MA 02114 USA. [Werner, L.; Neuberg, D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kuang, Y.] Dana Farber Canc Inst, Ctr Clin & Translat Res, Boston, MA 02115 USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jbrown2@partners.org FU NCI NIH HHS [P01 CA092625, 2P01CA092625, K23 CA115682, CA-103244, R21 CA103244] NR 8 TC 38 Z9 39 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2010 VL 24 IS 11 BP 1972 EP 1975 DI 10.1038/leu.2010.199 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 678EV UT WOS:000284057400022 PM 20844565 ER PT J AU Miller, E Decker, MR Raj, A Reed, E Marable, D Silverman, JG AF Miller, Elizabeth Decker, Michele R. Raj, Anita Reed, Elizabeth Marable, Danelle Silverman, Jay G. TI Intimate Partner Violence and Health Care-Seeking Patterns Among Female Users of Urban Adolescent Clinics SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Intimate partner violence; Adolescent dating violence; Sexual violence; Physical violence; Adolescent health screening ID DATING VIOLENCE; SEXUAL EXPERIENCES; DOMESTIC VIOLENCE; MENTAL-HEALTH; WOMEN; RISK; CONSEQUENCES; RELIABILITY; PREVALENCE; PREGNANCY AB To assess the prevalence of intimate partner violence (IPV) and associations with health care-seeking patterns among female patients of adolescent clinics, and to examine screening for IPV and IPV disclosure patterns within these clinics. A self-administered, anonymous, computerized survey was administered to female clients ages 14-20 years (N = 448) seeking care in five urban adolescent clinics, inquiring about IPV history, reasons for seeking care, and IPV screening by and IPV disclosure to providers. Two in five (40%) female urban adolescent clinic patients had experienced IPV, with 32% reporting physical and 21% reporting sexual victimization. Among IPV survivors, 45% reported abuse in their current or most recent relationship. IPV prevalence was equally high among those visiting clinics for reproductive health concerns as among those seeking care for other reasons. IPV victimization was associated with both poor current health status (AOR 1.57, 95% CI 1.03-2.40) and having foregone care in the past year (AOR 2.59, 95% CI 1.20-5.58). Recent IPV victimization was associated only with past 12 month foregone care (AOR 2.02, 95% CI 1.18-3.46). A minority (30%) reported ever being screened for IPV in a clinical setting. IPV victimization is pervasive among female adolescent clinic attendees regardless of visit type, yet IPV screening by providers appears low. Patients reporting poor health status and foregone care are more likely to have experienced IPV. IPV screening and interventions tailored for female patients of adolescent clinics are needed. C1 [Miller, Elizabeth] Univ Calif Davis, Sch Med, Dept Pediat, Sacramento, CA 95817 USA. [Decker, Michele R.; Reed, Elizabeth; Silverman, Jay G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Raj, Anita] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Marable, Danelle] Massachusetts Gen Hosp, MGH Ctr Community Hlth Improvement, Boston, MA 02114 USA. RP Miller, E (reprint author), Univ Calif Davis, Sch Med, Dept Pediat, Ticon 2,2516 Stockton Blvd,Rm 382, Sacramento, CA 95817 USA. EM elizabeth.miller@ucdmc.ucdavis.edu RI Miller, Elizabeth/E-7939-2012 FU NICHD NIH HHS [K12 HD051958]; PHS HHS [U36/CCU300430-23] NR 50 TC 34 Z9 34 U1 2 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD NOV PY 2010 VL 14 IS 6 BP 910 EP 917 DI 10.1007/s10995-009-0520-z PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 669PC UT WOS:000283361700010 PM 19760162 ER PT J AU Maciejewski, ML Smith, VA Livingston, EH Kavee, AL Kahwati, LC Henderson, WG Arterburn, DE AF Maciejewski, Matthew L. Smith, Valerie A. Livingston, Edward H. Kavee, Andrew L. Kahwati, Leila C. Henderson, William G. Arterburn, David E. TI Health Care Utilization and Expenditure Changes Associated With Bariatric Surgery SO MEDICAL CARE LA English DT Article DE bariatric; surgery; expenditures; cost; utilization; veterans; weight loss ID LONG-TERM MORTALITY; MORBIDLY OBESE-PATIENTS; GASTRIC BYPASS-SURGERY; OF-VETERANS-AFFAIRS; RISK ADJUSTMENT; SURGICAL CARE; COSTS; OUTCOMES; QUALITY; IMPACT AB Context: Bariatric surgery provides significant reductions in weight and comorbidity, and has the potential to reduce health care utilization. It is unknown whether health care utilization and expenditures are reduced for veterans after bariatric surgery. Objectives: To examine health care utilization and expenditures of severely obese individuals before and after bariatric surgery within the Veterans Health Administration. Design, Setting, and Patients: We conducted a retrospective, longitudinal cohort study of health care use and expenditures among all veterans who underwent bariatric surgery in 1 of 12 approved Department of Veterans Affairs bariatric centers from 2000 to 2006. Bariatric patients were identified via Current Procedural Terminology-4 codes from a database of major surgical procedures maintained by the National Surgical Quality Improvement Program. Main Outcome Measure: The main outcomes of interest for our analysis were multivariable adjusted inpatient and outpatient health care utilization and expenditures in the 3 years prior to surgery and in the 3 years after surgery. Results: Between 2000 and 2006, 846 veterans had bariatric surgery, 25% of whom underwent a laparoscopic procedure. The mean initial body mass index was 48.5, the mean age was 51; and 73% were male. In multivariable models including all years of data, outpatient, inpatient, and overall expenditures significantly decreased in the years after surgery because of higher clinical resources required in the months before and during surgery. When excluding the 6 months leading up to surgery and the 6 months just after surgery, outpatient expenditures remained lower in the post-surgical period, but inpatient and overall expenditures were significantly higher. Conclusion: Our analyses indicate that this cohort of older, male bariatric surgery patients does not achieve a reduction in health care expenditures 3 years after their procedure. These results are at variance from other, similar published studies and may reflect differences in study populations or systems of care. C1 [Maciejewski, Matthew L.; Smith, Valerie A.; Kavee, Andrew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Livingston, Edward H.] Univ Texas SW Med Ctr Dallas, Div Gastrointestinal & Endocrine Surg, Dallas, TX 75390 USA. [Livingston, Edward H.] Vet Adm N Texas Hlth Care Syst, Dallas, TX USA. [Livingston, Edward H.] Univ Texas Arlington, Arlington, TX 76019 USA. [Kahwati, Leila C.] Natl Ctr Hlth Promot & Dis Prevent, Dept Vet Affairs, Off Patient Care Serv, Durham, NC USA. [Henderson, William G.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Henderson, William G.] Univ Colorado, Sch Publ Hlth, Dept Biostat, Aurora, CO USA. [Henderson, William G.] Univ Colorado, Colorado Hlth Outcomes Program, Aurora, CO USA. [Arterburn, David E.] Grp Hlth Res Inst Seattle, Seattle, WA USA. [Arterburn, David E.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care 152, 411 W Chapel Hill St,Suite 600, Durham, NC 27705 USA. EM matthew.maciejewski@va.gov FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 05-201]; Takeda Pharmaceuticals; Surgical Review Corporation; Amgen; Texas Instruments FX Supported by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs, project number IIR 05-201. Supported by Takeda Pharmaceuticals and the Surgical Review Corporation, and owns stock in Amgen (to M. L. M.) and from Texas Instruments, and he serves as a contributing editor to JAMA (to E. H. L.). NR 34 TC 15 Z9 15 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2010 VL 48 IS 11 BP 989 EP 998 DI 10.1097/MLR.0b013e3181ef9cf7 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 671HB UT WOS:000283490600007 PM 20940651 ER PT J AU Kirchhoff, AC Leisenring, W Krull, KR Ness, KK Friedman, DL Armstrong, GT Stovall, M Park, ER Oeffinger, KC Hudson, MM Robison, LL Wickizer, T AF Kirchhoff, Anne C. Leisenring, Wendy Krull, Kevin R. Ness, Kirsten K. Friedman, Debra L. Armstrong, Gregory T. Stovall, Marilyn Park, Elyse R. Oeffinger, Kevin C. Hudson, Melissa M. Robison, Leslie L. Wickizer, Thomas TI Unemployment Among Adult Survivors of Childhood Cancer A Report From the Childhood Cancer Survivor Study SO MEDICAL CARE LA English DT Article DE pediatric cancer; cancer survivorship; employment; socioeconomic factors ID LONG-TERM SURVIVORS; HEALTH-STATUS; COHORT AB Background: Adult childhood cancer survivors report high levels of unemployment, although it is unknown whether this is because of health or employability limitations. Objectives: We examined 2 employment outcomes from 2003 in the Childhood Cancer Survivor Study (CCSS): (1) health-related unemployment and (2) unemployed but seeking work. We compared survivors with a nearest-age CCSS sibling cohort and examined demographic and treatment-related risk groups for each outcome. Methods: We studied 6339 survivors and 1967 siblings >= 25 years of age excluding those unemployed by choice. Multivariable generalized linear models evaluated whether survivors were more likely to be unemployed than siblings and whether certain survivors were at a higher risk for unemployment. Results: Survivors (10.4%) reported health-related unemployment more often than siblings (1.8%; Relative Risk [RR], 6.07; 95% Confidence Interval [CI], 4.32-8.53). Survivors (5.7%) were more likely to report being unemployed but seeking work than siblings (2.7%; RR, 1.90; 95% CI, 1.43-2.54). Health-related unemployment was more common in female survivors than males (Odds Ratio [OR], 1.73; 95% CI, 1.43-2.08). Cranial radiotherapy doses >= 25 Gy were associated with higher odds of unemployment (health-related: OR, 3.47; 95% CI, 2.54-4.74; seeking work: OR, 1.77; 95% CI, 1.15-2.71). Unemployed survivors reported higher levels of poor physical functioning than employed survivors, and had lower education and income and were more likely to be publicly insured than unemployed siblings. Conclusions: Childhood cancer survivors have higher levels of unemployment because of health or being between jobs. High-risk survivors may need vocational assistance. C1 [Kirchhoff, Anne C.; Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Kirchhoff, Anne C.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Krull, Kevin R.; Ness, Kirsten K.; Armstrong, Gregory T.; Hudson, Melissa M.; Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Friedman, Debra L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Park, Elyse R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wickizer, Thomas] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. RP Kirchhoff, AC (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA. EM akirchho@fhcrc.org FU National Cancer Institute [U24 CA55727]; Cancer Center Support (CORE) [CA 21765]; American Syrian Lebanese Associated Charities (ALSAC) FX The Childhood Cancer Survivor Study is funded by the National Cancer Institute (U24 CA55727, PI: L. L. Robison). Support to St. Jude Children's Research Hospital also provided by the Cancer Center Support (CORE) grant (CA 21765) and by the American Syrian Lebanese Associated Charities (ALSAC). Participating sites and Principal Investigators are provided in Appendix. NR 32 TC 35 Z9 35 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD NOV PY 2010 VL 48 IS 11 BP 1015 EP 1025 DI 10.1097/MLR.0b013e3181eaf880 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 671HB UT WOS:000283490600010 PM 20940653 ER PT J AU Stern, TA AF Stern, Theodore A. TI Psychiatry for the Internist Preface SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Stern, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Warren Bldg,Room 605, Boston, MA 02114 USA. EM TStern@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2010 VL 94 IS 6 SI SI BP XIII EP XIV DI 10.1016/j.mcna.2010.08.036 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 678MI UT WOS:000284079600001 PM 20951269 ER PT J AU Beck, BJ Gordon, C AF Beck, B. J. Gordon, Christopher TI An Approach to Collaborative Care and Consultation: Interviewing, Cultural Competence, and Enhancing Rapport and Adherence SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Collaborative care; Cultural competence; Rapport; Adherence; Primary care; Consultation psychiatry ID MENTAL-HEALTH-CARE; PATIENT-PHYSICIAN RELATIONSHIP; RANDOMIZED CONTROLLED-TRIAL; SHARED DECISION-MAKING; LATE-LIFE DEPRESSION; COST-EFFECTIVENESS; PANIC DISORDER; UNITED-STATES; MANAGEMENT; COMMUNICATION AB Although changes in the US health care system promote a population-based approach, increases in population diversity emphasize the need for culturally competent, patient-centered, participatory care. Despite this perceived conflict, the global view has improved the recognition of mental health issues as a driver of overall health as well as health care spending. This recognition, along with the many forces that keep mental health care in the primary care sector, actually encourages the development of collaborative models that capitalize on the primary care provider's opportunity to leverage their rapport with the patient to improve access to, and comfort with, specialty mental health services. Engaging patients in their own path to recovery or well-being improves engagement in, and adherence to, the treatment plan and ultimately improves outcomes. C1 [Beck, B. J.] Massachusetts Gen Hosp, Dept Psychiat, Robert B Andrews Unit, Boston, MA 02114 USA. [Beck, B. J.; Gordon, Christopher] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Beck, B. J.] Beacon Hlth Strategies LLC, Med Affairs, Woburn, MA 01801 USA. [Gordon, Christopher] Advocates Inc, Framingham, MA 01702 USA. RP Beck, BJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Robert B Andrews Unit, ACC 812,15 Parkman St, Boston, MA 02114 USA. EM bbeck@partners.org NR 59 TC 2 Z9 2 U1 6 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2010 VL 94 IS 6 SI SI BP 1075 EP + DI 10.1016/j.mcna.2010.08.001 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 678MI UT WOS:000284079600002 PM 20951270 ER PT J AU Brendel, RW Wei, MH Edersheim, JG AF Brendel, Rebecca Weintraub Wei, Marlynn H. Edersheim, Judith G. TI An Approach to the Patient in Crisis: Assessments of the Risk of Suicide and Violence SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Suicidal ideation; Psychiatric disorder; Violence; Personality disorder ID PRIMARY-CARE PATIENTS; PSYCHIATRIC-PATIENTS; COMMUNITY VIOLENCE; MENTAL-DISORDERS; CLOZAPINE TREATMENT; LITHIUM TREATMENT; SUBSTANCE-ABUSE; GUN OWNERSHIP; BEHAVIOR; SCHIZOPHRENIA AB Suicide is one of the leading causes of death in the United States and is defined as intentional self-harm with the intent of causing death. Various mental disorders may be a cause for increased violence. This article outlines the elements of the risk assessment (for harm to self and/or others) in patients in crisis and addresses which contributing factors may be modifiable. This article also proposes a practical framework for the management of risk regarding suicide and violence. C1 [Brendel, Rebecca Weintraub; Wei, Marlynn H.; Edersheim, Judith G.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Brendel, Rebecca Weintraub; Wei, Marlynn H.; Edersheim, Judith G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Brendel, RW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM rbrendel@partners.org NR 112 TC 4 Z9 4 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2010 VL 94 IS 6 SI SI BP 1089 EP + DI 10.1016/j.mcna.2010.08.002 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 678MI UT WOS:000284079600003 PM 20951271 ER PT J AU Querques, J Kontos, N AF Querques, John Kontos, Nicholas TI An Approach to the Patient with Dysregulated Mood: Major Depression and Bipolar Disorder SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Bipolar disorder; Major depressive disorder; Dysregulated mood; Dysphoria ID NATIONAL COMORBIDITY SURVEY; SURVEY REPLICATION; PREVALENCE AB Major depressive disorder (M DD) and bipolar disorder are chronic relapsing-remitting illnesses whose effects on mood, behavior, and thinking exact a heavy toll on patients' physical and mental health and on their capacity for satisfying relationships and employment. In the inpatient setting, these affective illnesses and their treatments can complicate the diagnosis, course, therapy, and prognosis of numerous medical conditions. In this article, the authors discuss a general approach for general internists, family practitioners, and other primary care providers to follow in caring for patients with suspected MDD or bipolar disorder. C1 [Querques, John; Kontos, Nicholas] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Querques, John; Kontos, Nicholas] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Querques, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM jguergues@partners.org NR 27 TC 1 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2010 VL 94 IS 6 SI SI BP 1117 EP + DI 10.1016/j.mcna.2010.08.011 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 678MI UT WOS:000284079600005 PM 20951273 ER PT J AU Huffman, JC Alpert, JE AF Huffman, Jeff C. Alpert, Jonathan E. TI An Approach to the Psychopharmacologic Care of Patients: Antidepressants, Antipsychotics, Anxiolytics, Mood Stabilizers, and Natural Remedies SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Psychopharmacology; Antidepressants; Anxiolytics; Mood stabilizers; Antipsychotics; Natural remedies ID MAJOR DEPRESSIVE DISORDER; BIPOLAR DISORDER; ATYPICAL ANTIPSYCHOTICS; PREGNANCY; DISCONTINUATION; LITHIUM; BENZODIAZEPINES; METAANALYSIS; VENLAFAXINE; RECURRENCE AB The number of safe and effective medication treatments for psychiatric illness has expanded substantially over the past 10 to 15 years. Knowing when and how to prescribe psychotropics-and knowing which medication to prescribe-can be challenging, but with knowledge of some basic principles, this task can be performed adeptly by physicians of all specialties. In this article, the authors discuss basic principles of psychopharmacology and outline an approach to using several commonly prescribed classes of medications. C1 [Huffman, Jeff C.; Alpert, Jonathan E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Huffman, Jeff C.; Alpert, Jonathan E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Alpert, Jonathan E.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Blake11, Boston, MA 02114 USA. EM Jhuffman@partners.org OI Alpert, Jonathan/0000-0002-4332-908X FU American Heart Association; National Institute of Mental Health; National Alliance for Research on Schizophrenia and Depression (NARSAD); Abbott Laboratories; Alkermes; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Cyberonics; Eli Lilly Company; Forest Pharmaceuticals Inc., GlaxoSmithkline; J & J Pharmaceuticals; Novartis; Organon Inc.; PamLab, LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories; Xian-Janssen; Organon; Belvoir Media Group; Informa Healthcare Publisher; Reed Medical Education FX Dr Huffman has received research funding from the American Heart Association. Dr Alpert has also received research funding from the National Institute of Mental Health, National Alliance for Research on Schizophrenia and Depression (NARSAD), Abbott Laboratories, Alkermes, Lichtwer Pharma GmbH, Lorex Pharmaceuticals; Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Cyberonics, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, J & J Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc., Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, Inc., and Wyeth-Ayerst Laboratories; has participated on advisory boards for or provided consultancy to Eli Lilly & Company, Pamlab LLC, and Pharmavite LLC; and has received speakers' honoraria from Eli Lilly & Company, Xian-Janssen, Organon, Belvoir Media Group, and Informa Healthcare Publisher. Drs Huffman and Alpert have received honoraria from Reed Medical Education for activities performed for the MGH Psychiatry Academy. NR 32 TC 4 Z9 4 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2010 VL 94 IS 6 SI SI BP 1141 EP + DI 10.1016/j.mcna.2010.08.009 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 678MI UT WOS:000284079600007 PM 20951275 ER PT J AU Schlozman, SC AF Schlozman, Steven C. TI An Approach to the Psychosocial Treatment of the Medically Ill Patient SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Psychosocial; Coping; Nonpharmacologic; Spiritual ID ROCKWELL,NORMAN VISITS; DOCTOR; ILLNESS; PROFESSIONALISM; PSYCHOTHERAPY; PHYSICIANS; MEDICINE; EMPATHY; HEALTH; VIEWS AB This article discusses some of the practices of psychosocial treatment. Broadly speaking, these practices include an emphasis on the doctor-patient relationship, the creation of a sound and lasting alliance., and the experience of trust and partnership that the physician fosters in helping the patient to negotiate the complex and uniquely individual experience of being ill. An argument is proposed that unless practitioners of medicine are mindful of the threats to the way they would like and are expected by their patients to practice medicine, they are unlikely to endorse changes actively or to pass the need for these changes onto the next generation of physicians. In this sense, keeping these concerns alive and the subject of ongoing discussion is crucial to the ongoing conceptualization of what it means to be a doctor. C1 [Schlozman, Steven C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schlozman, Steven C.] MGH McLean Program Child Psychiat, Boston, MA USA. [Schlozman, Steven C.] Harvard Univ, Grad Sch Educ, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM sschlozman@partners.org NR 29 TC 2 Z9 2 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2010 VL 94 IS 6 SI SI BP 1161 EP + DI 10.1016/j.mcna.2010.08.012 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 678MI UT WOS:000284079600008 PM 20951276 ER PT J AU Freudenreich, O Kontos, N Nejad, SH Gross, AF AF Freudenreich, Oliver Kontos, Nicholas Nejad, Shamim H. Gross, Anne F. TI An Approach to Symptoms at the Interface of Medicine and Psychiatry: Pain, Insomnia, Weight Loss and Anorexia, Fatigue and Forgetfulness, and Sexual Dysfunction SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Symptoms; Pain; Insomnia; Weight loss; Fatigue; Sexual dysfunction ID MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; ERECTILE DYSFUNCTION; SOMATIC SYMPTOMS; DOUBLE-BLIND; DIABETIC-NEUROPATHY; RESIDUAL SYMPTOMS; PRIMARY CARE; ANTIDEPRESSANTS; EFFICACY AB Primary care physicians commonly deal with patients who present with a somatic complaint for which no clear organic etiology can be found. This article discusses how a psychiatrist thinks about somatic symptoms (eg, pain, insomnia, weight loss and loss of appetite, fatigue and forgetfulness, sexual dysfunction) in a patient who might have depression. The management of a patient in whom no satisfactory medical or psychiatric diagnosis can be made is also reviewed briefly. C1 [Kontos, Nicholas] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Freudenreich, Oliver] Massachusetts Gen Hosp, Dept Med, Div Psychiat & Med, Infect Dis Psychiat Consultat Serv, Boston, MA 02114 USA. [Freudenreich, Oliver; Nejad, Shamim H.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat & Med, Boston, MA 02114 USA. RP Freudenreich, O (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM ofreudenreich@partners.org FU Pfizer FX Oliver Freudenreich, MD, has received research grant support from Pfizer. The other authors have nothing to disclose. NR 69 TC 2 Z9 2 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2010 VL 94 IS 6 SI SI BP 1217 EP + DI 10.1016/j.mcna.2010.08.006 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 678MI UT WOS:000284079600011 PM 20951279 ER PT J AU Brendel, RW Wei, MH Schouten, R Edersheim, JG AF Brendel, Rebecca Weintraub Wei, Marlynn H. Schouten, Ronald Edersheim, Judith G. TI An Approach to Selected Legal Issues: Confidentiality, Mandatory Reporting, Abuse and Neglect, Informed Consent, Capacity Decisions, Boundary Issues, and Malpractice Claims SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Medicolegal issues; Malpractice; Informed consent; Reporting obligations ID PSYCHOTHERAPIST-PATIENT PRIVILEGE; TARASOFF DUTY; COMPETENCY; DOCTRINE; VIOLENCE; HIPAA; LAWS AB Medical practice occurs within a legal and regulatory context. This article covers several of the legal issues that frequently arise in the general medical setting. While this article provides an overview of approaches to informed consent, boundary issues, and malpractice claims, it is critical for clinicians to be familiar with the specific requirements and standards in the jurisdictions in which they practice. As a general rule, it is most important that physicians recognize that the best way to avoid legal problems is to be aware of legal requirements in the jurisdictions in which they practice, but to think clinically and not legally in the provision of consistent and sound clinical care to their patients. C1 [Brendel, Rebecca Weintraub; Wei, Marlynn H.; Schouten, Ronald; Edersheim, Judith G.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Brendel, Rebecca Weintraub; Wei, Marlynn H.; Schouten, Ronald; Edersheim, Judith G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Brendel, RW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM rbrendel@partners.org NR 41 TC 8 Z9 8 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2010 VL 94 IS 6 SI SI BP 1229 EP + DI 10.1016/j.mcna.2010.08.003 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 678MI UT WOS:000284079600012 PM 20951280 ER PT J AU Stallard, E Kinosian, B Zbrozek, AS Yashin, AI Glick, HA Stern, Y AF Stallard, Eric Kinosian, Bruce Zbrozek, Arthur S. Yashin, Anatoliy I. Glick, Henry A. Stern, Yaakov TI Estimation and Validation of a Multiattribute Model of Alzheimer Disease Progression SO MEDICAL DECISION MAKING LA English DT Article DE clinical assessment; outcomes; staging of dementia ID GLOBAL DETERIORATION SCALE; COST-EFFECTIVENESS; DEMENTIA; PREDICTORS; MEMBERSHIP; SELECTION; FEATURES; GRADE; TIME; CARE AB Objectives. To estimate and validate a multiattribute model of the clinical course of Alzheimer disease (AD) from mild AD to death in a high-quality prospective cohort study, and to estimate the impact of hypothetical modifications to AD progression rates on costs associated with Medicare and Medicaid services. Data and Methods. The authors estimated sex-specific longitudinal Grade of Membership (GoM) models for AD patients (103 men, 149 women) in the initial cohort of the Predictors Study (1989-2001) based on 80 individual measures obtained every 6 mo for 10 y. These models were replicated for AD patients (106 men, 148 women) in the 2nd Predictors Study cohort (1997-2007). Model validation required that the disease-specific transition parameters be identical for both Predictors Study cohorts. Medicare costs were estimated from the National Long Term Care Survey. Results. Sex-specific models were validated using the 2nd Predictors Study cohort with the GoM transition parameters constrained to the values estimated for the 1st Predictors Study cohort; 57 to 61 of the 80 individual measures contributed significantly to the GoM models. Simulated, cost-free interventions in the rate of progression of AD indicated that large potential cost offsets could occur for patients at the earliest stages of AD. Conclusions. AD progression is characterized by a small number of parameters governing changes in large numbers of correlated indicators of AD severity. The analysis confirmed that the progression of AD represents a complex multidimensional physiological process that is similar across different study cohorts. The estimates suggested that there could be large cost offsets to Medicare and Medicaid from the slowing of AD progression among patients with mild AD. The methodology appears generally applicable in AD modeling. C1 [Stallard, Eric; Yashin, Anatoliy I.] Duke Univ, Dept Sociol, Durham, NC 27706 USA. [Stallard, Eric; Yashin, Anatoliy I.] Duke Univ, Ctr Populat Hlth & Aging, Durham, NC USA. [Kinosian, Bruce; Glick, Henry A.] Univ Penn Hlth Syst, Div Gen Internal Med, Philadelphia, PA USA. [Kinosian, Bruce] Philadelphia VA Med Ctr, CHERP, Philadelphia, PA USA. [Zbrozek, Arthur S.] Wyeth Pharmaceut, Global Hlth Outcomes Assessment, Collegeville, PA USA. [Stern, Yaakov] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Stern, Yaakov] Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. [Stern, Yaakov] Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. RP Kinosian, B (reprint author), Ralston House,Rm226,3615 Chestnut St, Philadelphia, PA 19104 USA. EM brucek@mail.med.upenn.edu FU Elan Pharmaceuticals; Wyeth Pharmaceuticals; National Institute on Aging [R01-AG028259, R01-AG030612, R01-AG07370] FX The primary financial support for this study was provided by a grant jointly funded by Elan Pharmaceuticals and Wyeth Pharmaceuticals. Funding for supplemental analysis of the National Long Term Care Survey was provided by the National Institute on Aging through grants R01-AG028259 and R01-AG030612. The Predictors Study is supported by a grant to Dr. Stern from the National Institute on Aging, grant R01-AG07370. The funding agreements ensured the authors' independence in designing the study, interpreting the data, and writing and publishing the report. The following author is employed by a primary sponsor: Arthur S. Zbrozek, Wyeth Pharmaceuticals. The helpful comments of Trent McLaughlin, PhD, Elan Pharmaceuticals, on this article are acknowledged. David L. Straley provided programming support at Duke University. Revision accepted for publication 6 January 2010. NR 35 TC 9 Z9 9 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2010 VL 30 IS 6 BP 625 EP 638 DI 10.1177/0272989X10363479 PG 14 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 698FU UT WOS:000285580100001 PM 21183754 ER PT J AU Hickam, DH AF Hickam, David H. TI Decision Aids: Evolving From Novelties to Effective Communication Tools SO MEDICAL DECISION MAKING LA English DT Editorial Material ID CHRONIC ILLNESS; MANAGEMENT C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. RP Hickam, DH (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM hickam@ohsu.edu NR 8 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2010 VL 30 IS 6 BP 699 EP 700 DI 10.1177/0272989X10387782 PG 2 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 698FU UT WOS:000285580100009 PM 21183757 ER PT J AU Elwyn, G Frosch, D Volandes, AE Edwards, A Montori, VM AF Elwyn, Glyn Frosch, Dominick Volandes, Angelo E. Edwards, Adrian Montori, Victor M. TI Investing in Deliberation: A Definition and Classification of Decision Support Interventions for People Facing Difficult Health Decisions SO MEDICAL DECISION MAKING LA English DT Article DE shared decision making; decision aids; decision support interventions; complex interventions ID CLUSTER RANDOMIZED-TRIAL; MAKING SKILL DEVELOPMENT; RISK COMMUNICATION AIDS; GENERAL-PRACTICE; FRAMEWORK; CARE; QUALITY; TECHNOLOGIES; PREFERENCES; CONSENSUS AB This article provides an analysis of 'decision aids', interventions to support patients facing tough decisions. Interest has increased since the concept of shared decision making has become widely considered to be a means of achieving desirable clinical outcomes. We consider the aims of these interventions and examine assumptions about their use. We propose three categories, interventions that are used in face-to-face encounters, those designed for use outside clinical encounters and those which are mediated, using telephone or other communication media. We propose the following definition: decision support interventions help people think about choices they face; they describe where and why choice exists; they provide information about options, including, where reasonable, the option of taking no action. These interventions help people to deliberate, independently or in collaboration with others, about options, by considering relevant attributes; they support people to forecast how they might feel about short, intermediate and long-term outcomes which have relevant consequences, in ways which help the process of constructing preferences and eventual decision making, appropriate to their individual situation. Although quality standards have been published for these interventions, we are also cautious about premature closure and consider that the need for short versions for use inside clinical encounters and long versions for external use requires further research. More work is also needed on the use of narrative formats and the translation of theory into practical designs. The interest in decision support interventions for patients heralds a transformation in clinical practice although many important areas remain unresolved. C1 [Elwyn, Glyn; Edwards, Adrian] Cardiff Univ, Clin Epidemiol Interdisciplinary Res Grp, Dept Publ Hlth & Primary Care, Cardiff CF14 4YS, S Glam, Wales. [Frosch, Dominick] Palo Alto Med Fdn, Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94301 USA. [Volandes, Angelo E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Montori, Victor M.] Mayo Clin, Coll Med, Knowledge & Encounter Res Unit, Rochester, MN USA. RP Elwyn, G (reprint author), Cardiff Univ, Clin Epidemiol Interdisciplinary Res Grp, Dept Publ Hlth & Primary Care, Heath Pk, Cardiff CF14 4YS, S Glam, Wales. EM elwyng@cardiff.ac.uk RI Elwyn, G./L-4292-2015; OI Elwyn, Glyn/0000-0002-0917-6286; Montori, Victor/0000-0003-0595-2898 NR 65 TC 84 Z9 86 U1 4 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2010 VL 30 IS 6 BP 701 EP 711 DI 10.1177/0272989X10386231 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 698FU UT WOS:000285580100010 PM 21088131 ER PT J AU Naik, AD Singh, H AF Naik, Aanand D. Singh, Hardeep TI Electronic Health Records to Coordinate Decision Making for Complex Patients: What Can We Learn from Wiki? SO MEDICAL DECISION MAKING LA English DT Article DE decision making; communication; electronic health records; disease management; reviews; quality and safety ID PRIMARY-CARE; EFFECTIVE COMMUNICATION; INFORMATION-TECHNOLOGY; SURVIVORSHIP CARE; MANAGEMENT; OUTCOMES; TRIALS; ERRORS AB Background. Processes of communication that guide decision making among clinicians collaboratively caring for complex patients are poorly understood and vary based on local contexts. In this paper, the authors characterize these processes and propose a wiki-style communication model to improve coordination of decision making among clinicians using an integrated electronic health record (EHR). Methods. A narrative review of current patterns of communication among clinicians sharing medical decisions focusing on the emerging and potential roles of EHRs to enhance communication among clinicians caring for complex patients. Results. The authors present the taxonomy of decision making and communication among clinicians caring for complex patients. They then adapt wiki-style communication to propose a novel model of communication among clinicians for decision making within multidisciplinary disease management programs. Future innovations using wiki-style communication among clinicians are also described and placed in the context of medical decisions by clinicians working together in disease management programs. Conclusions. EHR-based wiki-style applications may have the potential to improve communication and care coordination among clinicians caring for complex patients. This could lead to improved quality and safety within multidisciplinary disease management programs. C1 [Naik, Aanand D.] Baylor Coll Med, Hlth Decis Making & Commun Program, Houston Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Naik, Aanand D.; Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Hlth Policy & Qual Program, Houston Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Naik, Aanand D.; Singh, Hardeep] Baylor Coll Med, John M Eisenberg Ctr Clin Decis & Commun Sci, Houston, TX 77030 USA. RP Naik, AD (reprint author), Houston HSR& Ctr Excellence, Michael E DeBakey VA 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.tmc.edu FU NCI NIH HHS [K23CA125585]; NIA NIH HHS [K23AG027144] NR 36 TC 15 Z9 15 U1 4 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2010 VL 30 IS 6 BP 722 EP 731 DI 10.1177/0272989X10385846 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 698FU UT WOS:000285580100012 PM 21183759 ER PT J AU Court, LE Seco, J Lu, XQ Ebe, K Mayo, C Ionascu, D Winey, B Giakoumakis, N Aristophanous, M Berbeco, R Rottman, J Bogdanov, M Schofield, D Lingos, T AF Court, Laurence E. Seco, Joao Lu, Xing-Qi Ebe, Kazuyu Mayo, Charles Ionascu, Dan Winey, Brian Giakoumakis, Nikos Aristophanous, Michalis Berbeco, Ross Rottman, Joerg Bogdanov, Madeleine Schofield, Deborah Lingos, Tania TI Use of a realistic breathing lung phantom to evaluate dose delivery errors SO MEDICAL PHYSICS LA English DT Article DE interplay effect; respiratory motion; IMRT; VMAT; rapid prototyping ID ORGAN MOTION; INTENSITY MODULATION; RESPIRATORY MOTION; IMRT TREATMENTS; RADIOTHERAPY; TARGETS; TUMORS AB Purpose: To compare the effect of respiration-induced motion on delivered dose (the interplay effect) for different treatment techniques under realistic clinical conditions. Methods: A flexible resin tumor model was created using rapid prototyping techniques based on a computed tomography (CT) image of an actual tumor. Twenty micro-MOSFETs were inserted into the tumor model and the tumor model was inserted into an anthropomorphic breathing phantom. Phantom motion was programed using the motion trajectory of an actual patient. A four-dimensional CT image was obtained and several treatment plans were created using different treatment techniques and planning systems: Conformal (Eclipse), step-and-shoot intensity-modulated radiation therapy (IMRT) (Pinnacle), step-and-shoot IMRT (XiO), dynamic IMRT (Eclipse), complex dynamic IMRT (Eclipse), hybrid IMRT [60% conformal, 40% dynamic IMRT (Eclipse)], volume-modulated arc therapy (VMAT) [single-arc (Eclipse)], VMAT [double-arc (Eclipse)], and complex VMAT (Eclipse). The complex plans were created by artificially pushing the optimizer to give complex multileaf collimator sequences. Each IMRT field was irradiated five times and each VMAT field was irradiated ten times, with each irradiation starting at a random point in the respiratory cycle. The effect of fractionation was calculated by randomly summing the measured doses. The maximum deviation for each measurement point per fraction and the probability that 95% of the model tumor had dose deviations less than 2% and 5% were calculated as a function of the number of fractions. Tumor control probabilities for each treatment plan were calculated and compared. Results: After five fractions, measured dose deviations were less than 2% for more than 95% of measurement points within the tumor model for all plans, except the complex dynamic IMRT, step-and-shoot IMRT (XiO), complex VMAT, and single-arc VMAT plans. Reducing the dose rate of the complex IMRT plans from 600 to 200 MU/min reduced the dose deviations to less than 2%. Dose deviations were less than 5% after five fractions for all plans, except the complex single-arc VMAT plan. Conclusions: Rapid prototyping techniques can be used to create realistic tumor models. For most treatment techniques, the dose deviations averaged out after several fractions. Treatments with unusually complicated multileaf collimator sequences had larger dose deviations. For IMRT treatments, dose deviations can be reduced by reducing the dose rate. For VMAT treatments, using two arcs instead of one is effective for reducing dose deviations. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3496356] C1 [Court, Laurence E.; Winey, Brian; Giakoumakis, Nikos; Aristophanous, Michalis; Berbeco, Ross; Rottman, Joerg; Bogdanov, Madeleine; Schofield, Deborah; Lingos, Tania] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Court, Laurence E.; Winey, Brian; Giakoumakis, Nikos; Aristophanous, Michalis; Berbeco, Ross; Rottman, Joerg; Bogdanov, Madeleine; Schofield, Deborah; Lingos, Tania] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Seco, Joao; Winey, Brian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lu, Xing-Qi] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02130 USA. [Ebe, Kazuyu] JA Jouetsu Hosp, Joetsu 3550063, Japan. [Mayo, Charles] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01655 USA. [Ionascu, Dan] William Beaumont Hosp, Royal Oak, MI 48073 USA. RP Court, LE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Unit 94, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM lecourt@mdanderson.org RI Seco, Joao/J-4451-2012 FU Kayes Family New Technology Grant FX This work was funded in part by a Kayes Family New Technology Grant. The authors thank Radiology Support Devices, Inc. for generously providing the dynamic breathing phantom used in this work. The authors also thank the reviewers and editors for their helpful comments. NR 20 TC 37 Z9 37 U1 2 U2 13 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2010 VL 37 IS 11 BP 5850 EP 5857 DI 10.1118/1.3496356 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 674MA UT WOS:000283747600031 PM 21158297 ER PT J AU Lu, HM Mann, G Cascio, E AF Lu, Hsiao-Ming Mann, Greg Cascio, Ethan TI Investigation of an implantable dosimeter for single-point water equivalent path length verification in proton therapy SO MEDICAL PHYSICS LA English DT Article DE particle therapy; in vivo dosimetry; range uncertainty; MOSFET; LET dependence ID VIVO RANGE VERIFICATION; CURRENT MODULATION; MOSFET DOSIMETER; RADIOTHERAPY AB Purpose: In vivo range verification in proton therapy is highly desirable. A recent study suggested that it was feasible to use point dose measurement for in vivo beam range verification in proton therapy, provided that the spread-out Bragg peak dose distribution is delivered in a different and rather unconventional manner. In this work, the authors investigate the possibility of using a commercial implantable dosimeter with wireless reading for this particular application. Methods: The traditional proton treatment technique delivers all the Bragg peaks required for a SOBP field in a single sequence, producing a constant dose plateau across the target volume. As a result, a point dose measurement anywhere in the target volume will produce the same value, thus providing no information regarding the water equivalent path length to the point of measurement. However, the same constant dose distribution can be achieved by splitting the field into a complementary pair of subfields, producing two oppositely "sloped" depth-dose distributions, respectively. The ratio between the two distributions can be a sensitive function of depth and measuring this ratio at a point inside the target volume can provide the water equivalent path length to the dosimeter location. Two types of field splits were used in the experiment, one achieved by the technique of beam current modulation and the other by manipulating the location and width of the beam pulse relative to the range modulator track. Eight MOSFET-based implantable dosimeters at four different depths in a water tank were used to measure the dose ratios for these field pairs. A method was developed to correct the effect of the well-known LET dependence of the MOSFET detectors on the depth-dose distributions using the columnar recombination model. The LET-corrected dose ratios were used to derive the water equivalent path lengths to the dosimeter locations to be compared to physical measurements. Results: The implantable dosimeters measured the dose ratios with a reasonable relative uncertainty of 1%-3% at all depths, except when the ratio itself becomes very small. In total, 55% of the individual measurements reproduced the water equivalent path lengths to the dosimeters within 1 mm. For three dosimeters, the difference was consistently less than 1 mm. Half of the standard deviations over the repeated measurements were equal or less than 1 mm. Conclusions: With a single fitting parameter, the LET-correction method worked remarkably well for the MOSFET detectors. The overall results were very encouraging for a potential method of in vivo beam range verification with millimeter accuracy. This is sufficient accuracy to expand range of clinical applications in which the authors could use the distal fall off of the proton depth dose for tight margins. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3504609] C1 [Lu, Hsiao-Ming; Cascio, Ethan] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Mann, Greg] Sicel Technol Inc, Morrisville, NC 27560 USA. RP Lu, HM (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, FHBPTC,Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02115 USA. EM hmlu@partners.org NR 20 TC 8 Z9 8 U1 1 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2010 VL 37 IS 11 BP 5858 EP 5866 DI 10.1118/1.3504609 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 674MA UT WOS:000283747600032 PM 21158298 ER PT J AU Jackson, EA Mathews, K Joffe, H Sutton-Tyrrell, KC Chae, C Crawford, S El Khoudary, SR Thurston, RC AF Jackson, Elizabeth A. Mathews, Karen Joffe, Hadine Sutton-Tyrrell, Kim C. Chae, Claudia Crawford, Sybil El Khoudary, Samar R. Thurston, Rebecca C. TI Menopausal Vasomotor Symptom Frequency and Blood Pressure: The Study of Women's Health Across the Nation (SWAN) SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 21st Annual Meeting of the North-American-Menopause-Society CY OCT 06-09, 2010 CL Chicago, IL SP N Amer Menopause Soc C1 [Jackson, Elizabeth A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Mathews, Karen; Sutton-Tyrrell, Kim C.; El Khoudary, Samar R.; Thurston, Rebecca C.] Univ Pittsburgh, Pittsburgh, PA USA. [Joffe, Hadine] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Crawford, Sybil] Univ Massachusetts, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2010 VL 17 IS 6 BP 1229 EP 1229 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 677LK UT WOS:000283993700097 ER PT J AU Maserejian, NN Parish, S Shifren, JL Huang, L Gerstenberger, EP Rosen, RC AF Maserejian, Nancy N. Parish, Sharon Shifren, Jan L. Huang, Liyuan Gerstenberger, Eric P. Rosen, Raymond C. TI Treatment Seeking and Healthcare Utilization in Women over Age 40 y with Clinically Diagnosed Hypoactive Sexual Desire Disorder SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 21st Annual Meeting of the North-American-Menopause-Society CY OCT 06-09, 2010 CL Chicago, IL SP N Amer Menopause Soc C1 [Maserejian, Nancy N.; Huang, Liyuan; Gerstenberger, Eric P.; Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA. [Parish, Sharon] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Parish, Sharon] Montefiore Med Ctr, Bronx, NY 10467 USA. [Shifren, Jan L.] Massachusetts Gen Hosp, Vincent OB GYN Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2010 VL 17 IS 6 BP 1239 EP 1240 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 677LK UT WOS:000283993700137 ER PT J AU Christopher, AB Arndt, A Cugini, C Dayey, ME AF Christopher, Aaron B. Arndt, Annette Cugini, Carla Dayey, Mary E. TI A streptococcal effector protein that inhibits Porphyromonas gingivalis biofilm development SO MICROBIOLOGY-SGM LA English DT Article ID GROUP-A STREPTOCOCCUS; ARGININE DEIMINASE; ORAL BACTERIA; INTERGENERIC COMMUNICATION; PERIODONTAL-DISEASE; CELL-PROLIFERATION; FIMBRIAE; EXPRESSION; MUTANS; IDENTIFICATION AB Dental plaque formation is a developmental process involving cooperation and competition within a diverse microbial community, approximately 70 % of which is composed of an array of streptococci during the early stages of supragingival plaque formation. In this study, 79 cell-free culture supernatants from a variety of oral streptococci were screened to identify extracellular compounds that inhibit biofilm formation by the oral anaerobe Porphyromonas gingivalis strain 381. The majority of the streptococcal supernatants (61 isolates) resulted in lysis of P. gingivalis cells, and some (17 isolates) had no effect on cell viability, growth or biofilm formation. One strain, however, produced a supernatant that abolished biofilm formation without affecting growth rate. Analysis of this activity led to the discovery that a 48 kDa protein was responsible for the inhibition. Protein sequence identification and enzyme activity assays identified the effector protein as an arginine deiminase. To identify the mechanism(s) by which this protein inhibits biofilm formation, we began by examining the expression levels of genes encoding fimbrial subunits; surface structures known to be involved in biofilm development. Quantitative RT-PCR analysis revealed that exposure of P. gingivalis cells to this protein for 1 h resulted in the downregulation of genes encoding proteins that are the major subunits of two distinct types of thin, single-stranded fimbriae (fimA and mfa1). Furthermore, this downregulation occurred in the absence of arginine deiminase enzymic activity. Hence, our data indicate that P. gingivalis can sense this extracellular protein, produced by an oral streptococcus (Streptococcus intermedius), and respond by downregulating expression of cell-surface appendages required for attachment and biofilm development. C1 [Arndt, Annette] Univ Ulm, Inst Microbiol & Biotechnol, Ulm, Germany. [Christopher, Aaron B.; Cugini, Carla; Dayey, Mary E.] Forsyth Inst, Dept Mol Genet, Boston, MA USA. RP Dayey, ME (reprint author), Forsyth Inst, Dept Mol Genet, Boston, MA USA. EM mdavey@forsyth.org FU Colgate Palmolive Company FX This work was supported by a grant from the Colgate Palmolive Company. NR 46 TC 26 Z9 27 U1 1 U2 7 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD NOV PY 2010 VL 156 SI SI BP 3469 EP 3477 DI 10.1099/mic.0.042671-0 PN 11 PG 9 WC Microbiology SC Microbiology GA 685XC UT WOS:000284660400027 PM 20705665 ER PT J AU Bigatello, LM Kistler, EB Noto, A AF Bigatello, L. M. Kistler, E. B. Noto, A. TI Limitations of volumetric indices obtained by transthoracic thermodilution SO MINERVA ANESTESIOLOGICA LA English DT Article DE Monitoring, physiologic; Stroke volume; Extravascular lung water ID EXTRAVASCULAR LUNG WATER; SINGLE TRANSPULMONARY THERMODILUTION; INDICATOR DILUTION MEASUREMENTS; PULMONARY-ARTERY CATHETER; CRITICALLY-ILL PATIENTS; CARDIAC-OUTPUT; CIRCULATION; PRESSURE; INJURY; DYE AB Transthoracic thermodilution (TTT) measures cardiac output without the need for right heart catheterization. In addition, two volumetric hemodynamic indices have been derived from the mathematical analysis of the TTT curve: the global end diastolic volume (a quantitative measure of cardiac preload) and the extravascular lung water volume (a quantitative measure of pulmonary edema). Despite the undeniable appeal of these two novel parameters, uncertainty exists regarding both the validity of their mathematical derivation and their physiological significance. This concise review attempts to discuss such concerns. (Minerva Anestesiol 2010;76:945-9) C1 [Bigatello, L. M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Anesthesiol Serv, Boston, MA 02115 USA. [Kistler, E. B.] Univ Calif San Diego, Dept Anesthesia, San Diego, CA 92103 USA. [Noto, A.] Univ Messina, Dept Cardiothorac & Vasc Anesthesia, Policlin G Martino, Messina, Italy. RP Bigatello, LM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Anesthesiol Serv, Boston, MA 02115 USA. EM luca.bigatello@va.gov RI Noto, Alberto/G-6468-2012 NR 24 TC 11 Z9 11 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD NOV PY 2010 VL 76 IS 11 BP 945 EP 949 PG 5 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 691XN UT WOS:000285114200011 PM 21102390 ER PT J AU Rao, S Zhen, S Roumiantsev, S McDonald, LT Yuan, GC Orkin, SH AF Rao, Sridhar Zhen, Shao Roumiantsev, Sergei McDonald, Lindsay T. Yuan, Guo-Cheng Orkin, Stuart H. TI Differential Roles of Sall4 Isoforms in Embryonic Stem Cell Pluripotency SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID OKIHIRO-SYNDROME; TRANSCRIPTIONAL NETWORK; CHROMATIN STATE; MURINE HOMOLOG; SELF-RENEWAL; CHIP-CHIP; GENE; EXPRESSION; NANOG; MUTATIONS AB Murine embryonic stem (ES) cells are defined by continuous self-renewal and pluripotency. A diverse repertoire of protein isoforms arising from alternative splicing is expressed in ES cells without defined biological roles. Sall4, a transcription factor essential for pluripotency, exists as two isoforms (Sall4a and Sall4b). Both isoforms can form homodimers and a heterodimer with each other, and each can interact with Nanog. By genomewide location analysis, we determined that Sall4a and Sall4b have overlapping, but not identical binding sites within the ES cell genome. In addition, Sall4b, but not Sall4a, binds preferentially to highly expressed loci in ES cells. Sall4a and Sall4b binding sites are distinguished by both epigenetic marks at target loci and their clustering with binding sites of other pluripotency factors. When ES cells expressing a single isoform of Sall4 are generated, Sall4b alone could maintain the pluripotent state, although it could not completely suppress all differentiation markers. Sall4a and Sall4b collaborate in maintenance of the pluripotent state but play distinct roles. Our work is novel in establishing such isoform-specific differences in ES cells. C1 [Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Karp Family Res Labs, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. [Rao, Sridhar; Zhen, Shao; McDonald, Lindsay T.; Yuan, Guo-Cheng; Orkin, Stuart H.] Childrens Hosp, Dana Farber Canc Inst, Dept Computat Biol, Boston, MA 02115 USA. [Rao, Sridhar; Zhen, Shao; Roumiantsev, Sergei; Orkin, Stuart H.] Massachusetts Gen Hosp Children, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Roumiantsev, Sergei] Div Newborn Med, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Karp Family Res Labs, Dana Farber Canc Inst,Dept Pediat Oncol, 300 Longwood Ave,Rm 7210, Boston, MA 02115 USA. EM orkin@bloodgroup.tch.harvard.edu FU NHLBI [5K08HL87951]; Claudia Adams Barr Award FX S.R. is funded by a Career Development Award from the NHLBI (5K08HL87951). S.H.O. is an investigator of the HHMI. G.Y. is supported by a Claudia Adams Barr Award. NR 49 TC 66 Z9 77 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2010 VL 30 IS 22 BP 5364 EP 5380 DI 10.1128/MCB.00419-10 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 673JX UT WOS:000283656700010 PM 20837710 ER PT J AU Lu, CF Mi, LZ Grey, MJ Zhu, JQ Graef, E Yokoyama, S Springer, TA AF Lu, Chafen Mi, Li-Zhi Grey, Michael J. Zhu, Jieqing Graef, Elizabeth Yokoyama, Shigeyuki Springer, Timothy A. TI Structural Evidence for Loose Linkage between Ligand Binding and Kinase Activation in the Epidermal Growth Factor Receptor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSMEMBRANE ALPHA-HELICES; CRYSTAL-STRUCTURE; EXTRACELLULAR DOMAIN; ERBB RECEPTORS; DIMERIZATION; PREDICTION; SOFTWARE; CELLS; MODEL AB The mechanisms by which signals are transmitted across the plasma membrane to regulate signaling are largely unknown for receptors with single-pass transmembrane domains such as the epidermal growth factor receptor (EGFR). A crystal structure of the extracellular domain of EGFR dimerized by epidermal growth factor (EGF) reveals the extended, rod-like domain IV and a small, hydrophobic domain IV interface compatible with flexibility. The crystal structure and disulfide cross-linking suggest that the 7-residue linker between the extracellular and transmembrane domains is flexible. Disulfide cross-linking of the transmembrane domain shows that EGF stimulates only moderate association in the first two alpha-helical turns, in contrast to association throughout the membrane over five alpha-helical turns in glycophorin A and integrin. Furthermore, systematic mutagenesis to leucine and phenylalanine suggests that no specific transmembrane interfaces are required for EGFR kinase activation. These results suggest that linkage between ligand-induced dimerization and tyrosine kinase activation is much looser than was previously envisioned. C1 [Lu, Chafen; Mi, Li-Zhi; Grey, Michael J.; Zhu, Jieqing; Graef, Elizabeth; Springer, Timothy A.] Harvard Univ, Immune Dis Inst, Sch Med, Boston, MA 02115 USA. [Lu, Chafen; Mi, Li-Zhi; Grey, Michael J.; Zhu, Jieqing; Graef, Elizabeth; Springer, Timothy A.] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Yokoyama, Shigeyuki] Univ Tokyo, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130033, Japan. RP Springer, TA (reprint author), Harvard Univ, Immune Dis Inst, Sch Med, 3 Blackfan Circle, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Mi, Li-Zhi/B-1371-2016; OI Mi, Li-Zhi/0000-0001-9907-5245; Yokoyama, Shigeyuki/0000-0003-3133-7338 FU American Cancer Society [PF-07-055-01-GMC]; NIH [HL-48675] FX M.J.G. was supported by a postdoctoral fellowship from the American Cancer Society (PF-07-055-01-GMC). This work was supported by NIH grant HL-48675. NR 38 TC 74 Z9 76 U1 2 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2010 VL 30 IS 22 BP 5432 EP 5443 DI 10.1128/MCB.00742-10 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 673JX UT WOS:000283656700015 PM 20837704 ER PT J AU Good, DM Zurbig, P Argiles, A Bauer, HW Behrens, G Coon, JJ Dakna, M Decramer, S Delles, C Dominiczak, AF Ehrich, JHH Eitner, F Fliser, D Frommberger, M Ganser, A Girolami, MA Golovko, I Gwinner, W Haubitz, M Herget-Rosenthal, S Jankowski, J Jahn, H Jerums, G Julian, BA Kellmann, M Kliem, V Kolch, W Krolewski, AS Luppi, M Massy, Z Melter, M Neususs, C Novak, J Peter, K Rossing, K Rupprecht, H Schanstra, JP Schiffer, E Stolzenburg, JU Tarnow, L Theodorescu, D Thongboonkerd, V Vanholder, R Weissinger, EM Mischak, H Schmitt-Kopplin, P AF Good, David M. Zuerbig, Petra Argiles, Angel Bauer, Hartwig W. Behrens, Georg Coon, Joshua J. Dakna, Mohammed Decramer, Stephane Delles, Christian Dominiczak, Anna F. Ehrich, Jochen H. H. Eitner, Frank Fliser, Danilo Frommberger, Moritz Ganser, Arnold Girolami, Mark A. Golovko, Igor Gwinner, Wilfried Haubitz, Marion Herget-Rosenthal, Stefan Jankowski, Joachim Jahn, Holger Jerums, George Julian, Bruce A. Kellmann, Markus Kliem, Volker Kolch, Walter Krolewski, Andrzej S. Luppi, Mario Massy, Ziad Melter, Michael Neusuess, Christian Novak, Jan Peter, Karlheinz Rossing, Kasper Rupprecht, Harald Schanstra, Joost P. Schiffer, Eric Stolzenburg, Jens-Uwe Tarnow, Lise Theodorescu, Dan Thongboonkerd, Visith Vanholder, Raymond Weissinger, Eva M. Mischak, Harald Schmitt-Kopplin, Philippe TI Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID ELECTRON-TRANSFER DISSOCIATION; SUPPORT VECTOR MACHINES; RESOLUTION PROTEOME/PEPTIDOME ANALYSIS; TAMM-HORSFALL PROTEIN; MASS-SPECTROMETRY; CAPILLARY-ELECTROPHORESIS; BIOMARKER DISCOVERY; PROTEOMIC ANALYSIS; 2-DIMENSIONAL ELECTROPHORESIS; SEQUENCE-ANALYSIS AB Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides. Molecular & Cellular Proteomics 9:2424-2437, 2010. C1 [Zuerbig, Petra; Dakna, Mohammed; Golovko, Igor; Schiffer, Eric; Mischak, Harald] Mosa Diagnost GmbH, D-30625 Hannover, Germany. [Good, David M.; Coon, Joshua J.] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA. [Coon, Joshua J.] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA. [Argiles, Angel] RD Nephrol, F-34090 Montpellier, France. [Bauer, Hartwig W.] Univ Munich, D-80539 Munich, Germany. [Behrens, Georg] Hannover Med Sch, Dept Clin Immunol, D-30625 Hannover, Germany. [Zuerbig, Petra] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, D-30625 Hannover, Germany. [Gwinner, Wilfried; Haubitz, Marion] Hannover Med Sch, Dept Nephrol, D-30625 Hannover, Germany. [Ehrich, Jochen H. H.] Hannover Med Sch, Childrens Hosp, D-30625 Hannover, Germany. [Decramer, Stephane; Schanstra, Joost P.] INSERM, U858 I2MR, F-31432 Toulouse, France. [Decramer, Stephane] CHU Toulouse, Hop Enfants, Pediat Nephrol Unit, F-31059 Toulouse, France. [Delles, Christian; Dominiczak, Anna F.; Mischak, Harald] Univ Glasgow, British Heart Fdn Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Coll Med Vet & Life Sci, Glasgow G12 8TA, Lanark, Scotland. [Eitner, Frank] RWTH Univ Hosp, Dept Nephrol & Clin Immunol, D-52074 Aachen, Germany. [Fliser, Danilo] Saarland Univ Hosp, Dept Internal Med 4, D-66421 Homburg, Germany. [Frommberger, Moritz; Schmitt-Kopplin, Philippe] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Ecol Chem, D-85764 Neuherberg, Germany. [Girolami, Mark A.] Univ Glasgow, Dept Comp Sci, Glasgow G12 8QQ, Lanark, Scotland. [Herget-Rosenthal, Stefan] Red Cross Hosp, Dept Med, D-28199 Bremen, Germany. [Jankowski, Joachim] Charite Hosp, Dept Nephrol, D-12200 Berlin, Germany. [Jahn, Holger] Univ Hosp Hamburg Eppendorf, Dept Psychiat, D-20246 Hamburg, Germany. [Jerums, George] Univ Melbourne, Dept Med Austin Hlth & No Hlth, Heidelberg, Vic 3081, Australia. [Julian, Bruce A.; Novak, Jan] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Julian, Bruce A.; Novak, Jan] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Kellmann, Markus] Thermo Fisher Sci, D-28199 Bremen, Germany. [Kliem, Volker] Lower Saxony Ctr Nephrol, Dept Nephrol, Transplantat Ctr, D-34346 Munden, Germany. [Kolch, Walter] Univ Coll Dublin, Dublin 4, Ireland. [Krolewski, Andrzej S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Luppi, Mario] Univ Modena & Reggio Emilia, Dept Oncol Hematol & Resp Dis, I-41100 Modena, Italy. [Massy, Ziad] INSERM, Dept Clin Pharmacol, ERI 12, F-80054 Amiens, France. [Massy, Ziad] INSERM, Dept Nephrol, ERI 12, F-80054 Amiens, France. [Massy, Ziad] Univ Picardie Jules Verne, Amiens Univ Hosp, F-80054 Amiens, France. [Melter, Michael] Univ Regensburg, Childrens Hosp, D-93053 Regensburg, Germany. [Neusuess, Christian] Univ Aalen, Dept Analyt Chem, D-73430 Aalen, Germany. [Peter, Karlheinz] Baker Heart Res Inst, Dept Atherothrombosis & Vasc, Melbourne, Vic 8008, Australia. [Rossing, Kasper; Tarnow, Lise] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Rupprecht, Harald] Clin Ctr Bayreuth, Dept Nephrol, D-95444 Bayreuth, Germany. [Stolzenburg, Jens-Uwe] Univ Leipzig, Dept Urol, D-04103 Leipzig, Germany. [Theodorescu, Dan] Univ Virginia, Dept Urol, Charlottesville, VA 22908 USA. [Thongboonkerd, Visith] Mahidol Univ, Siriraj Hosp, Fac Med, Bangkok 10700, Thailand. [Thongboonkerd, Visith] Mahidol Univ, Ctr Res Complex Syst Sci, Bangkok 10700, Thailand. [Vanholder, Raymond] Ghent Univ Hosp, Dept Internal Med, B-9000 Ghent, Belgium. RP Zurbig, P (reprint author), Mosa Diagnost GmbH, Mellendorfer Str 7-9, D-30625 Hannover, Germany. EM zuerbig@mosaiques-diagnostics.com RI Jahn, Holger/A-9255-2008; Mischak, Harald/E-8685-2011; THONGBOONKERD, VISITH /C-6920-2009; Schmitt-Kopplin, Philippe/H-6271-2011; Peter, Karlheinz/E-8772-2010; Luppi, Mario/J-3668-2016; Behrens, Georg/Q-4486-2016; OI Jahn, Holger/0000-0003-3607-7651; Schmitt-Kopplin, Philippe/0000-0003-0824-2664; Peter, Karlheinz/0000-0002-8040-2258; Luppi, Mario/0000-0002-0373-1154; Kolch, Walter/0000-0001-5777-5016 FU National Institutes of Health [DK067638, DK075868, DK078244, DK061525, DK080301, DK082753]; Biotechnology Training Program Predoctoral Fellowship [5T32GM08349]; Eurotransbio [ETB-2006-016]; Lower Saxony Ministry of Economy [203.19-32329-5-461]; InGenious HyperCare [LSHM-CT-2006-037093]; British Heart Foundation [RG/02/012]; Federal Ministry of Education and Research [NGFN/01GR0807]; Biotechnology and Biological Sciences Research Council; Engineering and Physical Sciences Research Council Interdisciplinary Research Collaboration in Proteomic Technology (IRColl) Grant Radical Solutions for Researching the Proteome (RASOR); Wellcome Trust [29240]; INSERM; Fondation pour la Recherche Medicale; European Union Prevention of Diabetic Complications (PREDICTIONS) [LSHM-CT-2005-018733]; European Union [LSHM-CT-2005-018733, HEALTH-F2-2009-241544] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK067638 (to A. S. K.); Grants DK075868, DK078244, DK061525, DK080301, and DK082753 (to B. A. J. and J. N.); and Biotechnology Training Program Predoctoral Fellowship Grant 5T32GM08349 (to D. M. G.). This work was also supported by Eurotransbio Grant ETB-2006-016 to the Urosysteomics consortium (www.urosysteomics.com) (to E. S. and H. M.), Lower Saxony Ministry of Economy Grant 203.19-32329-5-461 (to A. G., E. M. W., and H. M.), and the Joslin Diabetes Center. H. Mischak is founder and co-owner of Mosaiques Diagnostics GmbH, which developed the CE-MS technology and the MosaiquesVisu software. P. Zurbig, M. Dakna, Igor Golovko, and Eric Schiffer are employees of Mosaiques Diagnostics GmbH.; Supported by InGenious HyperCare Grant LSHM-CT-2006-037093 and British Heart Foundation Grant RG/02/012.; Supported by Federal Ministry of Education and Research Grant NGFN/01GR0807.; Supported by the Biotechnology and Biological Sciences Research Council and Engineering and Physical Sciences Research Council Interdisciplinary Research Collaboration in Proteomic Technology (IRColl) Grant Radical Solutions for Researching the Proteome (RASOR) and Wellcome Trust Joint Infrastructure Fund Proteomics Grant 29240.; Supported by INSERM, the "Direction Regional de la Recherche Clinique" (Centre Hospitalier Universitaire de Toulouse, France) under the Interface program and by the Fondation pour la Recherche Medicale.; Supported by European Union Prevention of Diabetic Complications (PREDICTIONS) Grant LSHM-CT-2005-018733.; Supported by European Union PREDICTIONS Grant LSHM-CT-2005-018733 and by InGenious HyperCare Grant LSHM-CT2006-037093.; Supported by European Union to Systems Biology towards Novel Chronic Kidney Disease Diagnosis and Treatment (sysKID) Grant HEALTH-F2-2009-241544. NR 71 TC 144 Z9 150 U1 4 U2 47 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2010 VL 9 IS 11 BP 2424 EP 2437 DI 10.1074/mcp.M110.001917 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 691BS UT WOS:000285055900008 PM 20616184 ER PT J AU Cha, SW Imielinski, MB Rejtar, T Richardson, EA Thakur, D Sgroi, DC Karger, BL AF Cha, Sangwon Imielinski, Marcin B. Rejtar, Tomas Richardson, Elizabeth A. Thakur, Dipak Sgroi, Dennis C. Karger, Barry L. TI In Situ Proteomic Analysis of Human Breast Cancer Epithelial Cells Using Laser Capture Microdissection: Annotation by Protein Set Enrichment Analysis and Gene Ontology SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID TRANSFER-RNA SYNTHETASES; NF-KAPPA-B; PROLIFERATOR-ACTIVATED RECEPTOR; SERUM RESPONSE FACTOR; ESTROGEN-RECEPTOR; TRANSCRIPTION FACTORS; EXPRESSION PROFILES; SHOTGUN PROTEOMICS; MASS-SPECTROMETRY; DUCTAL CARCINOMA AB Identification of molecular signatures that allow detection of the transition from normal breast epithelial cells to malignant invasive cells is a critical component in the development of diagnostic, therapeutic, and preventative strategies for human breast cancer. Substantial efforts have been devoted to deciphering breast cancer etiology at the genome level, but only a limited number of studies have appeared at the proteome level. In this work, we compared individual in situ proteome profiles of nonpatient matched nine noncancerous, normal breast epithelial (NBE) samples with nine estrogen receptor (ER)-positive (luminal subtype), invasive malignant breast epithelial (MBE) samples by combining laser capture microdissection (LCM) and quantitative shotgun proteomics. A total of 12,970 unique peptides were identified from the 18 samples, and 1623 proteins were selected for quantitative analysis using spectral index (SpI) as a measure of protein abundance. A total of 298 proteins were differentially expressed between NBE and MBE at 95% confidence level, and this differential expression correlated well with immunohistochemistry (IHC) results reported in the Human Protein Atlas (HPA) database. To assess pathway level patterns in the observed expression changes, we developed protein set enrichment analysis (PSEA), a modification of a well-known approach in gene expression analysis, Gene Set Enrichment Analysis (GSEA). Unlike single gene-based functional term enrichment analyses that only examines pathway overrepresentation of proteins above a given significance threshold, PSEA applies a weighted running sum statistic to the entire expression data to discover significantly enriched protein groups. Application of PSEA to the expression data in this study revealed not only well-known ER-dependent and cellular morphology-dependent protein abundance changes, but also significant alterations of downstream targets for multiple transcription factors (TFs), suggesting a role for specific gene regulatory pathways in breast tumorigenesis. A parallel GOMiner analysis revealed both confirmatory and complementary data to PSEA. The combination of the two annotation approaches yielded extensive biological feature mapping for in depth analysis of the quantitative proteomic data. Molecular & Cellular Proteomics 9:2529-2544, 2010. C1 [Imielinski, Marcin B.; Richardson, Elizabeth A.; Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Imielinski, Marcin B.; Richardson, Elizabeth A.; Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Cha, Sangwon; Rejtar, Tomas; Thakur, Dipak] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 149 13th St, Charlestown, MA 02129 USA. EM dsgroi@partners.org; b.karger@neu.edu RI Cha, Sangwon/C-6917-2008 OI Cha, Sangwon/0000-0003-2819-3417 FU Susan G. Komen Breast Cancer Foundation; National Institutes of Health [GM15847, R01CA112021]; NCI National Institutes of Health; Avon Foundation FX This work was supported by the Susan G. Komen Breast Cancer Foundation (BLK and DCS), National Institutes of Health grant GM15847 (BLK), National Institutes of Health grant R01CA112021 (DCS), the NCI National Institutes of Health Specialized Programs of Research Excellence in breast cancer at Massachusetts General Hospital (DCS) and the Avon Foundation (DCS). NR 79 TC 44 Z9 45 U1 1 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2010 VL 9 IS 11 BP 2529 EP 2544 DI 10.1074/mcp.M110.000398 PG 16 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 691BS UT WOS:000285055900016 PM 20739354 ER PT J AU Walker, SR Chaudhury, M Nelson, EA Frank, DA AF Walker, Sarah R. Chaudhury, Mousumi Nelson, Erik A. Frank, David A. TI Microtubule-Targeted Chemotherapeutic Agents Inhibit Signal Transducer and Activator of Transcription 3 (STAT3) Signaling SO MOLECULAR PHARMACOLOGY LA English DT Article ID BREAST-CANCER CELLS; TYROSINE PHOSPHORYLATION; SERINE PHOSPHORYLATION; MULTIPLE-MYELOMA; IDENTIFICATION; PHOSPHATASE; EXPRESSION; BINDING; SOCS-1; CIS AB The transcription factor signal transducer and activator of transcription 3 (STAT3) is inappropriately activated in the majority of breast tumors, especially in aggressive and invasive ones. In addition to driving the expression of genes promoting malignancy, STAT3 associates with tubulin and can promote cell migration. Because microtubule-targeted drugs are among the most active agents used in the treatment of breast cancer, we examined whether microtubule-based chemotherapy modulates STAT3 activity. When treated with paclitaxel or vinorelbine, breast cancer cells with constitutive activation of STAT3 display a loss of STAT3 phosphorylation, and paclitaxel disrupts the interaction of STAT3 with tubulin. Paclitaxel also inhibits cytokine-induced STAT3 activation. This effect is specific for microtubule-targeted agents, because other chemotherapeutic drugs, such as doxorubicin, have no effect on STAT3. The loss of STAT3 tyrosine phosphorylation is also reflected in an inhibition of expression of STAT3 target genes. This effect is not restricted to breast cancer, because similar effects are also seen in ovarian cancer and prostate cancer cells. Thus, in addition to their role in disrupting microtubule function, microtubule-targeted agents also suppress STAT3 signaling. This may be an important component of their activity, raising the possibility that microtubule targeted therapy may be particularly effective in tumors characterized by STAT3 activation. C1 [Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu FU Breast Cancer Research Foundation; Brent Leahey Fund FX This research was supported by the Breast Cancer Research Foundation; Susan G. Komen for the Cure; and the Brent Leahey Fund. NR 26 TC 26 Z9 28 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2010 VL 78 IS 5 BP 903 EP 908 DI 10.1124/mol.110.066316 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 666VB UT WOS:000283148700013 PM 20693278 ER PT J AU Nierenberg, AA Akiskal, HS Angst, J Hirschfeld, RM Merikangas, KR Petukhova, M Kessler, RC AF Nierenberg, A. A. Akiskal, H. S. Angst, J. Hirschfeld, R. M. Merikangas, K. R. Petukhova, M. Kessler, R. C. TI Bipolar disorder with frequent mood episodes in the national comorbidity survey replication (NCS-R) SO MOLECULAR PSYCHIATRY LA English DT Article DE bipolar disorder; rapid-cycling bipolar disorder; mania; hypomania; national comorbidity survey replication (NCS-R); comorbidity; treatment ID TREATMENT ENHANCEMENT PROGRAM; WORLD-HEALTH-ORGANIZATION; WEEKLY SYMPTOMATIC STATUS; DSM-IV; NATURAL-HISTORY; RATING-SCALE; VALIDITY; VERSION; PREVALENCE; DISABILITY AB Virtually nothing is known about the epidemiology of rapid cycling bipolar disorder (BPD) in community samples. Nationally representative data are reported here for the prevalence and correlates of a surrogate measure of DSM-IV rapid cycling BPD from the National Comorbidity survey Replication (NCS-R), a national survey of the US household population. DSM-IV disorders were assessed in the NCS-R with the WHO Composite International Diagnostic Interview (CIDI). Although the CIDI did not assess rapid cycling, it did assess the broader category of 12-month BPD with frequent mood episodes (FMEs), having at least four episodes of mania/hypomania or major depression in the 12 months before interview. Roughly one-third of NCS-R respondents with lifetime DSM-IV BPD and half with 12-month BPD met criteria for FME. FME was associated with younger age-of-onset (of BP-I, but not BP-II) and higher annual persistence (73% of the years since first onset of illness with an episode) than non-FME BPD. No substantial associations of FME vs non-FME BPD were found with socio-demographics, childhood risk factors (parental mental disorders, other childhood adversities) or comorbid DSM-IV disorders. However, FME manic episodes had greater clinical severity than non-FME episodes (assessed with a fully structured version of the Young Mania Rating Scale) and FME hypomanic episodes had greater role impairment than non-FME episodes (assessed with the Sheehan Disability Scales). Whether these indicators of severity merely reflect attenuated effects of rapid cycling or independent effects of sub-threshold rapid cycling warrants further study given the high proportion of lifetime cases who met criteria for FME. Molecular Psychiatry (2010) 15, 1075-1087; doi:10.1038/mp.2009.61; published online 30 June 2009 C1 [Petukhova, M.; Kessler, R. C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Nierenberg, A. A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Akiskal, H. S.] Univ Calif San Diego, Int Mood Ctr, San Diego, CA 92103 USA. [Akiskal, H. S.] VA Psychiat Serv, San Diego, CA USA. [Angst, J.] Univ Zurich, Hosp Psychiat, Zurich, Switzerland. [Hirschfeld, R. M.] Univ Texas Med Branch, Dept Psychiat & Behav Sci, Galveston, TX USA. [Merikangas, K. R.] NIMH, Intramural Res Program, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM kessler@hcp.med.harvard.edu FU National Institute of Mental Health (NIMH) [U01-MH60220]; National Institute of Drug Abuse, the Substance Abuse and Mental Health Services Administration; Robert Wood Johnson Foundation [044780]; John W Alden Trust; John D and Catherine T MacArthur Foundation; Pfizer Foundation; US Public Health Service [R13 MH066849, R01 MH069864, R01 DA016558]; Eli Lilly and Company; Glaxo-SmithKline; Ortho-McNeil Pharmaceutical, Inc; Pan American Health Organization FX The National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse, the Substance Abuse and Mental Health Services Administration, the Robert Wood Johnson Foundation (Grant #044780) and the John W Alden Trust. Additional support for preparation of this paper was provided by Ortho-McNeil Janssen Scientific Affairs, LLC. Collaborating NCS-R investigators include Ronald C Kessler (Principal Investigator, Harvard Medical School), Kathleen Merikangas (Co-Principal Investigator, NIMH), James Anthony (Michigan State University), William Eaton (The Johns Hopkins University), Meyer Glantz (NIDA), Doreen Koretz (Harvard University), Jane McLeod (Indiana University), Mark Olfson (Columbia University College of Physicians and Surgeons), Harold Pincus (University of Pittsburgh), Greg Simon (Group Health Cooperative), T Bedirhan Ustun (World Health Organization), Michael Von Korff (Group Health Cooperative), Philip Wang (Harvard Medical School), Kenneth Wells (UCLA), Elaine Wethington (Cornell University) and Hans-Ulrich Wittchen (Max Planck Institute of Psychiatry). The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies or US Government. A complete list of NCS publications and the full text of all NCS-R instruments can be found at http://www.hcp.med.harvard.edu/ncs. Send correspondence to NCS@hcp.med.harvard.edu. The NCS-R is carried out in conjunction with the World Health Organization World Mental Health (WMH) Survey Initiative. We thank the staff of the WMH Data Collection and Data Analysis Coordination Centers for assistance with instrumentation, fieldwork and consultation on data analysis. These activities were supported by the John D and Catherine T MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13 MH066849, R01 MH069864, and R01 DA016558), Eli Lilly and Company, Glaxo-SmithKline, Ortho-McNeil Pharmaceutical, Inc. and the Pan American Health Organization. A complete list of WMH publications and instruments can be found at (http://www.hcp.med.harvard.edu/wmhcidi). The views expressed in this article do not necessarily represent the view of the NIMH, NIH or HHS of the US Government. NR 41 TC 12 Z9 12 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2010 VL 15 IS 11 BP 1075 EP 1087 DI 10.1038/mp.2009.61 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 669LP UT WOS:000283352400004 PM 19564874 ER PT J AU Brehme, M Vidal, M AF Brehme, Marc Vidal, Marc TI A global protein-lipid interactome map SO MOLECULAR SYSTEMS BIOLOGY LA English DT Editorial Material ID GENOME-REDUCED BACTERIUM C1 [Brehme, Marc] Proteostasis Therapeut Inc, Cambridge, MA 02139 USA. [Brehme, Marc; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Brehme, Marc; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Brehme, Marc; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Brehme, M (reprint author), Proteostasis Therapeut Inc, 200 Technol Sq,Suite 402, Cambridge, MA 02139 USA. EM marc.brehme@proteostasis.com RI Brehme, Marc/G-8697-2015 OI Brehme, Marc/0000-0003-0694-331X NR 10 TC 3 Z9 3 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD NOV PY 2010 VL 6 AR 443 DI 10.1038/msb.2010.100 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 691GI UT WOS:000285067900018 PM 21119635 ER PT J AU Williams, DA Thrasher, AJ Baum, C AF Williams, David A. Thrasher, Adrian J. Baum, Christopher TI Transatlantic Consortium Spotlights Need for Changes in Gene Therapy Trials SO MOLECULAR THERAPY LA English DT Editorial Material C1 [Williams, David A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Thrasher, Adrian J.] Inst Child Hlth, Mol Immunol Unit, London, England. [Baum, Christopher] Hannover Med Sch, D-3000 Hannover, Germany. RP Williams, DA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. FU Wellcome Trust [090233] NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD NOV PY 2010 VL 18 IS 11 BP 1892 EP 1892 DI 10.1038/mt.2010.227 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 674CX UT WOS:000283712400002 PM 21042294 ER PT J AU Subramanya, S Armant, M Salkowitz, JR Nyakeriga, AM Haridas, V Hasan, M Bansal, A Goepfert, PA Wynn, KK Ladell, K Price, DA Manjunath, N Kan-Mitchell, J Shankar, P AF Subramanya, Sandesh Armant, Myriam Salkowitz, Janelle R. Nyakeriga, Alice M. Haridas, Viraga Hasan, Maroof Bansal, Anju Goepfert, Paul A. Wynn, Katherine K. Ladell, Kristin Price, David A. Manjunath, N. Kan-Mitchell, June Shankar, Premlata TI Enhanced Induction of HIV-specific Cytotoxic T Lymphocytes by Dendritic Cell-targeted Delivery of SOCS-1 siRNA SO MOLECULAR THERAPY LA English DT Article ID CYTOKINE SIGNALING SOCS; SMALL INTERFERING RNA; IN-VIVO; ANTITUMOR IMMUNITY; NEGATIVE REGULATORS; MELANOMA PATIENTS; ANTIGEN; SUPPRESSORS; INFECTION; VACCINE AB Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the activation of T cells. RNA interference (RNAi)-mediated silencing of negative immunoregulatory molecules expressed by DCs may provide a strategy to enhance the potency of DC-based vaccines and immunotherapy. Ablation of suppressor of cytokine signaling-1 (SOCS-1) in antigen-presenting cells has been shown to enhance cellular immune response in mice. Here, we used a previously reported DC-targeting approach to deliver small interfering RNA (siRNA) against SOCS-1 to human myeloid-derived DCs (MDDCs). SOCS1-silencing in MDDCs resulted in enhanced cytokine responses to lipopolysaccharide (LPS) and a strong mixed-lymphocyte reaction. Moreover, only DCs treated with SOCS-1 siRNA, and not controls, elicited strong primary in vitro responses to well-characterized HLA-A*0201-restricted Melan-A/MART-1 and human immunodeficiency virus (HIV) Gag epitopes in naive CD8(+) T cells from healthy donors. Finally, stimulation of CD8(+) T cells from HIV-seropositive subjects with SOCS1-silenced DCs resulted in an augmented polyfunctional cytotoxic T-lymphocyte (CTL) response, suggesting that SOCS-1 silencing can restore functionally compromised T cells in HIV infection. Collectively, these results demonstrate the feasibility of DC3-9dR-mediated manipulation of DC function to enhance DC immunogenicity for potential vaccine or immunotherapeutic applications. C1 [Subramanya, Sandesh; Hasan, Maroof; Manjunath, N.; Shankar, Premlata] Texas Tech Univ, Dept Biomed Sci, Ctr Excellence Infect Dis, Paul L Foster Sch Med,Hlth Sci Ctr, El Paso, TX USA. [Subramanya, Sandesh; Armant, Myriam; Haridas, Viraga; Manjunath, N.; Shankar, Premlata] Harvard Univ, Immune Dis Inst, Sch Med, Boston, MA USA. [Salkowitz, Janelle R.; Nyakeriga, Alice M.; Kan-Mitchell, June] Univ Texas El Paso, Dept Biol Sci, El Paso, TX 79968 USA. [Bansal, Anju; Goepfert, Paul A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Wynn, Katherine K.; Ladell, Kristin; Price, David A.] Cardiff Univ, Dept Infect Immun & Biochem, Sch Med, Cardiff, S Glam, Wales. RP Shankar, P (reprint author), Texas Tech Univ, Dept Biomed Sci, Ctr Excellence Infect Dis, Paul L Foster Sch Med,Hlth Sci Ctr, 5001 El Paso Dr, El Paso, TX USA. EM premlata.shankar@ttuhsc.edu RI Ladell, Kristin/K-2475-2013; Price, David/C-7876-2013; Ladell, Kristin/C-8301-2013 OI Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938 FU NIH [AI071882] FX We thank Joseph Steigner (Immune Disease Institute) and Zach Brower (University of Texas at El Paso) for technical assistance with blood collection and PBMC isolation. This work was supported by NIH grant AI071882 to P.S. D.A.P. is a Medical Research Council (UK) Senior Clinical Fellow. The authors declared no conflict of interest. NR 48 TC 12 Z9 13 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD NOV PY 2010 VL 18 IS 11 BP 2028 EP 2037 DI 10.1038/mt.2010.148 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 674CX UT WOS:000283712400015 PM 20648001 ER PT J AU Wan, JB Zhang, QW Hong, SJ Guan, J Ye, WC Li, SP Lee, MYS Wang, YT AF Wan, Jian-Bo Zhang, Qing-Wen Hong, Si-Jia Guan, Jia Ye, Wen-Cai Li, Shao-Ping Lee, Ming-Yuen Simon Wang, Yi-Tao TI 5,6-Didehydroginsenosides from the Roots of Panax notoginseng SO MOLECULES LA English DT Article DE Panax notoginseng; triterpene saponins; didehydroginsenosides ID DAMMARANE-SAPONINS; SANCHI-GINSENG; MICE; PROTOPANAXATRIOL; LEAVES; RC; RD AB Two minor novel dammarane-type saponins-5,6-didehydroginsenoside Rd (1) and 5,6-didehydroginsenoside Rb1 (2)-were isolated from the dried roots of Panax notoginseng along with sixteen known saponins. The structures of the new compounds were elucidated on the basis of spectroscopic and chemical methods. C1 [Wan, Jian-Bo; Zhang, Qing-Wen; Hong, Si-Jia; Guan, Jia; Li, Shao-Ping; Lee, Ming-Yuen Simon; Wang, Yi-Tao] Univ Macau, Inst Chinese Med Sci, Taipa, Peoples R China. [Wan, Jian-Bo] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wan, Jian-Bo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ye, Wen-Cai] Jinan Univ, Coll Pharm, Inst Tradit Chinese Med & Nat Prod, Guangzhou 510632, Guangdong, Peoples R China. RP Zhang, QW (reprint author), Univ Macau, Inst Chinese Med Sci, Taipa, Peoples R China. EM wjbcpu@hotmail.com; qwzhang@umac.mo; brendajia0901@hotmail.com; ya67402@umac.mo; chywc@yahoo.com.cn; spli@umac.mo; simonlee@umac.mo; ytwang@umac.mo RI Zhang, Qing-Wen/F-9419-2011; Wan, Jian-Bo/D-8368-2014; Wang, Yitao/O-5184-2016 OI Wan, Jian-Bo/0000-0002-6750-2617; FU Macao Science and Technology Development Fund [013/2008/A1]; Research committee of University of Macau [UL016/09-Y1/CMS/WYT01/ICMS] FX This research was supported by grants from Macao Science and Technology Development Fund (013/2008/A1) and Research committee of University of Macau (UL016/09-Y1/CMS/WYT01/ICMS). NR 28 TC 10 Z9 14 U1 0 U2 9 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD NOV PY 2010 VL 15 IS 11 BP 8169 EP 8176 DI 10.3390/molecules15118169 PG 8 WC Chemistry, Organic SC Chemistry GA 684VR UT WOS:000284582100045 PM 21072027 ER PT J AU Pomerantz, MM Freedman, ML AF Pomerantz, Mark M. Freedman, Matthew L. TI Genetics of Prostate Cancer Risk SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE family history; genetic markers; human genome; linkage analysis; prostate cancer ID GENOME-WIDE ASSOCIATION; FAMILY-HISTORY; SUSCEPTIBILITY LOCUS; CHROMOSOME 8Q24; BREAST-CANCER; DOMINANT INHERITANCE; SEGREGATION ANALYSIS; SUGGESTIVE EVIDENCE; COLORECTAL-CANCER; DEGREE RELATIVES AB For decades, physicians and researchers have recognized that family history is a significant risk factor for piostate cancer The identification of the genes responsible for inherited risk, however, proved difficult With the sequencing of the human genome and the completion of the initial phases of the International HapMap Project, the tools are available to scan the entire genome and find genetic markers for disease Since 2006, more than 30 inherited variants strongly associated with prostate cancer have been reported As the inherited component of the disease is revealed, efforts are ongoing to translate genetic findings into the clinic Mt Sinai J Med 77 643-654, 2010 (C) 2010 Mount Sinai School of Medicine C1 [Pomerantz, Mark M.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 103 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD NOV-DEC PY 2010 VL 77 IS 6 BP 643 EP 654 DI 10.1002/msj.20222 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 691KY UT WOS:000285079900007 PM 21105126 ER PT J AU Uemura, K Farner, KC Hashimoto, T Nasser-Ghodsi, N Wolfe, MS Koo, EH Hyman, BT Berezovska, O AF Uemura, Kengo Farner, Katherine C. Hashimoto, Tadafumi Nasser-Ghodsi, Navine Wolfe, Michael S. Koo, Edward H. Hyman, Bradley T. Berezovska, Oksana TI Substrate docking to gamma-secretase allows access of gamma-secretase modulators to an allosteric site SO NATURE COMMUNICATIONS LA English DT Article ID AMYLOID PRECURSOR PROTEIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BETA-PROTEIN; PRESENILIN-1 MUTATIONS; CATALYTIC PORE; A-BETA-42; CONFORMATION; INHIBITORS; CLEAVAGE; COMMON AB gamma-Secretase generates the peptides of Alzheimer's disease, A beta(40) and A beta(42), by cleaving the amyloid precursor protein within its transmembrane domain. gamma-Secretase also cleaves numerous other substrates, raising concerns about gamma-secretase inhibitor off-target effects. Another important class of drugs, gamma-secretase modulators, alter the cleavage site of gamma-secretase on amyloid precursor protein, changing the A beta(42)/A beta(40) ratio, and are thus a promising therapeutic approach for Alzheimer's disease. However, the target for gamma-secretase modulators is uncertain, with some data suggesting that they function on gamma-secretase, whereas others support their binding to the amyloid precursor. In this paper we address this controversy by using a fluorescence resonance energy transfer-based assay to examine whether gamma-secretase modulators alter Presenilin-1/gamma-secretase conformation in intact cells in the absence of its natural substrates such as amyloid precursor protein and Notch. We report that the gamma-secretase allosteric site is located within the gamma-secretase complex, but substrate docking is needed for gamma-secretase modulators to access this site. C1 [Uemura, Kengo; Farner, Katherine C.; Hashimoto, Tadafumi; Nasser-Ghodsi, Navine; Hyman, Bradley T.; Berezovska, Oksana] Massachusetts Gen Hosp, Alzheimer Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Wolfe, Michael S.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Wolfe, Michael S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Koo, Edward H.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Berezovska, O (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. EM oberezovska@partners.org RI Hashimoto, Tadafumi/A-7723-2013 FU NIH [AG 26593, AG 15379] FX This work was supported by NIH Grants AG 26593 (to OB) and AG 15379 (to O.B. and B. T. H.). We are grateful to Drs Jones, Hou and Bacskai (MGH) for assistance with the FLIM setup, and to Professor Takeshi Iwatsubo (Tokyo University) for providing expression construct for CLAC-P. NR 30 TC 29 Z9 29 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD NOV PY 2010 VL 1 AR 130 DI 10.1038/ncomms1129 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 732YE UT WOS:000288224800028 PM 21119643 ER PT J AU Speliotes, EK Willer, CJ Berndt, SI Monda, KL Thorleifsson, G Jackson, AU Allen, HL Lindgren, CM Luan, J Magi, R Randall, JC Vedantam, S Winkler, TW Qi, L Workalemahu, T Heid, IM Steinthorsdottir, V Stringham, HM Weedon, MN Wheeler, E Wood, AR Ferreira, T Weyant, RJ Segre, AV Estrada, K Liang, LM Nemesh, J Park, JH Gustafsson, S Kilpelanen, TO Yang, JA Bouatia-Naji, N Esko, T Feitosa, MF Kutalik, Z Mangino, M Raychaudhuri, S Scherag, A Smith, AV Welch, R Zhao, JH Aben, KK Absher, DM Amin, N Dixon, AL Fisher, E Glazer, NL Goddard, ME Heard-Costa, NL Hoesel, V Hottenga, JJ Johansson, A Johnson, T Ketkar, S Lamina, C Li, SX Moffatt, MF Myers, RH Narisu, N Perry, JRB Peters, MJ Preuss, M Ripatti, S Rivadeneira, F Sandholt, C Scott, LJ Timpson, NJ Tyrer, JP van Wingerden, S Watanabe, RM White, CC Wiklund, F Barlassina, C Chasman, DI Cooper, MN Jansson, JO Lawrence, RW Pellikka, N Prokopenko, I Shi, JX Thiering, E Alavere, H Alibrandi, MTS Almgren, P Arnold, AM Aspelund, T Atwood, LD Balkau, B Balmforth, AJ Bennett, AJ Ben-Shlomo, Y Bergman, RN Bergmann, S Biebermann, H Blakemore, AIF Boes, T Bonnycastle, LL Bornstein, SR Brown, MJ Buchanan, TA Busonero, F Campbell, H Cappuccio, FP Cavalcanti-Proenca, C Chen, YDI Chen, CM Chines, PS Clarke, R Coin, L Connell, J Day, INM den Heijer, M Duan, JB Ebrahim, S Elliott, P Elosua, R Eiriksdottir, G Erdos, MR Eriksson, JG Facheris, MF Felix, SB Fischer-Posovszky, P Folsom, AR Friedrich, N Freimer, NB Fu, M Gaget, S Gejman, PV Geus, EJC Gieger, C Gjesing, AP Goel, A Goyette, P Grallert, H Grassler, J Greenawalt, DM Groves, CJ Gudnason, V Guiducci, C Hartikainen, AL Hassanali, N Hall, AS Havulinna, AS Hayward, C Heath, AC Hengstenberg, C Hicks, AA Hinney, A Hofman, A Homuth, G Hui, J Igl, W Iribarren, C Isomaa, B Jacobs, KB Jarick, I Jewell, E John, U Jorgensen, T Jousilahti, P Jula, A Kaakinen, M Kajantie, E Kaplan, LM Kathiresan, S Kettunen, J Kinnunen, L Knowles, JW Kolcic, I Konig, IR Koskinen, S Kovacs, P Kuusisto, J Kraft, P Kvaloy, K Laitinen, J Lantieri, O Lanzani, C Launer, LJ Lecoeur, C Lehtimaki, T Lettre, G Liu, JJ Lokki, ML Lorentzon, M Luben, RN Ludwig, B Manunta, P Marek, D Marre, M Martin, NG McArdle, WL McCarthy, A McKnight, B Meitinger, T Melander, O Meyre, D Midthjell, K Montgomery, GW Morken, MA Morris, AP Mulic, R Ngwa, JS Nelis, M Neville, MJ Nyholt, DR O'Donnell, CJ O'Rahilly, S Ong, KK Oostra, B Pare, G Parker, AN Perola, M Pichler, I Pietilainen, KH Platou, CGP Polasek, O Pouta, A Rafelt, S Raitakari, O Rayner, NW Ridderstrale, M Rief, W Ruokonen, A Robertson, NR Rzehak, P Salomaa, V Sanders, AR Sandhu, MS Sanna, S Saramies, J Savolainen, MJ Scherag, S Schipf, S Schreiber, S Schunkert, H Silander, K Sinisalo, J Siscovick, DS Smit, JH Soranzo, N Sovio, U Stephens, J Surakka, I Swift, AJ Tammesoo, ML Tardif, JC Teder-Laving, M Teslovich, TM Thompson, JR Thomson, B Tonjes, A Tuomi, T van Meurs, JBJ van Ommen, GJ Vatin, V Viikari, J Visvikis-Siest, S Vitart, V Vogel, CIG Voight, BF Waite, LL Wallaschofski, H Walters, GB Widen, E Wiegand, S Wild, SH Willemsen, G Witte, DR Witteman, JC Xu, JF Zhang, QY Zgaga, L Ziegler, A Zitting, P Beilby, JP Farooqi, IS Hebebrand, J Huikuri, HV James, AL Kahonen, M Levinson, DF Macciardi, F Nieminen, MS Ohlsson, C Palmer, LJ Ridker, PM Stumvoll, M Beckmann, JS Boeing, H Boerwinkle, E Boomsma, DI Caulfield, MJ Chanock, SJ Collins, FS Cupples, LA Smith, GD Erdmann, J Froguel, P Gronberg, H Gyllensten, U Hall, P Hansen, T Harris, TB Hattersley, AT Hayes, RB Heinrich, J Hu, FB Hveem, K Illig, T Jarvelin, MR Kaprio, J Karpe, F Khaw, KT Kiemeney, LA Krude, H Laakso, M Lawlor, DA Metspalu, A Munroe, PB Ouwehand, WH Pedersen, O Penninx, BW Peters, A Pramstaller, PP Quertermous, T Reinehr, T Rissanen, A Rudan, I Samani, NJ Schwarz, PEH Shuldiner, AR Spector, TD Tuomilehto, J Uda, M Uitterlinden, A Valle, TT Wabitsch, M Waeber, G Wareham, NJ Watkins, H Wilson, JF Wright, AF Zillikens, MC Chatterjee, N McCarroll, SA Purcell, S Schadt, EE Visscher, PM Assimes, TL Borecki, IB Deloukas, P Fox, CS Groop, LC Haritunians, T Hunter, DJ Kaplan, RC Mohlke, KL O'Connell, JR Peltonen, L Schlessinger, D Strachan, DP van Duijn, CM Wichmann, HE Frayling, TM Thorsteinsdottir, U Abecasis, GR Barroso, I Boehnke, M Stefansson, K North, KE McCarthy, MI Hirschhorn, JN Ingelsson, E Loos, RJF AF Speliotes, Elizabeth K. Willer, Cristen J. Berndt, Sonja I. Monda, Keri L. Thorleifsson, Gudmar Jackson, Anne U. Allen, Hana Lango Lindgren, Cecilia M. Luan, Jian'an Maegi, Reedik Randall, Joshua C. Vedantam, Sailaja Winkler, Thomas W. Qi, Lu Workalemahu, Tsegaselassie Heid, Iris M. Steinthorsdottir, Valgerdur Stringham, Heather M. Weedon, Michael N. Wheeler, Eleanor Wood, Andrew R. Ferreira, Teresa Weyant, Robert J. Segre, Ayellet V. Estrada, Karol Liang, Liming Nemesh, James Park, Ju-Hyun Gustafsson, Stefan Kilpelaenen, Tuomas O. Yang, Jian Bouatia-Naji, Nabila Esko, Tonu Feitosa, Mary F. Kutalik, Zoltan Mangino, Massimo Raychaudhuri, Soumya Scherag, Andre Smith, Albert Vernon Welch, Ryan Zhao, Jing Hua Aben, Katja K. Absher, Devin M. Amin, Najaf Dixon, Anna L. Fisher, Eva Glazer, Nicole L. Goddard, Michael E. Heard-Costa, Nancy L. Hoesel, Volker Hottenga, Jouke-Jan Johansson, Asa Johnson, Toby Ketkar, Shamika Lamina, Claudia Li, Shengxu Moffatt, Miriam F. Myers, Richard H. Narisu, Narisu Perry, John R. B. Peters, Marjolein J. Preuss, Michael Ripatti, Samuli Rivadeneira, Fernando Sandholt, Camilla Scott, Laura J. Timpson, Nicholas J. Tyrer, Jonathan P. van Wingerden, Sophie Watanabe, Richard M. White, Charles C. Wiklund, Fredrik Barlassina, Christina Chasman, Daniel I. Cooper, Matthew N. Jansson, John-Olov Lawrence, Robert W. Pellikka, Niina Prokopenko, Inga Shi, Jianxin Thiering, Elisabeth Alavere, Helene Alibrandi, Maria T. S. Almgren, Peter Arnold, Alice M. Aspelund, Thor Atwood, Larry D. Balkau, Beverley Balmforth, Anthony J. Bennett, Amanda J. Ben-Shlomo, Yoav Bergman, Richard N. Bergmann, Sven Biebermann, Heike Blakemore, Alexandra I. F. Boes, Tanja Bonnycastle, Lori L. Bornstein, Stefan R. Brown, Morris J. Buchanan, Thomas A. Busonero, Fabio Campbell, Harry Cappuccio, Francesco P. Cavalcanti-Proenca, Christine Chen, Yii-Der Ida Chen, Chih-Mei Chines, Peter S. Clarke, Robert Coin, Lachlan Connell, John Day, Ian N. M. den Heijer, Martin Duan, Jubao Ebrahim, Shah Elliott, Paul Elosua, Roberto Eiriksdottir, Gudny Erdos, Michael R. Eriksson, Johan G. Facheris, Maurizio F. Felix, Stephan B. Fischer-Posovszky, Pamela Folsom, Aaron R. Friedrich, Nele Freimer, Nelson B. Fu, Mao Gaget, Stefan Gejman, Pablo V. Geus, Eco J. C. Gieger, Christian Gjesing, Anette P. Goel, Anuj Goyette, Philippe Grallert, Harald Graessler, Juergen Greenawalt, Danielle M. Groves, Christopher J. Gudnason, Vilmundur Guiducci, Candace Hartikainen, Anna-Liisa Hassanali, Neelam Hall, Alistair S. Havulinna, Aki S. Hayward, Caroline Heath, Andrew C. Hengstenberg, Christian Hicks, Andrew A. Hinney, Anke Hofman, Albert Homuth, Georg Hui, Jennie Igl, Wilmar Iribarren, Carlos Isomaa, Bo Jacobs, Kevin B. Jarick, Ivonne Jewell, Elizabeth John, Ulrich Jorgensen, Torben Jousilahti, Pekka Jula, Antti Kaakinen, Marika Kajantie, Eero Kaplan, Lee M. Kathiresan, Sekar Kettunen, Johannes Kinnunen, Leena Knowles, Joshua W. Kolcic, Ivana Koenig, Inke R. Koskinen, Seppo Kovacs, Peter Kuusisto, Johanna Kraft, Peter Kvaloy, Kirsti Laitinen, Jaana Lantieri, Olivier Lanzani, Chiara Launer, Lenore J. Lecoeur, Cecile Lehtimaeki, Terho Lettre, Guillaume Liu, Jianjun Lokki, Marja-Liisa Lorentzon, Mattias Luben, Robert N. Ludwig, Barbara Manunta, Paolo Marek, Diana Marre, Michel Martin, Nicholas G. McArdle, Wendy L. McCarthy, Anne McKnight, Barbara Meitinger, Thomas Melander, Olle Meyre, David Midthjell, Kristian Montgomery, Grant W. Morken, Mario A. Morris, Andrew P. Mulic, Rosanda Ngwa, Julius S. Nelis, Mari Neville, Matt J. Nyholt, Dale R. O'Donnell, Christopher J. O'Rahilly, Stephen Ong, Ken K. Oostra, Ben Pare, Guillaume Parker, Alex N. Perola, Markus Pichler, Irene Pietilaeinen, Kirsi H. Platou, Carl G. P. Polasek, Ozren Pouta, Anneli Rafelt, Suzanne Raitakari, Olli Rayner, Nigel W. Ridderstrale, Martin Rief, Winfried Ruokonen, Aimo Robertson, Neil R. Rzehak, Peter Salomaa, Veikko Sanders, Alan R. Sandhu, Manjinder S. Sanna, Serena Saramies, Jouko Savolainen, Markku J. Scherag, Susann Schipf, Sabine Schreiber, Stefan Schunkert, Heribert Silander, Kaisa Sinisalo, Juha Siscovick, David S. Smit, Jan H. Soranzo, Nicole Sovio, Ulla Stephens, Jonathan Surakka, Ida Swift, Amy J. Tammesoo, Mari-Liis Tardif, Jean-Claude Teder-Laving, Maris Teslovich, Tanya M. Thompson, John R. Thomson, Brian Toenjes, Anke Tuomi, Tiinamaija van Meurs, Joyce B. J. van Ommen, Gert-Jan Vatin, Vincent Viikari, Jorma Visvikis-Siest, Sophie Vitart, Veronique Vogel, Carla I. G. Voight, Benjamin F. Waite, Lindsay L. Wallaschofski, Henri Walters, G. Bragi Widen, Elisabeth Wiegand, Susanna Wild, Sarah H. Willemsen, Gonneke Witte, Daniel R. Witteman, Jacqueline C. Xu, Jianfeng Zhang, Qunyuan Zgaga, Lina Ziegler, Andreas Zitting, Paavo Beilby, John P. Farooqi, I. Sadaf Hebebrand, Johannes Huikuri, Heikki V. James, Alan L. Kaehoenen, Mika Levinson, Douglas F. Macciardi, Fabio Nieminen, Markku S. Ohlsson, Claes Palmer, Lyle J. Ridker, Paul M. Stumvoll, Michael Beckmann, Jacques S. Boeing, Heiner Boerwinkle, Eric Boomsma, Dorret I. Caulfield, Mark J. Chanock, Stephen J. Collins, Francis S. Cupples, L. Adrienne Smith, George Davey Erdmann, Jeanette Froguel, Philippe Greonberg, Henrik Gyllensten, Ulf Hall, Per Hansen, Torben Harris, Tamara B. Hattersley, Andrew T. Hayes, Richard B. Heinrich, Joachim Hu, Frank B. Hveem, Kristian Illig, Thomas Jarvelin, Marjo-Riitta Kaprio, Jaakko Karpe, Fredrik Khaw, Kay-Tee Kiemeney, Lambertus A. Krude, Heiko Laakso, Markku Lawlor, Debbie A. Metspalu, Andres Munroe, Patricia B. Ouwehand, Willem H. Pedersen, Oluf Penninx, Brenda W. Peters, Annette Pramstaller, Peter P. Quertermous, Thomas Reinehr, Thomas Rissanen, Aila Rudan, Igor Samani, Nilesh J. Schwarz, Peter E. H. Shuldiner, Alan R. Spector, Timothy D. Tuomilehto, Jaakko Uda, Manuela Uitterlinden, Andre Valle, Timo T. Wabitsch, Martin Waeber, Gerard Wareham, Nicholas J. Watkins, Hugh Wilson, James F. Wright, Alan F. Zillikens, M. Carola Chatterjee, Nilanjan McCarroll, Steven A. Purcell, Shaun Schadt, Eric E. Visscher, Peter M. Assimes, Themistocles L. Borecki, Ingrid B. Deloukas, Panos Fox, Caroline S. Groop, Leif C. Haritunians, Talin Hunter, David J. Kaplan, Robert C. Mohlke, Karen L. O'Connell, Jeffrey R. Peltonen, Leena Schlessinger, David Strachan, David P. van Duijn, Cornelia M. Wichmann, H-Erich Frayling, Timothy M. Thorsteinsdottir, Unnur Abecasis, Goncalo R. Barroso, Ines Boehnke, Michael Stefansson, Kari North, Kari E. McCarthy, Mark I. Hirschhorn, Joel N. Ingelsson, Erik Loos, Ruth J. F. CA MAGIC TI Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GASTRIC-INHIBITORY POLYPEPTIDE; MELANOCORTIN-4 RECEPTOR GENE; GLUCOSE-HOMEOSTASIS; COMMON VARIANTS; ADULT OBESITY; EARLY-ONSET; FTO GENE; FAT MASS; RISK AB Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. C1 [Brown, Morris J.] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge, England. [Speliotes, Elizabeth K.; Vedantam, Sailaja; Guiducci, Candace; Thomson, Brian; Hirschhorn, Joel N.] Broad Inst, Metab Initiat & Program Med & Populat Genet, Cambridge, MA USA. [Speliotes, Elizabeth K.; Kaplan, Lee M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Willer, Cristen J.; Jackson, Anne U.; Stringham, Heather M.; Weyant, Robert J.; Welch, Ryan; Scott, Laura J.; Jewell, Elizabeth; Teslovich, Tanya M.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Berndt, Sonja I.; Park, Ju-Hyun; Shi, Jianxin; Chanock, Stephen J.; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Monda, Keri L.; North, Kari E.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Walters, G. Bragi; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Allen, Hana Lango; Weedon, Michael N.; Wood, Andrew R.; Perry, John R. B.; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England. [Lindgren, Cecilia M.; Maegi, Reedik; Randall, Joshua C.; Ferreira, Teresa; Prokopenko, Inga; Goel, Anuj; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil R.; Watkins, Hugh; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Lindgren, Cecilia M.; Prokopenko, Inga; Bennett, Amanda J.; Groves, Christopher J.; Hassanali, Neelam; Neville, Matt J.; Rayner, Nigel W.; Robertson, Neil R.; Karpe, Fredrik; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Luan, Jian'an; Kilpelaenen, Tuomas O.; Zhao, Jing Hua; Ong, Ken K.; Sandhu, Manjinder S.; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England. [Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Winkler, Thomas W.; Heid, Iris M.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany. [Qi, Lu; Workalemahu, Tsegaselassie; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Qi, Lu; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Qi, Lu; Chasman, Daniel I.; Kaplan, Lee M.; Ridker, Paul M.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA. [Heid, Iris M.; Lamina, Claudia; Thiering, Elisabeth; Chen, Chih-Mei; Gieger, Christian; Grallert, Harald; Rzehak, Peter; Heinrich, Joachim; Illig, Thomas; Peters, Annette; Wichmann, H-Erich] Helmholtz Zentrum Munchen, German Res Ctr, Inst Epidemiol, Neuherberg, Germany. [Wheeler, Eleanor; Sandhu, Manjinder S.; Soranzo, Nicole; Ouwehand, Willem H.; Deloukas, Panos; Peltonen, Leena; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge, England. [Segre, Ayellet V.; Kathiresan, Sekar; Voight, Benjamin F.; McCarroll, Steven A.; Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Segre, Ayellet V.; Nemesh, James; Raychaudhuri, Soumya; Kathiresan, Sekar] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Nemesh, James; Raychaudhuri, Soumya; Kathiresan, Sekar] MIT, Cambridge, MA 02139 USA. [Segre, Ayellet V.; Voight, Benjamin F.; McCarroll, Steven A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Estrada, Karol; Amin, Najaf; Rivadeneira, Fernando; van Wingerden, Sophie; Hofman, Albert; van Meurs, Joyce B. J.; Witteman, Jacqueline C.; Uitterlinden, Andre; van Duijn, Cornelia M.] Erasmus Med Ctr MC, Dept Epidemiol, Rotterdam, Netherlands. [Estrada, Karol; Peters, Marjolein J.; Rivadeneira, Fernando; van Meurs, Joyce B. J.; Uitterlinden, Andre; Zillikens, M. Carola] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Estrada, Karol; Peters, Marjolein J.; Rivadeneira, Fernando; Hofman, Albert; van Meurs, Joyce B. J.; Witteman, Jacqueline C.; Uitterlinden, Andre; Zillikens, M. Carola; van Duijn, Cornelia M.] Netherlands Consortium Healthy Aging NCHA, Netherlands Genom Initiat NGI Sponsored, Rotterdam, Netherlands. [Liang, Liming; Kraft, Peter; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Liang, Liming; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gustafsson, Stefan; Wiklund, Fredrik; Greonberg, Henrik; Hall, Per; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Yang, Jian; Visscher, Peter M.] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia. [Bouatia-Naji, Nabila; Cavalcanti-Proenca, Christine; Gaget, Stefan; Lecoeur, Cecile; Meyre, David; Vatin, Vincent; Froguel, Philippe] Inst Pasteur, CNRS, UMR8199, IBL, F-59019 Lille, France. [Bouatia-Naji, Nabila; Cavalcanti-Proenca, Christine; Gaget, Stefan; Lecoeur, Cecile; Meyre, David; Nelis, Mari; Vatin, Vincent; Froguel, Philippe] Univ Lille Nord France, Lille, France. [Esko, Tonu; Alavere, Helene; Nelis, Mari; Tammesoo, Mari-Liis; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Teder-Laving, Maris; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Nelis, Mari; Teder-Laving, Maris; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Feitosa, Mary F.; Ketkar, Shamika; Zhang, Qunyuan; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Kutalik, Zoltan; Johnson, Toby; Bergmann, Sven; Folsom, Aaron R.; Marek, Diana; Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Kutalik, Zoltan; Johnson, Toby; Bergmann, Sven; Marek, Diana] Swiss Inst Bioinformat, Lausanne, Switzerland. [Mangino, Massimo; Soranzo, Nicole; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. [Raychaudhuri, Soumya] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA USA. [Scherag, Andre; Boes, Tanja] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Smith, Albert Vernon; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert Vernon; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Aben, Katja K.; Kiemeney, Lambertus A.] Comprehens Canc Ctr E, Nijmegen, Netherlands. [Absher, Devin M.; Waite, Lindsay L.] Hudson Alpha Inst Biotechnol, Huntsville, AL USA. [Dixon, Anna L.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. [Fisher, Eva; Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Nuthetal, Germany. [Glazer, Nicole L.] Univ Washington, Dept Med, Seattle, WA USA. [Glazer, Nicole L.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Goddard, Michael E.] Univ Melbourne, Parkville, Vic 3052, Australia. [Goddard, Michael E.] Dept Primary Ind, Melbourne, Australia. [Heard-Costa, Nancy L.; Atwood, Larry D.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Hoesel, Volker] Tech Univ Munich, Chair Biomath, D-8046 Garching, Germany. [Hottenga, Jouke-Jan; Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ VU Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Johansson, Asa; Igl, Wilmar; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden. [Johansson, Asa] Norwegian Univ Sci & Technol NTNU, Fac Med, Dept Canc Res & Mol Med, Trondheim, Norway. [Johnson, Toby] Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. [Johnson, Toby; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Genome Ctr, London, England. [Johnson, Toby; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. [Lamina, Claudia] Innsbruck Med Univ3, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria. [Moffatt, Miriam F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Narisu, Narisu; Bonnycastle, Lori L.; Chines, Peter S.; Erdos, Michael R.; Morken, Mario A.; Swift, Amy J.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. [Preuss, Michael; Koenig, Inke R.; Ziegler, Andreas] Univ Klinikum Schleswig Holstein, Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Ripatti, Samuli; Pellikka, Niina; Kettunen, Johannes; Perola, Markus; Silander, Kaisa; Surakka, Ida; Widen, Elisabeth; Kaprio, Jaakko; Peltonen, Leena] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Ripatti, Samuli; Pellikka, Niina; Kettunen, Johannes; Perola, Markus; Silander, Kaisa; Surakka, Ida; Peltonen, Leena] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Publ Hlth Genom, Helsinki, Finland. [Sandholt, Camilla; Gjesing, Anette P.; Hansen, Torben; Pedersen, Oluf] Hagedorn Res Inst, Gentofte, Denmark. [Timpson, Nicholas J.; Day, Ian N. M.; Smith, George Davey; Lawlor, Debbie A.] MRC Ctr Causal Anal Translat Epidemiol, Dept Social Med, Bristol, Avon, England. [Tyrer, Jonathan P.] Univ Cambridge, Dept Oncol, Cambridge, England. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.; Bergman, Richard N.; Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [White, Charles C.; Ngwa, Julius S.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Barlassina, Christina; Macciardi, Fabio] Univ Milan, Dept Med Surg & Dent, Milan, Italy. [Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Cooper, Matthew N.; Lawrence, Robert W.; Hui, Jennie; Palmer, Lyle J.] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Crawley, WA, Australia. [Jansson, John-Olov] Univ Gothenburg, Dept Physiol, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden. [Alibrandi, Maria T. S.; Lanzani, Chiara; Manunta, Paolo] Univ Vita Salute San Raffaele, Div Nephrol & Dialysis, Milan, Italy. [Almgren, Peter; Groop, Leif C.] Lund Univ, Dept Clin Sci, Ctr Diabet, Malmo, Sweden. [Arnold, Alice M.; McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Arnold, Alice M.] Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA. [Balkau, Beverley] Ctr Res Epidemiol & Publ Hlth, INSERM, Ctr Rech Epidimiol & Sante Populat CESP, U1018, Villejuif, France. [Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France. [Balmforth, Anthony J.; Hall, Alistair S.] Univ Leeds, LIGHT, MCRC, Leeds, W Yorkshire, England. [Ben-Shlomo, Yoav] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Biebermann, Heike; Wiegand, Susanna; Krude, Heiko] Charite, Inst Expt Paediat Endocrinol, D-13353 Berlin, Germany. [Blakemore, Alexandra I. F.; Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Bornstein, Stefan R.; Ludwig, Barbara] Univ Dresden, Dept Med 3, Dresden, Germany. [Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Div Endocrinol, Los Angeles, CA 90033 USA. [Busonero, Fabio; Sanna, Serena; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. [Campbell, Harry; Wild, Sarah H.; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Cappuccio, Francesco P.] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Chen, Yii-Der Ida; Haritunians, Talin] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Clarke, Robert] Radcliffe Infirm, Clin Trial Serv Unit, Oxford OX2 6HE, England. [Coin, Lachlan; Elliott, Paul; Sovio, Ulla; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, London, England. [Connell, John] Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland. [den Heijer, Martin; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6525 ED Nijmegen, Netherlands. [den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands. [Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] Northshore Univ Healthsyst, Evanston, IL USA. [Ebrahim, Shah] London Sch Hyg & Trop Med, London WC1, England. [Ebrahim, Shah] S Asia Network Chron Dis, New Delhi, India. [Elliott, Paul] Ctr Environm & Hlth, MRC Hlth Protect Agcy HPA, London, England. [Elosua, Roberto] Ctr Invest Biomed Red CIBER Epidemiol & Salud Pub, Barcelona, Spain. [Elosua, Roberto] Inst Municipal Invest Med, E-08003 Barcelona, Spain. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland. [Facheris, Maurizio F.; Hicks, Andrew A.; Pichler, Irene; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy. [Facheris, Maurizio F.; Hicks, Andrew A.; Pichler, Irene; Pramstaller, Peter P.] Univ Lubeck, Lubeck, Germany. [Facheris, Maurizio F.; Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Felix, Stephan B.] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany. [Fischer-Posovszky, Pamela; Wabitsch, Martin] Dept Pediat & Adolescent Med, Pediat Endocrinol Diabet & Obes Unit, Ulm, Germany. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Friedrich, Nele; Schipf, Sabine; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem & Lab Med, Greifswald, Germany. [Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. [Fu, Mao; Shuldiner, Alan R.; O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Goel, Anuj; Watkins, Hugh] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Goyette, Philippe; Lettre, Guillaume; Tardif, Jean-Claude] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Graessler, Juergen] Univ Dresden, Dept Med 3, Dresden, Germany. [Greenawalt, Danielle M.] Merck & Co Inc, Merck Res Labs, Boston, MA USA. [Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland. [Havulinna, Aki S.; Jousilahti, Pekka; Koskinen, Seppo; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland. [Hayward, Caroline; Vitart, Veronique; Wright, Alan F.] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat & Midwest Alcoholism Res Ctr, St Louis, MO USA. [Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany. [Hengstenberg, Christian] Univ Regensburg, Med Ctr, Regensburg, Germany. [Hinney, Anke; Scherag, Susann; Vogel, Carla I. G.; Hebebrand, Johannes] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, Essen, Germany. [Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Hui, Jennie; Beilby, John P.; Stumvoll, Michael] PathWest Lab Western Australia, Dept Mol Genet, QEII Med Ctr, Nedlands, WA, Australia. [Hui, Jennie; Beilby, John P.; James, Alan L.; Palmer, Lyle J.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn Inc, Nedlands, WA 6009, Australia. [Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Iribarren, Carlos] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [Jacobs, Kevin B.] NCI, SAIC Frederick Inc, Core Genotyping Facil, Frederick, MD 21701 USA. [Jarick, Ivonne] Univ Marburg, Inst Med Biometry & Epidemiol, Marburg, Germany. [John, Ulrich] Ernst Moritz Arndt Univ Greifswald, Inst Epidemiol & Sozialmed, Greifswald, Germany. [Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Jorgensen, Torben] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Populat Studies Unit, Turku, Finland. [Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Kajantie, Eero] Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland. [Kajantie, Eero] Univ Helsinki, Hosp Dist Helsinki & Uusimaa HUS, Helsinki, Finland. [Kaplan, Lee M.] Massachusetts Gen Hosp, Massachusetts Gen Hosp MGH Weight Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Boston Univ, Framingham, MA USA. [Kathiresan, Sekar; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kinnunen, Leena; Tuomilehto, Jaakko; Valle, Timo T.] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Knowles, Joshua W.; Quertermous, Thomas; Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Kolcic, Ivana; Polasek, Ozren; Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41000, Croatia. [Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Kvaloy, Kirsti; Midthjell, Kristian; Platou, Carl G. P.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway. [Laitinen, Jaana] Finnish Inst Occupat Hlth, Oulu, Finland. [Lantieri, Olivier] Inst Interreg Sante IRSA, La Riche, France. [Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA. [Lehtimaeki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaeki, Terho] Tampere Univ Hosp, Tampere, Finland. [Lettre, Guillaume; Tardif, Jean-Claude] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Liu, Jianjun] Genome Inst Singapore, Singapore, Singapore. [Lokki, Marja-Liisa] Univ Helsinki, Transplantat Lab, Haartman Inst, Helsinki, Finland. [Lorentzon, Mattias; Ohlsson, Claes] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, Gothenburg, Sweden. [Luben, Robert N.; Sandhu, Manjinder S.; Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [Marre, Michel] Bichat Claude Bernard Univ Hosp, AP HP, Dept Endocrinol Diabetol & Nutr, Paris, France. [Marre, Michel] Univ Nancy 1, Cardiovasc Genet Res Unit, Nancy, France. [Martin, Nicholas G.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia. [McArdle, Wendy L.] Univ Bristol, Dept Social Med, Avon Longitudinal Study Parents & Children ALSPAC, Bristol, Avon, England. [McCarthy, Anne] Bord Taighde Slainte, Res Board, Div Hlth, Dublin, Ireland. [Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany. [Meitinger, Thomas] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany. [Melander, Olle; Ridderstrale, Martin] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Montgomery, Grant W.] Queensland Inst Med Res, Mol Epidemiol Lab, Brisbane, Qld 4006, Australia. [Mulic, Rosanda; Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia. [Nyholt, Dale R.] Queensland Inst Med Res, Neurogenet Lab, Brisbane, Qld 4006, Australia. [O'Donnell, Christopher J.] NHLBI, NIH, Framingham, MA USA. [O'Rahilly, Stephen; Farooqi, I. Sadaf] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England. [Oostra, Ben] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Parker, Alex N.] Amgen Inc, Cambridge, MA USA. [Pietilaeinen, Kirsi H.; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Pietilaeinen, Kirsi H.; Rissanen, Aila] Univ Helsinki, Cent Hosp, Dept Psychiat, Obes Res Unit, Helsinki, Finland. [Platou, Carl G. P.] Nord Trondelag Hlth Trust, Levanger Hosp, Dept Med, Levanger, Norway. [Polasek, Ozren] Gen Info Ltd, Zagreb, Croatia. [Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu, Finland. [Rafelt, Suzanne; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Rief, Winfried] Univ Marburg, Marburg, Germany. [Ruokonen, Aimo] Univ Oulu, Dept Clin Sci & Clin Chem, Oulu, Finland. [Rzehak, Peter; Wichmann, H-Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Saramies, Jouko] S Karelia Cent Hosp, Lappeenranta, Finland. [Savolainen, Markku J.] Univ Oulu, Dept Clin Sci & Internal Med, Oulu, Finland. [Schipf, Sabine] Inst Community Med, Greifswald, Germany. [Schreiber, Stefan] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Kiel, Germany. [Schreiber, Stefan] Univ Kiel, Dept Internal Med 1, Kiel, Germany. [Schunkert, Heribert; Erdmann, Jeanette] Univ Lubeck, Med Klin 2, Lubeck, Germany. [Sinisalo, Juha; Nieminen, Markku S.] Univ Helsinki, Cent Hosp, Cardiovasc Lab, Div Cardiol, Helsinki, Finland. [Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA USA. [Smit, Jan H.; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Inst Extramuraal Geneeskundig Onderzoek EMGO Inst, Dept Psychiat, Amsterdam, Netherlands. [Stephens, Jonathan; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England. [Stephens, Jonathan; Ouwehand, Willem H.] Natl Hlth Serv NHS Blood & Transplant, Cambridge Ctr, Cambridge, England. [Thompson, John R.; Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc, Leicester, Leics, England. [Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Toenjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, Leipzig, Germany. [Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. [Tuomi, Tiinamaija] Univ Helsinki, Res Program Mol Med, Helsinki, Finland. [van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Ctr Med Syst Biol, Leiden, Netherlands. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland. [Visvikis-Siest, Sophie] INSERM, Cardiovasc Genet team, CIC 9501, Nancy, France. [Witte, Daniel R.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Xu, Jianfeng] Wake Forest Univ, Ctr Human Genom, Winston Salem, NC 27109 USA. [Zitting, Paavo] Lapland Cent Hosp, Dept Physiatr, Rovaniemi, Finland. [Beilby, John P.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Huikuri, Heikki V.] Univ Oulu, Dept Internal Med, SF-90220 Oulu, Finland. [James, Alan L.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Kaehoenen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Kaehoenen, Mika] Tampere Univ Hosp, Tampere, Finland. [Levinson, Douglas F.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Macciardi, Fabio] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. Univ Leipzig, Leipziger Interdisziplinarer Forsch Komplex Mol U, Leipzig, Germany. [Beckmann, Jacques S.] Univ Hosp, CHUV, Serv Med Genet, Lausanne, Switzerland. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark. [Hayes, Richard B.] NYU, Med Ctr, New York, NY 10016 USA. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Substance Abuse Serv, Unit Child & Adolescent Mental Hlth, Helsinki, Finland. [Karpe, Fredrik; McCarthy, Mark I.] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LJ, England. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Pedersen, Oluf] Univ Copenhagen, Inst Biomed Sci, Copenhagen, Denmark. [Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, Lubeck, Germany. [Reinehr, Thomas] Univ Witten Herdecke, Vest Hosp Children & Adolescents, Inst Paediat Nutr Med, Datteln, Germany. [Schwarz, Peter E. H.] Univ Dresden, Dept Med 3, Dresden, Germany. [Tuomilehto, Jaakko] Baltimore Vet Adm, Geriatr Res & Educ Clin Ctr, Med Ctr, Baltimore, MD USA. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Shuldiner, Alan R.; Waeber, Gerard] Univ Hosp, CHUV, Dept Internal Med, Lausanne, Switzerland. [Purcell, Shaun; Peltonen, Leena] MIT, Cambridge, MA 02139 USA. [Purcell, Shaun; Peltonen, Leena] Broad Inst Harvard, Cambridge, MA 02139 USA. [Purcell, Shaun] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Schadt, Eric E.] Pacific Biosci, Menlo Pk, CA USA. [Schadt, Eric E.] Sage Bionetworks, Seattle, WA USA. [Borecki, Ingrid B.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA USA. [Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA. [Strachan, David P.] Univ London, Div Community Hlth Sci, London, England. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England. [North, Kari E.] Univ N Carolina, Sch Publ Hlth, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Brown, MJ (reprint author), Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge, England. EM boehnke@umich.edu; kstefans@decode.is; kari_north@unc.edu; mark.mccarthy@drl.ox.ac.uk; joelh@broadinstitute.org; erik.ingelsson@ki.se; ruth.loos@mrc-epid.cam.ac.uk RI Mulic, Rosanda/D-6914-2017; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Ziegler, Andreas/G-4246-2012; Macciardi, Fabio/N-3768-2014; Aben, Katja/G-9686-2016; Yang, Jian/A-5852-2010; Smith, Albert/K-5150-2015; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Coin, Lachlan/A-9001-2014; Schwarz, Peter/B-5127-2013; Konig, Inke/A-4544-2009; Erdmann, Jeanette/A-4417-2009; Davey Smith, George/A-7407-2013; Kiemeney, Lambertus/D-3357-2009; Visvikis-Siest, Sophie/H-2324-2014; Pramstaller, Peter/C-2357-2008; Cooper, Matthew/J-4420-2014; Palmer, Lyle/K-3196-2014; Witte, Daniel/C-1722-2008; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Montgomery, Grant/B-7148-2008; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; kinnunen, leena/B-7059-2012; Li, Shengxu/D-8915-2012; Spector, Tim/F-6533-2012; Ridderstrale, Martin/F-7678-2012; Kilpelainen, Tuomas/F-8569-2012; Lango Allen, Hana/G-9026-2012; Rudan, Igor/I-1467-2012; Johansson, Asa/G-5270-2011; Deloukas, Panos/B-2922-2013; Thiering, Elisabeth/B-3342-2013; Grallert, Harald/B-3424-2013; Nyholt, Dale/C-8384-2013; Colaus, PsyColaus/K-6607-2013; Lamina, Claudia/F-7608-2010; Kaplan, Robert/A-2526-2011; Aspelund, Thor/C-5983-2008; Peters, Annette/A-6117-2011; Abecasis, Goncalo/B-7840-2010; Polasek, Ozren/B-6002-2011; Schreiber, Stefan/B-6748-2008; Hinney, Anke/D-6953-2011; Meyre, David/D-7315-2011; Beckmann, Jacques S /A-9772-2008; Voight, Benjamin/F-1775-2011; Aspelund, Thor/F-4826-2011; Segre, Ayellet/E-9800-2010; OI Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Thiering, Elisabeth/0000-0002-5429-9584; Soranzo, Nicole/0000-0003-1095-3852; Peters, Marjolein/0000-0003-3167-9063; Bouatia-Naji, Nabila/0000-0001-5424-2134; Willer, Cristen/0000-0001-5645-4966; Kaakinen, Marika/0000-0002-9228-0462; Ziegler, Andreas/0000-0002-8386-5397; Macciardi, Fabio/0000-0003-0537-4266; Aben, Katja/0000-0002-0214-2147; Yang, Jian/0000-0003-2001-2474; Smith, Albert/0000-0003-1942-5845; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Coin, Lachlan/0000-0002-4300-455X; Schwarz, Peter/0000-0001-6317-7880; Davey Smith, George/0000-0002-1407-8314; Kiemeney, Lambertus/0000-0002-2368-1326; Visvikis-Siest, Sophie/0000-0001-8104-8425; Cooper, Matthew/0000-0003-1139-3682; Palmer, Lyle/0000-0002-1628-3055; Witte, Daniel/0000-0002-0769-2922; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Montgomery, Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457; kinnunen, leena/0000-0001-8739-4812; Lango Allen, Hana/0000-0002-7803-8688; Rudan, Igor/0000-0001-6993-6884; Johansson, Asa/0000-0002-2915-4498; Deloukas, Panos/0000-0001-9251-070X; Aspelund, Thor/0000-0002-7998-5433; Polasek, Ozren/0000-0002-5765-1862; Schreiber, Stefan/0000-0003-2254-7771; Hinney, Anke/0000-0001-5659-0706; Beckmann, Jacques S /0000-0002-9741-1900; Pichler, Irene/0000-0001-8251-0757; Heard-Costa, Nancy/0000-0001-9730-0306; Goddard, Michael/0000-0001-9917-7946; Magi, Reedik/0000-0002-2964-6011; Marre, Michel/0000-0002-3071-1837; sanna, serena/0000-0002-3768-1749; Monsalve, Beatriz Elena/0000-0002-5994-866X; Johnson, Toby/0000-0002-5998-3270; Cappuccio, Francesco Paolo/0000-0002-7842-5493; Myers, Richard/0000-0002-8365-2674; Cupples, L. Adrienne/0000-0003-0273-7965; Brown, Matthew A/0000-0003-0538-8211; Abecasis, Goncalo/0000-0003-1509-1825; Esko, Tonu/0000-0003-1982-6569; Manunta, Paolo/0000-0003-3976-9696; Zgaga, Lina/0000-0003-4089-9703; Luben, Robert/0000-0002-5088-6343; Gieger, Christian/0000-0001-6986-9554; Scherag, Andre/0000-0002-9406-4704; Hayes, Richard/0000-0002-0918-661X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Farooqi, Sadaf/0000-0001-7609-3504; Tuomi, Tiinamaija/0000-0002-8306-6202; John, Ulrich/0000-0003-0587-5298; Karpe, Fredrik/0000-0002-2751-1770; Jorgensen, Torben/0000-0001-9453-2830; Watkins, Hugh/0000-0002-5287-9016; Perola, Markus/0000-0003-4842-1667; Visscher, Peter/0000-0002-2143-8760; Eriksson, Johan/0000-0002-2516-2060; Ouwehand, Willem/0000-0002-7744-1790; Kaprio, Jaakko/0000-0002-3716-2455; Timpson, Nicholas/0000-0002-7141-9189; Lawlor, Debbie A/0000-0002-6793-2262; Bergmann, Sven/0000-0002-6785-9034; Sinisalo, Juha/0000-0002-0169-5137; de Geus, Eco/0000-0001-6022-2666; Martin, Nicholas/0000-0003-4069-8020 FU Academy of Finland [10404, 77299, 104781, 114382, 117797, 120315]; ADA; Amgen; Agency for Science, Technology and Research of Singapore (AstarSTAR); ALF/LUA; Althingi (the Icelandic Parliament); AstraZeneca; Augustinus Foundation; Australian National Health and Medical Research Council [241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672]; Australian Research Council (ARC) [DP0770096]; Becket Foundation; Biocenter (Finland); Biomedicum Helsinki Foundation; Boston Obesity Nutrition Research Center; British Diabetes Association [1192]; British Heart Foundation [97020, PG/02/128]; Busselton Population Medical Research Foundation; Cambridge Institute for Medical Research; Cambridge National Institute of Health Research (NIHR) Comprehensive Biomedical Research Centre; CamStrad (UK); Cancer Research UK; Centre for Medical Systems Biology (The Netherlands); Centre for Neurogenomics and Cognitive Research (The Netherlands); Chief Scientist Office of the Scottish Government; Contrat Plan Etat Region (France); Danish Centre for Health Technology Assessment; Danish Diabetes Association; Danish Heart Foundation; Danish Pharmaceutical Association; Danish Research Council; Deutsche Forschungsgemeinschaft (DFG) [HE 1446/4-1]; Department of Health (UK); Diabetes UK; Diabetes and Inflammation Laboratory; Donald W. Reynolds Foundation; Dresden University of Technology; Emil and Vera Cornell Foundation; Erasmus Medical Center (Rotterdam); Erasmus University (Rotterdam); European Commission [QLG1-CT-2000-01643, QLG2-CT-2002-01254, LSHC-CT-2005, LSHG-CT-2006-018947, LSHG-CT-2004-518153, LSH-2006-037593, LSHM-CT-2007-037273, HEALTH- F2-2008-ENGAGE, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550, 205419, 212111, 245536, SOC 9520140805F02, WLRT-2001-01254]; Federal Ministry of Education and Research (Germany) [01AK803, 01EA9401, 01GI0823, 01GI0826, 01GP0209, 01GP0259, 01GS0820, 01GS0823, 01GS0824, 01GS0825, 01GS0830, 01GS0831, 01IG07015, 01KU0903, 01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Federal State of Mecklenburg-West Pomerania; European Social Fund; Eve Appeal; Finnish Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Finnish Foundation for Pediatric Research, Finnish Medical Society; Finska Lakaresallskapet, Paivikki and Sakari Sohlberg Foundation, Folkhalsan Research Foundation; Fond Europeen pour le Developpement Regional (France); Fondation LeDucq (Paris, France); Foundation for Life and Health in Finland; Foundation for Strategic Research (Sweden); Genetic Association Information Network; German Research Council [KFO-152]; German National Genome Research Net 'NGFNplus' [FKZ 01GS0823]; German Research Center for Environmental Health; Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Goteborg Medical Society; Great Wine Estates Auctions; Gyllenberg Foundation; Health Care Centers in Vasa, Narpes and Korsholm; Healthway, Western Australia; Helmholtz Center Munich; Helsinki University Central Hospital, Hjartavernd (the Icelandic Heart Association); INSERM (France); Ib Henriksen Foundation; Interdisziplinares Zentrum fur Klinische Forschung (IZKF) [B27]; Jalmari and Rauha Ahokas Foundation; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International (JDRF); Karolinska Institute; Knut and Alice Wallenberg Foundation; Leenaards Foundation; Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP); Lundberg Foundation; Marie Curie Intra-European Fellowship; Medical Research Council (UK) [G0000649, G0000934, G9521010D, G0500539, G0600331, G0601261]; Ministry of Cultural Affairs and Social Ministry of the Federal State of Mecklenburg-West Pomerania; Ministry for Health, Welfare and Sports (The Netherlands); Ministry of Education (Finland); Ministry of Education, Culture and Science (The Netherlands); Ministry of Internal Affairs and Health (Denmark); Ministry of Science, Education and Sport of the Republic of Croatia [216-1080315-0302]; Ministry of Science, Research and the Arts Baden-Wurttemberg; Montreal Heart Institute Foundation; Municipal Health Care Center and Hospital in Jakobstad; Municipality of Rotterdam; Narpes Health Care Foundation; National Cancer Institute; National Health and Medical Research Council of Australia; National Institute for Health Research Cambridge Biomedical Research Centre; National Institute for Health Research Oxford Biomedical Research Centre FX Funding was provided by Academy of Finland (10404, 77299, 104781, 114382, 117797, 120315, 121584, 124243, 126775, 126925, 127437, 129255, 129269, 129306, 129494, 129680, 130326, 209072, 210595, 213225, 213506 and 216374); ADA Mentor-Based Postdoctoral Fellowship; Amgen; Agency for Science, Technology and Research of Singapore (A*STAR); ALF/LUA research grant in Gothenburg; Althingi (the Icelandic Parliament); AstraZeneca; Augustinus Foundation; Australian National Health and Medical Research Council (241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485 and 613672); Australian Research Council (ARC grant DP0770096); Becket Foundation; Biocenter (Finland); Biomedicum Helsinki Foundation; Boston Obesity Nutrition Research Center; British Diabetes Association (1192); British Heart Foundation (97020; PG/02/128); Busselton Population Medical Research Foundation; Cambridge Institute for Medical Research; Cambridge National Institute of Health Research (NIHR) Comprehensive Biomedical Research Centre; CamStrad (UK); Cancer Research UK; Centre for Medical Systems Biology (The Netherlands); Centre for Neurogenomics and Cognitive Research (The Netherlands); Chief Scientist Office of the Scottish Government; Contrat Plan Etat Rrgion (France); Danish Centre for Health Technology Assessment; Danish Diabetes Association; Danish Heart Foundation; Danish Pharmaceutical Association; Danish Research Council; Deutsche Forschungsgemeinschaft (DFG; HE 1446/4-1); Department of Health (UK); Diabetes UK; Diabetes and Inflammation Laboratory; Donald W.; Reynolds Foundation; Dresden University of Technology Funding Grant; Emil and Vera Cornell Foundation; Erasmus Medical Center (Rotterdam); Erasmus University (Rotterdam); European Commission (DG XII; QLG1-CT-2000-01643, QLG2-CT-2002-01254, LSHC-CT-2005, LSHG-CT-2006-018947, LSHG-CT-2004-518153, LSH-2006-037593, LSHM-CT-2007-037273, HEALTH-F2-2008ENGAGE, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550, FP7/2007-2013, 205419, 212111, 245536, SOC 95201408 05F02 and WLRT-2001-01254); Federal Ministry of Education and Research (Germany) (01AK803, 01EA9401, 01GI0823, 01GI0826, 01GP0209, 01GP0259, 01GS0820, 01GS0823, 01GS0824, 01GS0825, 01GS0830, 01GS0831, 01IG07015, 01KU0903, 01ZZ9603, 01ZZ0103, 01ZZ0403 and 03ZIK012); Federal State of Mecklenburg-West Pomerania; European Social Fund; Eve Appeal; Finnish Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Finnish Foundation for Pediatric Research, Finnish Medical Society; Finska Lakaresallskapet, Paivikki and Sakari Sohlberg Foundation, Folkhalsan Research Foundation; Fond Europeen pour le Developpement Regional (France); Fondation LeDucq (Paris, France); Foundation for Life and Health in Finland; Foundation for Strategic Research (Sweden); Genetic Association Information Network; German Research Council (KFO-152); German National Genome Research Net 'NGFNplus' (FKZ 01GS0823); German Research Center for Environmental Health; Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Goteborg Medical Society; Great Wine Estates Auctions; Gyllenberg Foundation; Health Care Centers in Vasa, Narpes and Korsholm; Healthway, Western Australia; Helmholtz Center Munich; Helsinki University Central Hospital, Hjartavernd (the Icelandic Heart Association); INSERM (France); Ib Henriksen Foundation; Interdisziplinares Zentrum fur Klinische Forschung (IZKF) (B27); Jalmari and Rauha Ahokas Foundation; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International (JDRF); Karolinska Institute; Knut and Alice Wallenberg Foundation; Leenards Foundation; Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP); Lundberg Foundation; Marie Curie Intra-European Fellowship; Medical Research Council (UK) (G0000649, G0000934, G9521010D, G0500539, G0600331 and G0601261, PrevMetSyn); Ministry of Cultural Affairs and Social Ministry of the Federal State of Mecklenburg-West Pomerania; Ministry for Health, Welfare and Sports (The Netherlands); Ministry of Education (Finland); Ministry of Education, Culture and Science (The Netherlands); Ministry of Internal Affairs and Health (Denmark); Ministry of Science, Education and Sport of the Republic of Croatia (216-1080315-0302); Ministry of Science, Research and the Arts Baden-Wurttemberg; Montreal Heart Institute Foundation; Municipal Health Care Center and Hospital in Jakobstad; Municipality of Rotterdam; Narpes Health Care Foundation; National Cancer Institute; National Health and Medical Research Council of Australia; National Institute for Health Research Cambridge Biomedical Research Centre; National Institute for Health Research Oxford Biomedical Research Centre; National Institute for Health Research comprehensive Biomedical Research Centre; US National Institutes of Health (263-MA-410953, AA07535, AA10248, AA014041, AA13320, AA13321, AA13326, CA047988, CA65725, CA87969, CA49449, CA67262, CA50385, DA12854, DK58845, DK46200, DK062370, DK063491, DK072193, HG002651, HL084729, HHSN268200625226C, HL71981, K23-DK080145, K99-HL094535, M01-RR00425, MH084698, N01-AG12100, NO1-AG12109, N01-H; 15103, N01-HC25195, N01-HC35129, N01-HC45133, N01-HC55015, N01-HC55016, N01-HC55018, N01-HC55019, N01-HC55020, N01-N01HC-55021, N01-HC55022, N01-HC55222, N01-HC75150, N01-HC85079, N01-HC85080, N01-HG-65403, N01-HC85081, N01-HC85082, N01-HC85083, N01-HC85084, N01-HC85085, N01-HC85086, N02-HL64278, P30-DK072488, R01-AG031890, R01-DK073490, R01-DK075787, R01DK068336, R01DK075681, R01-HL59367, R01-HL086694, R01-HL087641, R01-HL087647, R01-HL087652, R01-HL087676, R01-HL087679, R01-HL087700, R01-HL088119, R01-MH59160, R01-MH59565, R01-MH59566, R01-MH59571, R01-MH59586, R01-MH59587, R01-MH59588, R01-MH60870, R01-MH60879, R01-MH61675, R01-MH63706, R01-MH67257, R01-MH79469, R01-MH79470, R01-MH81800, RL1-MH083268, UO1-CA098233, U01-DK062418, U01-GM074518, U01-HG004402, U01-HG004399, U01-HL72515, U01-HL080295, U01-HL084756, U54-RR020278, T32-HG00040, UL1-RR025005 and Z01-HG000024); National Alliance for Research on Schizophrenia and Depression (NARSAD); Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Organisation for Scientific Research (NWO) (904-61-090, 904-61-193, 480-04-004, 400-05-717, SPI 56-464-1419, 175.010.2005.011 and 911-03-012); Nord-Trondelag County Council; Nordic Center of Excellence in Disease Genetics; Novo Nordisk Foundation; Norwegian Institute of Public Health; Ollqvist Foundation; Oxford NIHR Biomedical Research Centre; Organization for the Health Research and Development (10-000-1002); Paavo Nurmi Foundation; Paul Michael Donovan Charitable Foundation; Perklen Foundation; Petrus and Augusta Hedlunds Foundation; Pew Scholar for the Biomedical Sciences; Public Health and Risk Assessment, Health and Consumer Protection (2004310); Research Foundation of Copenhagen County; Research Institute for Diseases in the Elderly (014-93-015; RIDE2); Robert Dawson Evans Endowment; Royal Society (UK); Royal Swedish Academy of Science; Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR, no. A305: 188); Siemens Healthcare, Erlangen, Germany; Sigrid Juselius Foundation; Signe and Ane Gyllenberg Foundation; Science Funding programme (UK); Social Insurance Institution of Finland; Sderberg's Foundation; South Tyrol Ministry of Health; South Tyrolean Sparkasse Foundation; State of Bavaria; Stockholm County Council (560183); Susan G. Komen Breast Cancer Foundation; Swedish Cancer Society; Swedish Cultural Foundation in Finland; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Medical Research Council (8691, K2007-66X-20270-01-3, K2010-54X-09894-19-3, K2010-54X-09894-19-3 and 2006-3832); Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation (33CSCO-122661, 310000-112552 and 3100AO-116323/1); Torsten and Ragnar Soderberg's Foundation; Universite Henri Poincare-Nancy 1, Region Lorraine, Communaute Urbaine du Grand Nancy; University Hospital Medical funds to Tampere; University Hospital Oulu, Finland; University of Oulu, Finland (75617); Vastra Gotaland Foundation; Walter E. Nichols, M. D., and Eleanor Nichols endowments; Wellcome Trust (068545, 072960, 075491, 076113, 077016, 079557, 079895, 081682, 083270, 085301 and 086596); Western Australian DNA Bank; Western Australian Genetic Epidemiology Resource; and Yrjo Jahnsson Foundation. NR 54 TC 1268 Z9 1297 U1 32 U2 277 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2010 VL 42 IS 11 BP 937 EP U53 DI 10.1038/ng.686 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 671VW UT WOS:000283540500010 PM 20935630 ER PT J AU Heid, IM Jackson, AU Randall, JC Winkler, TW Qi, L Steinthorsdottir, V Thorleifsson, G Zillikens, MC Speliotes, EK Magi, R Workalemahu, T White, CC Bouatia-Naji, N Harris, TB Berndt, SI Ingelsson, E Willer, CJ Weedon, MN Luan, JA Vedantam, S Esko, T Kilpelainen, TO Kutalik, Z Li, SX Monda, KL Dixon, AL Holmes, CC Kaplan, LM Liang, LM Min, JL Moffatt, MF Molony, C Nicholson, G Schadt, EE Zondervan, KT Feitosa, MF Ferreira, T Allen, HL Weyant, RJ Wheeler, E Wood, AR Estrada, K Goddard, ME Lettre, G Mangino, M Nyholt, DR Purcell, S Smith, AV Visscher, PM Yang, JA McCarroll, SA Nemesh, J Voight, BF Absher, D Amin, N Aspelund, T Coin, L Glazer, NL Hayward, C Heard-Costa, NL Hottenga, JJ Johansson, A Johnson, T Kaakinen, M Kapur, K Ketkar, S Knowles, JW Kraft, P Kraja, AT Lamina, C Leitzmann, MF McKnight, B Morris, AP Ong, KK Perry, JRB Peters, MJ Polasek, O Prokopenko, I Rayner, NW Ripatti, S Rivadeneira, F Robertson, NR Sanna, S Sovio, U Surakka, I Teumer, A van Wingerden, S Vitart, V Zhao, JH Cavalcanti-Proenca, C Chines, PS Fisher, E Kulzer, JR Lecoeur, C Narisu, N Sandholt, C Scott, LJ Silander, K Stark, K Tammesoo, ML Teslovich, TM Timpson, NJ Watanabe, RM Welch, R Chasman, DI Cooper, MN Jansson, JO Kettunen, J Lawrence, RW Pellikka, N Perola, M Vandenput, L Alavere, H Almgren, P Atwood, LD Bennett, AJ Biffar, R Bonnycastle, LL Bornstein, SR Buchanan, TA Campbell, H Day, INM Dei, M Dorr, M Elliott, P Erdos, MR Eriksson, JG Freimer, NB Fu, M Gaget, S Geus, EJC Gjesing, AP Grallert, H Grassler, J Groves, CJ Guiducci, C Hartikainen, AL Hassanali, N Havulinna, AS Herzig, KH Hicks, AA Hui, JN Igl, W Jousilahti, P Jula, A Kajantie, E Kinnunen, L Kolcic, I Koskinen, S Kovacs, P Kroemer, HK Krzelj, V Kuusisto, J Kvaloy, K Laitinen, J Lantieri, O Lathrop, GM Lokki, ML Luben, RN Ludwig, B McArdle, WL McCarthy, A Morken, MA Nelis, M Neville, MJ Pare, G Parker, AN Peden, JF Pichler, I Pietilainen, KH Platou, CGP Pouta, A Ridderstrale, M Samani, NJ Saramies, J Sinisalo, J Smit, JH Strawbridge, RJ Stringham, HM Swift, AJ Teder-Laving, M Thomson, B Usala, G van Meurs, JBJ van Ommen, GJ Vatin, V Volpato, CB Wallaschofski, H Walters, GB Widen, E Wild, SH Willemsen, G Witte, DR Zgaga, L Zitting, P Beilby, JP James, AL Kahonen, M Lehtimaki, T Nieminen, MS Ohlsson, C Palmer, LJ Raitakari, O Ridker, PM Stumvoll, M Tonjes, A Viikari, J Balkau, B Ben-Shlomo, Y Bergman, RN Boeing, H Smith, GD Ebrahim, S Froguel, P Hansen, T Hengstenberg, C Hveem, K Isomaa, B Jorgensen, T Karpe, F Khaw, KT Laakso, M Lawlor, DA Marre, M Meitinger, T Metspalu, A Midthjell, K Pedersen, O Salomaa, V Schwarz, PEH Tuomi, T Tuomilehto, J Valle, TT Wareham, NJ Arnold, AM Beckmann, JS Bergmann, S Boerwinkle, E Boomsma, DI Caulfield, MJ Collins, FS Eiriksdottir, G Gudnason, V Gyllensten, U Hamsten, A Hattersley, AT Hofman, A Hu, FB Illig, T Iribarren, C Jarvelin, MR Kao, WHL Kaprio, J Launer, LJ Munroe, PB Oostra, B Penninx, BW Pramstaller, PP Psaty, BM Quertermous, T Rissanen, A Rudan, I Shuldiner, AR Soranzo, N Spector, TD Syvanen, AC Uda, M Uitterlinden, A Volzke, H Vollenweider, P Wilson, JF Witteman, JC Wright, AF Abecasis, GR Boehnke, M Borecki, IB Deloukas, P Frayling, TM Groop, LC Haritunians, T Hunter, DJ Kaplan, RC North, KE O'Connell, JR Peltonen, L Schlessinger, D Strachan, DP Hirschhorn, JN Assimes, TL Wichmann, HE Thorsteinsdottir, U van Duijn, CM Stefansson, K Cupples, LA Loos, RJF Barroso, I McCarthy, MI Fox, CS Mohlke, KL Lindgren, CM AF Heid, Iris M. Jackson, Anne U. Randall, Joshua C. Winkler, Thomas W. Qi, Lu Steinthorsdottir, Valgerdur Thorleifsson, Gudmar Zillikens, M. Carola Speliotes, Elizabeth K. Maegi, Reedik Workalemahu, Tsegaselassie White, Charles C. Bouatia-Naji, Nabila Harris, Tamara B. Berndt, Sonja I. Ingelsson, Erik Willer, Cristen J. Weedon, Michael N. Luan, Jianan Vedantam, Sailaja Esko, Tonu Kilpelaeinen, Tuomas O. Kutalik, Zoltan Li, Shengxu Monda, Keri L. Dixon, Anna L. Holmes, Christopher C. Kaplan, Lee M. Liang, Liming Min, Josine L. Moffatt, Miriam F. Molony, Cliona Nicholson, George Schadt, Eric E. Zondervan, Krina T. Feitosa, Mary F. Ferreira, Teresa Allen, Hana Lango Weyant, Robert J. Wheeler, Eleanor Wood, Andrew R. Estrada, Karol Goddard, Michael E. Lettre, Guillaume Mangino, Massimo Nyholt, Dale R. Purcell, Shaun Smith, Albert Vernon Visscher, Peter M. Yang, Jian McCarroll, Steven A. Nemesh, James Voight, Benjamin F. Absher, Devin Amin, Najaf Aspelund, Thor Coin, Lachlan Glazer, Nicole L. Hayward, Caroline Heard-Costa, Nancy L. Hottenga, Jouke-Jan Johansson, Asa Johnson, Toby Kaakinen, Marika Kapur, Karen Ketkar, Shamika Knowles, Joshua W. Kraft, Peter Kraja, Aldi T. Lamina, Claudia Leitzmann, Michael F. McKnight, Barbara Morris, Andrew P. Ong, Ken K. Perry, John R. B. Peters, Marjolein J. Polasek, Ozren Prokopenko, Inga Rayner, Nigel W. Ripatti, Samuli Rivadeneira, Fernando Robertson, Neil R. Sanna, Serena Sovio, Ulla Surakka, Ida Teumer, Alexander van Wingerden, Sophie Vitart, Veronique Zhao, Jing Hua Cavalcanti-Proenca, Christine Chines, Peter S. Fisher, Eva Kulzer, Jennifer R. Lecoeur, Cecile Narisu, Narisu Sandholt, Camilla Scott, Laura J. Silander, Kaisa Stark, Klaus Tammesoo, Mari-Liis Teslovich, Tanya M. Timpson, Nicholas John Watanabe, Richard M. Welch, Ryan Chasman, Daniel I. Cooper, Matthew N. Jansson, John-Olov Kettunen, Johannes Lawrence, Robert W. Pellikka, Niina Perola, Markus Vandenput, Liesbeth Alavere, Helene Almgren, Peter Atwood, Larry D. Bennett, Amanda J. Biffar, Reiner Bonnycastle, Lori L. Bornstein, Stefan R. Buchanan, Thomas A. Campbell, Harry Day, Ian N. M. Dei, Mariano Doerr, Marcus Elliott, Paul Erdos, Michael R. Eriksson, Johan G. Freimer, Nelson B. Fu, Mao Gaget, Stefan Geus, Eco J. C. Gjesing, Anette P. Grallert, Harald Graessler, Juergen Groves, Christopher J. Guiducci, Candace Hartikainen, Anna-Liisa Hassanali, Neelam Havulinna, Aki S. Herzig, Karl-Heinz Hicks, Andrew A. Hui, Jennie Igl, Wilmar Jousilahti, Pekka Jula, Antti Kajantie, Eero Kinnunen, Leena Kolcic, Ivana Koskinen, Seppo Kovacs, Peter Kroemer, Heyo K. Krzelj, Vjekoslav Kuusisto, Johanna Kvaloy, Kirsti Laitinen, Jaana Lantieri, Olivier Lathrop, G. Mark Lokki, Marja-Liisa Luben, Robert N. Ludwig, Barbara McArdle, Wendy L. McCarthy, Anne Morken, Mario A. Nelis, Mari Neville, Matt J. Pare, Guillaume Parker, Alex N. Peden, John F. Pichler, Irene Pietilainen, Kirsi H. Platou, Carl G. P. Pouta, Anneli Ridderstrale, Martin Samani, Nilesh J. Saramies, Jouko Sinisalo, Juha Smit, Jan H. Strawbridge, Rona J. Stringham, Heather M. Swift, Amy J. Teder-Laving, Maris Thomson, Brian Usala, Gianluca van Meurs, Joyce B. J. van Ommen, Gert-Jan Vatin, Vincent Volpato, Claudia B. Wallaschofski, Henri Walters, G. Bragi Widen, Elisabeth Wild, Sarah H. Willemsen, Gonneke Witte, Daniel R. Zgaga, Lina Zitting, Paavo Beilby, John P. James, Alan L. Kahonen, Mika Lehtimaki, Terho Nieminen, Markku S. Ohlsson, Claes Palmer, Lyle J. Raitakari, Olli Ridker, Paul M. Stumvoll, Michael Toenjes, Anke Viikari, Jorma Balkau, Beverley Ben-Shlomo, Yoav Bergman, Richard N. Boeing, Heiner Smith, George Davey Ebrahim, Shah Froguel, Philippe Hansen, Torben Hengstenberg, Christian Hveem, Kristian Isomaa, Bo Jorgensen, Torben Karpe, Fredrik Khaw, Kay-Tee Laakso, Markku Lawlor, Debbie A. Marre, Michel Meitinger, Thomas Metspalu, Andres Midthjell, Kristian Pedersen, Oluf Salomaa, Veikko Schwarz, Peter E. H. Tuomi, Tiinamaija Tuomilehto, Jaakko Valle, Timo T. Wareham, Nicholas J. Arnold, Alice M. Beckmann, Jacques S. Bergmann, Sven Boerwinkle, Eric Boomsma, Dorret I. Caulfield, Mark J. Collins, Francis S. Eiriksdottir, Gudny Gudnason, Vilmundur Gyllensten, Ulf Hamsten, Anders Hattersley, Andrew T. Hofman, Albert Hu, Frank B. Illig, Thomas Iribarren, Carlos Jarvelin, Marjo-Riitta Kao, W. H. Linda Kaprio, Jaakko Launer, Lenore J. Munroe, Patricia B. Oostra, Ben Penninx, Brenda W. Pramstaller, Peter P. Psaty, Bruce M. Quertermous, Thomas Rissanen, Aila Rudan, Igor Shuldiner, Alan R. Soranzo, Nicole Spector, Timothy D. Syvanen, Ann-Christine Uda, Manuela Uitterlinden, Andre Voelzke, Henry Vollenweider, Peter Wilson, James F. Witteman, Jacqueline C. Wright, Alan F. Abecasis, Goncalo R. Boehnke, Michael Borecki, Ingrid B. Deloukas, Panos Frayling, Timothy M. Groop, Leif C. Haritunians, Talin Hunter, David J. Kaplan, Robert C. North, Kari E. O'Connell, Jeffrey R. Peltonen, Leena Schlessinger, David Strachan, David P. Hirschhorn, Joel N. Assimes, Themistocles L. Wichmann, H-Erich Thorsteinsdottir, Unnur van Duijn, Cornelia M. Stefansson, Kari Cupples, L. Adrienne Loos, Ruth J. F. Barroso, Ines McCarthy, Mark I. Fox, Caroline S. Mohlke, Karen L. Lindgren, Cecilia M. CA MAGIC TI Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; BODY-FAT; METABOLIC RISK; ABDOMINAL ADIPOSITY; GLUCOSE-HOMEOSTASIS; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; COMMON VARIANTS; OBESITY AB Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. C1 [Randall, Joshua C.; Maegi, Reedik; Ferreira, Teresa; Morris, Andrew P.; Prokopenko, Inga; Rayner, Nigel W.; Robertson, Neil R.; Peden, John F.; McCarthy, Mark I.; Lindgren, Cecilia M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Heid, Iris M.; Winkler, Thomas W.; Leitzmann, Michael F.] Regensburg Univ Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany. [Heid, Iris M.; Lamina, Claudia; Grallert, Harald; Illig, Thomas; Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Jackson, Anne U.; Willer, Cristen J.; Weyant, Robert J.; Scott, Laura J.; Teslovich, Tanya M.; Welch, Ryan; Stringham, Heather M.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Qi, Lu; Workalemahu, Tsegaselassie; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Qi, Lu; Kaplan, Lee M.; Chasman, Daniel I.; Ridker, Paul M.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA. [Qi, Lu; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Walters, G. Bragi; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Zillikens, M. Carola; Estrada, Karol; Peters, Marjolein J.; Rivadeneira, Fernando; van Meurs, Joyce B. J.; Uitterlinden, Andre] Erasmus Med Ctr MC, Dept Internal Med, Rotterdam, Netherlands. [Zillikens, M. Carola; Estrada, Karol; Peters, Marjolein J.; Rivadeneira, Fernando; van Meurs, Joyce B. J.; Hofman, Albert; Uitterlinden, Andre; Witteman, Jacqueline C.; van Duijn, Cornelia M.] NGI, NCHA, Rotterdam, Netherlands. [Speliotes, Elizabeth K.; Vedantam, Sailaja; Guiducci, Candace; Thomson, Brian; Hirschhorn, Joel N.] Broad Inst, Metab Initiat, Cambridge, MA USA. [Speliotes, Elizabeth K.; Vedantam, Sailaja; Guiducci, Candace; Thomson, Brian; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Speliotes, Elizabeth K.; Kaplan, Lee M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [White, Charles C.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Bouatia-Naji, Nabila; Cavalcanti-Proenca, Christine; Lecoeur, Cecile; Gaget, Stefan; Vatin, Vincent; Froguel, Philippe] Inst Pasteur, IBL, UMR8199, CNRS, F-59019 Lille, France. [Bouatia-Naji, Nabila; Cavalcanti-Proenca, Christine; Lecoeur, Cecile; Gaget, Stefan; Vatin, Vincent; Froguel, Philippe] Univ Lille Nord France, Lille, France. [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Weedon, Michael N.; Allen, Hana Lango; Wood, Andrew R.; Perry, John R. B.; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England. [Luan, Jianan; Kilpelaeinen, Tuomas O.; Li, Shengxu; Ong, Ken K.; Zhao, Jing Hua; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England. [Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Esko, Tonu; Tammesoo, Mari-Liis; Alavere, Helene; Nelis, Mari; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Nelis, Mari; Teder-Laving, Maris; Metspalu, Andres] Estonian Bioctr, Tartu, Estonia. [Esko, Tonu; Nelis, Mari; Teder-Laving, Maris; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Kutalik, Zoltan; Johnson, Toby; Kapur, Karen; Beckmann, Jacques S.; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Kutalik, Zoltan; Johnson, Toby; Kapur, Karen; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland. [Monda, Keri L.; North, Kari E.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Dixon, Anna L.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. [Holmes, Christopher C.] MRC Harwell, Oxford, England. [Holmes, Christopher C.; Nicholson, George] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Kaplan, Lee M.] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Liang, Liming; Kraft, Peter; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Liang, Liming; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Min, Josine L.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Moffatt, Miriam F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Molony, Cliona] Merck & Co Inc, Merck Res Labs, Boston, MA USA. [Schadt, Eric E.] Pacific Biosci, Menlo Pk, CA USA. [Schadt, Eric E.] Sage Bionetworks, Seattle, WA USA. [Zondervan, Krina T.] Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England. [Feitosa, Mary F.; Ketkar, Shamika; Kraja, Aldi T.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Wheeler, Eleanor; Soranzo, Nicole; Deloukas, Panos; Peltonen, Leena; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge, England. [Estrada, Karol; Amin, Najaf; Rivadeneira, Fernando; van Wingerden, Sophie; van Meurs, Joyce B. J.; Hofman, Albert; Uitterlinden, Andre; Witteman, Jacqueline C.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Goddard, Michael E.] Univ Melbourne, Parkville, Vic 3052, Australia. [Goddard, Michael E.] Dept Primary Ind, Melbourne, Vic, Australia. [Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Mangino, Massimo; Soranzo, Nicole; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Nyholt, Dale R.] Queensland Inst Med Res, Neurogenet Lab, Brisbane, Qld 4006, Australia. [Purcell, Shaun; McCarroll, Steven A.; Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Purcell, Shaun; McCarroll, Steven A.; Nemesh, James; Voight, Benjamin F.; Peltonen, Leena] MIT, Cambridge, MA 02139 USA. [Purcell, Shaun] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Smith, Albert Vernon; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert Vernon; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Visscher, Peter M.; Yang, Jian] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia. [McCarroll, Steven A.; Nemesh, James; Voight, Benjamin F.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [McCarroll, Steven A.; Voight, Benjamin F.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Absher, Devin] Hudson Alpha Inst Biotechnol, Huntsville, AL USA. [Coin, Lachlan; Sovio, Ulla; Elliott, Paul; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Glazer, Nicole L.] Univ Washington, Dept Med, Seattle, WA USA. [Glazer, Nicole L.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Hayward, Caroline; Vitart, Veronique; Wright, Alan F.] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Heard-Costa, Nancy L.; Atwood, Larry D.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Hottenga, Jouke-Jan; Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Univ Amsterdam, Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands. [Johansson, Asa; Igl, Wilmar; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden. [Johansson, Asa] Norwegian Univ Sci & Technol NTNU, Fac Med, Dept Canc Res & Mol Med, Trondheim, Norway. [Johnson, Toby] Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. [Johnson, Toby; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, Barts & London Genome Ctr, London, England. [Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Kaakinen, Marika; Herzig, Karl-Heinz; Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Knowles, Joshua W.; Quertermous, Thomas; Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Lamina, Claudia] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria. [McKnight, Barbara; Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Polasek, Ozren; Kolcic, Ivana; Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia. [Polasek, Ozren] Gen Info Ltd, Zagreb, Croatia. [Prokopenko, Inga; Rayner, Nigel W.; Robertson, Neil R.; Bennett, Amanda J.; Groves, Christopher J.; Hassanali, Neelam; Neville, Matt J.; Karpe, Fredrik; McCarthy, Mark I.; Lindgren, Cecilia M.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Ripatti, Samuli; Surakka, Ida; Silander, Kaisa; Kettunen, Johannes; Pellikka, Niina; Perola, Markus; Widen, Elisabeth; Kaprio, Jaakko; Peltonen, Leena] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Ripatti, Samuli; Surakka, Ida; Silander, Kaisa; Kettunen, Johannes; Pellikka, Niina; Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Publ Hlth Genom, Helsinki, Finland. [Sanna, Serena; Dei, Mariano; Usala, Gianluca; Uda, Manuela] Ist Neurogenet & Neurofarmacol CNR, Cagliari, Italy. [Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Chines, Peter S.; Narisu, Narisu; Bonnycastle, Lori L.; Erdos, Michael R.; Morken, Mario A.; Swift, Amy J.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. [Fisher, Eva; Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany. [Kulzer, Jennifer R.; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sandholt, Camilla; Gjesing, Anette P.; Hansen, Torben; Pedersen, Oluf] Hagedorn Res Inst, Gentofte, Denmark. [Stark, Klaus] Univ Regensburg, Med Ctr, Clin & Policlin Internal Med 2, Regensburg, Germany. [Timpson, Nicholas John; Day, Ian N. M.; Smith, George Davey; Lawlor, Debbie A.] MRC Ctr Causal Anal Translat Epidemiol, Dept Social Med, Bristol, Avon, England. [Watanabe, Richard M.; Buchanan, Thomas A.; Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Phys & Biophys, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Cooper, Matthew N.; Lawrence, Robert W.; Hui, Jennie; Palmer, Lyle J.] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Crawley, WA, Australia. [Jansson, John-Olov] Univ Gothenburg, Inst Neurosci & Physiol, Dept Physiol, Sahlgrenska Acad, Gothenburg, Sweden. [Vandenput, Liesbeth; Ohlsson, Claes] Univ Gothenburg, Inst Med, Dept Internal Med, Sahlgrenska Acad, Gothenburg, Sweden. [Almgren, Peter; Groop, Leif C.] Lund Univ, Ctr Diabet, Dept Clin Sci, Malmo, Sweden. [Biffar, Reiner] Zentrum Zahn Mund & Kieferheilkunde, Greifswald, Germany. [Bornstein, Stefan R.; Graessler, Juergen; Ludwig, Barbara] Univ Dresden, Dept Med 3, Dresden, Germany. [Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Div Endocrinol, Los Angeles, CA 90033 USA. [Campbell, Harry; Wild, Sarah H.; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Doerr, Marcus] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany. [Elliott, Paul] Ctr Environm & Hlth, MRC Hlth Protect Agcy HPA, London, England. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.; Kajantie, Eero; Peltonen, Leena] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.; Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland. [Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. [Fu, Mao; Shuldiner, Alan R.; O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland. [Havulinna, Aki S.; Jousilahti, Pekka; Koskinen, Seppo; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland. [Herzig, Karl-Heinz] Univ Oulu, Dept Physiol, Inst Biomed, Oulu, Finland. [Herzig, Karl-Heinz] Kuopio Univ Hosp, Dept Psychiat, SF-70210 Kuopio, Finland. [Hicks, Andrew A.; Pichler, Irene; Volpato, Claudia B.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy. [Hui, Jennie; Beilby, John P.] QEII Med Ctr, Dept Mol Genet, PathW Lab Western Australia, Nedlands, WA, Australia. [Hicks, Andrew A.; Pichler, Irene; Volpato, Claudia B.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany. [Hui, Jennie; Beilby, John P.; James, Alan L.; Palmer, Lyle J.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn Inc, Nedlands, WA, Australia. [Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Populat Studies Unit, Turku, Finland. [Kajantie, Eero] Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland. [Kinnunen, Leena; Tuomilehto, Jaakko; Valle, Timo T.] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany. [Kroemer, Heyo K.] Ernst Moritz Arndt Univ Greifswald, Inst Pharmakol, Greifswald, Germany. [Krzelj, Vjekoslav; Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kvaloy, Kirsti; Platou, Carl G. P.; Hveem, Kristian; Midthjell, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway. [Laitinen, Jaana] Finnish Inst Occupat Hlth, Oulu, Finland. [Lantieri, Olivier] Inst Interreg Sante IRSA, La Riche, France. [Lathrop, G. Mark] Ctr Natl Genotypage, Paris, France. [Lokki, Marja-Liisa] Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland. [Luben, Robert N.; Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [McArdle, Wendy L.] Univ Bristol, Dept Social Med, Avon Longitudinal Study Parents & Children ALSPAC, Bristol, Avon, England. [McCarthy, Anne] Res Board, Div Hlth, Dublin, Ireland. [Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Parker, Alex N.] Amgen Inc, Cambridge, MA USA. [Peden, John F.] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Pietilainen, Kirsi H.; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Finnish Twin Cohort Study, Helsinki, Finland. [Pietilainen, Kirsi H.; Rissanen, Aila] Univ Helsinki, Cent Hosp, Dept Psychiat, Obes Res Unit, Helsinki, Finland. [Platou, Carl G. P.] Levanger Hosp, Nord Trondelag Hlth Trust, Dept Med, Levanger, Norway. [Ridderstrale, Martin] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England. [Samani, Nilesh J.] Glenfield Hosp, Biomed Res Unit Cardiovasc Dis, Leicester Natl Inst Hlth Res NIHR, Leicester, Leics, England. [Saramies, Jouko] S Karelia Cent Hosp, Lappeenranta, Finland. [Sinisalo, Juha; Nieminen, Markku S.] Univ Helsinki, Cent Hosp, Cardiovasc Lab, Div Cardiol, Helsinki, Finland. [Smit, Jan H.; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Inst Extramuraal Geneeskundig Onderzoek EMGO Inst, Amsterdam, Netherlands. [Strawbridge, Rona J.; Hamsten, Anders] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden. [van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Ctr Med Syst Biol, Leiden, Netherlands. [Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem & Lab Med, Greifswald, Germany. [Witte, Daniel R.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Zitting, Paavo] Lapland Cent Hosp, Dept Physiatr, Rovaniemi, Finland. [Beilby, John P.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [James, Alan L.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Kahonen, Mika; Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Dept Med, Leipzig, Germany. [Stumvoll, Michael] Univ Leipzig, Leipziger Interdisziplinarer Forschungskomplex Mo, Leipzig, Germany. [Toenjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, Leipzig, Germany. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Balkau, Beverley] INSERM Ctr Rech Epidemiol & Sante Populat CESP, F-01018 Villejuif, France. [Balkau, Beverley] Univ Paris Sud 11, Unit Mixte Rech Sante UMRS 1018, Villejuif, France. [Ben-Shlomo, Yoav] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Ebrahim, Shah] London Sch Hyg & Trop Med, London WC1, England. [Ebrahim, Shah] S Asia Network Chron Dis, New Delhi, India. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark. [Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany. [Hengstenberg, Christian] Univ Regensburg, Med Ctr, Innere Med 2, Regensburg, Germany. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Jorgensen, Torben] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Karpe, Fredrik; McCarthy, Mark I.] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LJ, England. [Marre, Michel] Bichat Claude Bernard Univ Hosp, AP HP, Dept Endocrinol Diabetol & Nutr, Paris, France. [Marre, Michel] Univ Henri Poincar Nancy 1, Cardiovasc Genet Res Unit, Nancy, France. [Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany. [Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Pedersen, Oluf] Univ Copenhagen, Inst Biomed Sci, Copenhagen, Denmark. [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Schwarz, Peter E. H.] Univ Dresden, Dept Med Prevent & Care Diabet 3, Dresden, Germany. [Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. [Tuomi, Tiinamaija] Univ Helsinki, Res Program Mol Med, Helsinki, Finland. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Arnold, Alice M.] Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA. [Beckmann, Jacques S.] Univ Lausanne Hosp, CHUV, Serv Med Genet, Lausanne, Switzerland. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Iribarren, Carlos] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol & Med, Baltimore, MD USA. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth, Helsinki, Finland. [Kaprio, Jaakko] Unit Child & Adolescent Mental Hlth, Substance Abuse Serv, Helsinki, Finland. [Oostra, Ben] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, Lubeck, Germany. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Shuldiner, Alan R.] Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA. [Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Voelzke, Henry] Inst Community Med, Greifswald, Germany. [Vollenweider, Peter] Univ Lausanne Hosp, CHUV, Dept Internal Med, Lausanne, Switzerland. [Borecki, Ingrid B.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Haritunians, Talin] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA. [Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [North, Kari E.] Univ N Carolina, Sch Publ Hlth, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA. [Strachan, David P.] Univ London, Div Community Hlth Sci, London, England. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland. [Barroso, Ines] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge, England. [Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham Heart Study, Framingham, MA USA. RP Lindgren, CM (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM iris.heid@klinik.uni-regensburg.de; mark.mccarthy@drl.ox.ac.uk; foxca@nhlbi.nih.gov; mohlke@med.unc.edu; celi@well.ox.ac.uk RI Lango Allen, Hana/G-9026-2012; Lamina, Claudia/F-7608-2010; Rudan, Igor/I-1467-2012; Deloukas, Panos/B-2922-2013; Grallert, Harald/B-3424-2013; Nyholt, Dale/C-8384-2013; Colaus, PsyColaus/K-6607-2013; Zondervan, Krina/M-1143-2013; Pramstaller, Peter/C-2357-2008; Cooper, Matthew/J-4420-2014; Strawbridge, Rona/H-5422-2012; Johansson, Asa/G-5270-2011; Palmer, Lyle/K-3196-2014; Schwarz, Peter/B-5127-2013; Davey Smith, George/A-7407-2013; Krzelj, Vjekoslav/D-6491-2017; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Polasek, Ozren/B-6002-2011; Beckmann, Jacques S /A-9772-2008; Voight, Benjamin/F-1775-2011; Aspelund, Thor/F-4826-2011; Stark, Klaus/D-3813-2009; Aspelund, Thor/C-5983-2008; kinnunen, leena/B-7059-2012; Li, Shengxu/D-8915-2012; Spector, Tim/F-6533-2012; Ridderstrale, Martin/F-7678-2012; Kilpelainen, Tuomas/F-8569-2012; Kaplan, Robert/A-2526-2011; Abecasis, Goncalo/B-7840-2010; Witte, Daniel/C-1722-2008; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Yang, Jian/A-5852-2010; Smith, Albert/K-5150-2015; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Coin, Lachlan/A-9001-2014; OI Lango Allen, Hana/0000-0002-7803-8688; Rudan, Igor/0000-0001-6993-6884; Deloukas, Panos/0000-0001-9251-070X; Zondervan, Krina/0000-0002-0275-9905; Cooper, Matthew/0000-0003-1139-3682; Strawbridge, Rona/0000-0001-8506-3585; Johansson, Asa/0000-0002-2915-4498; Palmer, Lyle/0000-0002-1628-3055; Kaakinen, Marika/0000-0002-9228-0462; Pichler, Irene/0000-0001-8251-0757; Heard-Costa, Nancy/0000-0001-9730-0306; Goddard, Michael/0000-0001-9917-7946; Magi, Reedik/0000-0002-2964-6011; Marre, Michel/0000-0002-3071-1837; sanna, serena/0000-0002-3768-1749; Johnson, Toby/0000-0002-5998-3270; Cupples, L. Adrienne/0000-0003-0273-7965; Schwarz, Peter/0000-0001-6317-7880; Davey Smith, George/0000-0002-1407-8314; Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Soranzo, Nicole/0000-0003-1095-3852; Zgaga, Lina/0000-0003-4089-9703; Bouatia-Naji, Nabila/0000-0001-5424-2134; Willer, Cristen/0000-0001-5645-4966; Polasek, Ozren/0000-0002-5765-1862; Beckmann, Jacques S /0000-0002-9741-1900; Stark, Klaus/0000-0002-7832-1942; Aspelund, Thor/0000-0002-7998-5433; kinnunen, leena/0000-0001-8739-4812; Witte, Daniel/0000-0002-0769-2922; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457; Yang, Jian/0000-0003-2001-2474; Smith, Albert/0000-0003-1942-5845; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Coin, Lachlan/0000-0002-4300-455X; Abecasis, Goncalo/0000-0003-1509-1825; Esko, Tonu/0000-0003-1982-6569; Peters, Marjolein/0000-0003-3167-9063; Luben, Robert/0000-0002-5088-6343; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Tuomi, Tiinamaija/0000-0002-8306-6202; Vandenput, Liesbeth/0000-0002-1712-6131; Karpe, Fredrik/0000-0002-2751-1770; Jorgensen, Torben/0000-0001-9453-2830; Visscher, Peter/0000-0002-2143-8760; Eriksson, Johan/0000-0002-2516-2060; Kaprio, Jaakko/0000-0002-3716-2455; Timpson, Nicholas/0000-0002-7141-9189; Lawlor, Debbie A/0000-0002-6793-2262; Bergmann, Sven/0000-0002-6785-9034; Sinisalo, Juha/0000-0002-0169-5137; de Geus, Eco/0000-0001-6022-2666 FU Academy of Finland [104781, 120315, 129269, 117797, 121584, 126925, 129418, 129568, 77299, 124243, 129680, 129494, 10404, 213506, 114382, 126775, 127437, 129255, 129306, 130326, 209072, 210595, 213225, 216374]; ADA [N02-HL-6-4278]; ALF/LUA Gothenburg; Althingi (the Icelandic Parliament); Amgen; Augustinus Foundation; Becket Foundation; Biocentrum Helsinki; Biomedicum Helsinki Foundation; Boston Obesity Nutrition Research Center [DK46200]; British Diabetes Association [1192]; British Diabetic Association Research; British Heart Foundation [97020, PG/02/128]; Busselton Population Medical Research Foundation; Cambridge NIHR Comprehensive Biomedical Research Centre; CamStrad; Chief Scientist Office of the Scottish Government; Contrat Plan Etat Region de France; Danish Centre for Health Technology Assessment; Danish Diabetes Association; Danish Ministry of Internal Affairs and Health; Danish Heart Foundation; Danish Pharmaceutical Association; Danish Research Council; DIAB Core (German Network of Diabetes); Diabetes UK; Donald W. Reynolds Foundation; Dresden University of Technology; Med Drive; EMGO+ institute; Emil and Vera Cornell Foundation; Erasmus Medical Center and Erasmus University, Rotterdam, The Netherlands; Estonian Government [SF0180142s08]; European Commission [2004310, 212111, 205419, 245536, DG XII, HEALTH-F4-2007-201413, FP7/2007-2013, QLG1-CT-2000-01643, QLG2-CT-2002-01254, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHG-CT-2004-512066, LSHM-CT-2007-037273, EU/WLRT-2001-01254, LSHG-CT-2004-518153, SOC 95201408 05F02]; Federal Ministry of Education and Research, Germany [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 01 EA 9401]; Federal State of Mecklenburg-West Pomerania; Finnish Diabetes Research Foundation; Finnish Diabetes Research Society; Finnish Foundation for Pediatric Research; Finnish Foundation of Cardiovascular Research; Finnish Medical Society; Finska Lakaresallskapet; Finnish Ministry of Education; Folkhalsan Research Foundation; Fond Europeen pour le Developpement Regional; Fondation LeDucq; Foundation for Life and Health in Finland; GEN-AU 'GOLD' from Austria; German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; German National Genome Research Net NGFN2 and NGFNplus [01GS0823, FKZ 01GS0823]; German Research Council [KFO-152]; GlaxoSmithKline; Goteborg Medical Society; Gyllenberg Foundation; Health Care Center in Vasa; Healthway, Western Australia; Helmholtz Center Munich; Helsinki University Central Hospital; Hjartavernd (the Icelandic Heart Association); Ib Henriksen Foundation; IZKF [B27]; Jalmari and Rauha Ahokas Foundation; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International (JDRF); Karolinska Institute and the Stockholm County Council [560183]; Knut and Alice Wallenberg Foundation; Lundbeck Foundation Centre of Applied Medical Genomics; Knut Krohn, Microarray Core Facility of the Interdisciplinary Centre for Clinical Research (IZKF), University of Leipzig, Germany; MC Health; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania, Germany; South Tyrol Ministry of Health; Ministry of Science, Education and Sport of the Republic of Croatia [216-1080315-0302]; Medical Research Council UK [G0000649, G0601261, G9521010D, G0000934, G0500539, G0600331]; Montreal Heart Institute Foundation; MRC Centre for Obesity-Related Metabolic Disease; Municipal Health Care Center and Hospital in Jakobstad; Municipality of Rotterdam; Narpes Health Care Foundation; National Health and Medical Research Council of Australia and the Great Wine Estates Auctions; Netherlands Centre for Medical Systems Biology [SPI 56-464-1419]; Netherlands Ministry for Health; Welfare and Sports; Netherlands Ministry of Education, Culture and Science; Netherlands Genomics Initiative; Netherlands Consortium [050-060-810]; Netherlands Organisation of Scientific Research Netherlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) Investments [175.010.2005.011, 911-03-012, 904-61-090, 904-61-193, 480-04-004, 400-05-717]; National Institute on Aging; US National Institutes of Health [CA047988, CA65725, CA87969, CA49449, CA67262, CA50385, DK075787, DK062370, DK58845, DK072193, K23-DK080145, K99HL094535, N01-HC85079, N01-HC85086, N01-HG-65403, N01-AG-12100, N01-HC-25195, N01-HC35129, N01-HC15103, N01-HC55222, N01-HC75150, N01-HC45133, N01-HC55015, N01-HC55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-AG-1-2109, HL71981, HG005581, HG002651, HL084729, HL043851, HHSN268200625226C, MH084698, P30-DK072488, R01 HL087652, R01-HL087641, R01-HL59367, R01-HL086694, R01-HL087647, R01-HL087679, R01-HL087700, R01-AG031890, R01-HL088119, R01-DK068336, R01-DK075681, R01-DK-073490, R01-DK075787, R01-MH63706, U01-HL72515, U01-GM074518, U01-HL084756, U01-HG004399, UO1-CA098233, UL1-RR025005, U01-HG004402, U01-DK062418, U01 HL080295, T32-HG00040, 263-MA-410953, 1RL1-MH083268-01, 1Z01-HG000024]; National Institute for Health Research (NIHR); Neuroscience Campus Amsterdam; Novo Nordisk Foundation; Novo Nordisk Inc.; Ollqvist Foundation; Paavo Nurmi Foundation; Paivikki and Sakari Sohlberg Foundation; Pew Scholarship for the Biomedical Sciences; Perklen Foundation; Petrus and Augusta Hedlunds Foundation; Research Institute for Diseases in the Elderly [014-93-015]; Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR) [A305:188]; Siemens Healthcare, Erlangen, Germany; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance Institution of Finland; Social Ministry of the Federal State of Mecklenburg-West Pomerania, Germany; South Tyrolean Sparkasse Foundation; State of Bavaria, Germany; Support for Science Funding programme; Swedish Cultural Foundation in Finland; Swedish Foundation for Strategic Research (SSF); Swedish Medical Research Council [8691, K2007-66X-20270-01-3, K2010-54X-09894-19-3]; Swedish Society of Medicine; Swiss National Science Foundation [33CSCO-122661]; Royal Society; Royal Swedish Academy of Science; Torsten and Ragnar Soderberg's Foundation; Turku University Hospitals; UK Department of Health Policy Research Programme; University and Research of the Autonomous Province of Bolzano; University Hospital Medical; University Hospital Oulu, Biocenter, University of Oulu, Finland [75617]; Vastra Gotaland Foundation; Wellcome Trust [077016/Z/05/Z, 068545/Z/02, 072960, 076113, 083270, 085301, 079557, 081682, 075491, 076113/B/04/Z, 091746/Z/10/Z, 079895, WT086596/Z/08/Z]; Western Australian Genetic Epidemiology Resource; Western Australian DNA Bank (both National Health and Medical Research Council of Australia Enabling Facilities); Yrjo Jahnsson Foundation; AstraZeneca AB; Lundberg Foundation; Swedish Heart-Lung Foundation; Research Foundation of Copenhagen County; Health care center in Nerpes; Health care center in Korsholm FX Funding for this study was provided by the Academy of Finland (grants 104781, 120315, 129269, 117797, 121584, 126925, 129418, 129568, 77299, 124243, 213506, 129680, 129494, 10404, 213506, 129680, 114382, 126775, 127437, 129255, 129306, 130326, 209072, 210595, 213225 and 216374); an ADA Mentor-Based Postdoctoral Fellowship grant; Affymetrix, Inc., for genotyping services (N02-HL-6-4278); ALF/LUA Gothenburg; Althingi (the Icelandic Parliament); Amgen; AstraZeneca AB; Augustinus Foundation; Becket Foundation; Biocentrum Helsinki; Biomedicum Helsinki Foundation; Boston Obesity Nutrition Research Center (DK46200); British Diabetes Association (1192); British Diabetic Association Research; British Heart Foundation (97020, PG/02/128); Busselton Population Medical Research Foundation; Cambridge NIHR Comprehensive Biomedical Research Centre; CamStrad; Chief Scientist Office of the Scottish Government; Contrat Plan Etat Region de France; Danish Centre for Health Technology Assessment; Danish Diabetes Association; Danish Ministry of Internal Affairs and Health; Danish Heart Foundation; Danish Pharmaceutical Association; Danish Research Council; DIAB Core (German Network of Diabetes); Diabetes UK; Donald W.; Reynolds Foundation; Dresden University of Technology Funding Grant, Med Drive; EMGO+ institute; Emil and Vera Cornell Foundation; Erasmus Medical Center and Erasmus University, Rotterdam, The Netherlands; Estonian Government SF0180142s08; European Commission (2004310, 212111, 205419, 245536, DG XII, HEALTH-F4-2007-201413, FP7/2007-2013, QLG1-CT-2000-01643, QLG2-CT-2002-01254, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHG-CT-2004-512066, LSHM-CT-2007-037273, EU/WLRT-2001-01254, LSHG-CT-2004-518153, SOC 95201408 05F02, Marie Curie Intra-European Fellowship); Federal Ministry of Education and Research, Germany (01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 01 EA 9401); Federal State of Mecklenburg-West Pomerania; Finnish Diabetes Research Foundation; Finnish Diabetes Research Society; Finnish Foundation for Pediatric Research; Finnish Foundation of Cardiovascular Research; Finnish Medical Society; Finska Lakaresallskapet; Finnish Ministry of Education; Folkhalsan Research Foundation; Fond Europeen pour le Developpement Regional; Fondation LeDucq; Foundation for Life and Health in Finland; GEN-AU 'GOLD' from Austria; German Bundesministerium fuer Forschung und Technology (# 01 AK 803 A-H, # 01 IG 07015 G); German National Genome Research Net NGFN2 and NGFNplus (01GS0823, FKZ 01GS0823); German Research Council (KFO-152); GlaxoSmithKline; Goteborg Medical Society; Gyllenberg Foundation; Health Care Centers in Vasa, Narpes and Korsholm; Healthway, Western Australia; Helmholtz Center Munich; Helsinki University Central Hospital; Hjartavernd ( the Icelandic Heart Association); Ib Henriksen Foundation; IZKF (B27); Jalmari and Rauha Ahokas Foundation; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International (JDRF); Karolinska Institute and the Stockholm County Council (560183); Knut and Alice Wallenberg Foundation; Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care; Knut Krohn, Microarray Core Facility of the Interdisciplinary Centre for Clinical Research (IZKF), University of Leipzig, Germany; Lundberg Foundation; MC Health; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania, Germany; South Tyrol Ministry of Health; Ministry of Science, Education and Sport of the Republic of Croatia (216-1080315-0302); Medical Research Council UK (G0000649, G0601261, 9521010D, G0000934, G0500539, G0600331, PrevMetSyn); Montreal Heart Institute Foundation; MRC Centre for Obesity-Related Metabolic Disease; Municipal Health Care Center and Hospital in Jakobstad; Municipality of Rotterdam; Narpes Health Care Foundation; National Health and Medical Research Council of Australia and the Great Wine Estates Auctions; Netherlands Centre for Medical Systems Biology (SPI 56-464-1419); Netherlands Ministry for Health, Welfare and Sports; Netherlands Ministry of Education, Culture and Science; Netherlands Genomics Initiative; Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Organisation of Scientific Research Netherlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) Investments (175.010.2005.; 011, 911-03-012, 904-61-090, 904-61-193, 480-04-004, 400-05-717); National Institute on Aging Intramural Research Program; US National Institutes of Health (CA047988, CA65725, CA87969, CA49449, CA67262, CA50385, DK075787, DK062370, DK58845, DK072193, K23-DK080145, K99HL094535, N01-HC85079 through N01-HC85086, N01-HG-65403, N01-AG-12100, N01-HC-25195, N01-HC35129, N01-HC15103, N01-HC55222, N01-HC75150, N01-HC45133, N01-HC55015, N01-HC55016, N01-HC-55018, N01-HC-5019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-AG-1-2109, HL71981, HG005581, HG002651, HL084729, HL043851, HHSN268200625226C, K23-DK080145, MH084698, P30-DK072488, R01-DK075787, R01 HL087652, R01-HL087641, R01-HL59367, R01-HL086694, R01-HL087647, R01-HL087679, R01-HL087700, R01-AG031890, R01-HL088119, R01-DK068336, R01-DK075681, R01-DK-073490, R01-DK075787, R01-MH63706, U01-HL72515, U01-GM074518, U01-HL084756, U01-HG004399, UO1-CA098233, UL1-RR025005, UL1-RR025005, U01-HG004402, U01-DK062418, U01 HL080295, T32-HG00040, 263-MA-410953, 1RL1-MH083268-01, intramural project 1Z01-HG000024); National Institute for Health Research (NIHR); Neuroscience Campus Amsterdam; Novo Nordisk Foundation; Novo Nordisk Inc., Research Foundation of Copenhagen County; Ollqvist Foundation; Paavo Nurmi Foundation; Paivikki and Sakari Sohlberg Foundation; Pew Scholarship for the Biomedical Sciences; Perklen Foundation; Petrus and Augusta Hedlunds Foundation; Research Institute for Diseases in the Elderly (014-93-015, RIDE, RIDE2); Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR, A305:188); Siemens Healthcare, Erlangen, Germany; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance Institution of Finland; Social Ministry of the Federal State of Mecklenburg-West Pomerania, Germany; South Tyrolean Sparkasse Foundation; State of Bavaria, Germany; Support for Science Funding programme; Swedish Cultural Foundation in Finland; Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish Medical Research Council (8691, K2007-66X-20270-01-3, K2010-54X-09894-19-3); Swedish Society of Medicine; Swiss National Science Foundation (33CSCO-122661); the Royal Society; the Royal Swedish Academy of Science; Torsten and Ragnar Soderberg's Foundation; Turku University Hospitals; UK Department of Health Policy Research Programme; University and Research of the Autonomous Province of Bolzano; University Hospital Medical funds to Tampere; University Hospital Oulu, Biocenter, University of Oulu, Finland (75617); Vastra Gotaland Foundation; Wellcome Trust (077016/Z/05/Z, 068545/Z/02, 072960, 076113, 083270, 085301, 079557, 081682, 075491, 076113/B/04/Z, 091746/Z/10/Z, 079895, WT086596/Z/08/Z, WT Research Career Development Fellowship; WT Career Development Award); Western Australian Genetic Epidemiology Resource and the Western Australian DNA Bank (both National Health and Medical Research Council of Australia Enabling Facilities); Yrjo Jahnsson Foundation. NR 61 TC 408 Z9 419 U1 8 U2 78 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2010 VL 42 IS 11 BP 949 EP U160 DI 10.1038/ng.685 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 671VW UT WOS:000283540500011 PM 20935629 ER PT J AU Yu, TW Mochida, GH Tischfield, DJ Sgaier, SK Flores-Sarnat, L Sergi, CM Topcu, M McDonald, MT Barry, BJ Felie, JM Sunu, C Dobyns, WB Folkerth, RD Barkovich, AJ Walsh, CA AF Yu, Timothy W. Mochida, Ganeshwaran H. Tischfield, David J. Sgaier, Sema K. Flores-Sarnat, Laura Sergi, Consolato M. Topcu, Meral McDonald, Marie T. Barry, Brenda J. Felie, Jillian M. Sunu, Christine Dobyns, William B. Folkerth, Rebecca D. Barkovich, A. James Walsh, Christopher A. TI Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture SO NATURE GENETICS LA English DT Article ID MITOTIC SPINDLE; CHROMOSOME SEGREGATION; BRAIN SIZE; ASPM GENE; CDK5RAP2; LOCUS; LIS1 AB Genes associated with human microcephaly, a condition characterized by a small brain, include critical regulators of proliferation, cell fate and DNA repair. We describe a syndrome of congenital microcephaly and diverse defects in cerebral cortical architecture. Genome-wide linkage analysis in two families identified a 7.5-Mb locus on chromosome 19q13.12 containing 148 genes. Targeted high throughput sequence analysis of linked genes in each family yielded > 4,000 DNA variants and implicated a single gene, WDR62, as harboring potentially deleterious changes. We subsequently identified additional WDR62 mutations in four other families. Magnetic resonance imaging and postmortem brain analysis supports important roles for WDR62 in the proliferation and migration of neuronal precursors. WDR62 is a WD40 repeat-containing protein expressed in neuronal precursors as well as in postmitotic neurons in the developing brain and localizes to the spindle poles of dividing cells. The diverse phenotypes of WDR62 suggest it has central roles in many aspects of cerebral cortical development. C1 [Yu, Timothy W.; Mochida, Ganeshwaran H.; Tischfield, David J.; Sgaier, Sema K.; Barry, Brenda J.; Felie, Jillian M.; Sunu, Christine; Walsh, Christopher A.] Childrens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Yu, Timothy W.; Mochida, Ganeshwaran H.; Tischfield, David J.; Sgaier, Sema K.; Barry, Brenda J.; Felie, Jillian M.; Sunu, Christine; Walsh, Christopher A.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Yu, Timothy W.; Mochida, Ganeshwaran H.; Tischfield, David J.; Sgaier, Sema K.; Barry, Brenda J.; Felie, Jillian M.; Sunu, Christine; Walsh, Christopher A.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Yu, Timothy W.; Mochida, Ganeshwaran H.; Tischfield, David J.; Sgaier, Sema K.; Barry, Brenda J.; Felie, Jillian M.; Sunu, Christine; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Yu, Timothy W.; Mochida, Ganeshwaran H.; Walsh, Christopher A.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Yu, Timothy W.; Mochida, Ganeshwaran H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Div Child Neurol, Boston, MA 02115 USA. [Sgaier, Sema K.] Bill & Melinda Gates Fdn, New Delhi, India. [Flores-Sarnat, Laura] Univ Calgary, Fac Med, Alberta Childrens Hosp, Dept Clin Neurosci,Div Paediat Neurol, Calgary, AB, Canada. [Sergi, Consolato M.] Univ Alberta Hosp, Dept Lab Med & Pathol, Walter Mackenzie Hlth Sci Ctr, Edmonton, AB T6G 2R7, Canada. [Sergi, Consolato M.] Med Univ Innsbruck, Inst Pathol, Innsbruck, Austria. [Topcu, Meral] Hacettepe Univ, Fac Med, Ihsan Dogramaci Childrens Hosp, Dept Pediat,Sect Pediat Neurol, TR-06100 Ankara, Turkey. [McDonald, Marie T.] Duke Univ, Dept Pediat, Div Med Genet, Durham, NC 27706 USA. [Dobyns, William B.] Univ Washington, Div Genet, Seattle, WA 98195 USA. [Folkerth, Rebecca D.] Brigham & Womens Hosp, Div Neuropathol, Boston, MA 02115 USA. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Walsh, CA (reprint author), Childrens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. EM christopher.walsh@childrens.harvard.edu OI Sergi, Consolato/0000-0002-2779-7879; Yu, Timothy/0000-0003-2988-7701; Dobyns, William/0000-0002-7681-2844 FU US National Institutes of Health (NIH) [P30-HD-18655]; Fidelity Foundation; NIH [T32 NS007484-08, HHSN268200782096C, N01-HG-65403]; Harvard- Massachusetts Institute of Technology Health Sciences and Technology; Beth Israel Deaconess Medical Center; Pfizer, Inc; Merck and Company, Inc.; Nancy Lurie Marks; National Alliance for Research on Schizophrenia and Depression (NARSAD); National Institute of Neurological Disorders and Stroke (NINDS) [RO1 NSR01-35129]; Fogarty International Center [R21 NS061772]; Dubai Harvard Foundation for Medical Research; Manton Center for Orphan Disease Research; Intellectual and Developmental Disabilities Research Centers [CHB DDRC, P30 HD18655]; National Human Genome Research Institute (NHGRI) FX We thank the many families and researchers who participated in this study; B. Chang and A. Poduri for expert review of MRI imaging findings; S. Lizarraga for contributions to genetic mapping; M. Aita and the In situ Hybridization Core Facility, University of North Carolina Neuroscience Center, Chapel Hill, North Carolina for performing in situ hybridizations; C. G. Woods for helpful discussions and for sharing data before publication; A. von Deimling from the Institut fur Pathologie, Heidelberg, for sectioning of the LIS-2601 brain; A. Nicholas and M. Khurshid for advice regarding immunohistochemistry; A. Hill and L. Bu at the MRDDRC (Mental Retardation Developmental Disability Research Center) Imaging Core for assistance with confocal microscopy (US National Institutes of Health (NIH) grant P30-HD-18655 and Fidelity Foundation); and R. Sean Hill for assistance with linkage analysis and helpful discussions. We are indebted to the members of the Microcephaly Collaborative (Supplementary Table 1) for contributing to the cohort from which these families were drawn. T.W.Y. was supported by a NIH T32 grant (T32 NS007484-08), the Clinical Investigator Training Program (CITP) at Harvard- Massachusetts Institute of Technology Health Sciences and Technology and Beth Israel Deaconess Medical Center in collaboration with Pfizer, Inc. and Merck and Company, Inc., and the Nancy Lurie Marks Junior Faculty MeRIT Fellowship. G.H.M. was supported by the Young Investigator Award of National Alliance for Research on Schizophrenia and Depression (NARSAD) as a NARSAD Lieber Investigator. Research was supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS) (RO1 NSR01-35129) and the Fogarty International Center (R21 NS061772) to C. A. W., the Dubai Harvard Foundation for Medical Research and the Manton Center for Orphan Disease Research. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is funded through a federal contract from the NIH to Johns Hopkins University, contract number HHSN268200782096C and NIH N01-HG-65403. Genotyping at Children's Hospital Boston was supported by the Intellectual and Developmental Disabilities Research Centers (CHB DDRC, P30 HD18655). Genotyping at the Broad Institute was supported by National Human Genome Research Institute (NHGRI). C.A.W. is an investigator of the Howard Hughes Medical Institute. NR 30 TC 118 Z9 123 U1 4 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2010 VL 42 IS 11 BP 1015 EP U145 DI 10.1038/ng.683 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 671VW UT WOS:000283540500022 PM 20890278 ER PT J AU Yan, N Regalado-Magdos, AD Stiggelbout, B Lee-Kirsch, MA Lieberman, J AF Yan, Nan Regalado-Magdos, Ashton D. Stiggelbout, Bart Lee-Kirsch, Min Ae Lieberman, Judy TI The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1 SO NATURE IMMUNOLOGY LA English DT Article ID ASSEMBLY PROTEIN SET; I INTERFERON; ADAPTER PROTEIN; GRANZYME-A; AUTOIMMUNE-DISEASE; HIV-1 INFECTION; KAPPA-B; DNA; COMPLEX; ALPHA AB Viral infection triggers innate immune sensors to produce type I interferon. However, infection of T cells and macrophages with human immunodeficiency virus (HIV) does not trip those alarms. How HIV avoids activating nucleic acid sensors is unknown. Here we found that the cytosolic exonuclease TREX1 suppressed interferon triggered by HIV. In Trex1(-/-) mouse cells and human CD4(+) T cells and macrophages in which TREX1 was inhibited by RNA-mediated interference, cytosolic HIV DNA accumulated and HIV infection induced type I interferon that inhibited HIV replication and spreading. TREX1 bound to cytosolic HIV DNA and digested excess HIV DNA that would otherwise activate interferon expression via a pathway dependent on the kinase TBK1, the adaptor STING and the transcription factor IRF3. HIV-stimulated interferon production in cells deficient in TREX1 did not involve known nucleic acid sensors. C1 [Yan, Nan; Regalado-Magdos, Ashton D.; Stiggelbout, Bart; Lieberman, Judy] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Yan, Nan; Regalado-Magdos, Ashton D.; Stiggelbout, Bart; Lieberman, Judy] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yan, Nan; Regalado-Magdos, Ashton D.; Stiggelbout, Bart; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Lee-Kirsch, Min Ae] Tech Univ Dresden, Childrens Hosp, Dresden, Germany. RP Lieberman, J (reprint author), Childrens Hosp, Immune Dis Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 FU US National Institutes of Health [AI45587, T32 HL066987]; Harvard Center for AIDS Research; Harvard Summer Honors Undergraduate Research Program; Deutsche Forschungsgemeinschaft [Le 1074/3-1] FX We thank D. Stetson (University of Washington) for wild-type, Trex1-/- and Trex1-/-Irf3-/- primary MEFs, under agreement with D. Barnes and T. Lindahl (Cancer Research UK); J. Jung (University of Southern California) for RIG-I-deficient (Ddx58-/-) MEFs; S. Harvey and F. Perrino (Wake Forest University) for wild-type and Trex1-/- transformed MEFs; A. Engelman (Dana-Farber Cancer Institute) for the HIV-luciferase plasmid (pNL4-3/Env-); D. Gabuzda (Dana-Farber Cancer Institute) for the HIV-GFP plasmid (pNL4-3/Env-); T. Fujita (Kyoto University) for antiserum to mouse IRF3; S. Nagata (Kyoto University) for the hemagglutinin-tagged MAVS plasmid; K. Fitzgerald (University of Massachusetts) for siRNA and inhibitors of RNA polymerase III; J. Hiscott (McGill University) for IFNB-luciferase plasmid; L. Gehrke (Harvard Medical School) for CMV-renilla luciferase plasmid; and members of the Lieberman lab for discussions. Supported by the US National Institutes of Health (AI45587 to J.L., and T32 HL066987 to N.Y.), the Harvard Center for AIDS Research (N.Y.), Harvard Summer Honors Undergraduate Research Program (A.D.R.-M.) and Deutsche Forschungsgemeinschaft (Le 1074/3-1 to M.A.L.-K.). NR 50 TC 251 Z9 255 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2010 VL 11 IS 11 BP 1005 EP U53 DI 10.1038/ni.1941 PG 11 WC Immunology SC Immunology GA 666PI UT WOS:000283127800010 PM 20871604 ER PT J AU Call, ME Wucherpfennig, KW Chou, JJ AF Call, Matthew E. Wucherpfennig, Kai W. Chou, James J. TI The structural basis for intramembrane assembly of an activating immunoreceptor complex SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; IMMUNE RECEPTORS; HIV-1 PROTEASE; CHEMICAL-SHIFT; GXXXG MOTIF; PROTEINS; MEMBRANE; ASSOCIATION; EXPRESSION; RESIDUES AB Many receptors that activate cells of the immune system are multisubunit membrane protein complexes in which ligand recognition and signaling functions are contributed by separate protein modules. Receptors and signaling subunits assemble through contacts among basic and acidic residues in their transmembrane domains to form the functional complexes. Here we report the nuclear magnetic resonance (NMR) structure of the membrane-embedded, heterotrimeric assembly formed by association of the DAP12 signaling module with the natural killer (NK) cell-activating receptor NKG2C. The main intramembrane contact site is formed by a complex electrostatic network involving five hydrophilic transmembrane residues. Functional mutagenesis demonstrated that similar polar intramembrane motifs are also important for assembly of the NK cell-activating NKG2D-DAP10 complex and the T cell antigen receptor (TCR)-invariant signaling protein CD3 complex. This structural motif therefore lies at the core of the molecular organization of many activating immunoreceptors. C1 [Call, Matthew E.; Chou, James J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA USA. RP Chou, JJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu; chou@cmcd.hms.harvard.edu RI Chou, James/N-9840-2013; OI Call, Matthew/0000-0001-5846-6469 FU Helen Hay Whitney Foundation; Charles A. King Trust; US National Institutes of Health [R01AI054520, R01HL084329, EB002026] FX We thank S.C. Blacklow (Harvard Medical School) for pMM-LR6 vector; M.J. Call and members of the Chou lab for reading the manuscript and discussions; and J. Pyrdol for assistance with initial construct design and expression trials. Supported by the Helen Hay Whitney Foundation (M.E.C.), the Charles A. King Trust (M.E.C.) and the US National Institutes of Health (R01AI054520 to K.W.W., R01HL084329 to J.J.C. and EB002026 to the Center for Magnetic Resonance at the Massachusetts Institute of Technology, where NMR data were collected). NR 35 TC 94 Z9 98 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2010 VL 11 IS 11 BP 1023 EP U73 DI 10.1038/ni.1943 PG 9 WC Immunology SC Immunology GA 666PI UT WOS:000283127800012 PM 20890284 ER PT J AU Lo, EH AF Lo, Eng H. TI Degeneration and repair in central nervous system disease SO NATURE MEDICINE LA English DT Article ID CEREBRAL ENDOTHELIAL-CELLS; AMYLOID-BETA PEPTIDES; ALZHEIMERS-DISEASE; DOPAMINERGIC-NEURONS; NEUROVASCULAR NICHE; PHYSIOLOGICAL ROLES; PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; MUTANT HUNTINGTIN; BLOOD-VESSELS AB Divergent disease triggers in neurodegeneration may induce convergent endogenous pathways in neuronal, glial and vascular elements as the central nervous system (CNS) attempts to compensate, remodel and recover. Dissecting these multicellular mechanisms and the integrative responses in cerebral blood flow and metabolism may allow us to understand the balance between injury and repair, validate new targets and define therapeutic time windows for neurodegeneration. C1 [Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lo, Eng H.] Harvard Univ, Sch Med, Boston, MA USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. EM lo@helix.mgh.harvard.edu FU NINDS NIH HHS [P01 NS055104] NR 65 TC 48 Z9 48 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2010 VL 16 IS 11 BP 1205 EP 1209 DI 10.1038/nm.2226 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 675TV UT WOS:000283860100026 PM 21052074 ER PT J AU Rouaux, C Arlotta, P AF Rouaux, Caroline Arlotta, Paola TI Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo SO NATURE NEUROSCIENCE LA English DT Article ID SUBTYPE-SPECIFIC GENES; PROJECTION NEURONS; CEREBRAL-CORTEX; SPECIFICATION; FOREBRAIN; PATHWAYS AB In the developing cerebral cortex, cell-extrinsic and cell-intrinsic signals govern the establishment of neuron subtype-specific identity. Here we show that, within the niche of the striatum, the expression of a single transcription factor, Fezf2, is sufficient to generate corticofugal neurons from progenitors fated to become medium spiny neurons. This demonstrates that a specific population of cortical projection neurons can be directed to differentiate outside of the cortex by cell-autonomous signaling. C1 [Rouaux, Caroline; Arlotta, Paola] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02115 USA. [Rouaux, Caroline; Arlotta, Paola] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Arlotta, Paola] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Arlotta, Paola] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Arlotta, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02115 USA. EM paola_arlotta@hms.harvard.edu FU US National Institutes of Health [NS062849]; Spastic Paraplegia Foundation; Harvard Stem Cell Institute; Harvard NeuroDiscovery Center; ALS Association FX We thank J. Macklis (Harvard University) for reagents and advice; E. Abdel-Azim, G. Srubek-Tomassy, F. Zhang and S. Lodato for their comments; R. Hevner, (University of Washington), C. Lois (M. I. T.), K. Campbell (University of Cincinnati) and Q. Ma (Harvard Medical School) for generous sharing of antibodies, probes and expression vectors; and A. Meleski, A. Merlino and Z. Trayes-Gibson for technical support. This work was partially supported by grants to P. A. from the US National Institutes of Health (NS062849), the Spastic Paraplegia Foundation, the Harvard Stem Cell Institute and the Harvard NeuroDiscovery Center to P. A.; C. R. was partially supported by a Milton-Safenowitz postdoctoral fellowship from the ALS Association. NR 14 TC 57 Z9 58 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2010 VL 13 IS 11 BP 1345 EP 1347 DI 10.1038/nn.2658 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 673KI UT WOS:000283658200012 PM 20953195 ER PT J AU Bosco, DA Morfini, G Karabacak, NM Song, YY Gros-Louis, F Pasinelli, P Goolsby, H Fontaine, BA Lemay, N McKenna-Yasek, D Frosch, MP Agar, JN Julien, JP Brady, ST Brown, RH AF Bosco, Daryl A. Morfini, Gerardo Karabacak, N. Murat Song, Yuyu Gros-Louis, Francois Pasinelli, Piera Goolsby, Holly Fontaine, Benjamin A. Lemay, Nathan McKenna-Yasek, Diane Frosch, Matthew P. Agar, Jeffrey N. Julien, Jean-Pierre Brady, Scott T. Brown, Robert H., Jr. TI Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS SO NATURE NEUROSCIENCE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; FAST AXONAL-TRANSPORT; HUMAN SUPEROXIDE-DISMUTASE; MOTOR-NEURON DISEASE; NEURODEGENERATIVE DISEASES; PROTEIN AGGREGATION; EXTRUDED AXOPLASM; SPINAL-CORDS; LINKED SOD1; MOUSE MODEL AB Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wildtype SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal transport in a manner similar to that of FALS-linked mutant SOD1. Our findings suggest that wild-type SOD1 can be pathogenic in SALS and identify an SOD1-dependent pathogenic mechanism common to FALS and SALS. C1 [Bosco, Daryl A.; Fontaine, Benjamin A.; Lemay, Nathan; McKenna-Yasek, Diane; Brown, Robert H., Jr.] Univ Massachusetts Med Ctr, Dept Neurol, Worcester, MA USA. [Morfini, Gerardo; Song, Yuyu; Brady, Scott T.] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL USA. [Karabacak, N. Murat; Agar, Jeffrey N.] Brandeis Univ, Dept Chem, Waltham, MA 02254 USA. [Gros-Louis, Francois; Julien, Jean-Pierre] Univ Laval, Dept Psychiat & Neurosci, Res Ctr CHUQ, Quebec City, PQ, Canada. [Pasinelli, Piera] Thomas Jefferson Univ, Farber Inst Neurosci, Weinberg Unit ALS Res, Philadelphia, PA 19107 USA. [Goolsby, Holly; Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Morfini, Gerardo; Song, Yuyu; Brady, Scott T.] Marine Biol Lab, Woods Hole, MA 02543 USA. RP Bosco, DA (reprint author), Univ Massachusetts Med Ctr, Dept Neurol, Worcester, MA USA. EM daryl.bosco@umassmed.edu; robert.brown@umassmed.edu RI Karabacak, N Murat/D-7227-2013; OI Karabacak, N Murat/0000-0003-2761-5593; Song, Yuyu/0000-0002-9196-1610 FU ALS Therapy Alliance-CVS Pharmacy; Marine Biological Laboratory; ALS Association; US National Institutes of Health; National Institute on Neurological Disorders and Stroke [RO1NS067206-01, U01NS05225-03, R01NS050557-05, 1RC1NS068391-01, 1RC2NS070342-01]; Canadian Institutes of Health Research; Angel Fund; ALS FX We are grateful to J. Landers and P. Sapp for DNA sequencing analysis of the SALS cases employed in this study, L. Hayward, A. Tiwari and R.-J. Chain for help with expression of recombinant wild-type SOD1, S. Berth, A. Leitman and M. Saparauskaite for help with axoplasm vesicle transport assays, A. Kaminska and L. Molla for help with biochemical experiments in squid axoplasm, M. Prudencio and D. Borchelt for cell lysates containing SOD1 G93 mutants, C. Vanderburg, E. Tamrazian, A. Bialik and the Diabetes and Endocrinology Research Center (University of Massachusetts Medical Center) for assistance with immunohistochemistry, K. Fitch and the Massachusetts Alzheimer Disease Research Center (P50AG005134) for assistance with human tissue samples, J. Zitzewitz for C6A/C111S-SOD1 protein, A. Weiss for assistance with mice, K. Green at the University of Massachusetts Medical Center Proteomics and Mass Spectrometry Facility for analysis of C6A/C111S-SOD1, and G. Petsko for insightful dialogue and support. We acknowledge financial support from the ALS Therapy Alliance-CVS Pharmacy (D. A. B. and G. M.), 2007/2008 Marine Biological Laboratory research fellowships (G. M.), the ALS Association (D. A. B., R. H. B. Jr, G. M. and S. T. B.), the US National Institutes of Health (D. A. B. (National Institute on Neurological Disorders and Stroke, RO1NS067206-01), R. H. B. Jr (National Institute on Neurological Disorders and Stroke, U01NS05225-03, R01NS050557-05, 1RC1NS068391-01 and 1RC2NS070342-01), S. T. B. and J.N.A.), Canadian Institutes of Health Research (J.-P.J.), the Angel Fund (R. H. B. Jr) and Project ALS (R.H.B.Jr). NR 50 TC 272 Z9 276 U1 4 U2 34 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2010 VL 13 IS 11 BP 1396 EP U133 DI 10.1038/nn.2660 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 673KI UT WOS:000283658200021 PM 20953194 ER PT J AU Jain, RK Stylianopoulos, T AF Jain, Rakesh K. Stylianopoulos, Triantafyllos TI Delivering nanomedicine to solid tumors SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; PEGYLATED-LIPOSOMAL DOXORUBICIN; METASTATIC BREAST-CANCER; RANDOMIZED PHASE-III; INTERSTITIAL FLUID PRESSURE; IN-VIVO; VASCULAR-PERMEABILITY; DRUG-DELIVERY; BLOOD-FLOW; EXTRACELLULAR-MATRIX AB Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. While the enhanced permeability and retention effect has served as a key rationale for using nanoparticles to treat solid tumors, it does not enable uniform delivery of these particles to all regions of tumors in sufficient quantities. This heterogeneous distribution of therapeutics is a result of physiological barriers presented by the abnormal tumor vasculature and interstitial matrix. These barriers are likely to be responsible for the modest survival benefit offered by many FDA-approved nanotherapeutics and must be overcome for the promise of nanomedicine in patients to be realized. Here, we review these barriers to the delivery of cancer therapeutics and summarize strategies that have been developed to overcome these barriers. Finally, we discuss design considerations for optimizing the delivery of nanoparticles to tumors. C1 [Jain, Rakesh K.; Stylianopoulos, Triantafyllos] Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. [Jain, Rakesh K.; Stylianopoulos, Triantafyllos] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU National institutes of Health [PO1-CA80124, RO1-CA126642, RO1-CA115767, RO1-CA85140, T32-CA73479]; Federal Share income Grant; DoD [BC095991]; Susan G. Komen Breast Cancer Foundation [KG091281] FX We thank L. Munn, Y. Boucher, S. Goel, V. Chahaun and B. Diop-Frimpong for their helpful comments on the manuscript. This work was supported by the National institutes of Health (PO1-CA80124, RO1-CA126642, RO1-CA115767, RO1-CA85140, T32-CA73479), a Federal Share income Grant, and a DoD Breast Cancer Research innovator award (BC095991). T. Stylianopoulos was supported by a post-doctoral research fellowship from the Susan G. Komen Breast Cancer Foundation (KG091281). NR 154 TC 945 Z9 960 U1 74 U2 612 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD NOV PY 2010 VL 7 IS 11 BP 653 EP 664 DI 10.1038/nrclinonc.2010.139 PG 12 WC Oncology SC Oncology GA 672HK UT WOS:000283573400010 PM 20838415 ER PT J AU Weisbord, SD Palevsky, PM AF Weisbord, Steven D. Palevsky, Paul M. TI ACUTE KIDNEY INJURY Kidney injury after contrast media: marker or mediator? SO NATURE REVIEWS NEPHROLOGY LA English DT News Item ID ACUTE-RENAL-FAILURE; CORONARY INTERVENTION; INDUCED NEPHROPATHY; CYSTATIN-C; MORTALITY C1 [Weisbord, Steven D.; Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. RP Weisbord, SD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Univ Dr, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 10 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD NOV PY 2010 VL 6 IS 11 BP 634 EP 636 DI 10.1038/nrneph.2010.129 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 671VQ UT WOS:000283539900002 PM 20981117 ER PT J AU Arnett, KL Hass, M McArthur, DG Ilagan, MXG Aster, JC Kopan, R Blacklow, SC AF Arnett, Kelly L. Hass, Matthew McArthur, Debbie G. Ilagan, Ma Xenia G. Aster, Jon C. Kopan, Raphael Blacklow, Stephen C. TI Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CRYSTAL-STRUCTURE; CSL; DNA; ACTIVATION; DROSOPHILA; MASTERMIND; PRESENILIN; LIGAND; GENES AB Ligand-induced proteolysis of Notch produces an intracellular effector domain that transduces essential signals by regulating the transcription of target genes. This function relies on the formation of transcriptional activation complexes that include intracellular Notch, a Mastermind co-activator and the transcription factor CSL bound to cognate DNA. These complexes form higher-order assemblies on paired, head-to-head CSL recognition sites. Here we report the X-ray structure of a dimeric human Notch1 transcription complex loaded on the paired site from the human HES1 promoter. The small interface between the Notch ankyrin domains could accommodate DNA bending and untwisting to allow a range of spacer lengths between the two sites. Cooperative dimerization occurred on the human and mouse Hes5 promoters at a sequence that diverged from the CSL-binding consensus at one of the sites. These studies reveal how promoter organizational features control cooperativity and, thus, the responsiveness of different promoters to Notch signaling. C1 [Arnett, Kelly L.; McArthur, Debbie G.; Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Arnett, Kelly L.; McArthur, Debbie G.; Aster, Jon C.; Blacklow, Stephen C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hass, Matthew; Ilagan, Ma Xenia G.; Kopan, Raphael] Washington Univ, Dept Dev Biol, St Louis, MO USA. RP Blacklow, SC (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM sblacklow@partners.org RI Arnett, Kelly/C-4816-2012; OI Arnett, Kelly/0000-0001-5117-3647; Ilagan, Ma Xenia/0000-0003-2888-4859 FU US National Institutes of Health [CA-092433, CA-119070] FX We thank W. Pear for discussions and review of the manuscript. Supported in part by US National Institutes of Health grants CA-092433 (to S.C.B.) and CA-119070 (to S.C.B. and J.C.A.). K.L.A. is a Postdoctoral Fellow of the American Cancer Society. NR 36 TC 52 Z9 53 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD NOV PY 2010 VL 17 IS 11 BP 1312 EP U269 DI 10.1038/nsmb.1938 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 674TQ UT WOS:000283773200007 PM 20972443 ER PT J AU Batchelor, T Mulholland, P Neyns, B Nabors, LB Campone, M Wick, A Mason, W Mikkelsen, T Phuphanich, S Ashby, LS DeGroot, JF Gattamancni, HR Cher, LM Rosenthal, MA Payer, F Xu, J Liu, Q van den Bent, M AF Batchelor, Tracy Mulholland, Paul Neyns, Bart Nabors, L. B. Campone, Mario Wick, Antje Mason, Warren Mikkelsen, Tom Phuphanich, Surasek Ashby, Lynn S. DeGroot, John F. Gattamancni, H. R. Cher, Lawrence M. Rosenthal, Mark A. Payer, Franz Xu, John Liu, Qi van den Bent, Martin TI THE EFFICACY OF CEDIRANIB AS MONOTHERAPY AND IN COMBINATION WITH LOMUSTINE COMPARED TO LOMUSTINE ALONE IN PATIENTS WITH RECURRENT GLIOBLASTOMA: A PHASE III RANDOMIZED STUDY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations National Clinical and Research Conference CY DEC 09-12, 2010 CL Hollywood, FL C1 [Batchelor, Tracy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mulholland, Paul] UCL, London, England. [Neyns, Bart] Univ Ziekenhuis Brussel, Brussels, Belgium. [Nabors, L. B.] Univ Alabama, Neurooncol Program, Birmingham, AL USA. [Campone, Mario] Ctr Rene Gauducheau, St Herblain, France. [Wick, Antje] Univ Heidelberg, D-6900 Heidelberg, Germany. [Mason, Warren] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Phuphanich, Surasek] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Ashby, Lynn S.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [DeGroot, John F.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gattamancni, H. R.] Christie Fdn Trust Hosp, Manchester, Lancs, England. [Rosenthal, Mark A.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Payer, Franz] Med Univ Graz, Graz, Austria. [Xu, John; Liu, Qi] AstraZeneca, Wilmington, NC USA. [van den Bent, Martin] Erasmus Univ Hosp, Daniel den Hoed Canc Ctr, Rotterdam, Netherlands. NR 0 TC 8 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2010 VL 12 SU 4 BP 75 EP 75 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 691LX UT WOS:000285082400320 ER PT J AU Eichler, AF Kahle, KT Wang, DL Joshi, VA Willers, H Engelman, JA Lynch, TJ Sequist, LV AF Eichler, April F. Kahle, Kristopher T. Wang, Daphne L. Joshi, Victoria A. Willers, Henning Engelman, Jeffrey A. Lynch, Thomas J. Sequist, Lecia V. TI EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer SO NEURO-ONCOLOGY LA English DT Article DE brain metastasis; EGFR (epidermal growth factor receptor); nonsmall cell lung cancer ID GROWTH-FACTOR-RECEPTOR; PROSPECTIVE PHASE-II; GENE-MUTATIONS; RADIATION-THERAPY; KINASE DOMAIN; GEFITINIB; ERLOTINIB; NSCLC; TRIAL; SENSITIVITY AB A small subset of patients with nonsmall cell lung cancer (NSCLC) harbors mutations in the epidermal growth factor receptor (EGFR) that predict unique sensitivity to EGFR tyrosine kinase inhibitors (TKIs). The characteristics and behavior of brain metastases (BMs) in these patients have not been well described. The longitudinal records of all NSCLC patients who underwent EGFR mutation screening at our center from August 2004 to November 2008 were reviewed for eligibility, and 93 patients were identified who developed BM during the course of their disease. Survival was estimated using the Kaplan-Meier method and the log-rank test. Multivariable predictors were assessed via the Cox proportional hazards model. Among the 93 patients with BM, 41 (44%) had mutations in EGFR, including 13 exon 19 deletions and 12 L858R mutations. Eighty-three percent of patients with BM were treated initially with whole brain radiation, either alone (53%) or in combination with craniotomy for neurosurgical resection (22%) or stereotactic radiosurgery (8%). Median survival from the time of BM was 11.7 months and was longer for patients with an EGFR mutation (14.5 vs 7.6 months, P = .09). On multivariable analysis, EGFR mutation (HR: 0.50, 95% CI: 0.30-0.82), age (HR: 1.03, 95% CI: 1.00-1.05), and active extracranial disease (HR: 3.30, 95% CI: 1.70-6.41) were independently associated with survival. In NSCLC patients with BM, EGFR mutation status is associated with improved survival, independent of age, functional status, extracranial disease status, and number of BMs. C1 [Eichler, April F.; Wang, Daphne L.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Eichler, April F.; Wang, Daphne L.; Joshi, Victoria A.; Willers, Henning; Engelman, Jeffrey A.; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Joshi, Victoria A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Lynch, Thomas J.] Yale Univ, Sch Med, Yale Comprehens Canc Ctr, New Haven, CT USA. [Eichler, April F.; Kahle, Kristopher T.; Joshi, Victoria A.; Engelman, Jeffrey A.; Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. RP Eichler, AF (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM aeichler@partners.org NR 38 TC 109 Z9 120 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2010 VL 12 IS 11 BP 1193 EP 1199 DI 10.1093/neuonc/noq076 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 673EU UT WOS:000283642700013 PM 20627894 ER PT J AU Rytkonen, KM Wigren, HK Kostin, A Porkka-Heiskanen, T Kalinchuk, AV AF Rytkonen, Kirsi-Marja Wigren, Henna-Kaisa Kostin, Andrey Porkka-Heiskanen, Tarja Kalinchuk, Anna V. TI Nitric oxide mediated recovery sleep is attenuated with aging SO NEUROBIOLOGY OF AGING LA English DT Article DE Sleep; Sleep homeostasis; Sleep deprivation; Aging; Nitric oxide; Inducible nitric oxide ID AGE-RELATED-CHANGES; ADENOSINE A(1) RECEPTOR; BASAL FOREBRAIN; HOMEOSTATIC REGULATION; RAT-BRAIN; EXTRACELLULAR ADENOSINE; PROLONGED WAKEFULNESS; CEREBRAL-CORTEX; IN-VITRO; OLD RATS AB Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in the cholinergic basal forebrain (BF) during sleep deprivation (SD) is implicated in adenosine (AD) release and induction of recovery sleep. Aging is associated with impairments in sleep homeostasis, such as decrease in non-rapid eye movement sleep (NREM) intensity following SD. We hypothesized that age related changes in sleep homeostasis may be induced by impairments in NO-mediated sleep induction. To test this hypothesis we measured levels of NO and iNOS in the BF during SD as well as recovery sleep after SD and NO-donor (DETA/NO) infusion into the BF in three age groups of rats (young, 4 months; middle-aged, 14 months; old, 24 months). We found that in aged rats as compared to young (1) recovery NREM sleep intensity was significantly decreased, (2) neither iNOS nor NO increased in the BF during SD, and (3) DETA/NO infusion failed to induce sleep. Together, these results support our hypothesis that aging impairs the mechanism through which NO in the BF induces sleep. (C) 2008 Elsevier Inc. All rights reserved. C1 [Kalinchuk, Anna V.] Harvard Univ, Sch Med, Dept Psychiat, W Roxbury, MA 02132 USA. [Kalinchuk, Anna V.] VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. [Rytkonen, Kirsi-Marja; Wigren, Henna-Kaisa; Kostin, Andrey; Porkka-Heiskanen, Tarja] Univ Helsinki, Inst Biomed, Helsinki, Finland. RP Kalinchuk, AV (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM anna_kalinchuk@hms.harvard.edu OI Stenberg, Tarja/0000-0003-1843-7625 FU Academy of Finland; Finnish Graduate School of Neuroscience; NIH; EU [LSHM-CT-2005-518189, MCRT-CT-2004-512362] FX This work was supported by the Academy of Finland; the Finnish Graduate School of Neuroscience; NIH; and EU grants LSHM-CT-2005-518189 and MCRT-CT-2004-512362. We would like to thank our technicians Ernst Mecke, Pirjo Saarelainen and Sari Levo-Siitari for their excellent assistance, and our students for their help in data acquisition and scoring. NR 49 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV PY 2010 VL 31 IS 11 BP 2011 EP 2019 DI 10.1016/j.neurobiolaging.2008.10.006 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 663SC UT WOS:000282907800017 PM 19058880 ER PT J AU Curcio-Morelli, C Charles, FA Micsenyi, MC Cao, Y Venugopal, B Browning, MF Dobrenis, K Cotman, SL Walkley, SU Slaugenhaupt, SA AF Curcio-Morelli, Cyntia Charles, Florie A. Micsenyi, Matthew C. Cao, Yi Venugopal, Bhuvarahamurthy Browning, Marsha F. Dobrenis, Kostantin Cotman, Susan L. Walkley, Steven U. Slaugenhaupt, Susan A. TI Macroautophagy is defective in mucolipin-1-deficient mouse neurons SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Mucolipidosis type IV; Lysosomal disease; Mucolipin 1; Macroautophagy; Neuronal storage ID MUCOLIPIDOSIS TYPE-IV; CHAPERONE-MEDIATED AUTOPHAGY; UBIQUITIN-PROTEASOME SYSTEM; LYSOSOMAL STORAGE DISORDERS; MONITORING AUTOPHAGY; MEMBRANE-PROTEIN; ALPHA-SYNUCLEIN; TRAFFICKING; DISEASE; MODEL AB Mucolipidosis type IV is a neurodegenerative lysosomal disease clinically characterized by psychomotor retardation, visual impairment, and achlorhydria. In this study we report the development of a neuronal cell model generated from cerebrum of Mcoln1(-/-) embryos. Prior functional characterization of MLIV cells has been limited to fibroblast cultures gleaned from patients. The current availability of the mucolipin-1 knockout mouse model Mcoln1(-/-) allows the study of mucolipin-1-defective neurons, which is important since the disease is characterized by severe neurological impairment. Electron microscopy studies reveal significant membranous intracytoplasmic storage bodies, which correlate with the storage morphology observed in cerebral cortex of Mcoln1(-/-) P7 pups and E17 embryos. The Mcoln1(-/-) neuronal cultures show an increase in size of LysoTracker and Lamp1 positive vesicles. Using this neuronal model system, we show that macroautophagy is defective in mucolipin-1-deficient neurons and that LC3-II levels are significantly elevated. Treatment with rapamycin plus protease inhibitors did not increase levels of LC3-II in Mcoln1(-/-) neuronal cultures, indicating that the lack of mucolipin-1 affects LC3-II clearance. P62/SQSTM1 and ubiquitin levels were also increased in Mcoln1(-/-) neuronal cultures, suggesting an accumulation of protein aggregates and a defect in macroautophagy which could help explain the neurodegeneration observed in MLIV. This study describes, for the first time, a defect in macroautophagy in mucolipin-1-deficient neurons, which corroborates recent findings in MLIV fibroblasts and provides new insight into the neuronal pathogenesis of this disease. (c) 2010 Elsevier Inc. All rights reserved. C1 [Curcio-Morelli, Cyntia; Charles, Florie A.; Cao, Yi; Venugopal, Bhuvarahamurthy; Browning, Marsha F.; Cotman, Susan L.; Slaugenhaupt, Susan A.] Harvard Univ, Ctr Human Genet Res, Massachusetts Gen Hosp, Sch Med,Richard B Simches Res Ctr,CPZN 5254, Boston, MA 02114 USA. [Micsenyi, Matthew C.; Dobrenis, Kostantin; Walkley, Steven U.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Rose F Kennedy Ctr Res Mental Retardat & Human De, Bronx, NY 10467 USA. RP Slaugenhaupt, SA (reprint author), Harvard Univ, Ctr Human Genet Res, Massachusetts Gen Hosp, Sch Med,Richard B Simches Res Ctr,CPZN 5254, 185 Cambridge St, Boston, MA 02114 USA. EM slaugenhaupt@chgr.mgh.harvard.edu FU National Institutes of Health [NS39995, HD045561, GM007748-31]; Mucolipidosis Type 4 Foundation; Executive Committee on Research, Massachusetts General Hospital FX This work was supported by the National Institutes of Health [NS39995 to S.A.S., HD045561 to S.U.W., GM007748-31 to C.C.-M.]; the Mucolipidosis Type 4 Foundation [C.C.-M.]; and by the Executive Committee on Research, Massachusetts General Hospital [C.C.-M.].; We thank Mr. Martin K. Selig at the Massachusetts General Hospital, Department of Pathology, for the outstanding electron microscopy work. NR 60 TC 30 Z9 31 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2010 VL 40 IS 2 BP 370 EP 377 DI 10.1016/j.nbd.2010.06.010 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 652WJ UT WOS:000282041300002 PM 20600908 ER PT J AU Chen, JJ Pike, GB AF Chen, J. Jean Pike, G. Bruce TI MRI measurement of the BOLD-specific flow-volume relationship during hypercapnia and hypocapnia in humans SO NEUROIMAGE LA English DT Article DE Cerebral blood flow; Venous cerebral blood volume; Grubb's relationship; Hypercapnia; Hypocapnia; Respiract; Sequential gas delivery; FMRI; VERVE; arterial spin labeling; QUIPSS II ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; SOMATOSENSORY STIMULATION; OXIDATIVE-METABOLISM; OXYGEN-CONSUMPTION; FUNCTIONAL MRI; DEPENDENT BOLD; RAT-BRAIN; BASE-LINE; SPIN-ECHO AB It is widely assumed in fMRI that the relationship between cerebral blood flow (CBF) and volume (CBV) changes observed during end-tidal CO(2) (PETCO(2)) perturbations is equivalent to that elicited by neuronal activation. This assumption has been validated in PET studies insofar as relating total flow to total CBV changes, but remains unconfirmed for venous CBV changes, which pertains to the primary vascular compartment modulating the BOLD signal In this study, we measured CBF and venous CBV changes in healthy subjects in response to graded hypercapnia and hypocapnia, induced using computerized end-tidal CO(2) targeting, with a Delta PETCO(2) range of between -6 and +9 mm Hg Hypercapnia was found to elicit robust increases in CBF and venous CBV, while hypocapnia produced decreases in both We used steady-state flow and volume changes to estimate the power-law relationship for cortical and subcortical brain regions, and did not observe significant difference between the two. The combined fit resulted in a power coefficient of 0 18 +/- 0 02. substantially lower than Grubb's coefficient of 0.38, but comparable to previous observations during neuronal activation. These results confirm that the BOLD-specific flow-volume relationship during CO(2) challenges is similar to that characterizing neuronal activation (C) 2010 Elsevier Inc All rights reserved C1 [Chen, J. Jean; Pike, G. Bruce] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. RP Chen, JJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RI Chen, J. Jean/A-2846-2013; Pike, Bruce/K-5562-2014 OI Chen, J. Jean/0000-0001-5469-7542; Pike, Bruce/0000-0001-8924-683X FU Natural Sciences and Engineering Research Council of Canada; Canadian Institutes of Health Research; Fonds de la Recherche en Sante du Quebec FX This research was supported by the Natural Sciences and Engineering Research Council of Canada (to J. J. C.) and the Canadian Institutes of Health Research and Fonds de la Recherche en Sante du Quebec (to G. B P.). The authors also thank Clarisse I. Mark for helpful discussions and assistance in experimental design. NR 69 TC 47 Z9 47 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 1 PY 2010 VL 53 IS 2 BP 383 EP 391 DI 10.1016/j.neuroimage.2010.07.003 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 648JB UT WOS:000281688000003 PM 20624474 ER PT J AU Hyde, DC Boas, DA Blair, C Carey, S AF Hyde, Daniel C. Boas, David A. Blair, Clancy Carey, Susan TI Near-infrared spectroscopy shows right parietal specialization for number in pre-verbal infants SO NEUROIMAGE LA English DT Article DE Near-infrared spectroscopy; Infancy; Cognitive development; Number; Brain specialization ID INTRAPARIETAL SULCUS; MAGNITUDE; CORTEX; DISCRIMINATION; NUMEROSITIES; ACTIVATION; ADULTS; SENSE; LOBE AB Bilateral regions of the intraparietal sulcus (IPS) appear to be functionally selective for both rudimentary non-symbolic number tasks and higher-level symbolic number tasks in adults and older children Furthermore, the ability to mentally represent and manipulate approximate non-symbolic numerical quantities is present from birth These factors leave open whether the specialization of the IPS develops through the experience of learning a symbolic number system or if It is already specialized before symbolic number acquisition. Using the newly emerging technique of functional Near-Infrared Spectroscopy (fNIRS) over left and right parietal and lateral occipital regions, we show right parietal specialization for number in 6-month-old infants. These results extend the current literature in three ways by successfully implementing an event-related NIRS design in infants, by showing parietal specialization for number occurs before the acquisition of language, and by suggesting number representation may be initially right lateralized and becomes bilateral through experience (C) 2010 Elsevier Inc All rights reserved C1 [Hyde, Daniel C.] Harvard Univ, Dept Psychol, Lab Dev Studies, WJH 1118, Cambridge, MA 02138 USA. [Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Boas, David A.] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA USA. [Blair, Clancy] NYU, Dept Appl Psychol, New York, NY USA. RP Hyde, DC (reprint author), Harvard Univ, Dept Psychol, Lab Dev Studies, WJH 1118, 33 Kirkland St, Cambridge, MA 02138 USA. FU National Institutes of Health [P41 RR14075, RO1 HD038338-09]; Consortium for Children, Families and Youth at Penn State FX We thank Christina Zhou, Ben Smith, Clark Van Den Berghe, and Andy Peters for help with data collection. We are grateful to Juliette Selb, Rickson Mesquita, and Tina Lloyd for their technical assistance. Finally, we thank Elizabeth Spelke and the Lab for Developmental Studies for their feedback and support during this project. This project was generous funded by the National Institutes of Health (P41 RR14075 to author D.A.B & RO1 HD038338-09 to author S.C.) and the Consortium for Children, Families and Youth at Penn State (to author C B). NR 39 TC 47 Z9 48 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 1 PY 2010 VL 53 IS 2 BP 647 EP 652 DI 10.1016/j.neuroimage.2010.06.030 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 648JB UT WOS:000281688000029 PM 20561591 ER PT J AU McDonald, CR Thesen, T Carlson, C Blumberg, M Girard, HM Trongnetrpunya, A Sherfey, JS Devinsky, O Kuzniecky, R Dolye, WK Cash, SS Leonard, MK Hagler, DJ Dale, AM Halgren, E AF McDonald, Carrie R. Thesen, Thomas Carlson, Chad Blumberg, Mark Girard, Holly M. Trongnetrpunya, Amy Sherfey, Jason S. Devinsky, Orrin Kuzniecky, Rubin Dolye, Werner K. Cash, Sydney S. Leonard, Matthew K. Hagler, Donald J., Jr. Dale, Anders M. Halgren, Eric TI Multimodal imaging of repetition priming: Using fMRI, MEG, and intracranial EEG to reveal spatiotemporal profiles of word processing SO NEUROIMAGE LA English DT Article DE fMRI; Magnetoencepholography; Intracranial EEG; Memory; Language; Gamma ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; OCCIPITOTEMPORAL CORTEX; GAMMA-OSCILLATIONS; PREFRONTAL CORTEX; COORDINATE SYSTEM; BRAIN ACTIVITY; POTENTIALS; RETRIEVAL; MEMORY AB Repetition priming is a core feature of memory processing whose anatomical correlates remain poorly understood In this study, we use advanced multimodal imaging (functional magnetic resonance imaging (fMRI) and magnetoencephalography; MEG) to investigate the spatiotemporal profile of repetition priming. We use intracranial electroencephalography (iEEG) to validate our fMRI/MEG measurements. Twelve controls completed a semantic judgment task with fMRI and MEG that included words presented once (new, 'N') and words that repeated (old. 'O') Six patients with epilepsy completed the same task during iEEG recordings Blood-oxygen level dependent (BOLD) responses for N vs. I words were examined across the cortical surface and within regions of interest. MEG waveforms for N vs. O words were estimated using a noise-normalized minimum norm solution, and used to interpret the timecourse of fMRI Spatial concordance was observed between fMRI and MEG repetition effects from 350 to 450 ms within bilateral occipitotemporal and medial temporal, left prefrontal, and left posterior temporal cortex Additionally, MEG revealed widespread sources within left temporoparietal regions, whereas fMRI revealed bilateral reductions in occipitotemporal and left superior frontal, and increases in inferior parietal, precuneus, and dorsolateral prefrontal activity BOLD suppression in left posterior temporal, left inferior prefrontal, and right occipitotemporal cortex correlated with MEG repetition-related reductions IEEG responses from all three regions supported the timecourse of MEG and localization of fMRI. Furthermore, iEEG decreases to repeated words were associated with decreased gamma power in several regions, providing evidence that gamma oscillations are tightly coupled to cognitive phenomena and reflect regional activations seen in the BOLD signal (C) 2010 Elsevier Inc All rights reserved C1 [McDonald, Carrie R.] Multimodal Imaging Lab, La Jolla, CA 92037 USA. [McDonald, Carrie R.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [McDonald, Carrie R.; Thesen, Thomas; Girard, Holly M.; Sherfey, Jason S.; Cash, Sydney S.; Leonard, Matthew K.; Hagler, Donald J., Jr.; Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Multimodal Imaging Lab, San Diego, CA 92103 USA. [Thesen, Thomas; Carlson, Chad; Blumberg, Mark; Trongnetrpunya, Amy; Devinsky, Orrin; Kuzniecky, Rubin] NYU, Comprehens Epilepsy Ctr, Dept Neurol, New York, NY USA. [Dolye, Werner K.] NYU, Dept Neurosurg, New York, NY 10016 USA. [Cash, Sydney S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Hagler, Donald J., Jr.; Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Leonard, Matthew K.] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA. RP McDonald, CR (reprint author), Multimodal Imaging Lab, 8950 Villa La Jolla Dr,Suite C101, La Jolla, CA 92037 USA. RI Dale, Anders/A-5180-2010; Frank, David/E-8213-2012; OI Devinsky, Orrin/0000-0003-0044-4632; Blumberg, Mark/0000-0001-6969-2955 FU National Institutes of Health (NIH) [K23NS056091, NS18741] FX The work was supported by National Institutes of Health (NIH) Grant K23NS056091 (C.R.M) and NS18741 (E H) NR 48 TC 41 Z9 42 U1 2 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 1 PY 2010 VL 53 IS 2 BP 707 EP 717 DI 10.1016/j.neuroimage.2010.06.069 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 648JB UT WOS:000281688000035 PM 20620212 ER PT J AU Cho, TA Venna, N AF Cho, Tracey A. Venna, Nagagopal TI Management of Acute, Recurrent, and Chronic Meningitides in Adults SO NEUROLOGIC CLINICS LA English DT Article DE Meningitis; Bacterial; Viral; Aseptic; Chronic; Management ID CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID CYTOLOGY; HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL-PRACTICE GUIDELINES; INFECTIOUS-DISEASES-SOCIETY; C-REACTIVE PROTEIN; TUBERCULOUS MENINGITIS; BACTERIAL-MENINGITIS; LYME-DISEASE; PNEUMOCOCCAL MENINGITIS AB Meningitis (inflammation of the pia, arachnoid, and sometimes dura) has diverse causes and presentations. Although viruses are the most common cause of acute meningitis, bacterial meningitides are more severe and important to exclude because morbidity and mortality are high. Chronic meningitis has a broader range of causes, including atypical bacteria, fungi, and noninfectious causes. Presentation is more insidious but, if untreated, significant damage or death may ensue. Recurrent meningitis has many of the same causes as chronic meningitis, but manifestations occur in discrete episodes. Distinguishing between acute, chronic, and recurrent meningitis is essential for proper diagnostic testing and treatment approaches. C1 [Cho, Tracey A.; Venna, Nagagopal] Massachusetts Gen Hosp, Neurol Infect Dis Sect, Dept Neurol, Boston, MA 02114 USA. [Cho, Tracey A.; Venna, Nagagopal] Harvard Univ, Sch Med, Boston, MA USA. RP Cho, TA (reprint author), Massachusetts Gen Hosp, Neurol Infect Dis Sect, Dept Neurol, WACC 835,55 Fruit St, Boston, MA 02114 USA. EM tcho@partners.org NR 117 TC 4 Z9 5 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2010 VL 28 IS 4 BP 1061 EP + DI 10.1016/j.ncl.2010.03.023 PG 30 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 658YT UT WOS:000282532300015 PM 20816277 ER PT J AU Handforth, A Homanics, GE Covey, DF Krishnan, K Lee, JY Sakimura, K Martin, FC Quesada, A AF Handforth, Adrian Homanics, Gregg E. Covey, Douglas F. Krishnan, Kathiresan Lee, Jae Yeol Sakimura, Kenji Martin, Fredricka C. Quesada, Arnulfo TI T-type calcium channel antagonists suppress tremor in two mouse models of essential tremor SO NEUROPHARMACOLOGY LA English DT Article DE Essential tremor; Harmaline; Ethosuximide; Zonisamide; Calcium channel; Cerebellum; Inferior olive ID HARMALINE-INDUCED TREMOR; RAT SENSORY NEURONS; ABSENCE SEIZURES; GABA(A) RECEPTOR; CEREBELLAR NEURONS; CA2+ CURRENT; ZONISAMIDE; ANTICONVULSANT; BLOCKADE; MICE AB Essential tremor is a common disorder that lacks molecular targets for therapeutic development. 1-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in essential tremor. We therefore tested whether compounds that antagonize T-type calcium channel currents suppress tremor in two mouse models that possess an essential tremor-like pharmacological response profile. Tremor was measured using digitized spectral motion power analysis with harmaline-induced tremor and in the GABA(A) receptor alpha 1 subunit-null model. Mice were given ethosuximide, zonisamide, the neuroactive steroid (3 beta,5 alpha,17 beta)-17-hydroxyestrane-3-carbonitrile (ECN), the 3,4-dihydroquinazoline derivative KYS05064, the mibefradil derivative NNC 55-0396, or vehicle. In non-sedating doses, each compound reduced harmaline-induced tremor by at least 50% (range of maximal suppression: 53-81%), and in the GABA(A) alpha 1-null model by at least 70% (range 70-93%). Because the 1-type calcium channel Cav3.1 is the dominant subtype expressed in the inferior olive, we assessed the tremor response of Cav3.1-deficient mice to harmaline, and found that null and heterozygote mice exhibit as much tremor as wild-type mice. In addition, ECN and NNC 55-0396 suppressed harmaline tremor as well in Cav3.1-null mice as in wild-type mice. The finding that five 1-type calcium antagonists suppress tremor in two animal tremor models suggests that 1-type calcium channels may be an appropriate target for essential tremor therapy development. It is uncertain whether medications developed to block only the Cav3.1 subtype would exhibit efficacy. Published by Elsevier Ltd. C1 [Handforth, Adrian] Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv W127, Los Angeles, CA 90073 USA. [Homanics, Gregg E.] Univ Pittsburgh, Dept Anesthesiol & Pharmacol, Pittsburgh, PA USA. [Homanics, Gregg E.] Univ Pittsburgh, Dept Biol Chem, Pittsburgh, PA USA. [Covey, Douglas F.; Krishnan, Kathiresan] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA. [Lee, Jae Yeol] Kyung Hee Univ, Coll Sci, Res Inst Basic Sci, Seoul, South Korea. [Lee, Jae Yeol] Kyung Hee Univ, Coll Sci, Dept Chem, Seoul, South Korea. [Sakimura, Kenji] Niigata Univ, Brain Res Inst, Dept Cellular Neurobiol, Niigata, Japan. [Martin, Fredricka C.; Quesada, Arnulfo] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Quesada, Arnulfo] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. RP Handforth, A (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv W127, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM charles.handforth@va.gov OI Homanics, Gregg/0000-0003-3641-8153; Lee, Jae Yeol/0000-0001-6622-6692 FU International Essential Tremor Foundation; Ralph M. Parsons Foundation; Veterans Affairs; NIH [AA10422, GM47969]; Korea Institute of Science and Technology FX Cav3.1 mice embryos were provided by the Riken BRC through the National Bio-Resource Project of the MEXT, Japan. This work was supported by the International Essential Tremor Foundation (AQ), The Ralph M. Parsons Foundation, Veterans Affairs (AH), NIH AA10422 (GEH), NIH GM47969 (DFC), and Vision 21 Program, Korea Institute of Science and Technology (JYL). We are grateful for the technical assistance of Brandon Bunker, Ana Artero, and Christopher Shin. NR 42 TC 21 Z9 21 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 2010 VL 59 IS 6 BP 380 EP 387 DI 10.1016/j.neuropharm.2010.05.012 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 670UR UT WOS:000283453300003 PM 20547167 ER PT J AU Janes, AC Pizzagalli, DA Richardt, S Frederick, BD Holmes, AJ Sousa, J Fava, M Evins, AE Kaufman, MJ AF Janes, Amy C. Pizzagalli, Diego A. Richardt, Sarah Frederick, Blaise de B. Holmes, Avram J. Sousa, Jessica Fava, Maurizio Evins, A. Eden Kaufman, Marc J. TI Neural Substrates of Attentional Bias for Smoking-Related Cues: An fMRI Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE fMRI; smoking; smoking emotional stroop; interference; interoception; memory ID MEDIAL TEMPORAL-LOBE; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; STROOP TASK; MEMORY; CESSATION; AMYGDALA; CORTEX; ACTIVATION; REACTIVITY AB Attentional bias for drug-related stimuli, as measured by emotional Stroop (ES) tasks, is predictive of treatment outcomes for tobacco smoking and other abused drugs. Characterizing relationships between smoking-related attentional bias and brain reactivity to smoking images may help in identifying neural substrates critical to relapse vulnerability. To this end, we investigated putative relationships between interference effects in an offline smoking ES task and functional MRI (fMRI) measures of brain reactivity to smoking vs neutral images in women smokers. Positive correlations were found between attentional bias and reactivity to smoking images in brain areas involved in emotion, memory, interoception, and visual processing, including the amygdala, hippocampus, parahippocampal gyrus, insula, and occipital cortex. These findings suggest that smokers with elevated attentional biases to smoking-related stimuli may more readily shift attention away from other external stimuli and toward smoking stimuli-induced internal states and emotional memories. Such attentional shifts may contribute to increased interference by smoking cues, possibly increasing relapse vulnerability. Treatments capable of inhibiting shifts to drug cue-induced memories and internal states may lead to personalized tobacco dependence treatment for smokers with high attentional bias to smoking-related stimuli. Neuropsychopharmacology (2010) 35, 2339-2345; doi: 10.1038/npp.2010.103; published online 11 August 2010 C1 [Janes, Amy C.; Richardt, Sarah; Frederick, Blaise de B.; Kaufman, Marc J.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Pizzagalli, Diego A.; Holmes, Avram J.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Sousa, Jessica; Fava, Maurizio; Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Janes, AC (reprint author), McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02178 USA. EM ajanes@mclean.harvard.edu RI Frederick, Blaise/G-6098-2012; Janes, Amy/A-5322-2013 OI Frederick, Blaise/0000-0001-5832-5279; Janes, Amy/0000-0002-3749-5006 FU ANT North America Inc.; AstraZeneca; Pfizer; Abbott Laboratories; Alkermes; Aspect Medical Systems; BioResearch; BrainCells, Inc.; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions; LLC; Eli Lilly Company; Forest Pharmaceuticals Inc.; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc.; Organon Inc., PamLab; Pfizer Inc.; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; GSK; Organon; Varian Inc. FX DAP: research support from ANT North America Inc. (Advanced Neuro Technology), consulting fees from ANT North America Inc. (Advanced Neuro Technology), and AstraZeneca for projects unrelated to the current study, and honoraria from AstraZeneca. AEE: research product support from Pfizer, and Speaker Honoraria from Reed Medical Education. MF: research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions, LLC, Eli Lilly & Company, Forest Pharmaceuticals Inc., Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc., Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, and Wyeth-Ayerst Laboratories.; MJK: research support from GSK, Organon, Varian Inc., NR 52 TC 45 Z9 50 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2010 VL 35 IS 12 BP 2339 EP 2345 DI 10.1038/npp.2010.103 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 664LA UT WOS:000282960200004 PM 20703221 ER PT J AU Chamczuk, AJ Ogilvy, CS Snyder, KV Ohta, H Siddiqui, AH Hopkins, LN Levy, EI AF Chamczuk, Andrea J. Ogilvy, Christopher S. Snyder, Kenneth V. Ohta, Hajime Siddiqui, Adnan H. Hopkins, L. Nelson Levy, Elad I. TI Elective Stenting for Intracranial Stenosis Under Conscious Sedation SO NEUROSURGERY LA English DT Article DE Anesthesia; Angioplasty; Intracranial atherosclerosis; Stenting ID INTERVENTIONAL NEURORADIOLOGY; ASSISTED ANGIOPLASTY; ARTERIAL-STENOSIS; WINGSPAN STENT; COMPLICATIONS; EXPERIENCE; PLACEMENT; DISEASE; SYSTEM AB BACKGROUND: Elective stenting for intracranial stenosis is under study as an effective means of reducing stroke risk. At most institutions, these procedures are performed and monitored after the induction of general anesthesia. OBJECTIVE: To report our success with elective intracranial stenting and angioplasty performed in conscious patients after the administration of mild sedatives and local anesthetic agents. METHODS: We retrospectively evaluated data from 66 patients who underwent elective intracranial stenting for atherosclerosis. Sixty-one procedures were performed under local anesthesia with mild sedation; 3 were performed under general anesthesia, and 2 were converted from local to general anesthesia during the procedure. Intraprocedural neurological changes were monitored and led to reevaluation of technique, immediate reimaging, modifying the endovascular procedure itself, or possibly mandating conversion to general anesthesia. RESULTS: Thirty-nine anterior and 27 posterior circulation stenotic segments were treated. Angiographic success was achieved in 95.5% of patients with an overall reduction in stenosis of 75.5 to 22.3%. Percutaneous angioplasty and stenting were used in 58 cases; 8 patients were treated with stenting alone. Three patients (4.9%) developed neurological deficits mandating alteration or adjustment of endovascular technique or immediate postoperative management to avoid permanent sequelae. A total of 8 periprocedural complications occurred, 2 of which resulted in permanent neurological deficit. The overall mortality rate was 3.2%. CONCLUSIONS: Stenting of intracranial atherosclerosis performed under conscious sedation is associated with complication rates and effectiveness similar to historical rates for general anesthesia. Conscious sedation confers the additional benefit of continuous neurological assessment during the procedure. C1 [Levy, Elad I.] Univ Buffalo Neurosurg, Millard Fillmore Gates Hosp, Dept Neurosurg, Buffalo, NY 14209 USA. [Chamczuk, Andrea J.; Ogilvy, Christopher S.; Snyder, Kenneth V.; Ohta, Hajime; Siddiqui, Adnan H.; Hopkins, L. Nelson; Levy, Elad I.] SUNY Buffalo, Dept Neurosurg, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Siddiqui, Adnan H.; Hopkins, L. Nelson; Levy, Elad I.] SUNY Buffalo, Dept Radiol, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Ogilvy, Christopher S.] Massachusetts Gen Hosp, Neurovasc Serv, Boston, MA 02114 USA. RP Levy, EI (reprint author), Univ Buffalo Neurosurg, Millard Fillmore Gates Hosp, Dept Neurosurg, 3 Gates Circle, Buffalo, NY 14209 USA. FU Abbott; Cordis; ev3/Covidien Vascular Therapies; Toshiba; Micrus; Valor Medical; University at Buffalo; National Institutes of Health [1R01NS064592-01A1]; Access Closure; Boston Scientific FX Dr Hopkins receives research study grants from Abbott (ACT 1 Choice), Boston Scientific (CABANA), Cordis (SAPPHIRE WW), and ev3/Covidien Vascular Therapies (CREATE) and a research grant from Toshiba (for the Toshiba Stroke Research Center); has an ownership/financial interest in Access Closure, Boston Scientific, Cordis, Micrus, and Valor Medical; serves on the Abbott Vascular Speakers' Bureau; receives honoraria from Bard, Boston Scientific, Cordis, and from the following for speaking at conferences - Complete Conference Management, Cleveland Clinic, and SCAT; receives royalties from Cordis (for the AngioGuard device), serves as a consultant to or on the advisory board for Abbott, AccessClosure, Bard, Boston Scientific, Cordis, Gore, Lumen Biomedical, Micrus, and Toshiba; and serves as the conference director for Nurcon Conferences/Strategic Medical Seminars LLC. Dr Levy receives research grant support (principal investigator: Stent-Assisted Recanalization in acute Ischemic Stroke, SARIS), other research support (devices), and honoraria from Boston Scientific and research support from Micrus Endovascular and ev3/Covidien Vascular Therapies; has ownership interests in Intratech Medical Ltd. and Mynx/Access Closure; serves as a consultant on the board of Scientific Advisors to Codman serves as a consultant per project and/or per hour for Micrus Endovascular, ev3/Covidien Vascular Therapies, and TheraSyn Sensors, Inc.; and receives fees for carotid stern training from Abbott Vascular and ev3/Covidien Vascular Therapies. Dr Levy receives no consulting salary arrangements. All consulting is per project and/or per hour. Dr Siddiqui has received research grants from the University at Buffalo and the National Institutes of Health (co-principal investigator: NINDS 1R01NS064592-01A1, Hemodynamic induction of pathologic remodeling leading to intracranial aneurysms); is a consultant for Codman Shurtleff, Inc., Concentric Medical, ev3/Covidien Vascular Therapies, and Micrus Endovascular; belongs to Cadman & Shurtleff, Inc. and Genentech speakers' bureaus; serves on an advisory board for Codman & Shurtleff, Inc.; and has received honoraria from Genentech, Neocure Group LLC, American Association of Neurological Surgeons' courses, an Emergency Medicine Conference, Abbott Vascular for training other neurointerventionists, and Codman Shurtleff, Inc. for carotid stent training. Dr Siddiqui receives no consulting salary arrangements. All consulting is per project and/or per hour. Dr Ogilvy serves as a consultant to Mizuho America. Drs Chamczuk, Ohta, and Snyder have no disclosures. NR 18 TC 15 Z9 16 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 2010 VL 67 IS 5 BP 1189 EP 1193 DI 10.1227/NEU.0b013e3181efbcac PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 671DF UT WOS:000283479500005 PM 20871450 ER PT J AU Vujanovic, AA Marshall-Berenz, EC Beckham, JC Bernstein, A Zvolensky, MJ AF Vujanovic, Anka A. Marshall-Berenz, Erin C. Beckham, Jean C. Bernstein, Amit Zvolensky, Michael J. TI Posttraumatic Stress Symptoms and Cigarette Deprivation in the Prediction of Anxious Responding among Trauma-Exposed Smokers: A Laboratory Test SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; DIOXIDE-ENRICHED AIR; NICOTINE DEPENDENCE; BIOLOGICAL CHALLENGE; ANXIETY SENSITIVITY; TOBACCO WITHDRAWAL; SMOKING-CESSATION; BODILY SENSATIONS; DISORDER; AVOIDANCE AB The present investigation examined the main and interactive effects of posttraumatic stress symptom severity and 12-hr cigarette deprivation (cf. smoking as usual) in the prediction of anxious responding during a 4-min 10% carbon dioxide (CO(2))-enriched air laboratory challenge. It was hypothesized that 12-hr cigarette deprivation would exacerbate the effects of posttraumatic stress symptom severity with regard to anxious responding during the challenge. Participants were 63 daily smokers (46.0% women; M(age) = 30.79, SD = 13.12, range = 18-60) who reported experiencing one or more traumatic events. The study consisted of two laboratory sessions. At the first session, participants were administered a structured diagnostic interview and completed self-reported measures. Eligible participants were randomly assigned to one of two conditions for the second session: (a) 12-hr cigarette deprivation or (b) noncigarette deprivation (i.e., smoking as usual). At the second session, participants' smoking status was biochemically verified, and all eligible participants then were administered the 10% CO(2)-enriched air laboratory challenge protocol. The main and interactive effects of posttraumatic stress symptom severity and the smoking-as-usual condition-not the hypothesized 12-hr cigarette deprivation condition-were significantly predictive of peri-challenge anxiety. The interactive effect of posttraumatic stress by smoking as usual was significant at Minutes 3 and 4 of the challenge specifically. The present investigation provided novel findings related to the roles of cigarette deprivation and smoking with regard to self-reported anxious responding, among trauma-exposed smokers, during a challenge paradigm. C1 [Vujanovic, Anka A.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Vujanovic, Anka A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Marshall-Berenz, Erin C.; Zvolensky, Michael J.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Beckham, Jean C.] Durham VA Med Ctr, Durham, NC USA. [Beckham, Jean C.] Duke Univ, Med Ctr, Durham, NC USA. [Bernstein, Amit] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel. RP Vujanovic, AA (reprint author), VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, 150 S Huntington Ave,116B-2, Boston, MA 02130 USA. EM anka.vujanovic@va.gov FU National Institute on Drug Abuse [1F31 DA21006-02] FX Data collection for this project was funded by a National Institute on Drug Abuse National Research Service Award (1F31 DA21006-02) granted to Dr. AAV. NR 36 TC 8 Z9 8 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD NOV PY 2010 VL 12 IS 11 BP 1080 EP 1088 DI 10.1093/ntr/ntq154 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 673QI UT WOS:000283677600003 PM 20847149 ER PT J AU Harner, H Hanlon, AL Garfinkel, M AF Harner, Holly Hanlon, Alexandra L. Garfinkel, Marian TI Effect of Iyengar Yoga on Mental Health of Incarcerated Women: A Feasibility Study SO NURSING RESEARCH LA English DT Article DE incarcerated women; mental health; prison; yoga ID PSYCHIATRIC-DISORDERS; STRESS REDUCTION; DEPRESSION; OSTEOARTHRITIS; INTERVENTION; PREVALENCE; INVENTORY; SYMPTOMS AB Background: Incarcerated women share a disproportionate burden of mental illness. Although psychotropic medications are available to women in prison, adjunctive treatment modalities, such as Iyengar yoga, may increase psychological well-being. Objectives: The purposes of this study were (a) to address the feasibility of providing a gender-responsive exercise intervention within a correctional institution and (b) to observe the effect of a group-format Iyengar yoga program that met two sessions a week for 12 weeks on levels of depression symptoms, anxiety symptoms, and perceived stress among incarcerated women. Methods: A repeated measures design, in which each participant served as her own control, was used. Participants completed three self-administered instruments: the Beck Depression Inventory, the Beck Anxiety Inventory, and the Perceived Stress Scale before treatment (baseline) and during treatment (Weeks 4, 8, and 12). Linear mixed effects models were used to examine statistically significant changes in mental health measures over time, taking advantage of all available data. Results: Although 21 women initially participated in the intervention, 6 women completed the 12-week intervention. A significant linear decrease was demonstrated in symptoms of depression over time, with mean values changing from 24.90 at baseline to 5.67 at Week 12. There was a marginally significant decrease in anxiety over time (12.00 at baseline to 7.33 at Week 12) and a nonlinear change in stress over time, with decreases from baseline to Week 4 and subsequent increases to Week 12. Discussion: Women who participated in this program experienced fewer symptoms of depression and anxiety over time. Findings from this study may be used to improve future interventions focusing on the health outcomes of incarcerated women. C1 [Harner, Holly] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Garfinkel, Marian] Temple Sch Med, Philadelphia, PA USA. [Garfinkel, Marian] Temple Univ, Sch Podiatr Med, Philadelphia, PA 19122 USA. RP Harner, H (reprint author), La Salle Univ, Sch Nursing & Hlth Sci, Philadelphia, PA 19141 USA. EM harner@lasalle.edu FU Boston College; Center for Health Equity Research at the University of Pennsylvania School of Nursing FX This research was supported by a research incentive grant from Boston College. The authors acknowledge the guidance of Iyengar yoga instructor Ms. Louise Colby and the research assistance from Angela Hou Liang, MSN, WHCNP-BC, and Meggie Gavin Galligan RN, BSN. The authors also thank the Center for Health Equity Research at the University of Pennsylvania School of Nursing for supporting the preparation of this manuscript. NR 35 TC 12 Z9 13 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD NOV-DEC PY 2010 VL 59 IS 6 BP 389 EP 399 DI 10.1097/NNR.0b013e3181f2e6ff PG 11 WC Nursing SC Nursing GA 675CH UT WOS:000283802200004 PM 20842067 ER PT J AU Preis, SR Massaro, JM Robins, SJ Hoffmann, U Vasan, RS Irlbeck, T Meigs, JB Sutherland, P D'Agostino, RB O'Donnell, CJ Fox, CS AF Preis, Sarah R. Massaro, Joseph M. Robins, Sander J. Hoffmann, Udo Vasan, Ramachandran S. Irlbeck, Thomas Meigs, James B. Sutherland, Patrice D'Agostino, Ralph B., Sr. O'Donnell, Christopher J. Fox, Caroline S. TI Abdominal Subcutaneous and Visceral Adipose Tissue and Insulin Resistance in the Framingham Heart Study SO OBESITY LA English DT Article ID FATTY-ACID-METABOLISM; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; MUSCLE COMPOSITION; MEASUREMENT SITE; RISK-FACTORS; OBESE MEN; SENSITIVITY; GLUCOSE AB Insulin resistance is associated with central obesity and an increased risk of cardiovascular disease. Our objective is to examine the association between abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) and insulin resistance, to determine which fat depot is a stronger correlate of insulin resistance, and to assess whether there was an interaction between SAT, VAT, and age, sex, or BMI. Participants without diabetes from the Framingham Heart Study (FHS), who underwent multidetector computed tomography to assess SAT and VAT (n = 3,093; 48% women; mean age 50.4 years; mean BMI 27.6 kg/m(2)), were evaluated. Insulin resistance was measured using the homeostasis model and defined as HOMA(IR) >= 75th percentile. Logistic regression models, adjusted for age, sex, smoking, alcohol, menopausal status, and hormone replacement therapy use, were used to assess the association between fat measures and insulin resistance. The odds ratio (OR) for insulin resistance per standard deviation increase in SAT was 2.5 (95% confidence interval (CI): 2.2-2.7; P < 0.0001), whereas the OR for insulin resistance per standard deviation increase in VAT was 3.5 (95% CI: 3.1-3.9; P < 0.0001). Overall, VAT was a stronger correlate of insulin resistance than SAT (P < 0.0001 for SAT vs. VAT comparison). After adjustment for BMI, the OR of insulin resistance for VAT was 2.2 (95% CI: 1.9-2.5; P < 0.0001). We observed an interaction between VAT and BMI for insulin (P interaction = 0.0004), proinsulin (P interaction = 0.003), and HOMA(IR) (P interaction = 0.003), where VAT had a stronger association in obese individuals. In conclusion, SAT and VAT are both correlates of insulin resistance; however, VAT is a stronger correlate of insulin resistance than SAT. C1 [Preis, Sarah R.; Robins, Sander J.; Vasan, Ramachandran S.; Sutherland, Patrice; D'Agostino, Ralph B., Sr.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Preis, Sarah R.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Irlbeck, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM foxca@nhlbi.nih.gov OI Preis, Sarah/0000-0002-9360-4166; Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; NIDDK [K24 DK080140]; GlaxoSmithKline; Sanofi-Aventis; [R01DK080739] FX This study was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195). R. S. V. was supported in part by R01DK080739. J.B.M. is supported by NIDDK K24 DK080140.; J.B.M. currently has research grants from GlaxoSmithKline and Sanofi-Aventis, and has consulting agreements with Eli Lilly, Interleukin Genetics, Kalypsys, and Outcomes Science. The other authors declared no conflict of interest. NR 32 TC 116 Z9 123 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD NOV PY 2010 VL 18 IS 11 BP 2191 EP 2198 DI 10.1038/oby.2010.59 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 671GE UT WOS:000283487700022 PM 20339361 ER PT J AU Bredella, MA Ghomi, RH Thomas, BJ Torriani, M Brick, DJ Gerweck, AV Misra, M Klibanski, A Miller, KK AF Bredella, Miriam A. Ghomi, Reza Hosseini Thomas, Bijoy J. Torriani, Martin Brick, Danielle J. Gerweck, Anu V. Misra, Madhusmita Klibanski, Anne Miller, Karen K. TI Comparison of DXA and CT in the Assessment of Body Composition in Premenopausal Women With Obesity and Anorexia Nervosa SO OBESITY LA English DT Article ID X-RAY ABSORPTIOMETRY; BIOELECTRICAL-IMPEDANCE ANALYSIS; SKELETAL-MUSCLE MEASUREMENT; FAT-FREE MASS; ADIPOSE-TISSUE; COMPUTED-TOMOGRAPHY; ABDOMINAL ADIPOSITY; LEG MUSCLE; RISK; ANTHROPOMETRY AB Accurate methods for assessing body composition in subjects with obesity and anorexia nervosa (AN) are important for determination of metabolic and cardiovascular risk factors and to monitor therapeutic interventions. The purpose of our study was to assess the accuracy of dual-energy X-ray absorptiometry (DXA) for measuring abdominal and thigh fat, and thigh muscle mass in premenopausal women with obesity, AN, and normal weight compared to computed tomography (CT). In addition, we wanted to assess the impact of hydration on DXA-derived measures of body composition by using bioelectrical impedance analysis (BIA). We studied a total of 91 premenopausal women (34 obese, 39 with AN, and 18 lean controls). Our results demonstrate strong correlations between DXA-and CT-derived body composition measurements in AN, obese, and lean controls (r = 0.77-0.95, P < 0.0001). After controlling for total body water (TBW), the correlation coefficients were comparable. DXA trunk fat correlated with CT visceral fat (r = 0.51-0.70, P < 0.0001). DXA underestimated trunk and thigh fat and overestimated thigh muscle mass and this error increased with increasing weight. Our study showed that DXA is a useful method for assessing body composition in premenopausal women within the phenotypic spectrum ranging from obesity to AN. However, it is important to recognize that DXA may not accurately assess body composition in markedly obese women. The level of hydration does not significantly affect most DXA body composition measurements, with the exceptions of thigh fat. C1 [Bredella, Miriam A.; Ghomi, Reza Hosseini; Thomas, Bijoy J.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Brick, Danielle J.; Gerweck, Anu V.; Misra, Madhusmita; Klibanski, Anne; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM mbredella@partners.org OI Hosseini Ghomi, Reza/0000-0003-4369-8237 FU [UL1 RR025758]; [HL077674]; [MO1 RR01066]; [M01 RR01066-27S1]; [K23RR23090] FX This work was supported in part by the following grants: UL1 RR025758, HL077674, MO1 RR01066, M01 RR01066-27S1, and K23RR23090. NR 39 TC 45 Z9 45 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD NOV PY 2010 VL 18 IS 11 BP 2227 EP 2233 DI 10.1038/oby.2010.5 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 671GE UT WOS:000283487700027 PM 20111013 ER PT J AU Ferriss, JS Brix, W Tambouret, R DeSimone, CP Stoler, M Modesitt, SC AF Ferriss, J. Stuart Brix, William Tambouret, Rosemary DeSimone, Christopher P. Stoler, Mark Modesitt, Susan C. TI Cervical Stromal Invasion Predicting Survival in Endometrial Cancer SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting on Womens Cancer of the Society-of-Gynecologic-Oncologists CY MAR 14-17, 2010 CL San Francisco, CA ID STAGE; CARCINOMA; ADENOCARCINOMA; RECURRENCE; WOMEN AB OBJECTIVE: To estimate the extent to which cervical stromal invasion would predict survival. METHODS: Cases of stage II endometrioid endometrial adenocarcinoma from three academic institutions were reviewed. A gynecologic pathologist reevaluated archived slides and measured the depth of cervical stromal invasion. Clinical data were abstracted and statistical analysis performed. RESULTS: Of 116 cases, 31 (27%) had gland involvement and 85 (73%) cervical stromal invasion. Cervical stromal invasion was categorized as the inner two thirds (n=59 [69%]) compared with the outer third (n=26 [31%]). Women with outer third cervical stromal invasion compared with those with inner two-thirds cervical stromal invasion were more likely to be aged at least 65 years (69% compared with 46%, P=.038), have at least 50% myometrial invasion (77% compared with 44%, P=.004), lymphvascular space invasion (46% compared with 20%, P=.016), and to have died (50% compared with 19%, P=.004). Overall survival for patients with no invasion and inner two-thirds cervical stromal invasion did not differ (106 compared with 146 months, P=.89). Survival for outer third cervical stromal invasion was 91 months (P=.021). Multivariable analysis found deep myometrial invasion (hazard ratio 3.1; confidence interval [CI], 1.2-8.2), lymphvascular space invasion (hazard ratio 3.2; CI 1.2-8.4), and outer third cervical stromal invasion (hazard ratio 2.8; CI 1.1-7.2) were independent predictors of death. CONCLUSION: Deep (outer third) cervical stromal invasion is an independent predictor of death in stage II endometrial cancers and these patients should receive radiation therapy. Superficial cervical stromal invasion did not increase risk of death and adjuvant radiation for this patient group may not be necessary. (Obstet Gynecol 2010;116:1035-41) C1 Univ Virginia, Thornton Gynecol Oncol Serv, Dept Obstet & Gynecol, Charlottesville, VA USA. Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Kentucky, Div Gynecol Oncol, Dept Obstet & Gynecol, Lexington, KY USA. RP Ferriss, JS (reprint author), Temple Univ Hosp & Med Sch, Gynecol Oncol Serv, Dept Obstet Gynecol & Reprod Sci, 3401 N Broad St,7-OPB, Philadelphia, PA 19140 USA. EM james.ferriss@tuhs.temple.edu OI Ferriss, James/0000-0002-2053-8604 NR 12 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2010 VL 116 IS 5 BP 1035 EP 1041 DI 10.1097/AOG.0b013e3181f73fc2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 669EK UT WOS:000283329000006 PM 20966686 ER PT J AU Cheng, YW Shaffer, BL Bryant, AS Caughey, AB AF Cheng, Yvonne W. Shaffer, Brian L. Bryant, Allison S. Caughey, Aaron B. TI Length of the First Stage of Labor and Associated Perinatal Outcomes in Nulliparous Women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID DYSFUNCTIONAL LABOR; PROLONGED 2ND-STAGE; NEONATAL OUTCOMES; ACTIVE MANAGEMENT; LATENT PHASE; PROGRESS; CURVE AB OBJECTIVE: To estimate whether length of the first stage of labor is associated with adverse maternal and neonatal outcomes. METHODS: This is a retrospective cohort study of nulliparous women with term, singleton gestations delivered in one academic center between 1990 and 2008. The length of the first stage was stratified into three subgroups: less than the 5th percentile, 5th to 95th percentile, and greater than the 95th percentile. Maternal and neonatal outcomes were compared using the x(2) test. Multivariable logistic regression models were used to control for confounders. RESULTS: Of the 10,661 nulliparous women meeting study criteria, the median (50th percentile) length of the first stage was 10.5 hours. Compared with women with a first stage between 2.8 and 30 hours (5th to 95th percentile thresholds), the risk of cesarean delivery was higher (6.1% compared with 13.5%; adjusted odds ratio [OR], 2.28, 95% confidence interval [CI], 1.92-2.72) in women with a first stage longer than 30 hours (greater than the 95th percentile). These women also had higher odds of chorioamnionitis (12.5% compared with 23.5%; adjusted OR, 1.58; 95% CI, 1.25-1.98) and neonatal admission to the neonatal intensive care unit (4.7% compared with 9.8%; adjusted OR, 1.53; 95% CI, 1.18-1.97) but no other associated adverse neonatal outcomes. CONCLUSION: Women with a prolonged first stage of labor have higher odds of cesarean delivery and chorioamnionitis, but their neonates are not at risk of increased morbidity. (Obstet Gynecol 2010;116:1127-35) C1 Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Div Maternal Fetal Med, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Obstet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gynecol, Boston, MA 02114 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Cheng, YW (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Div Perinatal Med & Genet, 505 Parnassus Ave,Box 0132, San Francisco, CA 94143 USA. EM yvecheng@hotmail.com FU UCSF; NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12 HD001262]; Robert Wood Johnson Foundation FX Dr. Cheng is supported by the UCSF Women's Reproductive Health Research Career Development Award, NIH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD001262).; Dr. Caughey is supported by the Robert Wood Johnson Foundation as a Physician Faculty Scholar. Dr. Bryant is supported by the Robert Wood Johnson Foundation as an Amos Medical Faculty Development Scholar. NR 19 TC 15 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2010 VL 116 IS 5 BP 1127 EP 1135 DI 10.1097/AOG.0b013e3181f5eaf0 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 669EK UT WOS:000283329000018 PM 20966698 ER PT J AU Madison, DL Lundblad, JR AF Madison, D. L. Lundblad, J. R. TI C-terminal binding protein and poly(ADP)ribose polymerase 1 contribute to repression of the p21(waf1/cip1) promoter SO ONCOGENE LA English DT Article DE Poly(ADP)ribose Polymerase; p21; CtBP; PARP inhibitor ID POLY(ADP-RIBOSE) POLYMERASE-1; GENE-EXPRESSION; ADENOVIRUS E1A; CELLULAR PHOSPHOPROTEIN; COREPRESSOR FUNCTION; NEGATIVE MODULATION; IONIZING-RADIATION; CANCER-CELLS; DNA-DAMAGE; TRANSCRIPTION AB Transcriptional repression by the C-terminal binding protein (CtBP) is proposed to require nicotinamide adenine dinucleotide dehydrogenase (NAD(H). Previous studies have implicated CtBP in transcriptional repression of the p21(waf1/cip1) gene. Similarly, the NAD-dependent poly(adenosine diphosphate) ribose polymerase 1 (PARP1) may affect p21 expression via its NAD-dependent enzymatic activity; we therefore asked if PARP1 and CtBP were functionally linked in regulating p21 transcription. We found that restraint of basal p21 transcription requires both CtBP and PARP1. PARP inhibition attenuated activation of p21 transcription by both p53-independent and p53-dependent processes, in a CtBP-dependent manner. CtBP1 + 2 or PARP1 + 2 knockdown partially activated p21 gene expression, suggesting relief of a corepressor function dependent on both proteins. We localized CtBP-responsive repression elements to the proximal promoter region, and found ZBRK1 overexpression could also overcome DNA damage-dependent, but not p53-dependent activation through this region. By chromatin immunoprecipitation we find dismissal of CtBP from the proximal promoter following DNA-damage, and that PARP1 associates with a CtBP corepressor complex in nuclear extracts. We propose a model in which both CtBP and PARP functionally interact in a corepressor complex as components of a molecular switch necessary for p21 repression, and following DNA damage signals activation of p21 transcription by corepressor dismissal and coactivator recruitment. Oncogene (2010) 29, 6027-6039; doi:10.1038/onc.2010.338; published online 16 August 2010 C1 [Madison, D. L.; Lundblad, J. R.] Oregon Hlth & Sci Univ, Div Endocrinol, Dept Med, Portland, OR 97239 USA. [Madison, D. L.] Portland VA Med Ctr, Endocrine Sect, Dept Hosp & Specialty Med, Portland, OR USA. RP Madison, DL (reprint author), Oregon Hlth & Sci Univ, Div Endocrinol, Dept Med, L-604,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM Madisond@ohsu.edu FU [NIDDK R01DK060133]; [NCI K08CA109158] FX This work as supported by Grants (NIDDK R01DK060133) to JRL and DLM (NCI K08CA109158). We thank J Hildebrand (University of Pittsburgh) for the CtBP MEFs, R Klein (OHSU) for access to and assistance with real time PCR, R Kwok (University of Michigan) for the p53 expression construct and Madeleine Pham and Loren Brown for technical assistance. NR 52 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 2010 VL 29 IS 45 BP 6027 EP 6039 DI 10.1038/onc.2010.338 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 678VA UT WOS:000284108700005 PM 20711239 ER PT J AU Nogueira, C Kim, KH Sung, H Paraiso, KHT Dannenberg, JH Bosenberg, M Chin, L Kim, M AF Nogueira, C. Kim, K-H Sung, H. Paraiso, K. H. T. Dannenberg, J-H Bosenberg, M. Chin, L. Kim, M. TI Cooperative interactions of PTEN deficiency and RAS activation in melanoma metastasis SO ONCOGENE LA English DT Article DE melanoma; PTEN; RAS; E-cadherin; AKT2; mouse model ID TUMOR-SUPPRESSOR GENE; MALIGNANT-MELANOMA; PROSTATE-CANCER; CELL-LINES; PTEN/MMAC1 ALTERATIONS; BRAF MUTATIONS; OVARIAN-CANCER; UP-REGULATION; KINASE-B; IN-VIVO AB Mitogen-activated protein kinase (MAPK) and AKT pathways are frequently co-activated in melanoma through overexpression of receptor tyrosine kinases, mutations in their signaling surrogates, such as RAS and BRAF, or loss of negative regulators such as PTEN. As RAS can be a positive upstream regulator of PI3-K, it has been proposed that the loss of PTEN and the activation of RAS are redundant events in melanoma pathogenesis. Here, in genetically engineered mouse models of cutaneous melanomas, we sought to better understand the genetic interactions between HRAS activation and PTEN inactivation in melanoma genesis and progression in vivo. We showed that HRAS activation cooperates with Pten+/- and Ink4a/Arf-/- to increase melanoma penetrance and promote metastasis. Correspondingly, gain-and loss-of-function studies established that Pten loss increases invasion and migration of melanoma cells and non-transformed melanocytes, and such biological activity correlates with a shift to phosphorylation of AKT2 isoform and E-cadherin down-regulation. Thus, Pten inactivation can drive the genesis and promote the metastatic progression of RAS activated Ink4a/Arf deficient melanomas. Oncogene (2010) 29, 6222-6232; doi:10.1038/onc.2010.349; published online 16 August 2010 C1 [Chin, L.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Chin, L.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Nogueira, C.; Dannenberg, J-H; Chin, L.; Kim, M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nogueira, C.] Univ Porto, Inst Mol Pathol & Immunol, IPATIMUP Med Fac, P-4100 Oporto, Portugal. [Kim, K-H; Sung, H.; Paraiso, K. H. T.; Kim, M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Comprehens Melanoma Res Ctr,Mol Oncol Dept, Tampa, FL 33612 USA. [Bosenberg, M.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, 44 Binney St, Boston, MA 02115 USA. EM Lynda_Chin@dfci.harvard.edu; Minjung.Kim@moffitt.org RI Nogueira, Cristina/N-4574-2015 OI Nogueira, Cristina/0000-0002-0853-5304 FU FCT [PRAXIS/BD/21794/99]; Claudia Adams Barr Program; Dermatology Foundation; Melanoma Research Foundation; Damon-Runyon Cancer Research Foundation; Dutch Cancer Society; NIH [UO1 CA84313, RO1 CA93947]; Bankhead Coley Pilot Research Award; American Cancer Society [93-032-13] FX C Nogueira was supported by a fellowship from FCT (PRAXIS/BD/21794/99). M Kim was supported by the Claudia Adams Barr Program, the Dermatology Foundation, and Melanoma Research Foundation. JH Dannenberg was supported by Damon-Runyon Cancer Research Foundation and the Dutch Cancer Society. This work was supported by grants from the NIH (UO1 CA84313; RO1 CA93947) to L Chin and from the Bankhead Coley Pilot Research Award and American Cancer Society Institutional Research Grant (#93-032-13) to M Kim. We thank Dr Jin Q Cheng (Moffitt Cancer Center) for helpful discussion and adenoviruses for PTEN and DN-AKT2 expression, and Dr Ronald A DePinho for critical reading of this paper. NR 58 TC 43 Z9 46 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 2010 VL 29 IS 47 BP 6222 EP 6232 DI 10.1038/onc.2010.349 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 685CG UT WOS:000284601700004 PM 20711233 ER PT J AU Zhu, AX Chabner, BA Tanabe, KK AF Zhu, Andrew X. Chabner, Bruce A. Tanabe, Kenneth K. TI New Trends and Novel Treatment for Hepatocellular Carcinoma: A Global Perspective SO ONCOLOGIST LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIAL; STAGING-SYSTEM; UNITED-STATES; CHEMOEMBOLIZATION; CLASSIFICATION; SORAFENIB; PROGNOSIS; JAPAN C1 [Zhu, Andrew X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Tucker Gosnell Ctr Gastrointestinal Canc, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Tucker Gosnell Ctr Gastrointestinal Canc, Lawrence House,POB 232,55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org NR 24 TC 8 Z9 8 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD NOV PY 2010 VL 15 SU 4 BP 1 EP 4 DI 10.1634/theoncologist.2010-S4-01 PG 4 WC Oncology SC Oncology GA 686IE UT WOS:000284689200001 PM 21115575 ER PT J AU Geiger-Gritsch, S Stollenwerk, B Miksad, R Guba, B Wild, C Siebert, U AF Geiger-Gritsch, Sabine Stollenwerk, Bjoern Miksad, Rebecca Guba, Beate Wild, Claudia Siebert, Uwe TI Safety of Bevacizumab in Patients with Advanced Cancer: A Meta-Analysis of Randomized Controlled Trials SO ONCOLOGIST LA English DT Article DE Bevacizumab; Vascular endothelial growth factor; VEGF; Anti-VEGF antibody; Cancer; Meta-analysis; Adverse events; Safety ID METASTATIC COLORECTAL-CANCER; ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; PHASE-II TRIAL; COST-EFFECTIVENESS; PLUS BEVACIZUMAB; BREAST-CANCER; COMBINATION; FLUOROURACIL; CHEMOTHERAPY AB Objective. We performed a meta-analysis on adverse events seen with bevacizumab to combine the existing evidence about its safety in patients with advanced cancer. Methods. A systematic literature search was conducted to identify published, randomized controlled trials of bevacizumab in cancer patients with data on adverse events available. The primary endpoint was "severe adverse event," a composite of grade 3 and 4 adverse events. Secondary endpoints for the exploratory analysis were individual adverse events. We used random-effects meta-analysis to combine data. Results. Thirteen eligible publications were identified and eight trials reported the primary endpoint. Compared with the control group, the bevacizumab group had a slightly higher risk for any severe adverse event (pooled relative risk, 1.10; 95% confidence interval [95% CI], 1.01-1.19). The pooled risk difference was 7% (95% CI, 1%-13%), with a number needed to harm of 14 treated patients. Exploratory analyses showed a statistically significant higher risk for eight of the 15 evaluated secondary endpoints: bevacizumab was associated with a fourfold higher risk for hypertension, epistaxis, and gastrointestinal hemorrhage/perforation; a threefold higher risk for any bleeding events; and a lower, but elevated risk for proteinuria, leukopenia, diarrhea, and asthenia. No statistically significant differences were found for any thrombotic event (arterial or venous), hemoptysis, cardiac event, thrombocytopenia, neutropenia, impaired wound healing, or death related to an adverse event. Conclusion. Treatment with bevacizumab was associated with a slightly higher risk for any severe (grade 3 or 4) adverse event in patients with cancer. The result may impact individual benefit-risk assessments and policy guidelines. The Oncologist 2010;15:1179-1191 C1 [Geiger-Gritsch, Sabine; Stollenwerk, Bjoern; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Informat Syst & Hlth Technol Asses, Inst Publ Hlth Med Decis Making & Hlth Technol, A-6060 Hall In Tirol, Austria. [Geiger-Gritsch, Sabine; Guba, Beate; Wild, Claudia] Ludwig Boltzmann Inst Hlth Technol Assessment, Vienna, Austria. [Miksad, Rebecca] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol & Oncol, Boston, MA 02215 USA. [Miksad, Rebecca; Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Miksad, Rebecca; Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Stollenwerk, Bjoern] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Hlth Econ & Hlth Care Management, Neuherberg, Germany. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Div Publ Hlth Decis Modeling Hlth Technol Assessm, Innsbruck, Austria. RP Geiger-Gritsch, S (reprint author), Ludwig Boltzmann Inst Hlth Technol Assessment, Vienna, Austria. EM sabine.geiger-gritsch@umit.at RI Stollenwerk, Bjorn/G-5408-2013; OI Miksad, Rebecca/0000-0003-3194-5122 FU Hoffmann-La Roche; U.S. government; Ludwig Boltzmann Institute of Health Technology Assessment, Vienna, Austria; UMIT-University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria FX Sabine Geiger-Gritsch: None; Bjoern Stollenwerk: None; Rebecca Miksad: None; Beate Guba: None; Claudia Wild: None; Uwe Siebert: Research funding/contracted research: Hoffmann-La Roche.; Editor-in-Chief Bruce Chabner discloses employment with Massachusetts General Hospital and Harvard, a consulting relationship with and honoraria received from sanofi-aventis, Redwood Pharmaceuticals, Allergan, Epizyme, PharmaMar, and GlaxoSmithKline, research funding from the U.S. government, and ownership interests with PharmaMar and Gilead Sciences.; This study was partly supported by the Ludwig Boltzmann Institute of Health Technology Assessment, Vienna, Austria, and UMIT-University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria. NR 45 TC 42 Z9 45 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD NOV PY 2010 VL 15 IS 11 BP 1179 EP 1191 DI 10.1634/theoncologist.2009-0155 PG 13 WC Oncology SC Oncology GA 687DY UT WOS:000284758000007 PM 21045188 ER PT J AU Iezzoni, LI Kilbridge, K Park, ER AF Iezzoni, Lisa I. Kilbridge, Kerry Park, Elyse R. TI Physical Access Barriers to Care for Diagnosis and Treatment of Breast Cancer Among Women With Mobility Impairments SO ONCOLOGY NURSING FORUM LA English DT Article ID PREVENTIVE SERVICES; HEALTH-CARE; DISABILITIES AB Purpose/Objectives: To explore the perceptions of patients with breast cancer with mobility impairments of the physical accessibility of healthcare facilities and equipment. Research Approach: Individual audiotaped interviews lasting one to two hours. Setting: Interviews in homes or workplaces or by telephone. Participants: 20 women with chronic mobility impairments who developed early-stage breast cancer prior to age 60. Three were recruited from oncologist panels and 17 from informal social networks of disabled women nationwide. Methodologic Approach: Qualitative analyses of interview transcripts to identify common themes. Main Research Variables: Extent and nature of mobility impairments and concerns raised by patients about barriers to care. Findings: The 20 participants identified issues with inaccessible equipment, including mammography machines, examining tables, and weight scales. The patients sometimes needed to insist on being transferred to an examining table when physicians preferred to examine them seated in their wheelchairs. When staff would transfer them, patients feared injury or felt badly when clinical personnel were injured during transfers. Other issues included difficulties with positioning and handling patients' uncontrollable movements. Even when clinical sites had accessible equipment, this equipment was sometimes unavailable for the appointment. Conclusions: Women with major mobility issues who developed breast cancer confronted numerous physical barriers during the course of their breast: cancer diagnosis and treatment. Interpretation: With the aging of the baby boomer generation, an increasing number of people with mobility impairments will be seeking healthcare services. Healthcare providers should be proactive in planning to accommodate these patients by considering accessibility whenever they acquire new equipment, renovate older structures, or build new facilities. They also should establish policies and procedures to ensure that equipment is available during appointments of patients with mobility issues and that staff are trained in safe transferring procedures. Ensuring accommodations and accessibility will benefit patients with impaired mobility and clinical staff. C1 [Iezzoni, Lisa I.; Kilbridge, Kerry] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Iezzoni, Lisa I.; Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Kilbridge, Kerry] Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. [Kilbridge, Kerry] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Park, Elyse R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. RP Iezzoni, LI (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. EM liezzoni@partners.org FU National Cancer Institute [NCI R21 CA122130] FX Lisa I. lezzoni, MD, MSc, is a professor in the Department of Medicine at Harvard Medical School and the director of the Mongan Institute for Health Policy at Massachusetts General Hospital, both in Boston; Kerry Kilbridge, MD, MSc, is an assistant in decision science in the general internal medicine unit at Massachusetts General Hospital, an instructor in the Department of Medicine at Harvard Medical School, and a visiting assistant professor in the Department of Public Health Sciences at the University of Virginia in Charlottesville; and Elyse R. Park, PhD, MPH, is a senior scientist at the Mongan Institute for Health Policy at Massachusetts General Hospital and an assistant professor in the Department of Psychiatry at Harvard Medical School. This research was funded by the National Cancer Institute (grant no. NCI R21 CA122130). lezzoni can be reached at liezzoni@partners.org, with copy to editor at ONFEditor@ons.org. (Submitted September 2009. Accepted for publication December 2, 2009.) NR 29 TC 23 Z9 23 U1 3 U2 12 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD NOV PY 2010 VL 37 IS 6 BP 711 EP 717 DI 10.1188/10.ONF.711-717 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 680SR UT WOS:000284255200007 PM 21059583 ER PT J AU George, M Margolis, ML AF George, Maureen Margolis, Mitchell L. TI Race and Lung Cancer Surgery-A Qualitative Analysis of Relevant Beliefs and Management Preferences SO ONCOLOGY NURSING FORUM LA English DT Article ID ALTERNATIVE MEDICINE USE; AFRICAN-AMERICAN ADULTS; FOCUS GROUPS; LOW-INCOME; BREAST-CANCER; COMPLEMENTARY THERAPIES; RACIAL DISPARITIES; PROSTATE-CANCER; ASTHMA; WOMEN AB Purpose/Objectives: To gain a better understanding of beliefs about the utility of lung cancer resection surgery and preferences for lung cancer management among African American and Caucasian adults. Research Approach: Qualitative. Setting: The Philadelphia Veterans Affairs Medical Center. Participants: 21 participants (9 African Americans and 12 Caucasians; 11 with chronic obstructive pulmonary disease and 10 with lung-cancer). Methodologic Approach: Three focus groups were conducted. Transcripts and field notes were coded, grouped into thematic categories, and explored in later focus groups. Main Research Variables: Beliefs about lung cancer resection surgery and management preferences. Findings: African Americans doubted that surgery was needed, questioned its efficacy, and preferred complementary and alternative medicine (CAM). African Americans and Caucasians believed that exposure to air during surgery could cause tumor spread and were skeptical that smoking caused lung cancer. Therefore, they had a sense of treatment futility. Conversely, Caucasians were impatient with forced waiting for surgery. Both groups believed that surgery would be better accepted if current patients met past surgical patients, obtained second opinions, and had trusting patient-provider relationships. Conclusions: Suspicion about surgeons' motives and perceived ineffectiveness of surgery, as well as support for CAM among African Americans, may contribute to key racial disparities in lung cancer care. Interpretation: If providers understand more clearly the beliefs and preferences that impede acceptance of surgical resection, then they can formulate educational interventions directed at overcoming patient resistance. The clinical utility of such individualized interventions could be evaluated in future studies. C1 [George, Maureen] Univ Penn, Sch Nursing, Ctr Hlth Dispar Res, Family & Community Hlth Div, Philadelphia, PA 19104 USA. [Margolis, Mitchell L.] Univ Penn, Med Ctr, Philadelphia Vet Affairs Med Ctr, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. RP George, M (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Dispar Res, Family & Community Hlth Div, Philadelphia, PA 19104 USA. EM mgeorge@nursing.upenn.edu FU Center for Health Equity Research and Promotion [LIP 72-011] FX Maureen George, PhD, RN, AE-C, is an assistant professor in the Family and Community Health Division, Center for Health Disparities Research, in the School of Nursing at the University of Pennsylvania, and Mitchell L. Margolis, MD, is a clinical associate professor of medicine in the Pulmonary, Allergy, and Critical Care Division of the Philadelphia Veterans Affairs Medical Center at the University of Pennsylvania Medical Center, both in Philadelphia. This study was supported by a grant from the Center for Health Equity Research and Promotion [LIP 72-011]. George can be reached at mgeorge@nursing.upenn.edu, with copy to editor at ONEEditor@ons.org. (Submitted August 2009. Accepted for publication October, 21, 2009.) NR 46 TC 14 Z9 14 U1 2 U2 6 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD NOV PY 2010 VL 37 IS 6 BP 740 EP 748 DI 10.1188/10.ONF.740-748 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 680SR UT WOS:000284255200009 PM 21059585 ER PT J AU Qiao, M Shi, Q Pardee, AB AF Qiao, Meng Shi, Qian Pardee, Arthur B. TI The pursuit of oncotargets through understanding defective cell regulation SO ONCOTARGET LA English DT Review DE oncotarget; cancer; biomarkers; therapy; systems biology ID HUMAN BREAST-CANCER; TUMOR PROGRESSION; SYSTEMS BIOLOGY; THERAPEUTIC TARGET; PROMOTES APOPTOSIS; RNA INTERFERENCE; B ACTIVATION; IN-VIVO; PROTEIN; MELANOMA AB More effective anticancer agents are essential, as has too often been demonstrated by the paucity of therapeutics which preserve life. Their discovery is very difficult. Many approaches are being applied, from testing folk medicines to automated high throughput screening of large chemical libraries. Mutations in cancer cells create dysfunctional regulatory systems. This Perspective summarizes an approach to applying defective molecular control mechanisms as oncotargets on which drug discoveries against cancer can be based. C1 [Qiao, Meng] Univ Calif Irvine, Irvine, CA 92697 USA. [Shi, Qian] Fudan Univ, Inst Biomed Sci, Shanghai 20003, Peoples R China. [Pardee, Arthur B.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Qiao, M (reprint author), Univ Calif Irvine, 140 Sprague Hall,839 Hlth Sci Rd, Irvine, CA 92697 USA. EM mqiao@uci.edu; shiqian@fudan.edu.cn NR 80 TC 4 Z9 4 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV PY 2010 VL 1 IS 7 BP 544 EP 551 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 802JM UT WOS:000293506100008 PM 21317450 ER PT J AU Sacco, A Roccaro, A Ghobrial, IM AF Sacco, Antonio Roccaro, Aldo Ghobrial, Irene M. TI Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia SO ONCOTARGET LA English DT Review DE malignancies; mTOR; PI3K; NVP-BEZ235; signal transduction ID MULTIPLE-MYELOMA; BINDING PARTNER; PATHWAY; RAPAMYCIN; BIOLOGY; RAPTOR; EXPRESSION; APOPTOSIS; PROGNOSIS; TARGET AB Tumorigenesis occurs due to synergistic interactions from a complex of signal transduction processes, including multiple onco-proteins and tumor suppressors such as Ras, Myc, PI3K/Akt/mTOR, Her-2/Neu, p53 and PTEN. Specifically, the PI3K/Akt and mTOR pathways have been shown to play a pivotal role on the initiation and progression of malignancies, enhancing cell survival by stimulating cell proliferation, and inhibiting apoptosis. Therefore, it is critical to examine therapeutic agents that explicitly target both the PI3K/Akt and mTOR signaling cascades in diseases, such as Waldenstrom Macroglobulinemia (WM), that harbor activation of the PI3K/Akt pathway. We demonstrated that dual targeting of the PI3K and mTOR pathways by the novel inhibitor NVP-BEZ235, exhibited toxicity on WM cells by directly targeting the tumor clone and indirectly through an effect on the bone marrow milieu. These findings suggest that dual targeting of the PI3K and mTOR pathways is a better modality of targeted therapy for tumors that harbor activation of the PI3K/mTOR pathways, such as in WM. C1 [Sacco, Antonio; Roccaro, Aldo; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Irene_Ghobrial@dfci.harvard.edu NR 24 TC 24 Z9 25 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV PY 2010 VL 1 IS 7 BP 578 EP 582 PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 802JM UT WOS:000293506100011 PM 21317453 ER PT J AU Jakobiec, FA Nguyen, J Bhat, P Fay, A AF Jakobiec, Frederick A. Nguyen, John Bhat, Pooja Fay, Aaron TI MDM2-Positive Atypical Lipomatous Neoplasm/Well-Differentiated Liposarcoma Versus Spindle Cell Lipoma of the Orbit SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Purpose: To distinguish, in a 36-year-old man, an atypical lipomatous neoplasm/well-differentiated liposarcoma from a spindle cell lipoma in a recurrent orbital tumor. Methods: Clinical, radiographic, and histopathologic evaluations coupled with immunohistochemical studies for CD34, factor XIII, bcl-2, S-100, muscle-specific actin, Ki-67, and MDM2. Results: MDM2 gene amplification was discovered in the CD34(+) tumor cells. An average Ki-67 proliferation index of 28% was ascertained for the original and recurrent lesions. These findings established the diagnosis of a well-differentiated liposarcoma with lipoma-like and spindle cell features and ruled out a spindle cell lipoma. Conclusion: Well-differentiated liposarcoma is a slow growing, infiltrative, and nonmetastasizing neoplasm that is microscopically and diagnostically challenging. It can be reliably separated from a benign spindle cell or an atypical lipoma by using the markers MDM2 and Ki-67. C1 [Jakobiec, Frederick A.; Bhat, Pooja] Massachusetts Eye & Ear Infirm, Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Nguyen, John; Fay, Aaron] Massachusetts Eye & Ear Infirm, Ophthalm Plast & Reconstruct Surg Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Cogan Eye Pathol Lab, Suite 321,243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 15 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV-DEC PY 2010 VL 26 IS 6 BP 413 EP 415 DI 10.1097/IOP.0b013e3181cd62eb PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 682KL UT WOS:000284402300007 PM 20639786 ER PT J AU Jakobiec, FA Zakka, FR Hatton, MP AF Jakobiec, Frederick A. Zakka, Fouad R. Hatton, Mark P. TI Eyelid Basal Cell Carcinoma Developing in an Epidermoid Cyst: A Previously Unreported Event SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LACRIMAL GLAND; DILATED PORE AB A 72-year-old woman presented with a 3 x 2 x 1-mm right lower eyelid micronodular, whitish solid lesion at the nasal eyelid margin that had caused madarosis. Local excision led to the microscopic discovery of 2 epidermoid cysts, one of which harbored a basal cell carcinoma arising from its orthokeratinizing squamous cell lining. Poral openings indicated that the cysts represented follicular infundibular ectasias. BER-EP4-positive immunostaining confirmed the basal cell nature of the neoplasm. This is the first example in the eyelid of an epidermoid cyst displaying malignant transformation. No matter how innocent they may appear, all small cystic or noncystic eyelid lesions should be submitted for pathologic evaluation. C1 [Jakobiec, Frederick A.; Zakka, Fouad R.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Zakka, Fouad R.; Hatton, Mark P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Hatton, Mark P.] Ophthalm Consultants Boston, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Room 321, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 9 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV-DEC PY 2010 VL 26 IS 6 BP 491 EP 494 DI 10.1097/IOP.0b013e3181d92972 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 682KL UT WOS:000284402300030 PM 20736874 ER PT J AU Luo, ZH Gardiner, M AF Luo, Zhonghui Gardiner, Matthew TI The Incidence of Intraocular Foreign Bodies and Other Intraocular Findings in Patients with Corneal Metal Foreign Bodies SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 725th Meeting of the New England Ophthalmological Society CY MAY 29, 2009 CL ENGLAND SP New England Ophthalmol Soc ID BODY AB Purpose: To review the findings of dilated fundus examinations (DFEs) in patients with the diagnosis of corneal metal foreign body (CMFB) and to assess the likelihood of concomitant intraocular foreign body (IOFB) in this clinical setting. Design: Retrospective, case review series. Participants: All 288 cases with a new diagnosis of CMFB that had a documented DFE in the emergency department at Massachusetts Eye and Ear Infirmary from January 1, 2008, to December 31, 2008. In addition, all 9 separate cases of metal IOFB seen in the same time period were also reviewed. Methods: The medical records of all patients were individually reviewed. Main Outcome Measures: The DFE findings of each visit were analyzed in addition to mechanism of injury, visual acuity and anterior segment abnormalities. Results: Of the 288 CMFB cases, all but 1 presented without corneal or conjunctival laceration. The etiologies of the injuries included low-and high-velocity impact. Best-corrected visual acuity ranged between 20/15 and 20/150. The anterior chamber (AC) reaction ranged from quiet to 4+ cells. None of the DFEs revealed an IOFB. Only 1 case had a posterior segment abnormality related to the injury-commotion retinae in the setting of an explosion. There were 14 cases with unrelated DFE findings. Among the separate 9 cases of metal IOFB reviewed, all had a history of high-velocity injury and evidence of corneal or conjunctival laceration. In 1 of the 9 cases, the IOFB was protruding from the cornea; in 2 cases, IOFBs were seen on DFE. Six cases were diagnosed by computed tomography. All documented AC examinations for this group of patients had significant findings such as 4+ cells, hyphema, or lens fragments. Conclusions: The finding of IOFB on a DFE for patients with a CMFB without clinical evidence of penetrating injury is very rare. C1 [Luo, Zhonghui; Gardiner, Matthew] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Gardiner, M (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Matthew_Gardiner@meei.harvard.edu OI Gardiner, Matthew/0000-0002-8864-2379 NR 7 TC 7 Z9 7 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2010 VL 117 IS 11 BP 2218 EP 2221 DI 10.1016/j.ophtha.2010.02.034 PG 4 WC Ophthalmology SC Ophthalmology GA 668JI UT WOS:000283264200027 PM 20557942 ER PT J AU Bhattacharyya, N Lin, HW AF Bhattacharyya, Neil Lin, Harrison W. TI Changes and consistencies in the epidemiology of pediatric adenotonsillar surgery, 1996-2006 SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID RECURRENT THROAT INFECTION; CHILDREN; TONSILLECTOMY; SLEEP AB OBJECTIVE: Determine changes in rates for pediatric adenotonsillar procedures over time with attention to infectious indications STUDY DESIGN: Historical cohort study. SETTING: Academic medical center. SUBJECTS AND METHODS: The National Survey of Ambulatory Surgery and the National Hospital Discharge Survey 1996 and 2006 releases were examined, extracting all cases of pediatric tonsillectomy, adenotonsillectomy, and adenoidectomy. The aggregate numbers and rates of adenotonsillar procedures performed overall and specifically for chronic infectious etiologies were determined. These procedure rates were then compared to determine differences in performance rates between 1996 and 2006. RESULTS: In 1996, an estimated 441,870 +/- 23,315 children underwent some form of adenotonsillar surgery in the ambulatory and inpatient settings (60,034 +/- 6994 tonsillectomies, 255,217 +/- 18,960 adenotonsillectomies, and 126,619 +/- 11,627 adenoidectomies), while in 2006, the total rose to 695,029 +/- 36,979 children (58,111 +/- 9645 tonsillectomies, 506,778 +/- 32,054 adenotonsillectomies, and 129,540 +/- 15,714 adenoidectomies). However, when examined according to infectious indications, a notable decline in the population rate of tonsillectomy from 0.62 per 1000 children in 1996 to 0.53 per 1000 in 2006 was found (P = 0.252). Moreover, the larger decline in the rate of adenotonsillectomy for infectious indications from 2.20 per 1000 to 1.46 per 1000 was significant (P = 0 003). There was no significant change adenoidectomy rates for chronic infectious etiologies (0 25 versus 021 per 1000, P = 0.326) CONCLUSION: Although there was an overall increase in the rate of performance of adenotonsillar surgery, population adjusted performance rates of these procedures specifically for infectious indications declined from 1996 to 2006. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation All rights reserved C1 [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. [Bhattacharyya, Neil; Lin, Harrison W.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 40 Z9 41 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2010 VL 143 IS 5 BP 680 EP 684 DI 10.1016/j.otohns.2010.06.918 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 673DT UT WOS:000283639900014 PM 20974339 ER PT J AU Bhattacharyya, N Shapiro, NL Vakharia, KT AF Bhattacharyya, Neil Shapiro, Nina L. Vakharia, Kalpesh T. TI Influence of race and ethnicity on access to care among children with frequent ear infections SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID OTITIS-MEDIA; RISK-FACTORS; HEALTH-CARE; DISPARITIES AB OBJECTIVE: Determine the impact of racial/ethnic disparities on access to care for children with frequent ear infections (FEI). Identify disparities to target for intervention. STUDY DESIGN: Cross-sectional analysis of national database SETTING: Academic medical center SUBJECTS AND METHODS: The National Health Interview Survey (1997 to 2006) was utilized to identify children with FEI (defined as three or more ear infections in the preceding year) Age, sex, race/ethnicity. income level. and insurance status were extracted. Access to care was measured by ability to afford medical care and prescription medications, specialist visitation, and emergency department visas Multivariate analysis determined the influence of demographic variables on the ability to access health care resources RESULTS: An annualized population of 4 65 +/- 0.08 million children reported FEI. Overall, 3.7 percent could not afford care, 5 6 percent could not afford prescriptions, and only 25.8 percent saw a specialist. A larger percentage of the black. (42.7%) and Hispanic children (34 5%) with FEI were below the poverty level, versus white children (12 4%; P < 0.001), 18.2 percent of Hispanic children were uninsured, versus 6.5 percent of white children (P < 0.001). On multivariate analysis, children with FEI that Were black or Hispanic had increased odds ratios relative to white children for 1) not being able to afford prescription medications (odds ratios [OR] 1.76 and 1.47, respectively, P < 0 002), 2) not being able to see a specialist (OR 1 62 and 1.86, respectively; P < 0001): and 3) visiting the emergency department (OR 2 50 and 1.32, respectively; P < 0 001) CONCLUSION: Racial/ethnic disparities among children with FEI significantly influence health care resource access and utilization. These disparities should be targeted for intervention (C) 2010 American Academy of Otolaryngology Head and Neck Surgery Foundation. All rights reserved. C1 [Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Brigham & Womens Hosp,Div Otolaryngol Head & Neck, Boston, MA 02115 USA. [Vakharia, Kalpesh T.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02115 USA. [Shapiro, Nina L.] Univ Calif Los Angeles, Div Otolaryngol Head & Neck Surg, Los Angeles, CA USA. RP Bhattacharyya, N (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Brigham & Womens Hosp,Div Otolaryngol, 45 Francis St, Boston, MA 02115 USA. NR 13 TC 12 Z9 12 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2010 VL 143 IS 5 BP 691 EP 696 DI 10.1016/j.otohns.2010.06.911 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 673DT UT WOS:000283639900016 PM 20974341 ER PT J AU Heist, EK Tondo, C Blendea, D Ruskin, JN Mansour, M AF Heist, E. Kevin Tondo, Claudio Blendea, Daniel Ruskin, Jeremy N. Mansour, Moussa TI Mapping and Ablation of Atypical AVNRT from the Morphologic Left Atrium in a Patient with Dextrocardia and Situs Inversus SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE ablation; SVT; electrophysiology-clinical ID NODAL REENTRANT TACHYCARDIA; SLOW PATHWAY ABLATION AB A 75-year-old woman with dextrocardia, situs inversus, and subpulmonic outflow obstruction presented with recurrent supraventricular tachycardia (SVT). This SVT was easily inducible during electrophysiology study, and pacing maneuvers during SVT were consistent with atypical, slow-slow atrioventricular nodal reentrant tachycardia (AVNRT). The His bundle was identified in the low postero-septal morphologic right atrium, at the typical anatomic site for slow pathway ablation of AVNRT. Mapping of the retrograde earliest atrial electrogram during AVNRT localized this site to the mid-septal morphologic left atrium, and cryoablation at this site terminated the AVNRT and rendered it noninducible. (PACE 2010; e106-e109). C1 [Heist, E. Kevin; Blendea, Daniel; Ruskin, Jeremy N.; Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiac Arrhythmia Unit, Ctr Heart, Boston, MA 02114 USA. [Tondo, Claudio] Univ Cattolica Sacro Cuore, St Camillo Forlanini Hosp, Cardiac Arrhythmia & Heart Failure Res Ctr, I-00168 Rome, Italy. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiac Arrhythmia Unit, Ctr Heart, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org FU Biotronik; St. Jude Medical FX EKH: Biotronik (speaker, research support), Boston Scientific (speaker), Medtronic (speaker), Sorin (speaker) St. Jude Medical (speaker, consultant, research support) NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD NOV PY 2010 VL 33 IS 11 BP e106 EP e109 DI 10.1111/j.1540-8159.2010.02730.x PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 669UA UT WOS:000283374500002 PM 20345629 ER PT J AU Cizginer, S Karaca, C Konuk, Y Kambadakone, AR Mino-Kenudson, M Macfarlane, CE Brugge, WR AF Cizginer, S. Karaca, C. Konuk, Y. Kambadakone, A. R. Mino-Kenudson, M. Macfarlane, C. E. Brugge, W. R. TI EUS-Guided Injection of Irinotecan Into the Pancreas SO PANCREAS LA English DT Meeting Abstract C1 [Cizginer, S.; Karaca, C.; Brugge, W. R.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Konuk, Y.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kambadakone, A. R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Macfarlane, C. E.] Biocompatibles UK Ltd, Farnham, Surrey, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2010 VL 39 IS 8 BP 1315 EP 1316 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 664FU UT WOS:000282946600075 ER PT J AU Mukherjee, R Huang, W Tepikin, AV Gukovskaya, A Criddle, DN Sutton, R AF Mukherjee, R. Huang, W. Tepikin, A. V. Gukovskaya, A. Criddle, D. N. Sutton, R. TI Alisporivir (Deb025) Prevents Necrosis in and Decreases the Severity of Experimental Pancreatitis SO PANCREAS LA English DT Meeting Abstract C1 [Mukherjee, R.; Huang, W.; Tepikin, A. V.; Criddle, D. N.] Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. [Mukherjee, R.; Huang, W.; Sutton, R.] Royal Liverpool Univ Hosp, NIHR Pancreas Biomed Res Unit, Liverpool, Merseyside, England. [Gukovskaya, A.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Gukovskaya, A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2010 VL 39 IS 8 BP 1335 EP 1335 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 664FU UT WOS:000282946600160 ER PT J AU Perez-Johnston, R Narin, O Mino-Kenudson, M Ingkakul, T Warshaw, AL Fernandez-del Castillo, C Sahani, VD AF Perez-Johnston, R. Narin, O. Mino-Kenudson, M. Ingkakul, T. Warshaw, A. L. Fernandez-del Castillo, C. Sahani, V. D. TI Frequency and Significance of Calcification in IPMN SO PANCREAS LA English DT Meeting Abstract C1 [Perez-Johnston, R.; Narin, O.; Sahani, V. D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ingkakul, T.; Warshaw, A. L.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2010 VL 39 IS 8 BP 1340 EP 1340 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 664FU UT WOS:000282946600181 ER PT J AU Rakonczay, Z Biczo, G Dosa, S Shalbuyeva, N Hracsko, Z Kukor, Z Venglovecz, V Varga, IS Ivanyi, B Wittmann, T Gukovskaya, A Takacs, T Hegyi, P AF Rakonczay, Z., Jr. Biczo, G. Dosa, S. Shalbuyeva, N. Hracsko, Z. Kukor, Z. Venglovecz, V. Varga, I. S. Ivanyi, B. Wittmann, T. Gukovskaya, A. Takacs, T. Hegyi, P. TI Mitochondial Injury Precedes NF-kappa B and Premature Trypsinogen Activation in L-lysine-induced Acute Pancreatitis in Rats SO PANCREAS LA English DT Meeting Abstract C1 [Rakonczay, Z., Jr.; Biczo, G.; Wittmann, T.; Takacs, T.; Hegyi, P.] Univ Szeged, Dept Med 1, Szeged, Hungary. [Dosa, S.; Ivanyi, B.] Univ Szeged, Dept Pathol, Szeged, Hungary. [Hracsko, Z.; Varga, I. S.] Univ Szeged, Dept Biochem & Mol Biol, Szeged, Hungary. [Venglovecz, V.] Univ Szeged, Dept Pharmacol & Pharmacotherapy, Szeged, Hungary. [Shalbuyeva, N.; Gukovskaya, A.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kukor, Z.] Semmelweis Univ, Dept Med Chem Mol Biol & Pathobiochem, H-1085 Budapest, Hungary. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2010 VL 39 IS 8 BP 1342 EP 1342 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 664FU UT WOS:000282946600188 ER PT J AU Valsangkar, NP Bush, DM Michaelson, JS Fernandez-del Castillo, C Warshaw, AL Thayer, SP AF Valsangkar, N. P. Bush, D. M. Michaelson, J. S. Fernandez-del Castillo, C. Warshaw, A. L. Thayer, S. P. TI Race Does Not Substantially Affect Outcomes in Patients With Pancreatic Cancer SO PANCREAS LA English DT Meeting Abstract C1 [Valsangkar, N. P.; Michaelson, J. S.; Fernandez-del Castillo, C.; Warshaw, A. L.; Thayer, S. P.] Mass Gen Hosp, Dept Surg, Boston, MA USA. [Bush, D. M.; Michaelson, J. S.] Mass Gen Hosp, Lab Quantitat Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2010 VL 39 IS 8 BP 1354 EP 1354 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 664FU UT WOS:000282946600242 ER PT J AU Hariri, LP Unizony, S Stone, J Mino-Kenudson, M Sharma, A Matsubara, O Mark, EJ AF Hariri, Lida P. Unizony, Sebastian Stone, John Mino-Kenudson, Mari Sharma, Amita Matsubara, Osamu Mark, Eugene J. TI Acute fibrinous and organizing pneumonia in systemic lupus erythematosus: A case report and review of the literature SO PATHOLOGY INTERNATIONAL LA English DT Article DE collagen vascular disease; connective tissue disease; diffuse alveolar damage; fibrinous organizing pneumonia; interstitial pneumonitis ID COLLAGEN VASCULAR-DISEASE; PULMONARY MANIFESTATIONS; LUNG-DISEASE AB Pulmonary manifestations of systemic lupus erythematosus (SLE) typically include pleuritis, alveolar hemorrhage, and infectious pneumonia due to immunosuppression with less common entities including bronchiolitis, interstitial pneumonia, and pulmonary fibrosis. More rare manifestations include organizing pneumonia (OP) and diffuse alveolar damage (DAD). A similar but distinct entity of acute fibrinous and organizing pneumonia (AFOP), characterized by intra-alveolar fibrin deposition and associated organizing pneumonia, has been reported in association with connective tissue disorders, but has not been described in association with SLE. Reported herein is a patient with SLE and accompanying antiphospholipid syndrome with recent pulmonary embolism, persistent respiratory symptomology, and persistent radiographic abnormalities who underwent lung biopsy displaying features of AFOP. This case in conjunction with previous literature indicates that AFOP can be a manifestation of connective tissue disease including SLE and may be an underreported variant of medical lung disease due to overlap in histological characteristics with OP and DAD. C1 [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Unizony, Sebastian; Stone, John] Massachusetts Gen Hosp, Dept Rheumatol, Boston, MA 02114 USA. [Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Matsubara, Osamu] Natl Def Med Coll, Dept Pathol, Tokorozawa, Saitama 359, Japan. RP Hariri, LP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren Bldg,Room 219, Boston, MA 02114 USA. EM lhariri@partners.org NR 21 TC 22 Z9 27 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD NOV PY 2010 VL 60 IS 11 BP 755 EP 759 DI 10.1111/j.1440-1827.2010.02586.x PG 5 WC Pathology SC Pathology GA 666ES UT WOS:000283096500008 PM 20946526 ER PT J AU Ginde, AA Sullivan, AF Corel, B Caceres, JA Camargo, CA AF Ginde, Adit A. Sullivan, Ashley F. Corel, Blanka Caceres, J. Alfredo Camargo, Carlos A., Jr. TI Reevaluation of the effect of mandatory interpreter legislation on use of professional interpreters for ED patients with language barriers SO PATIENT EDUCATION AND COUNSELING LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 14-17, 2009 CL New Orleans, LA SP Soc Acad Emergency Med DE Interpreters; Language barriers; Emergency department; Immigrants; Communication ID EMERGENCY AB Objective: We sought to compare emergency department (ED) use of professional interpreters in 2008 to previously reported 2002 data. Methods: We surveyed consecutive adult patients for two 24-h periods at 4 Boston EDs in 2008. We used identical questions as in our 2002 study to assess English language barriers and to measure use and type of interpreter for those with language barriers. Results: We enrolled 498 patients (66% of eligible). Of these, 8% had a significant English language barrier, but any interpreter was used for only 69% of these patients; the corresponding data for 2002 were 11% and 89%, respectively. In 2008, compared to 2002, professional interpreter use was similar (18% vs. 15%; p = 0.70), but a friend or family member interpreted more often (59% vs. 24%; p < 0.001), and hospital staff less often (10% vs. 47%; p < 0.001). Conclusion: We found that use of professional interpreters by Boston ED patients with language barriers remained low, despite publicity of the state mandatory interpreter law. However, a majority were comfortable with a friend or family member serving as the interpreter for the clinical encounter, a finding that may contribute to the limited usage of professional interpreters. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Ginde, Adit A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. [Sullivan, Ashley F.; Corel, Blanka; Caceres, J. Alfredo; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 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@ucdenver.edu RI Siry, Bonnie/D-7189-2017 NR 9 TC 14 Z9 14 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD NOV PY 2010 VL 81 IS 2 BP 204 EP 206 DI 10.1016/j.pec.2010.01.023 PG 3 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 673WY UT WOS:000283696100012 PM 20193999 ER PT J AU Deep, KS Hunter, A Murphy, K Volandes, A AF Deep, Kristy S. Hunter, Ashley Murphy, Kevin Volandes, Angelo TI "It helps me see with my heart": How video informs patients' rationale for decisions about future care in advanced dementia SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Advance care planning; Advanced dementia; Decision aids; Video; End-of-life decision making; Communication; Death and dying; Advance directives ID RANDOMIZED CONTROLLED-TRIAL; TREATMENT PREFERENCES; ETHNIC-DIFFERENCES; LIFE; END; DIRECTIVES; COMMUNICATION; CANCER; DEATH; PHYSICIANS AB Objective: To explore how a video of a patient with advanced dementia impacts the rationale for patients' decisions about future care. Methods: Participants were read a verbal description of advanced dementia and asked their preferences for future care-either life-prolonging, limited, or comfort care-and the rationale for that choice. Participants then watched a video of a patient with advanced dementia and again stated their preferred level of care and the rationale. Thematic content analysis was utilized to develop common themes among the rationale of participants in each response category. Results: We interviewed 120 participants. The rationale of those who initially chose life-prolonging or limited care (47/120) emphasized lengthening life and cited an inherent good of medical treatment. Those who initially chose comfort care (60/120) focused on avoiding suffering and quality of life. Post-video, 107/120 participants chose comfort care and the rationale focused on the experience of the patient and family rather than treatment-centered considerations. Participants found great value in the video images. Conclusions: While pre-video reasoning reflects general beliefs about extending life and the inherent good of treatment, the post-video reasoning reveals more focus on the experience of the actual patient and family. Practice implications: Video may serve an important role in advanced care planning by enriching the understanding of the condition and allowing one to imagine a future health state. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Deep, Kristy S.] Univ Kentucky, Coll Med, Dept Med, Div Gen Internal Med, Lexington, KY 40536 USA. [Volandes, Angelo] Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA 02114 USA. RP Deep, KS (reprint author), Univ Kentucky, Dept Internal Med, 740 S Limestone, Lexington, KY 40536 USA. EM Klshef0@email.uky.edu NR 28 TC 8 Z9 9 U1 3 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD NOV PY 2010 VL 81 IS 2 BP 229 EP 234 DI 10.1016/j.pec.2010.02.004 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 673WY UT WOS:000283696100016 PM 20194000 ER PT J AU Rodriguez-Galindo, C AF Rodriguez-Galindo, Carlos TI CLINICAL RESEARCH IN PEDIATRIC RARE CANCERS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 775 EP 776 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200005 ER PT J AU Roberts, C AF Roberts, C. TI THE MOLECULAR BASIS OF ONCOGENESIS IN RHABDOID TUMORS AND IMPLICATIONS FOR THERAPY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Roberts, C.] Dana Farber Canc Inst, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 777 EP 777 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200010 ER PT J AU Drotar, D Alderfer, M Ewing, L Katz, E Muriel, A Wetherington, C Rohan, J Vinks, S AF Drotar, D. Alderfer, Melissa Ewing, Lin Katz, Ernest Muriel, Anna Wetherington, Crista Rohan, Jennifer Vinks, Sander TI MULTISITE STUDY OF ADHERENCE TO 6MP TREATMENT IN PEDIATRIC LEUKEMIA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Alderfer, Melissa] Univ Penn, Sch Med, CHOP Canc Ctr, Philadelphia, PA 19104 USA. [Ewing, Lin] Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Katz, Ernest] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA. [Muriel, Anna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wetherington, Crista] Childrens Med Ctr, Ctr Pediat Psychiat, Dallas, TX 75235 USA. [Rohan, Jennifer] Cincinnati Childrens Hosp Med Ctr, Div Behav Med Clin Psych, Cincinnati, OH USA. [Vinks, Sander] Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, Cincinnati, OH 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 779 EP 779 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200016 ER PT J AU Cantor, A Woo, A Akie, T Karen, W AF Cantor, Alan Woo, Andrew Akie, Thomas Karen, Wieland TI INCREASED INTERFERON-ALPHA SIGNALING DURING MEGAKARYOCYTE ONTOGENY: IMPLICATIONS FOR THE SPONTANEOUS RESOLUTION OF DOWN SYNDROME TRANSIENT MYELOPROLIFERATIVE DISORDER SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Cantor, Alan; Woo, Andrew; Akie, Thomas] Childrens Hosp, Boston, MA 02115 USA. [Cantor, Alan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Karen, Wieland] Tech Univ Munich, Childrens Hosp, Munich, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 795 EP 795 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200074 ER PT J AU Aguilar, L Manzanera, A Moran, C Kieran, M Goldberg, J Portnow, J New, P Chiocca, EA Aguilar-Cordova, E Brace-O'Neill, J AF Aguilar, Laura Manzanera, Andrea Moran, Claudia Kieran, Mark Goldberg, John Portnow, Jana New, Pamela Chiocca, E. Antonio Aguilar-Cordova, Estuardo Brace-O'Neill, Jill TI TRANSITION OF ADV-TK GENE TRANSFER APPROACH FROM ADULT TO PEDIATRIC ONCOLOGY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Aguilar, Laura] Childrens Hosp Boston, Auburndale, MA USA. [Aguilar, Laura] Advantagene Inc, Hematol Oncol, Auburndale, MA USA. [Manzanera, Andrea; Moran, Claudia] Advantagene Inc, Clin Res, Auburndale, MA USA. [Kieran, Mark; Brace-O'Neill, Jill] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldberg, John] Univ Miami, Miami, FL USA. [New, Pamela] Methodist Hosp, Methodist Neurol Inst, Houston, TX 77030 USA. [Chiocca, E. Antonio] Ohio State Univ, Columbus, OH 43210 USA. [Aguilar-Cordova, Estuardo] Advantagene Inc, Res, Auburndale, MA USA. [Brace-O'Neill, Jill] Advantagene, Pediat Oncol, Boston, MA 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 796 EP 796 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200078 ER PT J AU Joffe, S Najita, J AF Joffe, Steven Najita, Julie TI CANCER PATIENTS' AND PARENTS' ATTITUDES TOWARDS BANKING OF TISSUES FOR RESEAR SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Joffe, Steven; Najita, Julie] Dana Farber Canc Inst, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 796 EP 797 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200079 ER PT J AU Friedrich, P Chu-Sanchez, MSA Arambu, IC Aristizabal, P Baez, F Fuentes, S Gamboa, Y Ortiz, R Rodriguez-Galindo, C Antillon-Klussmans, F AF Friedrich, Paola Ah Chu-Sanchez, Maria Sabina Carolina Arambu, Ingrid Aristizabal, Paula Baez, Fulgencio Fuentes, Soad Gamboa, Yessica Ortiz, Roberta Rodriguez-Galindo, Carlos Antillon-Klussmans, Federico TI CURRENT BARRIERS FOR SUCCESSFUL TREATMENT OF CHILDREN WITH SARCOMA IN LOW INCOME COUNTRIES: A CLOSER LOOK SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Friedrich, Paola; Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ah Chu-Sanchez, Maria Sabina] Hosp Nino Panama, Panama City, Panama. [Carolina Arambu, Ingrid] Hosp Materno Infantil, Tegucigalpa, Honduras. [Aristizabal, Paula] Rady Childrens Hosp, San Diego, CA USA. [Aristizabal, Paula] Hosp Gen Tijuana, San Diego, CA USA. [Baez, Fulgencio; Ortiz, Roberta] Hosp Infantil La Mascota, Managua, Nicaragua. [Fuentes, Soad] Hosp Nacl Ninos Benjamin Bloom, San Salvador, El Salvador. [Gamboa, Yessica] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica. [Antillon-Klussmans, Federico] Unidad Nacl Oncol Pediat, Guatemala City, Guatemala. 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 797 EP 797 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200080 ER PT J AU Frazier, L Billmire, D Schlatter, M Krailo, M Cullen, J Rodriguez-Galindo, C Amatruda, J Egler, R Malogolowkin, M Olson, T Rescorla, F Ross, J Davis, M Frazier, AL AF Frazier, Lindsay Billmire, Deborah Schlatter, Marc Krailo, Mark Cullen, John Rodriguez-Galindo, Carlos Amatruda, James Egler, Rachel Malogolowkin, Marcio Olson, Tom Rescorla, Fred Ross, Jonathan Davis, Mary Frazier, A. Lindsay TI STAGE I GERM CELL TUMORS: OUTCOME OF A WATCH AND WAIT STRATEGY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Frazier, Lindsay; Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Billmire, Deborah] Indiana Univ, Dept Pediat Surg, Indianapolis, IN USA. [Krailo, Mark] Univ So Calif, Arcadia, CA USA. [Amatruda, James] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Egler, Rachel; Ross, Jonathan] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Olson, Tom] Emory Univ, Atlanta, GA 30322 USA. [Rescorla, Fred] Riley Hosp Children, Indianapolis, IN USA. [Davis, Mary] St Vincent Childrens Hosp, Grand Rapids, MI USA. [Malogolowkin, Marcio] Childrens Hosp Los Angeles, Los Angeles, CA 90027 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 805 EP 805 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200105 ER PT J AU Hale, J Dang, H Krailo, M Olson, T Donachie, P Nicholson, J Billmire, D Thornton, C Frazier, L AF Hale, Juliet Dang, Ha Krailo, Mark Olson, Thomas Donachie, Paul Nicholson, James Billmire, Deborah Thornton, Claire Frazier, Lindsay TI PAEDIATRIC MEDIASTINAL GERM CELL TUMOURS: ARE ALL PATIENTS HIGH RISK? SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Hale, Juliet] Newcastle Upon Tyne Hosp NHS Trust, Newcastle Upon Tyne, Tyne & Wear, England. [Dang, Ha] Natl Childhood Canc Fdn, Childrens Oncol Grp, Arcadia, CA USA. [Krailo, Mark] Univ So Calif, Coll Med, Arcadia, CA USA. [Olson, Thomas] Emory Univ, Sch Med, Div Paediat Haematol Oncol, Atlanta, GA USA. [Donachie, Paul] Univ Leicester, CCLG Data Ctr, Leicester, Leics, England. [Nicholson, James] Addenbrookes Hosp, Dept Paediat Oncol, Cambridge, England. [Billmire, Deborah] Riley Childrens Hosp, Indianapolis, IN USA. [Thornton, Claire] Royal Hosp, Dept Pathol, Belfast, Antrim, North Ireland. [Frazier, Lindsay] Dana Farber Canc Inst, Boston, MA 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 805 EP 805 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200107 ER PT J AU Pulsifer, M Delgado, I Tarbell, N Kuhlthau, K MacDonald, S Yock, T AF Pulsifer, Margaret Delgado, Irene Tarbell, Nancy Kuhlthau, Karen MacDonald, Shannon Yock, Torunn TI NEUROBEHAVIORAL FUNCTIONING IN PEDIATRIC BRAIN TUMOR PATIENTS AFTER PROTON BEAM RADIATION TREATMENT SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Pulsifer, Margaret; Delgado, Irene; Tarbell, Nancy; Kuhlthau, Karen; MacDonald, Shannon; Yock, Torunn] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 807 EP 807 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200113 ER PT J AU Bernt, K Faber, J Punt, N Davis, T Kung, A Armstrong, S AF Bernt, Kathrin Faber, Joerg Punt, Natalie Davis, Tina Kung, Andrew Armstrong, Scott TI DOT1L AND HISTONE 3 LYSINE 79 METHYLATION AS A THERAPEUTIC TARGET IN MIXED LINEAGE LEUKEMIA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Bernt, Kathrin; Faber, Joerg; Punt, Natalie; Kung, Andrew; Armstrong, Scott] Childrens Hosp, Dana Farber Canc Inst, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 812 EP 812 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200130 ER PT J AU Friedrich, P Chu-Sanchez, MSA Antillon-Klussman, F Arambu, IC Aristizabal, P Fuentes, S Gamboa, Y Ortiz, R Rodriguez-Galindo, C Baez, F AF Friedrich, Paola Ah Chu-Sanchez, Maria Sabina Antillon-Klussman, Federico Carolina Arambu, Ingrid Aristizabal, Paula Fuentes, Soad Gamboa, Yessika Ortiz, Roberta Rodriguez-Galindo, Carlos Baez, Fulgencio TI HIGH TUMOR BURDEN, HIGH RATE OF ABANDONMENT AND FEAR OF DISABLING SURGERY ARE AMONG THE INNERMOST BARRIERS TO TREATMENT OF PEDIATRIC SARCOMA IN RESOUCE-LIMITED SETTINGS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Friedrich, Paola; Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ah Chu-Sanchez, Maria Sabina] Hosp Nino Panama, Panama City, Panama. [Antillon-Klussman, Federico] Unidad Nacl Oncol Pediat, Guatemala City, Guatemala. [Carolina Arambu, Ingrid] Hosp Materno Infantil, Tegucigalpa, Honduras. [Aristizabal, Paula] Rady Childrens Hosp San Diego, San Diego, CA USA. [Aristizabal, Paula] Hosp Gen Tijuana, San Diego, CA USA. [Fuentes, Soad] Hosp Nacl Ninos Benjamin Bloom, San Salvador, El Salvador. [Gamboa, Yessika] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica. [Ortiz, Roberta; Baez, Fulgencio] Hosp Infantil La Mascota, Managua, Nicaragua. 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 815 EP 815 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200139 ER PT J AU Truong, T Cook, EF Weeks, JC Joffe, S AF Truong, Tony Cook, E. Francis Weeks, Jane C. Joffe, Steven TI KNOWLEDGE AND UNDERSTANDING OF THE INFORMED CONSENT PROCESS AMONG PARENTS OF CHILDREN ENROLLED ON CANCER CLINICAL TRIALS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Truong, Tony] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Cook, E. Francis] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 824 EP 824 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200167 ER PT J AU Frumm, S Fan, ZP Ross, KN Gupta, S VerPlank, L Suh, BC Duvall, J Marcaurelle, L Tolliday, N Stegmaier, K AF Frumm, Stacey Fan, Zi Peng Ross, Kenneth N. Gupta, Supriya VerPlank, Lynn Suh, Byung-Chul Duvall, Jeremy Marcaurelle, Lisa Tolliday, Nicola Stegmaier, Kimberly TI INTEGRATING DIVERSITY-ORIENTED SYNTHESIS AND EXPRESSION-BASED SCREENING TO IDENTIFY NEW INDUCERS OF NEUROBLASTOMA DIFFERENTIATION SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Frumm, Stacey; Fan, Zi Peng; Stegmaier, Kimberly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ross, Kenneth N.] Broad Inst, Canc Program, Cambridge, MA 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 826 EP 826 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200175 ER PT J AU Peyrl, A Azizi, A Reismueller, B Kieran, M Heinrich, M Czech, T Dieckmann, K Slave, I AF Peyrl, Andreas Azizi, Amedeo Reismueller, Bettina Kieran, Mark Heinrich, Monika Czech, Thomas Dieckmann, Karin Slave, Irene TI METRONOMIC ANTIANGIOGENIC THERAPY IN CHILDREN WITH RECURRENT BRAIN TUMORS OF DIFFERENT HISTOLOGIES SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Peyrl, Andreas; Azizi, Amedeo; Reismueller, Bettina; Heinrich, Monika; Slave, Irene] Med Univ Vienna, Dept Pediat, Vienna, Austria. [Kieran, Mark] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Czech, Thomas] Med Univ Vienna, Dept Neurosurg, Vienna, Austria. [Dieckmann, Karin] Med Univ Vienna, Dept Radiotherapy, Vienna, Austria. 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 829 EP 829 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200185 ER PT J AU Julio, M Hoffman, J Robinson, P Comeau, M Case, MA Buia, S AF Julio, Margaret Hoffman, Jill Robinson, Patricia Comeau, Michael Case, Mary Ann Buia, Stephanie TI MANAGING ONCOLOGY PATIENT'S PAIN IN THE OUTPATIENT SETTING SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Julio, Margaret; Hoffman, Jill; Robinson, Patricia; Comeau, Michael; Case, Mary Ann; Buia, Stephanie] Dana Farber Canc Inst, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 830 EP 830 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200189 ER PT J AU Gutierrez, A Dahlberg, S Neuberg, D Zhang, JH Grebliunaite, R Sanda, T Protopopov, A Kutok, J Larson, R Borowitz, M Loh, M Winter, S Mullighan, C Silverman, L Chin, L Hunger, S Sallan, S Look, T AF Gutierrez, Alejandro Dahlberg, Suzanne Neuberg, Donna Zhang, Jianhua Grebliunaite, Ruta Sanda, Takaomi Protopopov, Alexei Kutok, Jeffery Larson, Richard Borowitz, Michael Loh, Mignon Winter, Stuart Mullighan, Charles Silverman, Lewis Chin, Lynda Hunger, Stephen Sallan, Stephen Look, Thomas TI ABSENCE OF BIALLELIC TCR gamma LOCUS DELETIONS PREDICTS EARLY TREATMENT FAILURE IN PEDIATRIC T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Zhang, Jianhua] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Gutierrez, Alejandro; Silverman, Lewis; Sallan, Stephen; Look, Thomas] Childrens Hosp, Boston, MA 02115 USA. [Kutok, Jeffery] Brigham & Womens Hosp, Boston, MA 02115 USA. [Larson, Richard; Winter, Stuart] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Borowitz, Michael] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Loh, Mignon] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mullighan, Charles] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci & Med Oncol, Boston, MA 02115 USA. [Hunger, Stephen] Univ Colorado, Sch Med, Aurora, CO USA. [Hunger, Stephen] Univ Colorado, Childrens Hosp, Aurora, CO 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 834 EP 834 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200202 ER PT J AU Hettmer, S Wagers, AJ AF Hettmer, Simone Wagers, Amy J. TI SKELETAL MUSCLE PRECURSOR CELLS SERVE AS A CANCER CELL-OF-ORIGIN IN A NEW, ERAS-DRIVEN IN VIVO MODEL OF EMBRYONAL RHABDOMYOSARCOMA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Hettmer, Simone] DFCI Childrens Hosp Boston, Boston, MA USA. [Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Wagers, Amy J.] Joslin Diabet Ctr, Dept Stem Cell & Regenerat Biol, Boston, MA 02215 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 834 EP 835 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200204 ER PT J AU Kendal, T Houlahan, K Showers, L AF Kendal, Temple Houlahan, Kathleen Showers, Lynne TI ONCOLOGY COMMUNITY OUTREACH PROGRAM SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Kendal, Temple; Showers, Lynne] Childrens Hosp, Boston, MA 02115 USA. [Houlahan, Kathleen] Dana Farber Childrens Hosp Canc Care, Boston, MA USA. [Houlahan, Kathleen] HSCT Childrens Hosp Boston, Boston, MA 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 838 EP 838 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200217 ER PT J AU Goldsby, R Chen, Y Yasui, Y Raber, S Li, LD Diefenbach, K Shnorhavorian, M Kadan-Lottick, N Kastrinos, F Stovall, M Oeffinger, K Sklar, C Armstrong, G Robison, L Diller, L AF Goldsby, Robert Chen, Yan Yasui, Yutaka Raber, Shannon Li, Linda Diefenbach, Karen Shnorhavorian, Margarett Kadan-Lottick, Nina Kastrinos, Fay Stovall, Marilyn Oeffinger, Kevin Sklar, Charles Armstrong, Greg Robison, Leslie Diller, Lisa TI LATE GASTROINTESTINAL SEQUELAE IN SURVIVORS OF CHILDHOOD CANCER: A REPORT FROM THE CHILDHOOD CANCER SURVIVOR STUDY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Goldsby, Robert; Raber, Shannon; Li, Linda] UCSF, San Francisco, CA USA. [Chen, Yan; Yasui, Yutaka] Univ Alberta, Edmonton, AB, Canada. [Diefenbach, Karen] Yale New Haven Childrens Hosp, New Haven, CT USA. [Shnorhavorian, Margarett] Seattle Childrens, Seattle, WA USA. [Kadan-Lottick, Nina] Yale Univ, Sch Med, New Haven, CT USA. [Kastrinos, Fay] Brigham & Womens Hosp, Boston, MA 02115 USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Oeffinger, Kevin; Sklar, Charles] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Armstrong, Greg; Robison, Leslie] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Diller, Lisa] Dana Farber Canc Inst, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 839 EP 839 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200220 ER PT J AU Fernandez, C Li, N Grundy, P Perlman, E Shambergers, R Ehrlich, P Mullen, E Dome, J AF Fernandez, Conrad Li, Ning Grundy, Paul Perlman, Elizabeth Shambergers, Robert Ehrlich, Peter Mullen, Elizabeth Dome, Jeff TI ATTITUDES AND PRACTICE TOWARDS THE MANAGEMENT OF VERY LOW RISK WILMS TUMOR IN THE CHILDREN'S ONCOLOGY GROUP SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Fernandez, Conrad] IWK Hlth Ctr, Halifax, NS, Canada. [Li, Ning] Childrens Oncol Data Ctr, Gainesville, FL USA. [Grundy, Paul] Stollery Childrens Hosp, Edmonton, AB, Canada. [Perlman, Elizabeth] Childrens Mem Med Ctr Chicago, Chicago, IL USA. [Shambergers, Robert; Mullen, Elizabeth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ehrlich, Peter] Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. [Dome, Jeff] Childrens Natl Med Ctr, Washington, DC 20010 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 841 EP 842 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200228 ER PT J AU Patenaude, A Hewitt, L Schneider, K Novokmet, A Druker, H Diller, L Malkin, D AF Patenaude, Andrea Hewitt, Larissa Schneider, Katherine Novokmet, Ana Druker, Harriet Diller, Lisa Malkin, David TI GENETIC KNOWLEDGE AND ATTITUDES TOWARDS GENOMIC RESEARCH: COMPARISON OF VIEWS OF YOUNG ADULT SURVIVORS OF PEDIATRIC CANCER: WITH AND WITHOUT HEREDITARY CANCER ETIOLOGY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Patenaude, Andrea] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hewitt, Larissa; Schneider, Katherine; Diller, Lisa] Dana Farber Canc Inst, Brookline, MA USA. [Novokmet, Ana; Druker, Harriet] Hosp Sick Children, Toronto, ON M5G 1X8, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 843 EP 843 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200233 ER PT J AU Berk, D AF Berk, Deborah TI THE BENEFITS OF GROUP PSYCHOSOCIAL ACTIVITIES FOR SIBLINGS OF CANCER PATIENTS: RESULTS OF A 7 YEAR QUALITATIVE STUDY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Berk, Deborah] Dana Farber Canc Inst, Div Pediat Psychol Oncol, Boston, MA 02115 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 846 EP 846 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200243 ER PT J AU Athale, U Grace, R Min, J Hochberg, J Nayiager, T Taghzouti, N Kelly, K Laverdiere, C Silverman, L AF Athale, Uma Grace, Rachael Min, Jie Hochberg, Jess Nayiager, Trishana Taghzouti, Nawel Kelly, Kara Laverdiere, Caroline Silverman, Lewis TI MANAGEMENT OF THROMBOEMBOLISM IN CHILDREN AND ADOLESCENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Athale, Uma; Min, Jie] McMaster Univ, Hamilton, ON, Canada. [Grace, Rachael] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hochberg, Jess] Columbia Univ, Med Ctr, New York, NY USA. [Nayiager, Trishana] McMaster Childrens Hosp, Hamilton, ON, Canada. [Taghzouti, Nawel; Laverdiere, Caroline] Hosp Ste Justine, Montreal, PQ, Canada. [Silverman, Lewis] Harvard Univ, Dana Farber Canc Inst, Childrens Hosp Boston, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 855 EP 856 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200280 ER PT J AU Kelly, K Orjuela, M Ladas, EJ O'Brien, J Belden, L Silverman, LB AF Kelly, Kara Orjuela, Manuela Ladas, Elena J. O'Brien, Jane Belden, Laura Silverman, Lewis B. TI LOW DIETARY INTAKE OF CALCIUM ASSOCIATED WITH INCREASED RISK OF FRACTURE IN MALES UNDERGOING TREATMENT FOR ACUTE LYMPHOBLASTIC LEUKEMIA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Kelly, Kara; Orjuela, Manuela; Ladas, Elena J.] Columbia Univ, Med Ctr, Div Pediat Oncol, New York, NY USA. [O'Brien, Jane; Belden, Laura; Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 855 EP 855 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200279 ER PT J AU Crompton, B Jesneck, J Li, PY Gupta, S VerPlank, L Winckler, W Palmer, M Tolliday, N Kung, A Stegmaier, K AF Crompton, Brian Jesneck, Jonathan Li, Puyao Gupta, Supriya VerPlank, Lynn Winckler, Wendy Palmer, Michelle Tolliday, Nicola Kung, Andrew Stegmaier, Kimberly TI MODULATING EWS/FLI WITH A CHEMICAL GENOMIC APPROACH SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Crompton, Brian; Jesneck, Jonathan; Kung, Andrew; Stegmaier, Kimberly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, Puyao] Harvard Univ, Sch Med, Boston, MA USA. [Gupta, Supriya; VerPlank, Lynn; Winckler, Wendy; Palmer, Michelle; Tolliday, Nicola] Broad Inst, Cambridge, MA 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 875 EP 875 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200350 ER PT J AU Koloyou, PE Giani, A Zhan, QA Frank, N Murray, TG Murphy, GF Frank, MH Ksander, BR AF Koloyou, Paraskevi-Evi Giani, Andrea Zhan, Qian Frank, Natasha Murray, Timothy G. Murphy, George F. Frank, Markus H. Ksander, Bruce R. TI ABCB5 IDENTIFIES TUMOR INITIATING CELLS IN RETINOBLASTOMA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Koloyou, Paraskevi-Evi; Ksander, Bruce R.] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA USA. [Giani, Andrea] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Zhan, Qian] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Frank, Natasha] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Murray, Timothy G.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Murphy, George F.] Brigham & Womens Hosp, Dermopathol Clin Serv, Boston, MA 02115 USA. [Frank, Markus H.] Harvard Univ, Childrens Hosp, Sch Med, 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 897 EP 898 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200431 ER EF