FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Renaud, B Coma, E Hayon, J Gurgui, M Longo, C Blancher, M Jouannic, I Betoulle, S Roupie, E Fine, MJ AF Renaud, B. Coma, E. Hayon, J. Gurgui, M. Longo, C. Blancher, M. Jouannic, I. Betoulle, S. Roupie, E. Fine, M. J. CA PNEUMOCOM Study Investigators TI Investigation of the ability of the Pneumonia Severity Index to accurately predict clinically relevant outcomes: a European study SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE adverse outcomes; community-acquired pneumonia; mortality; Pneumonia Severity Index; prediction rules; validity ID COMMUNITY-ACQUIRED PNEUMONIA; LOW-RISK PATIENTS; CONTROLLED-TRIAL; CARE; MANAGEMENT; VALIDATION; GUIDELINES; DIAGNOSIS; RULE; HOSPITALIZATION AB In order to confirm the validity of the Pneumonia Severity Index (PSI) for patients in Europe, data from adults with pneumonia who were enrolled in two prospective multicentre studies, conducted in France (Pneumocom-1, n = 925) and Spain (Pneumocom-2, n = 853), were compared with data from the original North American study (Pneumonia PORT, n = 2287). The primary outcome was 28-day mortality; secondary outcomes were subsequent hospitalisation for outpatients, and intensive care unit admission and length of stay for inpatients. All outcomes within individual risk classes, and mortality rates in low-risk (PSI I-III) and higher-risk patients, were compared across the three cohorts. Overall mortality rates were 4.7% in Pneumonia PORT, 6.3% in Pneumocom-2 and 10.6% in Pneumocom-1 (p < 0.01), ranging from 0.4% to 1.6% (p 0.06) for low-risk patients and from 13.0% to 19.1% (p 0.24) for high-risk patients. Despite significant differences in baseline patient characteristics, none of the study outcomes differed within the low-risk classes. The sensitivity and negative predictive value of low-risk classification for mortality exceeded 93% and 98%, respectively. Thus, in two independent European cohorts, the PSI predicted patient outcomes accurately and reliably, particularly for low-risk patients. These findings confirm the validity of the PSI when applied to patients from Europe. C1 Hop Henri Mondor AP HP, Serv Accueil & Urgence, F-94000 Creteil, France. Ctr Hosp Univ Henri Mondor AP HP, Dept Emergency Med, Creteil, France. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. Hosp Mataro, Dept Emergency Med, Mataro, Spain. Ctr Hosp Intercommunal, Dept Emergency Med, St Germain En Laye, France. Hosp Santa Creu & Sant Pau, Dept Emergency Med, Barcelona, Spain. Ctr Hosp Reg Hotel Dieu, Dept Emergency Med, Nantes, France. Ctr Hosp Univ Grenoble, Dept Emergency Med, Rennes, France. Ctr Hosp Univ Rennes, Dept Emergency Med, Rennes, France. Ctr Hosp Gen Dangouleme, Dept Emergency Med, Angouleme, France. Ctr Hosp Univ Caen, Dept Emergency Med, Caen, France. RP Renaud, B (reprint author), Hop Henri Mondor AP HP, Serv Accueil & Urgence, 51 Ave Marechal Delattre Tassigny, F-94000 Creteil, France. EM bertrand.renaud@hmn.aphp.fr FU NIAID NIH HHS [K24 AI00149] NR 32 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD SEP PY 2007 VL 13 IS 9 BP 923 EP 931 DI 10.1111/j.1469-0691.2007.01772.x PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 197YW UT WOS:000248594300012 PM 17617186 ER PT J AU Vucic, S Black, K Baldassari, LE Chong, PST Dawson, KT Cros, D AF Vucic, S. Black, K. Baldassari, L. E. Chong, P. Siao Tick Dawson, K. T. Cros, D. TI Long-term effects of intravenous immunoglobulin in CIDP SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE CIDP; IVIg; conduction block ID INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY; RANDOMIZED CONTROLLED TRIAL; PLASMA-EXCHANGE; DOUBLE-BLIND; POLYNEUROPATHY; IVIG; CRITERIA AB Objective: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired demyelinating disease of the peripheral nervous system characterized by muscle weakness, areflexia or hyporeflexia, and sensory disturbances. Although short-term efficacy of intravenous immunoglobulin (IVIg) has been demonstrated in randomized-controlled trials, the data pertaining to long-term outcome in CIDP are limited. Consequently, the aim of the present study was to assess the long-term effects of IVIg on neurophysiological parameters in CIDP. Methods: Neurophysiological records from 11 CIDP patients, treated with IVIg for >= 12 months, were reviewed. Nerve conduction studies were assessed at baseline, 1-year, and last follow-up. Results: There was a significant reduction in the frequency of conduction blocks (pre-treatment nerve segments affected 61%; last follow-up 39%, P < 0.01) and a reduction in ongoing axonal loss (pre-treatment regions with spontaneous activity, 47%; post-treatment 29%, P < 0.01) with IVIg treatment. Further, there was significant improvement in sensory nerve conduction studies with IVIg treatment (sensory amplitudes reduced pre-treatment, 90% nerves tested; post-treatment, 62%, P < 0.01). Conclusions: The present study suggests that long-term IVIg maintenance therapy improves neurophysiological parameters in CIDP. However, CIDP patients remain IVIg dependent and new conduction blocks may develop. Significance: The present study suggests that long-term IVIg maintenance therapy improves neuro physiological parameters in CIDP, possibly by reducing the immune response and thereby fostering nerve healing. (C) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ New S Wales, Prince Wales Clin Sch, Prince Wales Med Res Inst, Kensington, NSW 2033, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Cros, D (reprint author), Univ New S Wales, Prince Wales Clin Sch, Prince Wales Med Res Inst, Kensington, NSW 2033, Australia. EM dcros@partners.org NR 30 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD SEP PY 2007 VL 118 IS 9 BP 1980 EP 1984 DI 10.1016/j.clinph.2007.05.001 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 209BW UT WOS:000249364200011 PM 17604689 ER PT J AU Smith, SR Bistis, K Zahka, NE Blais, MA AF Smith, Steven R. Bistis, Kimberly Zahka, Nicole E. Blais, Mark A. TI Perceptual-organizational characteristics of the rorschach task SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE neuropsychological assessment; rey-osterreith complex figure; rorschach; visuospatial; perception ID OSTERRIETH COMPLEX FIGURE; INKBLOT METHOD; ADOLESCENTS; DISORDER; CHILDREN; VALIDITY; RELIABILITY; PRODUCTIONS; SYSTEM; SAMPLE AB The present study was designed to begin to explore the perceptual and vuisuospatial organization required to respond to the Rorschach task. Prei,ious research has shown a relative independence of Rorschach scores from other measures of neurocognitive functioning (e.g., Zillner & Perry, 1996). However, many of the neuropsychological measures used in pres,ious studies did not require the patient to organize a complex visuospatial stimulus in the same way that the Rorschach does. lit this study, data from 27 children and adolescents administered the Rorschach and the Rey-Osterreith Complex Figure Test (ROCF) were examined. Results of analyses indicated that, accounting for age and Fail Scale IQ, there were a number of significant relationships between accuracy of ROCF renditions and Rorschach measures of developmental quality and perceptual accuracy. Implications for the understanding the nature of the Rorschach response process and its utility in clinical neuropsychology are discussed. C1 Univ Calif Santa Barbara, Dept Counseling, Santa Barbara, CA 93106 USA. Univ Calif Santa Barbara, Sch Psychol, Santa Barbara, CA 93106 USA. Erich Lindemann Mental Hlth Ctr, Dept Psychiat, Boston, MA USA. Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Smith, SR (reprint author), Univ Calif Santa Barbara, Dept Counseling, Santa Barbara, CA 93106 USA. EM ssmith@education.ucsb.edu NR 57 TC 4 Z9 4 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD SEP PY 2007 VL 21 IS 5 BP 789 EP 799 DI 10.1080/13854040600800995 PG 11 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 210KO UT WOS:000249455300005 PM 17676544 ER PT J AU Berenji, GR Iker, E Glass, EC AF Berenji, Gholam R. Iker, Emily Glass, Edwin C. TI Lymphoscintigraphic findings in chylous reflux in a lower extremity SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE lymphoscintigraphy; chylous reflux; swollen extremities ID NONINVASIVE EVALUATION; LYMPHEDEMA; DISORDERS; CHYLURIA C1 Med Imaging Ctr So Calif, Santa Monica, CA USA. Lymphedema Ctr Santa Monica, Santa Monica, CA USA. RP Glass, EC (reprint author), VA Greater Los Angeles Healthcare Syst, Nucl Med Serv 115, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM edwin.glass@va.gov NR 16 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD SEP PY 2007 VL 32 IS 9 BP 725 EP 728 DI 10.1097/RLU.0b013e318123eddd PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 203EX UT WOS:000248959000013 PM 17710029 ER PT J AU Schiller, DS Fung, HB AF Schiller, Daryl S. Fung, Horatio B. TI Posaconazole: An extended-spectrum triazok antifungal agent SO CLINICAL THERAPEUTICS LA English DT Review DE posaconazole; invasive fungal infections; neutropenia; graft-vs-host disease; oropharyngeal candidiasis ID IN-VITRO ACTIVITIES; ANTIMICROBIAL SURVEILLANCE PROGRAM; BLOOD-STREAM INFECTIONS; SCH 56592 POSACONAZOLE; STEM-CELL TRANSPLANT; OF-THE-LITERATURE; AMPHOTERICIN-B; CRYPTOCOCCUS-NEOFORMANS; ASPERGILLUS-FUMIGATUS; INVASIVE ASPERGILLOSIS AB Background: The incidence of invasive fungal infections (IFIs) caused by opportunistic filamentous molds is increasing, along with emerging fungal resistance. Posaconazole, a structural analogue of itraconazole that was approved for marketing in the United States in 2006, appears to be a promising antifungal agent. Objective: This article provides an overview of the pharmacology, efficacy, and tolerability of posaconazole when used for the prophylaxis and treatment of various common and rare fungal infections. Methods: Relevant information was identified through a search of MEDLINE (1966-April 2007), International Pharmaceutical Abstracts (1970-April 2007), and abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy using the terms posaconazole and SCH 56592. Additional resources were found by searching the reference lists of the identified articles and the US Food and Drug Administration Web site. Results: Posaconazole is available as an oral suspension. It is highly distributed to various sites, including bone, the central nervous system, and eye tissue. Its Vd is 2447 L when administered in multiple daily doses (up to 800 mg/d) in the presence of a highfat meal. Because it is excreted mostly as unchanged drug in the feces (77%), posaconazole can be administered to patients with poor renal function without any dose adjustment. Posaconazole has shown in vitro and in vivo activity against a wide variety of fungi, including those that are rare and relatively resistant. Two clinical trials have compared posaconazole with fluconazole or itraconazole for the prophylaxis of IFIs in immunocomprormsed patients. The first, a randomized, double-blind trial in 600 recipients of hematopoletic stem cell transplants, found that overall rates zole and fluconazole (5% vs 9%, respectively). The other, a randomized, open-label trial in 602 neutropenic patients, reported significantly fewer IFIs in patients receiving posaconazole compared with those receiving fluconazole or itraconazole (>2% vs >8%, respectively; P = 0.001). An additional 2 trials have investigated posaconazole for the treatment of oropharyngeal candidiasis (OPC) in patients with HIV infection. A randomized, controlled, evaluator-blinded study in 350 HIV-infected patients with OPC found similar 14-day clinical success rates with posaconazole and fluconazole (91.7% and 92.5%, respectively; 95% CI, -6.61 to 5.04), whereas an open-label study in 176 HIV-infected patients with a history of refractory OPC reported a 28-day clinical success rate of 75%. Numerous small studies and case reports have described successful posaconazole treatment of zygomycosis, aspergillosis, fusariosis, endemic dimorphic fungal infection, and superficial and subcutaneous fungal infections that were refractory to conventional antifungal agents or in patients who were unable to tolerate these agents. Posaconazole has been well tolerated. The most common complaints have been gastrointestinal in nature, including nausea (7%-8%) and diarrhea (3%-11%), although these have rarely led to permanent discontinuation of therapy. Other common adverse effects have included vomiting (4%-7%), headache (2%-8%), and liver enzyme elevations (2%-3%). Conclusions: Posaconazole suspension administered at up to 800 mg/d is a reasonable alternative to conventional antifungal agents for the prevention and treatment of IFIs in high-risk populations. It may also be suitable in patients with infections caused by rare or relatively resistant fungi, and those who are unable to tolerate long-term therapy with other antifungal agents. C1 James J Peters Vet Adm Med Ctr, Med Surg Patient Care Ctr, Bronx, NY 10468 USA. St Barnabas Hosp, Dept Pharm Serv, Livingston, NJ USA. RP Fung, HB (reprint author), James J Peters Vet Adm Med Ctr, Med Surg Patient Care Ctr, 130 W Kings Bridge Rd, Bronx, NY 10468 USA. EM horatio.fung@va.gov NR 140 TC 50 Z9 57 U1 1 U2 10 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP PY 2007 VL 29 IS 9 BP 1862 EP 1886 DI 10.1016/j.clinthera.2007.09.015 PG 25 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 222GH UT WOS:000250283700005 PM 18035188 ER PT J AU Hendrickson, RG Spivak, L Horowitz, BZ AF Hendrickson, R. G. Spivak, L. Horowitz, B. Z. TI Clinical characteristics of methamphetamine body stuffers SO CLINICAL TOXICOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Oregon Poison Ctr, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0731-3810 J9 CLIN TOXICOL JI Clin. Toxicol. PD SEP PY 2007 VL 45 IS 6 MA 22 BP 608 EP 609 PG 2 WC Toxicology SC Toxicology GA 214UE UT WOS:000249762900023 ER PT J AU Anzueto, A AF Anzueto, Antonio TI Disease modification in chronic obstructive pulmonary disease SO CLINICS IN CHEST MEDICINE LA English DT Article ID FLUTICASONE PROPIONATE; MAINTENANCE THERAPY; LUNG-FUNCTION; COPD PATIENTS; SALMETEROL; TIOTROPIUM; EFFICACY; HEALTH; LONG; REHABILITATION AB Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease in which patients experience a progressive decline in lung function, worsening exercise capacity, and frequent exacerbations. Based on clinical evidence, the progression of COPD could be modified by focus on earlier diagnosis; risk reduction through smoking cessation; symptom reduction with pharmacotherapy, improving health-related quality of life, and pulmonary rehabilitation; and decreasing complications by reducing exacerbations. Smoking cessation has been shown to slow lung function decline and reduce mortality, including deaths due to cardiovascular disease, lung cancer, and other respiratory disease (including COPD). C1 Audie L Murphy Mem Vet Adm Med Ctr, Pulm Dis Sect, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. RP Anzueto, A (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Pulm Dis Sect, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd,111 E, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu NR 28 TC 1 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD SEP PY 2007 VL 28 IS 3 BP 609 EP + DI 10.1016/j.ccm.2007.05.001 PG 9 WC Respiratory System SC Respiratory System GA 214FB UT WOS:000249720300010 PM 17720047 ER PT J AU Tannous, Z AF Tannous, Zeina TI Fractional resurfacing SO CLINICS IN DERMATOLOGY LA English DT Article ID CARBON-DIOXIDE LASER; FACIAL RHYTIDES; SKIN; PHOTOTHERMOLYSIS AB Fractional resurfacing produces a distinctive thermal damage pattern by creating discrete columns of thermal damage referred to as microthermal treatment zones. It characteristically spares the tissue surrounding each microthermal treatment zone leading to fast epidermal repair. Fractional resurfacing has been successfully used in treating a variety of skin conditions including melasma, dyschromia, lentigenes, wrinkles, and acne scars with minimal downtime. It is safer to use off the face and in darker skin types. (c) 2007 Published by Elsevier Inc. C1 Boston VA Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Dermatol Laser & Cosmet Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Tannous, Z (reprint author), Boston VA Med Ctr, Boston, MA USA. EM ztatinous1@hotmail.com NR 27 TC 47 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD SEP-OCT PY 2007 VL 25 IS 5 BP 480 EP 486 DI 10.1016/j.clindermatol.2007.05.007 PG 7 WC Dermatology SC Dermatology GA 216KU UT WOS:000249877700007 PM 17870526 ER PT J AU Klein, D O'Brien, CP AF Klein, Donald O'Brien, Charles P. TI Introduction SO CNS SPECTRUMS LA English DT Editorial Material C1 [Klein, Donald] Columbia Univ, New York, NY 10027 USA. [Klein, Donald] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Klein, Donald] New York Presbyterian Hosp, New York, NY 10021 USA. [O'Brien, Charles P.] Univ Penn, Inst Neurol Sci, Philadelphia, PA 19104 USA. [O'Brien, Charles P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Klein, D (reprint author), Columbia Univ, New York, NY 10027 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD SEP PY 2007 VL 12 IS 9 SU 16 BP 2 EP 2 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 256BP UT WOS:000252703000001 ER PT J AU Biederman, J Mick, E Spencer, T Doyle, R Joshi, G Hammerness, P Kotarski, M Aleardi, M Wozniak, J AF Biederman, Joseph Mick, Eric Spencer, Thomas Doyle, Robert Joshi, Gagan Hammerness, Paul Kotarski, Megan Aleardi, Megan Wozniak, Janet TI An open-label trial of aripiprazole monotherapy in children and adolescents with bipolar disorder SO CNS SPECTRUMS LA English DT Article ID MANIA RATING-SCALE; DOUBLE-BLIND; RISPERIDONE; OLANZAPINE; SCHIZOPHRENIA; TOLERABILITY; RELIABILITY; DIVALPROEX; VALIDITY AB Introduction: Aripiprazole is a novel second-generation antipsychotic approved for the treatment of bipolar disorder in adults but there is no systematic data available in pediatric bipolar disorder. Methods:This was an 8-week, open-label, prospective study of aripiprazole 9.4 +/- 4.2 mg/day monotherapy to assess the efficacy and tolerability of this compound in,treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale, Clinical Global Impressions-Improvement scale, and Brief Psychiatric Rating Scale. Adverse events we're assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. Results: Fifteen of the 19 bipolar youth (79%) completed the study. Aripiprazole treatment was associated with clinically and statistically significant improvement in mean Young Mania Rating Scale scores (-18.0 +/- 6.9, P<.0001). With the important exception of two cases of extrapyramidal symptoms that precipitated dropout, aripiprazole was well tolerated with no statistically significant increase in body weight (1.8 +/- 1.7 kg, P=.2). Conclusion: Open-label aripiprazole treatment was beneficial in the treatment of mania in youth with bipolar disorder. Future placebo-controlled, double blind studies are warranted. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Off, Joint Program, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Bipolar Clin & Res Program, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Off, Joint Program, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145 NR 23 TC 50 Z9 50 U1 5 U2 6 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD SEP PY 2007 VL 12 IS 9 BP 683 EP 689 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 213BU UT WOS:000249641700009 PM 17805214 ER PT J AU Marci, CD Glick, DM Lou, R Douguerty, DD AF Marci, Carl D. Glick, Debra M. Lou, Rebecca Douguerty, Daim D. TI Autonomic and prefrontal cortex responses to autobiographical recall of emotions SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article ID HEART-RATE-VARIABILITY; AMYGDALA; STIMULI; DEPRESSION; METAANALYSIS; DISORDER; VALENCE; IMAGERY; ANGER; PET AB The present study combined measures of regional cerebral blood flow (rCBF) using positron emission tomography (PET) with measures of the autonomic nervous system using skin conductance (SC), heart rate (HR), and the high frequency band of heart rate variability (HRV) in ten healthy participants who were exposed to autobiographical scripts of memories for three target emotions: anger, happiness, and sadness. According to the results, anger was the only emotion to show a significant increase in sympathetic activity, accompanied by a significant decrease in HRV when compared with a neutral script. Anger was also the only emotion to show significant changes in rCBF in the prefrontal cortex. By contrast, the results for the happy and sad conditions showed no significant increase in sympathetic activity and no changes in rCBF in the prefrontal cortex in comparison with the neutral script. The findings suggest that a relative increase in sympathetic activity with a reciprocal decrease in parasympathetic activity may be necessary to generate frontal activity in autobiographical recall of emotions. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Marci, CD (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM cmarci@partners.org FU NIMH NIH HHS [F32MH072073, K23MH001735] NR 37 TC 37 Z9 37 U1 0 U2 8 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD SEP PY 2007 VL 7 IS 3 BP 243 EP 250 DI 10.3758/CABN.7.3.243 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 223UH UT WOS:000250397300007 PM 17993210 ER PT J AU Simon, NM Shear, KM Thompson, EH Zalta, AK Perlman, C Reynolds, CF Frank, E Melhem, NM Silowash, R AF Simon, Naomi M. Shear, Katherine M. Thompson, Elizabeth H. Zalta, Alyson K. Perlman, Carol Reynolds, Charles F. Frank, Ellen Melhem, Nadine M. Silowash, Russell TI The prevalence and correlates of psychiatric comorbidity in individuals with complicated grief SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID BEREAVEMENT-RELATED DEPRESSION; TRAUMATIC GRIEF; DIAGNOSTIC-CRITERIA; DISORDER DISTINCT; SUICIDAL IDEATION; RATING-SCALE; REPLICATION; ANXIETY; STRESS; RISK AB Background: Complicated grief (CG), variously called pathological or traumatic grief, is a debilitating syndrome that is not currently included in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) nomenclature. One issue that remains under debate is whether this condition can be clearly distinguished from other psychiatric disorders, such as major depression and posttraumatic stress disorder, with which CG frequently coexists. Methods: Using a structured clinical interview for CG and the Structured Clinical Interview for DSM-IV trained experienced raters conducted careful diagnostic assessments of individuals seeking treatment of bereavernent-related distress. All study participants met criteria for a current CG syndrome. Liberal criteria were used to diagnose DSM-IV disorders, making no attempt to decide if symptoms could be explained by grief. Results: Of 206 who met the criteria for CG, 25% had no evidence of a Current DSM-IV Axis I disorder. When present, psychiatric comorbidity was associated with significantly greater severity of grief, however, even after adjustment for the presence of comorbidity, severity of CG symptoms was associated with greater work and social impairment. Limitations: It is likely that our study underestimated the rate of CG without comorbidity because fewer DSM diagnoses would have been made if a judgment about grief had been taken into consideration. Conclusions: Our data provide further Support for the need to identify CG as a psychiatric disorder. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Columbia Univ, Sch Social Work, New York, NY 10027 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nsimon@partners.org RI Melhem, Nadine/G-1510-2013; OI Zalta, Alyson/0000-0002-5159-8431 FU NIMH NIH HHS [P30 MH71944, MH30915, MH60783] NR 32 TC 82 Z9 84 U1 2 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD SEP-OCT PY 2007 VL 48 IS 5 BP 395 EP 399 DI 10.1016/j.comppsych.2007.05.002 PG 5 WC Psychiatry SC Psychiatry GA 206OS UT WOS:000249193400001 PM 17707245 ER PT J AU Chia, S Raffel, OC Takano, M Tearney, GJ Bouma, BE Jang, IK AF Chia, Stanley Raffel, O. Christopher Takano, Masamichi Tearney, Guillermo J. Bouma, Brett E. Jang, Ik-Kyung TI In-vivo comparison of coronary plaque characteristics using optical coherence tomography in women vs. men with acute coronary syndrome SO CORONARY ARTERY DISEASE LA English DT Article DE lipid-rich plaque; sex; thin-cap fibroatheroma ID SYNDROME EVALUATION WISE; GENDER-DIFFERENCES; RISK-FACTORS; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES; MYOCARDIAL-INFARCTION; HEART-DISEASE; MORPHOLOGY; SEX; THROMBOSIS AB Objective Women with acute coronary syndromes (ACS) have worse outcomes than men. Data on sex differences of culprit plaque characteristics are lacking. Intravascular optical coherence tomography (OCT) is a high-resolution imaging technique capable of in-vivo plaque characterization. The aim of this study was to compare culprit plaque characteristics in women and men presenting with ACS. Methods Patients undergoing coronary angiography after ACS were enrolled. We performed OCT imaging on the culprit lesions. Previously validated criteria for OCT plaque characterization were used: lipid was quantified on crosssectional image and lipid-rich plaque was defined as >= 2 involved quadrants; fibrous cap thickness was measured at the thinnest point and thin-cap fibroatheroma was defined as lipid-rich plaque with fibrous cap thickness less than 65 gm. Results Forty-two patients (33 men and nine women) were included. No significant sex differences were found in baseline characteristics. Lipid-rich plaques were identified in majority of patients. No significant difference, however, was seen in the frequency of lipid-rich plaques, thin-cap fibroatheroma or minimum fibrous cap thickness (79 vs. 89%; 45 vs. 67%; 53.8 vs. 45.4 mu m, respectively; P= NS) between men and women. Incidence of calcification, thrombus and plaque disruption were also similar. Conclusions No significant sex difference was seen in culprit plaque characteristics determined by OCT imaging in patients who presented with ACS. Coron Artery Dis 18:423-427 (c) 2007 Lippincott Williams & Wilkins. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Chiba Hokusoh Hosp, Nippon Med Sch, Dept Internal Med, Chiba, Japan. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St GRB 800, Boston, MA 02114 USA. EM ijang@partners.org FU NHLBI NIH HHS [R01-HL70039] NR 25 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD SEP PY 2007 VL 18 IS 6 BP 423 EP 427 DI 10.1097/MCA.0b013e3282583be8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 206JU UT WOS:000249180500002 PM 17700211 ER PT J AU Yasuhara, S Asai, A Sahani, ND Martyn, JAJ AF Yasuhara, Shingo Asai, Akihiro Sahani, Nita D. Martyn, J. A. Jeevendra TI Mitochondria, endoplasmic reticulum, and alternative pathways of cell death in critical illness SO CRITICAL CARE MEDICINE LA English DT Article DE apoptosis; necrosis; oncosis; autophagy; burn injury; sepsis; multiple organ dysfunction syndrome; pharmacotherapy AB Dying cells are distinguished by their biochemical and morphologic traits and categorized into three subtypes: apoptosis, oncosis (necrosis), and cell death with autophagy. Each of these types of cell death plays critical roles in tissue morphogenesis during normal development and in the pathogenesis of human diseases. Given that tissue homeostasis is controlled by the intricate balance between degeneration and regeneration, it is essential to understand the mechanisms of different forms of cell death to establish and improve therapeutic interventions for prevention and rescue of these cell death-related disorders. Critical illness, including sepsis, trauma, and burn injury, is often complicated by multiple organ dysfunction syndrome and is accompanied by increased cell death in parenchymal and nonparenchymal tissues. Accumulating evidence suggests that augmented cell death plays an important role in the organ failure in critical illness. We discuss possible therapeutic approaches for prevention of cell death, particularly apoptotic cell death. (Crit Care Med 2007; 35[Suppl.]:S488-S495) C1 [Yasuhara, Shingo] Shriners Hosp Children, Dept Anesthesiol & Crit Care, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yasuhara, S (reprint author), Shriners Hosp Children, Dept Anesthesiol & Crit Care, Massachusetts Gen Hosp, Boston, MA USA. EM shingo_yasuhara@yahoo.com; jmartyn@etherdome.mgh.harvard.edu OI Asai, Akihiro/0000-0003-3029-5754 FU NIGMS NIH HHS [R01 GM055082] NR 72 TC 19 Z9 21 U1 0 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 SEP PY 2007 VL 35 IS 9 SU S BP S488 EP S495 DI 10.1097/01.CCM.0000278045.91575.30 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA V24GW UT WOS:000208399900010 PM 17713398 ER PT J AU Bastepe, M AF Bastepe, Murat TI The GNAS locus: Quintessential complex gene encoding Gs alpha, XL alpha s, and other imprinted transcripts SO CURRENT GENOMICS LA English DT Review ID STIMULATORY-G-PROTEIN; PSEUDOHYPOPARATHYROIDISM-TYPE-IB; ALBRIGHT HEREDITARY OSTEODYSTROPHY; PROGRESSIVE OSSEOUS HETEROPLASIA; NUCLEOTIDE-BINDING PROTEIN; HORMONE-RELATED PEPTIDE; NEUROENDOCRINE SECRETORY PROTEIN; INCREASED INSULIN SENSITIVITY; GRADIENT GEL-ELECTROPHORESIS; SIGNAL-TRANSDUCTION PROTEIN AB The currently estimated number of genes in the human genome is much smaller than previously predicted. As an explanation for this disparity, most individual genes have multiple transcriptional units that represent a variety of biologically important gene products. GNAS exemplifies a gene of such complexity. One of its products is the subunit of the stimulatory heterotrimeric G protein (Gs alpha), a ubiquitous signaling protein essential for numerous different cellular responses. Loss-of-function and gain-of-function mutations within Gs alpha-coding GNAS exons are found in various human disorders, including Albright's hereditary osteodystrophy, pseudohypoparathyroidism, fibrous dysplasia of bone, and some tumors of different origin. While Gs alpha expression in most tissues is biallelic, paternal Gs alpha expression is silenced in a small number of tissues, playing an important role in the development of phenotypes associated with GNAS mutations. Additional products derived exclusively from the paternal GNAS allele include XL alpha s, a protein partially identical to Gs alpha and two non-coding RNA molecules, the A/B transcript and the antisense transcript. The maternal GNAS allele leads to NESP55, a chromogranin-like neuroendocrine secretory protein. In vivo animal models have demonstrated the importance of each of the exclusively imprinted GNAS products in normal mammalian physiology. However, although one or more of these products are also disrupted by most naturally occurring GNAS mutations, their roles in disease pathogenesis remain unknown. To further our understanding of the significance of this gene in physiology and pathophysiology, it will be important to elucidate the cellular roles and the mechanisms regulating the expression of each GNAS product. C1 [Bastepe, Murat] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Bastepe, Murat] Harvard Univ, Sch Med, Boston, MA USA. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, 50 Blossom St,Their 10, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu NR 168 TC 27 Z9 27 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2029 EI 1875-5488 J9 CURR GENOMICS JI Curr. Genomics PD SEP PY 2007 VL 8 IS 6 BP 398 EP 414 DI 10.2174/138920207783406488 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 273UC UT WOS:000253956200005 PM 19412439 ER PT J AU Delgado-Escueta, AV AF Delgado-Escueta, Antonio V. TI Advances in Lafora progressive myoclonus epilepsy SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review ID CARBOHYDRATE-BINDING DOMAIN; POLYGLUCOSAN BODY DISEASE; PROTEIN PHOSPHATASE; GENE-PRODUCT; GLYCOGEN; MUTATIONS; FORM; INTERACTS; TARGETS; R5 AB Lafora progressive myoclonus epilepsy is an autosomal recessive, fatal, generalized polyglucosan storage disorder that occurs in childhood or adolescence with stimulus sensitive epilepsy (resting and action myoclonias, grand mal and absence), dementia, ataxia and rapid neurologic deterioration. Mutations in EPM2A/laforin cause 58% of cases and mutations in EPM2B/malin cause 35% of cases. Accumulating evidence points to Lafora disease as primarily a disorder of cell death with impaired clearance of misfolded proteins, as shown by ubiquitin-positive aggressomes in HeLa cells transfected with mutated laforin, ubiquitin-positive polyglucosan inclusion bodies, and malin/E3 ubiquitin ligase polyubiquitination of laforin. How polyglucosan inclusion bodies accumulate is still a mystery. Polyglucosan accumulates hypothetically because of an overactive polyglucosan biosynthetic pathway or a breakdown in polyglucosan degradation. Five separate laboratories are looking for the biochemical pathways that connect laforin and malin to polyglucosan synthesis or degradation. A curative therapy for human Lafora disease with laforin replacement therapy using neutral pegylated immunoliposomes is being investigated. C1 VA Greater Los Angeles Healthcare Syst, Epilepsy Genet Genom Labs, Comprehens Epilepsy Program, Los Angeles, CA 90073 USA. RP Delgado-Escueta, AV (reprint author), VA Greater Los Angeles Healthcare Syst, Epilepsy Genet Genom Labs, Comprehens Epilepsy Program, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM escueta@ucla.edu NR 37 TC 50 Z9 51 U1 0 U2 2 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD SEP PY 2007 VL 7 IS 5 BP 428 EP 433 DI 10.1007/s11910-007-0066-7 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 279RH UT WOS:000254371800010 PM 17764634 ER PT J AU Willingham, FF Brugge, WR AF Willingham, Field F. Brugge, William R. TI Taking notes: translumenal flexible endascopy and endascopic surgery SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE endoscopy; laparoscopy; minimally invasive; surgical procedures ID PROSPECTIVE RANDOMIZED-TRIAL; PORCINE MODEL; LAPAROSCOPIC CHOLECYSTECTOMY; COLONOSCOPIC APPENDECTOMY; ENDOSCOPIC APPENDECTOMY; ABDOMINAL EXPLORATION; ADHESION-FORMATION; GASTRIC BYPASS; NOTES SURVIVAL; RISK-FACTORS AB Purpose of review To review the current state of natural orifice surgery and examine the concerns, challenges, and opportunities presented by translumenal research. Recent findings Translumenal endoscopic procedures have been the focus of extensive research. Researchers have reported natural orifice translumenal endoscopic surgery in a swine model in several areas involving the abdominal cavity. Diagnostic procedures have included endoscopic peritoneoscopy, liver biopsy, lymphadenectomy, and abdominal exploration. Several gynecologic procedures including tubal ligation, oophorectomy, and partial hysterectomy have been demonstrated using current commercial endoscopes. Gastrointestinal surgical procedures, including gastrojejunostomy, cholecystectomy, splenectomy, and distal pancreatectomy have been performed successfully via transgastric and/or transcolonic approaches. There have been no studies of natural orifice translumenal endoscopic surgery procedures published in humans. While fundamental questions about the emerging technology have not been scrutinized, limitations of the large animal model will pose a challenge to the development of large randomized trials. Summary While natural orifice translumenal endoscopic surgery may represent a paradigm shift and may offer significant benefits to patients, rigorous testing of the techniques is lacking and current data have been drawn from case series. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM wbrugge@partners.org OI Willingham, Field/0000-0002-7071-3001 NR 45 TC 22 Z9 25 U1 0 U2 0 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 SEP PY 2007 VL 23 IS 5 BP 550 EP 555 DI 10.1097/MOG.0b013e32828621b3 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 203EK UT WOS:000248957700010 PM 17762562 ER PT J AU Mount, DB AF Mount, David B. TI Collectrin and the kidney SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Editorial Material ID MOUSE; EXPRESSION; SNAP-23; MICE C1 Harvard Univ, Brigham & Womens Hosp, Inst Med,VA Boston Healthcare Syst, Div Renal,Dept Gen Internal Med, Boston, MA 02115 USA. RP Mount, DB (reprint author), Harvard Univ, Brigham & Womens Hosp, Inst Med,VA Boston Healthcare Syst, Div Renal,Dept Gen Internal Med, Room 542,4Blackfan Circle, Boston, MA 02115 USA. EM dmount@rics.bwh.harvard.edu NR 14 TC 4 Z9 4 U1 0 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 SEP PY 2007 VL 16 IS 5 BP 427 EP 429 DI 10.1097/MNH.0b013e3282e9acc5 PG 3 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 206KM UT WOS:000249182300007 PM 17693757 ER PT J AU Sindic, A Chang, MH Mount, DB Romeroa, MF AF Sindic, Aleksandra Chang, Min-Hwang Mount, David B. Romeroa, Michael F. TI Renal physiology of SLC26 anion exchangers SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE bicarbonate; Cl-; formate; hypertension; oxalate kidney stones; sulfate ID CONGENITAL CHLORIDE DIARRHEA; MEDULLARY COLLECTING DUCT; DYSPLASIA SULFATE TRANSPORTER; CL-/HCO3-EXCHANGER; INTERCALATED CELLS; MOTOR PROTEIN; MOUSE KIDNEY; STAS DOMAIN; FUNCTIONAL-CHARACTERIZATION; DIFFERENTIAL REGULATION AB Purpose of review The multifunctional anion exchanger family (Slc26) encompasses 11 identified genes, but only 10 encode real proteins (Slc26a10 is a pseudogene). Most of the Slc26 proteins function primarily as anion exchangers, exchanging sulfate, iodide, formate, oxalate, hydroxyl ion, and bicarbonate anions, whereas other Slc26 proteins function as chloride ion channels or anion-gated molecular motors. The aim of this review is to present recent studies on the molecular function of the Slc26 family and its role in renal physiology and pathophysiology. Recent findings In proximal tubules, Slc26a1 (Sat-1) mediates sulfate and oxalate transport across the basolateral membrane, while Slc26a6 (CFEX, Pat-1) mediates a variety of anion exchange at the apical membrane to facilitate transcellular sodium chloride absorption. Targeted deletion of murine Slc26a6 leads to intestinal hyperabsorption of oxalate, hyperoxaluria, and kidney stones. Slc26a4 (pendrin) and Slc26a7 are expressed in intercalated cells, and are involved in acid-base homeostasis and blood pressure regulation. Messenger RNA for Slc26a2, Slc26a9, and Slc26al 1 is also present in the kidney, yet the roles of these family members in renal physiology or pathophysiology are not clear. Summary Members of this multifunctional anion transporter family play evolving roles in the etiology of nephrolithiasis (Slc26a6) and hypertension (Slc26a4 and Slc26a6). Other Slc26 family members (Slc26a2, SIc26a9, Slc26a11) express mRNA in the kidney but their roles in renal physiology are not yet known. C1 Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Div Gen Internal Med, Boston, MA USA. RP Romeroa, MF (reprint author), Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, 200 1st St SW,Guggenheim 9-21D, Rochester, MN 55905 USA. EM romero.michael@mayo.edu FU NIDDK NIH HHS [DK056218, DK57708] NR 64 TC 49 Z9 52 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2007 VL 16 IS 5 BP 484 EP 490 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 206KM UT WOS:000249182300016 PM 17693766 ER PT J AU Bartling, SH Majdani, O Gupta, R Rodt, T Dullin, C Fitzgerald, PF Becker, H AF Bartling, S. H. Majdani, O. Gupta, R. Rodt, T. Dullin, C. Fitzgerald, P. F. Becker, H. TI Large scan field, high spatial resolution flat-panel detector based volumetric CT of the whole human skull base and for maxillofacial imaging SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Article; Proceedings Paper CT 7th Congress of the European-Skull-Base-Society CY 2005 CL Fulda, GERMANY SP European Skull Base Soc DE computerized tomography; skull base; maxillofacial; flat-panel detector ID BEAM COMPUTED-TOMOGRAPHY; COCHLEAR IMPLANT-SURGERY; X-RAY SCATTER; TEMPORAL BONE; IN-VITRO; SUBMILLIMETER ACCURACY; NAVIGATION; SYSTEM; IMAGER; DEHISCENCE AB Objectives: To assess the feasibility of flat-panel detector based volumetric CT (fpVCT) scanning of the whole human skull base and maxillofacial region, which has thus far only been demonstrated on small, excised specimens. Flat-panel detectors offer more favourable imaging properties than image intensifiers. It is therefore likely that they will replace them in cone-beam CT scanners that are currently used to scan parts of the skull base and maxillofacial region. Furthermore, the resolution of current CT imaging limits diagnosis, surgical planning and intraoperative navigation within these regions. fpVCT might overcome these limitations because it offers higher resolution of high contrast structures than current CT. Methods: Three embalmed cadaver heads were scanned in two scanners: an experimental fpVCT that offers a scan field large enough for a whole human head, and in a current multislice CT (MSCT). 28 structures were compared. Results: Both scanners produced bone images of diagnostic quality. Small high contrast structures such as parts of the ossicular chain and thin bony laminas were better delineated in fpVCT than in MSCT. fpVCT of maxillofacial region and skull base was rated superior to MSCT (P = 0.002) as found in this limited, experimental study. Conclusions: High spatial resolution fpVCT scanning of both regions in a whole human head is feasible and might be slightly superior to MSCT. fpVCT could improve diagnostic accuracy in selected cases, as well as surgical planning and intraoperative navigation accuracy. C1 Hannover Med Sch, Dept Neuroradiol, D-30625 Hannover, Germany. Hannover Med Sch, Dept Otorhinolaryngol, D-30625 Hannover, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hannover Med Sch, Dept Neurosurg, D-30625 Hannover, Germany. Goettingen Univ Hosp, Dept Diagnost Radiol, D-37075 Gottingen, Germany. Syst & Applicat Lab, GE Global Res, Moscow 123098, Russia. RP Bartling, SH (reprint author), Hannover Med Sch, Dept Neuroradiol, OE 8210 Carl Neuberg Str 1, D-30625 Hannover, Germany. EM soenkebartling@gmx.de NR 44 TC 16 Z9 19 U1 1 U2 4 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD SEP PY 2007 VL 36 IS 6 BP 317 EP 327 DI 10.1259/dmfr/19164138 PG 11 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA 207RN UT WOS:000249268900002 PM 17699701 ER PT J AU Oviedo, NJ Levin, M AF Oviedo, Nestor J. Levin, Michael TI smedinx-11 is a planarian stem cell gap junction gene required for regeneration and homeostasis SO DEVELOPMENT LA English DT Article DE planarian; gap junctional communication; stem cell; regeneration ID LEFT-RIGHT ASYMMETRY; SCHMIDTEA-MEDITERRANEA; PROGENITOR CELLS; COMMUNICATION; EXPRESSION; FAMILY; MORPHOGENESIS; MAINTENANCE; GERMLINE; PROTEINS AB The largely unknown mechanisms that regulate adult stem cells probably involve signals from neighboring differentiated cells. Gap junction channels providing direct cell-cell communication via small molecules are a crucial component of morphogenesis and normal physiology. However, no specific gap junction protein has yet been functionally linked to adult/somatic stem cell behavior in vivo or to organ regeneration. We report the identification and characterization of smedinx-11 - an innexin gap junction channel gene expressed in the adult stem cells (neoblasts) of the planarian Schmidtea mediterranea. smedinx-11 RNAi treatment inhibits regeneration and abrogates neoblast maintenance. Moreover, smedinx-11 expression is enriched in an irradiation-sensitive subpopulation('X2') and is required for proper expression of other stem cell-specific markers. Analyses of the smedinx-11 downregulation phenotype revealed a striking anterior-posterior neoblast gradient. Our data demonstrate a novel role for gap junction proteins and suggest gap junction-mediated signaling as a new and tractable control point for adult, somatic stem cell regulation. C1 Harvard Univ, Sch Dent Med, Ctr Regenrat & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Ctr Regenrat & Dev Biol, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCRR NIH HHS [C06 RR11244]; NICHD NIH HHS [R21 HD055850]; NIGMS NIH HHS [F32 GM078774, F32 GM078774-01A1, F32 GM078774-02] NR 54 TC 67 Z9 68 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP 1 PY 2007 VL 134 IS 17 BP 3121 EP 3131 DI 10.1242/dev.006635 PG 11 WC Developmental Biology SC Developmental Biology GA 199JU UT WOS:000248692900008 PM 17670787 ER PT J AU Heckman, BM Chakravarty, G Vargo-Gogola, T Gonzales-Rimbau, M Hadsell, DL Lee, AV Settleman, J Rosen, JM AF Heckman, Brandy M. Chakravarty, Geetika Vargo-Gogola, Tracy Gonzales-Rimbau, Maria Hadsell, Darryl L. Lee, Adrian V. Settleman, Jeffrey Rosen, Jeffrey M. TI Crosstalk between the p 1 90-B RhoGAP and lGF signaling pathways is required for embryonic mammary bud development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE p190-b; ARHGAP5; IGF-1R; IRS-1; IRS-2; mammary bud; epithelial-mesenchymal ID GTPASE-ACTIVATING PROTEIN; TERMINAL END BUDS; I IGF-I; DUCTAL MORPHOGENESIS; BREAST-CANCER; CELL-MIGRATION; GLAND; MOUSE; INSULIN; GROWTH AB P 190-B RhoGAP (p 190-B, also known as ARHGAP5) has been shown to play an essential role in invasion of the terminal end buds (TEBs) into the surrounding fat pad during mammary gland ductal morphogenesis. Here we report that embryos with a homozygous p 190-B gene deletion exhibit major defects in embryonic mammary bud development. Overall, p 190-B-deficient buds were smaller in size, contained fewer cells, and displayed characteristics of impaired mesenchymal proliferation and differentiation. Consistent with the reported effects of p190-B deletion on IGF-1R signaling, IGF-1R-deficient embryos also displayed a similar small mammary bud phenotype. However, unlike the p 190-B-deficient embryos, the IGF-1R-deficient embryos exhibited decreased epithelial proliferation and did not display mesenchymal defects. Because both IGF and p190-B signaling affect IRS-1/2, we examined IRS-1/2 double knockout embryonic mammary buds. These embryos displayed major defects similar to the p190-B-deficient embryos including smaller bud size. Importantly, like the p190-B-deficient buds, proliferation of the IRS-1/2-deficient mesenchyme was impaired. These results indicate that IGF signaling through p190-B and IRS proteins is critical for mammary bud formation and ensuing epithelial-mesenchymal interactions necessary to sustain mammary bud morphogenesis. (c) 2007 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Agr Res Serv Childrens Nutr Res Ctr, US Dept Agr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Breast Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Rosen, JM (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. EM jrosen@bcm.edu FU NCI NIH HHS [CA94118, CA030195-22, K99 CA127361, K99 CA127361-01, P01 CA030195, P01 CA030195-25, 1K99CA127361-01, R01 CA094118] NR 42 TC 26 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 2007 VL 309 IS 1 BP 137 EP 149 DI 10.1016/j.ydbio.2007.07.002 PG 13 WC Developmental Biology SC Developmental Biology GA 209CZ UT WOS:000249367500012 PM 17662267 ER PT J AU Inouye, KE Shi, H Howard, JK Daly, CH Lord, GM Rollins, BJ Flier, JS AF Inouye, Karen E. Shi, Hang Howard, Jane K. Daly, Christine H. Lord, Graham M. Rollins, Barrett J. Flier, Jeffrey S. TI Absence of CC chemokine ligand 2 does not limit obesity-associated infiltration of macrophages into adipose tissue SO DIABETES LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; LINKED INSULIN-RESISTANCE; NECROSIS-FACTOR-ALPHA; CC-CHEMOKINE; WEIGHT-LOSS; MICE; INFLAMMATION; EXPRESSION; MCP-1; RECRUITMENT AB Macrophage recruitment to adipose tissue in obesity contributes to enhanced adipose tissue inflammatory activity and thus may underlie obesity-associated metabolic dysfunction. Obese adipose tissue exhibits increases in CC chemokine ligand 2 (CCL2, or monocyte chemoattractant protein-1), an important macrophage-recruiting factor. We therefore hypothesized that elevated CCL2 may contribute to obesity-associated adipose tissue macrophage recruitment. Male 6-week-old CCL2(-/-) and wild-type mice (n = 11-14 per group) were fed standard and high-fat diets until 34 weeks of age. At 12-16 and 25-29 weeks of age, blood was collected for plasma glucose and hormone measurements, and glucose tolerance and insulin tolerance tests were performed. Adipose tissue was collected at 34 weeks for analysis of macrophage infiltration. Surprisingly, CCL2(-/-) mice on high-fat diet showed no reductions in adipose tissue macrophages. CCL2(-/-) mice on standard and high-fat diet were also glucose intolerant and had mildly increased plasma glucose and decreased serum adiponectin levels compared with wild-type mice. On high-fat diet, CCL2(-/-) mice also gained slightly more weight and were hyperinsulinemic compared with wild-type mice. Because macrophage levels were unchanged in CCL2(-/-) mice, the phenotype appears to be caused by lack of CCL2 itself. The fact that metabolic function was altered in CCL2(-/-) mice, despite no changes in adipose tissue macrophage levels, suggests that CCL2 has effects on metabolism that are independent of its macrophage-recruiting capabilities. Importantly, we conclude that CCL2 is not critical for adipose tissue macrophage recruitment. The dominant factor for recruiting macrophages in adipose tissue during obesity therefore remains to be identified. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol,Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Flier, JS (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Finard 202, Boston, MA 02215 USA. EM jflier@bidmc.harvard.edu RI Lord, Graham/B-3797-2011 FU Medical Research Council [G108/380]; Wellcome Trust NR 39 TC 137 Z9 139 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2007 VL 56 IS 9 BP 2242 EP 2250 DI 10.2337/db07-0425 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208FF UT WOS:000249304500008 PM 17473219 ER PT J AU King, AJF Fernandes, JR Hollister-Lock, J Nienaber, CE Bonner-Weir, S Weir, GC AF King, Aileen J. F. Fernandes, Justin R. Hollister-Lock, Jennifer Nienaber, Cameron E. Bonner-Weir, Susan Weir, Gordon C. TI Normal relationship of beta- and non-beta-cells not needed for successful islet transplantation SO DIABETES LA English DT Article ID EMBRYONIC STEM-CELLS; INSULIN-PRODUCING CELLS; PANCREATIC-ISLETS; A-CELL; GLUCAGON-RELEASE; SINGLE-DONOR; B-CELLS; RAT; DIFFERENTIATION; TISSUE AB Islets are composed mostly of beta-cells, and therefore stemcell research has concentrated on generating purified beta-cells, neglecting the other endocrine cell types in the islet. We investigated the presence of endocrine non-beta-cells after islet transplantation. In addition, we studied whether the transplantation of pure beta-cells, in volumes similar to that used in islet transplantation, would suffice to reverse hyperglycemia, in diabetic mice. Rat islets were dispersed and beta-cells were purified by fluorescence-activated cell sorting according to their endogenous fluorescence. After reaggregation, 600 islet equivalents of the purified beta-cell aggregates were implanted into diabetic SCID mice. In mice implanted with beta-cell-enriched aggregates, the hyperglycemia was reversed and good graft function over a 12-week period was observed with regard to glucose and insulin levels, glucose tolerance tests, and graft insulin content. The endocrine cell composition of the beta-cell-enriched aggregates remained constant; before and 12 weeks after transplantation, the beta-cell-enriched aggregates comprised 95% beta-cells and 5% endocrine non-p-cells. However, islet grafts, despite originally having comprised 75% beta-cells and 25% endocrine non-beta-cells, comprised just 5% endocrine non-beta-cells after transplantation, indicating a loss of these cells. beta-Cell-enriched aggregates can effectively reverse hyperglycemia in mice, and transplanted intact islets are depleted in non-beta-cells. It is therefore likely that islet non-beta-cells are not essential for successful islet transplantation. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Kings Coll London, Div Reprod & Endocrinol, London, England. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu RI King, Aileen/I-5935-2013 OI King, Aileen/0000-0001-5759-7985 FU NIDDK NIH HHS [DK-36836] NR 38 TC 27 Z9 29 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2007 VL 56 IS 9 BP 2312 EP 2318 DI 10.2337/db07-0191 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208FF UT WOS:000249304500015 PM 17563059 ER PT J AU Johnson, SB Baughcum, AE Hood, K Rafkin-Mervis, LE Schatz, DA AF Johnson, Suzanne Bennett Baughcum, Amy E. Hood, Korey Rafkin-Mervis, Lisa E. Schatz, Desmond A. CA DPT-Study Grp TI Participant and parent experiences in the parenteral insulin arm of the Diabetes Prevention Trial for Type 1 Diabetes SO DIABETES CARE LA English DT Article ID CHILDREN; LEUKEMIA AB OBJECTIVE - To assess participant and parent experiences in the parenteral insulin arm of the Diabetes Prevention Trial for Type 1 Diabetes (DPT-1). RESEARCH DESIGN AND METHODS - Before trial results were publicized, surveys were completed by 82 intervention participants (the intervention group) (who received annual 4-day insulin infusions and daily insulin injections), 81 closely monitored control subjects (the closely monitored group), and 135 parents of children in the trial. RESULTS - Survey results suggest that participant perspective (adult, child, parent, and study procedures, and group assignment have important implications when planning sex), clinical trials. Parents rated the trial more favorably but worried about hypoglycemia and diabetes onset. Children had the least favorable reaction to the study. Parents preferred assignment to the intervention group; child/adult participants preferred assignment to the closely monitored group. The intervention group rated the annual 4-day insulin infusions more negatively than all other study procedures. Intervention group participants/parents reported poorer insulin injection adherence over the course of the study. Intervention group participants, parents, and female subjects expressed an interest in additional psychosocial support during the trial. Random assignment was viewed negatively by both study groups. Close observation for diabetes onset Was viewed as the most favorable aspect of the study. Behaviors outside of the study protocol to prevent or delay diabetes onset were common and should be monitored in future prevention studies. CONCLUSIONS - Overall, most participants were positive about the trial, and many expressed optimism about the intervention's potential for success. These results have implications for study design, recruitment, and retention procedures in future prevention trials. C1 Dept Med Humanities & Socia Sci, Tallahassee, FL 32306 USA. Florida State Coll Med, Dept Med Humanities & Social Sci, Tallahassee, FL USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. Univ Miami, Sch Med, Diabet Res Inst, Miami, FL USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. RP Johnson, SB (reprint author), Dept Med Humanities & Socia Sci, 1115 W Call St, Tallahassee, FL 32306 USA. EM suzanne.johnson@med.fsu.edu NR 10 TC 12 Z9 12 U1 0 U2 0 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 SEP PY 2007 VL 30 IS 9 BP 2193 EP 2198 DI 10.2337/dc06-2422 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 210IA UT WOS:000249448700003 PM 17563348 ER PT J AU Gonzalez, JS Safren, SA Cagliero, E Wexler, DJ Delahanty, L Wittenberg, E Blais, MA Meigs, JB Grant, RW AF Gonzalez, Jeffrey S. Safren, Steven A. Cagliero, Enrico Wexler, Deborah J. Delahanty, Linda Wittenberg, Eve Blais, Mark A. Meigs, James B. Grant, Richard W. TI Depression, self-care, and medication adherence in type 2 diabetes SO DIABETES CARE LA English DT Article ID COMORBID DEPRESSION; GLYCEMIC CONTROL; SYMPTOMS; METAANALYSIS; ASSOCIATION; QUALITY; IMPACT AB OBJECTIVE - We examined the association between depression, measured as either a continuous symptom severity score or a clinical disorder variable, with self-care behaviors in type 2 diabetes. RESEARCH DESIGN AND METHODS - We surveyed 879 type 2 diabetic patients from two primary care clinics using the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS), the Summary of Diabetes Self-Care Activities, and self-reported medication adherence. RESULTS - Of the patients, 19% met the criteria for probable major depression (HANDS score >= 9), and an additional 66.5% reported at least some depressive symptoms. After controlling for covariates, patients with probable major depression reported significantly fewer days' adherent to diet, exercise, and glucose self-monitoring regimens (P < 0.01) and 2.3-fold increased odds of missing medication doses in the previous week (95% CI 1.5-3.6, P < 0.001) compared with all other respondents. Continuous depressive symptom severity scores were I better predictors of nonadherence to diet, exercise, and medications than categorically defined probable major depression. Major depression was a better predictor of glucose monitoring. Among the two-thirds of patients not meeting the criteria for major depression (HANDS score < 9, n = 709), increasing HANDS scores were incrementally associated with poorer self-care behaviors (P < 0.01). CONCLUSIONS - These findings challenge the conceptualization of depression as a categorical risk factor for nonadherence and suggest that even low levels of depressive symptomatology are associated with nonadherence to important aspects of diabetes self-care. in significant improvements in diabetes self-care. C1 Massachusetts Gen Hosp, Dept Psychiat, WACC 812, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Diabet Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gen Med Div, Boston, MA USA. RP Gonzalez, JS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 812, 15 Parkman St, Boston, MA 02114 USA. EM jsgonzalez@partners.org OI Grant, Richard/0000-0002-6164-8025 FU AHRQ HHS [K02 HS014010, 1 K02 HS014010]; NIDDK NIH HHS [K23 DK067452, K23 DK067452-04, K23 DK080228]; NIMH NIH HHS [1R01MH078571-01, R01 MH078571] NR 26 TC 202 Z9 205 U1 2 U2 23 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 SEP PY 2007 VL 30 IS 9 BP 2222 EP 2227 DI 10.2337/dc07-0158 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 210IA UT WOS:000249448700008 PM 17536067 ER PT J AU Xu, P Cuthbertson, D Greenbaum, C Palmer, JP Krischer, JP AF Xu, Ping Cuthbertson, David Greenbaum, Carla Palmer, Jerry P. Krischer, Jeffrey P. CA Diabetes Prevention Trial-Type 1 S TI Role of insulin resistance in predicting progression to type 1 diabetes SO DIABETES CARE LA English DT Article ID BETA-CELL FUNCTION; GLUCOSE-TOLERANCE TEST; RISK-FACTOR; SENSITIVITY; CHILDREN; AUTOANTIBODIES; IDDM AB OBJECTIVE - The purpose of this study was to determine whether insulin resistance is a risk factor for the development of type 1 diabetes in autoantibody-positive first-degree relatives of diabetic family members. RESEARCH DESIGN AND METHODS - Subjects (n = 186) who had a projected 25-50% risk for diabetes and subjects (n = 170) who had a projected > 50% risk for type 1 diabetes in 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial-Type 1. We assessed insulin secretion with the first-phase insulin response (FPIR) and insulin resistance with homeostasis model assessment of insulin resistance (HOMA-IR) from an intravenous glucose tolerance test. The median follow-up was 4.3 years for moderate-risk subjects and 3.7 years for high-risk subjects. RESULTS- During the follow-up period, 53 subjects in the moderate-risk group and 70 subjects in the high-risk group developed type 1 diabetes. After adjustments for confounders using multivariate analysis, HOMA-IR and the FPIR-to-HOMA-IR ratio were significantly associated with type 1 diabetes in both risk groups. in the moderate-risk population, the hazard ratio (HR) of HOMA-IR was 2.70 (95% CI 1.45-5.06) and the HR of FPIR-to-HOMA-IR was 0.32 (95% CI 0.18-0.57). in the high-risk population, the HR of HOMA-IR was 1.83 (95% CI 1.19-2.82) and the HR of FPIR-to-HOMA-IR was 0.56 (95% CI 0.40-0.78). CONCLUSIONS - There is clear evidence of the association between insulin resistance and progression to type 1 diabetes. The combination of FPIR and HOMA-IR could be used as a better metabolic indicator for type 1 diabetes risk for prediction and suggests possible intervention strategies for diabetes prevention. C1 Univ S Florida, Pediat Epidemiol Ctr, Div Informat & Biostat, Tampa, FL 33612 USA. Benaroya Res Inst Virginia Mason, Seattle, WA USA. Univ Washington, Vet Affairs Puget Sound, Seattle, WA 98195 USA. RP Krischer, JP (reprint author), Univ S Florida, Pediat Epidemiol Ctr, Div Informat & Biostat, 3650 Spectrum Blvd,Suite 100, Tampa, FL 33612 USA. EM jpkrischer@epi.usf.edu NR 24 TC 56 Z9 59 U1 0 U2 0 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 SEP PY 2007 VL 30 IS 9 BP 2314 EP 2320 DI 10.2337/dc06-2389 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 210IA UT WOS:000249448700030 PM 17536068 ER PT J AU Nadeau, KJ Ehlers, LB Aguirre, LE Reusch, JEB Draznin, B AF Nadeau, K. J. Ehlers, L. B. Aguirre, L. E. Reusch, J. E. B. Draznin, B. TI Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone SO DIABETES OBESITY & METABOLISM LA English DT Article DE diabetes; insulin sensitivity; lipid metabolism; muscle lipid; PPAR ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; ELEMENT-BINDING PROTEIN-1C; RECEPTOR-ALPHA ACTIVATORS; TRANSCRIPTION FACTORS; OXIDATIVE CAPACITY; HEPATIC STEATOSIS; GENE-EXPRESSION; FATTY RATS; EXERCISE; RESISTANCE AB Aim: Intramyocellular triglyceride (IMTG) correlates with insulin resistance, but there is no clear causal relationship. Insulin resistance and associated hyperinsulinaemia may increase IMTG, via the insulin-regulated transcription factor, sterol regulatory element-binding protein 1 (SREBP-1). PPAR agonists may also affect IMTG via changes in insulin sensitivity, SREBP-1 or other factors. Methods: We examined skeletal muscle IMTG and SREBP-1 expression, and metabolic parameters in Zucker diabetic fatty rats (ZDF) after 25 weeks of PPAR-g or PPAR-a administration. Results: Compared with Zucker lean rats (ZL), untreated ZDF had significantly higher weights, serum glucose, insulin, free fatty acids, total cholesterol and triglycerides. IMTG and SREBP-1c messenger RNA (mRNA) were also higher in untreated ZDF; both were decreased by fenofibrate (FF). Rosiglitazone (Rosi), despite marked improvement in glycaemia, hyperinsulinaemia and hyperlipidaemia, failed to affect SREBP-1 expression, and increased body weight and IMTG. Rosi/FF combination caused less weight gain and no IMTG increase, despite metabolic effects similar to Rosi alone. Conclusions: IMTG and SREBP-1c mRNA are high in the ZDF. FF and Rosi both improved insulin sensitivity but had opposite effects on IMTG. Thus, there was a clear discordance between insulin sensitivity and IMTG with PPAR agonists, indicating that IMTG and insulin sensitivity do not share a simple relationship. C1 Univ Colorado, Childrens Hosp, Hlth Sci Ctr, Dept Pediat,Div Pediat Endocrinol, Denver, CO 80218 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Endocrinol Diabet & Metab, Denver, CO 80218 USA. Denver VA Med Ctr, Vet Affairs Res Serv, Denver, CO 80218 USA. RP Nadeau, KJ (reprint author), Univ Colorado, Childrens Hosp, Hlth Sci Ctr, Dept Pediat,Div Pediat Endocrinol, Box 265,1056 E 19th Ave, Denver, CO 80218 USA. EM nadeaukj@hotmail.com OI Aguirre, Lina/0000-0003-0711-314X FU NCRR NIH HHS [1K23 RR020038-01]; NIDDK NIH HHS [5 P30 DK48520-10]; PHS HHS [R01-DIC06741, P0156481] NR 49 TC 12 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD SEP PY 2007 VL 9 IS 5 BP 714 EP 723 DI 10.1111/j.1463-1326.2006.00696.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 203HO UT WOS:000248965900012 PM 17697064 ER PT J AU Fujii, N Seifert, MM Kane, EM Peter, LE Ho, RC Winstead, S Hirshman, MF Goodyear, LJ AF Fujii, Nobuharu Seifert, Matthew. M. Kane, Erin M. Peter, Lauren E. Ho, Richard C. Winstead, Schuyler Hirshman, Michael F. Goodyear, Laurie J. TI Role of AMP-activated protein kinase in exercise capacity, whole body glucose homeostasis, and glucose transport in skeletal muscle - Insight from analysis of a transgenic mouse model SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT 13th Korea-Japan Symposium on Diabetes Mellitus CY NOV 11-12, 2005 CL Seoul, SOUTH KOREA DE AMP-activated protein kinase; exercise capacity; skeletal muscle ID CONTRACTION; INSULIN; METABOLISM AB To examine the role of muscle AMP-activated protein kinase (AMPK) in maximal exercise capacity, whole body glucose homeostasis, and glucose transport in skeletal muscle, we generated muscle-specific transgenic mice carrying cDNAs of inactive AMPK alpha 2 (alpha 2i TG). Fed blood glucose was slightly higher in alpha 2i TG mice compared to wild type littermates, however, the difference was not statistically significant. In alpha 2i TG mice, glucose tolerance was slightly impaired in male, but not in female mice, compared to wild type littermates. Maximal exercise capacity was dramatically reduced in alpha 2i TG mice, suggesting that AMPK alpha 2 has a critical role in skeletal muscle during exercise. We confirmed that known insulin-independent stimuli of glucose transport including mitochondrial respiration inhibition, hyperosmolarity, and muscle contraction increased both ANIPK alpha 1 and alpha 2 activities in isolated EDL muscle in wild type mice. While, alpha 2 activation was severely blunted and a I activation was only slightly reduced in alpha 2i TG mice by these insulin independent stimuli compared to wild type mice. Mitochondrial respiration inhibition-induced glucose transport was fully inhibited in isolated EDL muscles in alpha 2i TG mice. However, contraction- or hyperosmolarity-induced glucose transport was nearly normal. These results suggest that AMPK alpha 2 activation is essential for some, but not all insulinindependent glucose transport. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Brigham & Womens Hosp, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Div Res, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM nobuharu.fujii@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR45670] NR 15 TC 32 Z9 32 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD SEP PY 2007 VL 77 SU 1 BP S92 EP S98 DI 10.1016/j.diabres.2007.01.040 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 211WO UT WOS:000249554200017 PM 17452058 ER PT J AU Lee, JS Kim, MS AF Lee, Jongsoon Kim, Myung-Sunny TI The role of GSK3 in glucose homeostasis and the development of insulin resistance SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT 13th Korea-Japan Symposium on Diabetes Mellitus CY NOV 11-12, 2005 CL Seoul, SOUTH KOREA DE GSK3; insulin signaling; glucose homeostasis ID GLYCOGEN-SYNTHASE KINASE-3; DEPENDENT DIABETES-MELLITUS; NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; ATP-CITRATE-LYASE; BETA-CATENIN; SKELETAL-MUSCLE; NEGATIVE REGULATOR; SUBSTRATE-SPECIFICITY; RECEPTOR SUBSTRATE-1 AB GSK3 has been implicated in the development of insulin resistance, primarily based on its role in regulation of glycogen synthesis. However. GSK3 is involved in many other important signaling cascades which may regulate glucose homeostasis and the development of insulin resistance. In addition, GSK3 is composed of two isoforms, GSK3 alpha and beta, which do not completely share their physiological roles, and this raises a possibility that GSK3 alpha and beta may function differently in glucose homeostasis. In this review, we will give an overview to examine potential mechanisms for the roles of GSK3 in the development of insulin resistance. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Lee, JS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM jongsoon.lee@joslin.harvard.edu FU NIDDK NIH HHS [DK36836, DK63225] NR 88 TC 61 Z9 65 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 EI 1872-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD SEP PY 2007 VL 77 SU 1 BP S49 EP S57 DI 10.1016/j.diabres.2007.01.033 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 211WO UT WOS:000249554200009 PM 17478001 ER PT J AU Boeni-Schnetzler, M Marselli, L Parnaud, G Ehses, JA Halban, PA Weir, GC Donath, MY AF Boeni-Schnetzler, M. Marselli, L. Parnaud, G. Ehses, J. A. Halban, P. A. Weir, G. C. Donath, M. Y. TI IL-1beta expression in human islets is induced by glucose and autostimulation, and increased in beta cells of individuals with type 2 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Univ Zurich Hosp, CH-8091 Zurich, Switzerland. Joslin Diabet Ctr, Boston, MA 02215 USA. CMU, Dept Genet Med & Dev, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0147 BP S178 EP S178 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600418 ER PT J AU Brorsson, CA Swiergala, E Bergholdt, R Rapacki, K Purcell, S Field, L Pociot, F AF Brorsson, C. A. Swiergala, E. Bergholdt, R. Rapacki, K. Purcell, S. Field, L. Pociot, F. TI Genome wide association scan for type 1 diabetes susceptibility genes in a Danish population SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. Tech Univ Lyngby, Ctr Biol Sequence Anal, Lyngby, Denmark. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0084 BP S40 EP S41 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600085 ER PT J AU Dominguez, H Kveiborg, B Nielsen, D Madsen, CR Kober, L Torp-Pedersen, C AF Dominguez, H. Kveiborg, B. Nielsen, D. Madsen, C. R. Kober, L. Torp-Pedersen, C. TI Postprandial endothelial dysfunction, hyperglycaemia and hyperinsulinaemia in insulin resistance: is there a link? SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Bispebjerg Hosp, DK-2400 Copenhagen, Denmark. Joslin Diabet Ctr, Boston, MA 02215 USA. Rigshosp, DK-2100 Copenhagen, Denmark. RI Torp-Pedersen, Christian/E-5931-2013; OI DOMINGUEZ, HELENA/0000-0002-7089-2636 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 1176 BP S482 EP S483 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395601176 ER PT J AU Haffner, SM Kahn, SE Zinman, B Holman, RR Viberti, GF Herman, WH Lachin, JM Kravitz, BG Heise, MA AF Haffner, S. M. Kahn, S. E. Zinman, B. Holman, R. R. Viberti, G. F. Herman, W. H. Lachin, J. M. Kravitz, B. G. Heise, M. A. TI Greater reductions in C-reactive protein with rosiglitazone than with glyburide or metformin despite greater weight gain SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Churchill Hosp, OCDEM, Diabet Trials Unit, Oxford OX3 7LJ, England. Kings Coll London, Dept Endocrinol & Diabet, Sch Med, London, England. Univ Michigan, Ann Arbor, MI 48109 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0074 BP S36 EP S36 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600075 ER PT J AU Herman, WH Haffner, SM Kahn, SE Zinman, B Holman, RR Viberti, GE Lachin, JM Kravitz, BG Heise, MA AF Herman, W. H. Haffner, S. M. Kahn, S. E. Zinman, B. Holman, R. R. Viberti, G. E. Lachin, J. M. Kravitz, B. G. Heise, M. A. TI ADOPT: The effectiveness of metformin versus glyburide in type 2 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Churchill Hosp, OCDEM, Diabet Trials Unit, Oxford OX3 7LJ, England. Kings Coll London, Sch Med, Dept Endocrinol & Diabet, London SE5 9PJ, England. George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0877 BP S362 EP S362 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600877 ER PT J AU Holman, RR Kahn, SE Haffner, SM Zinman, B Viberti, GF Herman, WH Lachin, JM Kravitz, BG Heise, MA AF Holman, R. R. Kahn, S. E. Haffner, S. M. Zinman, B. Viberti, G. F. Herman, W. H. Lachin, J. M. Kravitz, B. G. Heise, M. A. TI Determinants of monotherapy failure in ADOPT - (A diabetes outcome progression trial) SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Churchill Hosp, OCDEM, Diabet Trial Unit, Oxford OX3 7LJ, England. VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Kings Coll London, Sch Med, Dept Endocrinol & Diabet, London WC2R 2LS, England. Univ Michigan, Ann Arbor, MI 48109 USA. George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0862 BP S356 EP S356 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600862 ER PT J AU Kahn, SE Haffner, SM Lachin, JM Herman, WH Zinman, B Holman, RR Heise, MA Aftring, RP Viberti, GF AF Kahn, S. E. Haffner, S. M. Lachin, J. M. Herman, W. H. Zinman, B. Holman, R. R. Heise, M. A. Aftring, R. P. Viberti, G. F. TI Increased incidence of fractures in women who received rosiglitazone in ADOPT (A Diabetes Outcome Progression Trial) SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Churchill Hosp, OCDEM, Diabet Trials Unit, Oxford OX3 7LJ, England. GlaxoSmithKline Inc, King Of Prussia, PA USA. Kings Coll London, Dept Endocrinol & Diabet, London WC2R 2LS, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0077 BP S37 EP S38 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600078 ER PT J AU Marchetti, P Masini, M Bugliani, M Lupi, R Marselli, L Del Prato, S Weir, G Eizirik, D Cnop, M AF Marchetti, P. Masini, M. Bugliani, M. Lupi, R. Marselli, L. Del Prato, S. Weir, G. Eizirik, D. Cnop, M. TI Endoplasmic reticulum stress markers in pancreatic beta cells from type 2 diabetic subjects SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Univ Pisa, Dept Endocrinol & Metab, I-56100 Pisa, Italy. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. Free Univ Brussels, Expt Med Lab, B-1050 Brussels, Belgium. RI Del Prato, Stefano/K-3405-2016 OI Del Prato, Stefano/0000-0002-5388-0270 NR 0 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0093 BP S44 EP S45 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600094 ER PT J AU Marselli, L Sgroi, DC Thorne, J Dahiya, S Torri, S Omer, A Del Prato, S Towia, L Otu, HH Sharma, A Bonner-Weir, S Marchetti, P Weir, GC AF Marselli, L. Sgroi, D. C. Thorne, J. Dahiya, S. Torri, S. Omer, A. Del Prato, S. Towia, L. Otu, H. H. Sharma, A. Bonner-Weir, S. Marchetti, P. Weir, G. C. TI Evidence of inflammatory markers in beta cells of type 2 diabetic subjects SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Univ Pisa, Pisa, Italy. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Del Prato, Stefano/K-3405-2016 OI Del Prato, Stefano/0000-0002-5388-0270 NR 0 TC 8 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0418 BP S178 EP S179 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600419 ER PT J AU Orho-Melander, M Melander, O Lyssenko, V Saxena, R de Bakker, P Burtt, N Voight, B Hirschorn, JN Tuomi, T Isomaa, B Taskinen, MR Hughes, TE Altshuler, D Groop, L Kathiresan, S AF Orho-Melander, M. Melander, O. Lyssenko, V. Saxena, R. de Bakker, P. Burtt, N. Voight, B. Hirschorn, J. N. Tuomi, T. Isomaa, B. Taskinen, M.-R. Hughes, T. E. Altshuler, D. Groop, L. Kathiresan, S. CA DGI TI A genome-wide association study identifies glucokinase regulatory protein (GCKR) locus as a novel regulator of blood triglyceride level SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Lund Univ, Malmo, Sweden. Harvard Univ, Broad Inst, Genet Anal Platform & Metab Initiat, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Helsinki Univ Hosp, Dept Med, Helsinki, Finland. Folkhalsan Res Ctr, Biomedicum, Helsinki, Finland. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0082 BP S40 EP S40 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600083 ER PT J AU Ternand, C Weinzimer, SA Laffel, LMB Howard, C Chang, CT Becker, DJ AF Ternand, C. Weinzimer, S. A. Laffel, L. M. B. Howard, C. Chang, C.-T. Becker, D. J. TI Continuous subcutaneous insulin infusion (CSII) of insulin aspart vs. insulin lispro in paediatric subjects (ages 4 to 18 years) with type 1 diabetes (T1D) SO DIABETOLOGIA LA English DT Meeting Abstract CT 43rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 18-21, 2007 CL Amsterdam, NETHERLANDS SP European Assco Study Diabet C1 Univ Minnesota, Childrens Hosp, Minneapolis, MN USA. Yale Univ, Sch Med, New Haven, CT USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Novo Nordisk Inc, CMR, Princeton, NJ USA. Childrens Hosp Pittsburgh, Dept Pediat Endocrinol, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2007 VL 50 SU 1 MA 0188 BP S83 EP S84 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 209NP UT WOS:000249395600189 ER PT J AU Knoepp, SM Kuebler, DL Wilbur, DC AF Knoepp, Stewart M. Kuebler, Diane L. Wilbur, David C. TI Resolution of equivocal results with the hybrid capture II high-risk HPV DNA test: A cytologic/histologic review of 191 cases SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE cervical cytology; human papillomavirus testing; SurePath; hybrid capture II; HPV ID ATYPICAL SQUAMOUS-CELLS; HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER; VIRAL LOAD; CARCINOGENESIS; PERFORMANCE; CYTOLOGY; WOMEN; AGE AB Introduction: The Hybrid Capture II (HC II, Digene) high-risk human papilloma virus (HPV) (hrHPV) DNA test is an in vitro nucleic acid hybridization assay that uses enhanced chemiluminescence for the qualitative and semiquantitative detection of hrHPV in cervical samples. Patient samples Lire concomitantly tested with positive and negative DNA controls and results reported as positive or negative on the basis of a ratio of relative light units to a cutoff value derived from the positive control (RLU/CO). Samples with a ratio < 1.0 RLU/CO are expressed as negative for hrHPV, samples with a ratio > 2.5 RLU/CO are expressed as positive for hrHPV, and samples with a ratio between these numbers are submitted for retesting. These "equivocal" values arc resulted as positive for hrHPV if either of 2 subsequent test values equals or exceeds 1.0 RLU/CO. Samples that show < 1.0 RLU/CO after 2 repeat tests are resulted as negative for hrHPV. Methods: In this study, we evaluated all hrHPV test results over a 17-month period in our institution. Initial tests showing an equivocal result were analyzed for final retesting result, and for all corresponding and subsequent cytology and histology results. All hrHPV tests were conducted on SurePath (TriPath) or ThinPrep (Cytyc) cervical Cytology Specimens using the HC II hrHPV DNA test. Subsequent hrHPV tests also were correlated with incident and follow-up findings. Results: A total of 4792 hrHPV test results were evaluated. Of these, 191 (4%) showed equivocal initial results. When retested, 178 of the 191 samples (93%) resulted positive for hrHPV on first retest and an additional 8 resulted positive for hrHPV on the second retest, bringing the total positive tests to 186 out of 191 (97.4%). Five samples (2.6%) out of 191 were finally expressed as negative for hrHPV. Corresponding cytologic interpretations for the 191 specimens were as follows: NILM-30, atypical squamous cell of undetermined significance (ASC-US)138, atypical squamous cells-cannot exclude HSIL-13 (ASCH-13), LSIL-9, and high-grade squamous intraepithelial lesion (HSIL)-1. Follow-up histology was available for 60 of the 191 equivocal cases and showed cervical intraepithelial neoplasia (CIN) II or CIN III in 7 cases, CIN I in 13 cases, and negative or reactive changes in 40 cases. Conclusions: On the basis of the results, repeat testing of equivocal specimens might not be necessary as these specimens are overwhelmingly found to be positive for hrHPV. Additionally, hrHPV tests falling in the equivocal range should be considered as definite positive tests, as follow-up results in this cohort demonstrate that significant histologic abnormalities are associated with 10.5% of these cases (20/191), and with 33% of those biopsied (20/60) cases. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. RP Knoepp, SM (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM stewart_knoepp@hms.harvard.edu NR 22 TC 13 Z9 13 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD SEP PY 2007 VL 16 IS 3 BP 125 EP 129 DI 10.1097/PDM.0b013e31805c99ae PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 205AV UT WOS:000249086000001 PM 17721319 ER PT J AU Leung, FW Chan, CC AF Leung, Felix W. Chan, Chi Chung TI Intragastric nitroglycerin at a vasodilatory dose attenuates acidified aspirin-induced gastric mucosal injury SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE nitroglycerin; gastric blood flow; gastric volume; gastric mucosal injury; acidified aspirin ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OXIDE-RELEASING ASPIRIN; NITRIC-OXIDE; NICOTINE PROTECTION; RELAXING FACTOR; RAT STOMACH; LESIONS; RISK; CYTOPROTECTION; PREVENTION AB Clinical studies reveal that aspirin intake to prevent myocardial and cerebral ischemia is associated with a significant increase in upper gastrointestinal hemorrhage requiring hospitalization and that nitroglycerin or long-acting nitrates significantly lower this risk. Nitroglycerin can increase gastric blood flow and slow gastric emptying. We hypothesized that both features contribute to its gastroprotective property. Fasted anesthetized rats (Study 1) and conscious mice (Studies 2 to 4) received intragastric nitroglycerin or vehicle. The effects of these two treatments on various parameters were assessed in Study 1, on blood pressure and gastric blood flow; Study 2, on acidified aspirin-induced gastric mucosal lesions; and Study 3, on the weight of gastric content. In Study 4, the effect of nitroglycerin, vehicle, or vehicle plus saline, on acidified aspirin-induced gastric mucosal lesion was assessed. Compared with vehicle, nitroglycerin decreased blood pressure and produced a mild but significant increase in gastric vascular conductance, blood flow, and volume of gastric content. The number and length of gastric mucosal lesions induced by acidified aspirin were significantly attenuated by intragastric nitroglycerin in a vasodilatory dose. Exogenous saline in a volume equivalent to the increase produced by nitroglycerin, however, did not attenuate the lesions. These experimental data are consistent with the clinical observation that nitrates lower the risk of aspirin-induced gastrointestinal complications. Confirmation of the efficacy of nitroglycerin and nitrates in preventing such aspirin-induced complications in controlled trials is worthy of consideration by clinical investigators. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Div Gastroenterol, Res & Med Serv, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Merck Frosst Ctr Therapeut Res, Dept Pharmacol, Quebec City, PQ, Canada. RP Leung, FW (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Div Gastroenterol, Res & Med Serv, 111G,16111 Plummer St, Sepulveda, CA 91343 USA. EM felix.leung@med.va.gov NR 28 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2007 VL 52 IS 9 BP 2229 EP 2235 DI 10.1007/s10620-006-9266-2 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 201CY UT WOS:000248810300033 PM 17420937 ER PT J AU Iannaccone, A Tedesco, SA Gallaher, KT Yamamoto, H Charles, S Dryja, TP AF Iannaccone, Alessandro Tedesco, Salvatore A. Gallaher, Kevin T. Yamamoto, Hiroyuki Charles, Steve Dryja, Thaddeus P. TI Fundus albipunctatus in a 6-year old girl due to compound heterozygous mutations in the RDH5 gene SO DOCUMENTA OPHTHALMOLOGICA LA English DT Article DE electroretinogram; Fundus albipunctatus; RDH5; retinitis punctata albescens; retinol dehydrogenase ID RETINALDEHYDE-BINDING PROTEIN; RETINITIS PUNCTATA ALBESCENS; DELAYED DARK-ADAPTATION; MACULAR DYSTROPHY; CLINICAL ELECTRORETINOGRAPHY; PIGMENT EPITHELIUM; BOTHNIA DYSTROPHY; VISUAL CYCLE; VITAMIN-A; 11-CIS-RETINOL AB We report a case study of Fundus Albipunctatus (FA) due to compound heterozygous mutations in RDH5, the gene encoding for the 11-cis-retinal dehydrogenase (RDH). A 6-year old Hispanic American female with a clinical presentation suggestive of FA underwent dark-adapted full-field flash electroretinography (ERG) at 30 and 120 min. The pattern of ERG abnormalities was consistent with the working diagnosis FA. However, only ERG responses to dim stimuli were profoundly affected, and maximal ERG responses were already near normal after only 30 min of dark adaptation. The patient also demonstrated a subnormal maximal ERG response b/a-wave ratio at 30 min that resolved after 120 min of dark adaptation. When measurable, dark-adapted post-receptoral responses were normal in timing under all circumstances, and became increasingly faster after prolonged dark adaptation. Cone-driven responses were completely normal at this young age. Sequencing of the RDH5 gene revealed two distinct missense mutations, a G238W mutation, previously reported in patients with FA, and a D128N mutation, which has not been reported before but is known to cause reduced 11-cis-RDH activity. These findings confirmed the clinical and functional diagnosis of FA and excluded that of retinitis punctata albescens (RPA). The behavior of dark-adapted ERG responses in FA displays characteristics that differ from those of RPA patients, which may be useful to differentiate functionally these two conditions at their common albipunctate stages. C1 Univ Tennessee, Ctr Hlth Sci, Hamilton Eye Inst, Retinal Degenerat & Ophthalm Genet Serv, Memphis, TN 38163 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Charles Retina Inst, Memphis, TN USA. Univ Parma, Dept Ophthalmol, I-43100 Parma, Italy. Nippon Steel Hirohata Hosp, Hirohata Ku, Himeji, Hyogo, Japan. RP Iannaccone, A (reprint author), Univ Tennessee, Ctr Hlth Sci, Hamilton Eye Inst, Retinal Degenerat & Ophthalm Genet Serv, 930 Madison Ave,Suite 731, Memphis, TN 38163 USA. EM iannacca@utmem.edu FU NEI NIH HHS [EY08683] NR 27 TC 17 Z9 17 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0012-4486 J9 DOC OPHTHALMOL JI Doc. Ophthalmol. PD SEP PY 2007 VL 115 IS 2 BP 111 EP 116 DI 10.1007/s10633-007-9054-0 PG 6 WC Ophthalmology SC Ophthalmology GA 209QQ UT WOS:000249403500007 PM 17476461 ER PT J AU Chen, TY Rosow, CE AF Chen, Tong-Yan Rosow, Carl E. TI Methylnaltrexone bromide SO DRUGS OF THE FUTURE LA English DT Article ID CECAL TRANSIT-TIME; QUATERNARY NARCOTIC-ANTAGONISTS; MORPHINE-INDUCED INHIBITION; OPIOID-INDUCED CONSTIPATION; PLACEBO-CONTROLLED TRIAL; INDUCED DELAY; GASTROINTESTINAL TRANSIT; ORAL METHYLNALTREXONE; BOWEL DYSFUNCTION; NALOXONE AB Opioids are widely used in patients with moderate to severe acute and chronic pain, but gastrointestinal side effects such as nausea and constipation can often be debilitating. Opioid-induced bowel dysfunction (OBD) is mediated by mu opioid receptors in both the central nervous system and bowel wall, but the "peripheral" bowel effects may be more important. M ethyl naltrexone (MNTX) is a derivative of naltrexone that does not cross the blood-brain barrier. It acts as a selective antagonist at peripheral opioid receptors without reversing central effects like analgesia. In preclinical and human volunteer studies, parenteral and oral MNTX consistently reversed OBD at doses that produced minimal side effects. Intravenous MNTX also reversed opioid inhibition of bladder function, suggesting a possible role in the treatment of opioid-induced urinary retention. Two phase III studies showed that s.c. administration of 0.15-0.3 mg/kg MNTX induced laxation in patients with advanced medical illness given chronic opioids. Additional studies of MNTX targeting postoperative ileus also show promise. An NDA submission is anticipated in early 2008. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Prous Sci, Barcelona 08080, Spain. RP Rosow, CE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM crosow@partners.org NR 35 TC 3 Z9 5 U1 1 U2 1 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD SEP PY 2007 VL 32 IS 9 BP 771 EP 775 DI 10.1358/dof.2007.032.09.1139032 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 226ES UT WOS:000250571000003 ER PT J AU Bortfeld, T AF Bortfeld, T. TI Particle therapy: Physical potential amid clinical realities SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Bortfeld, T.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 80 BP 24 EP 24 DI 10.1016/S1359-6349(07)70194-5 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000071 ER PT J AU Winer, E AF Winer, E. TI Neoadjuvant antiHER2 therapy SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Winer, E.] Dana Farber Canc Inst, Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 87 BP 25 EP 25 DI 10.1016/S1359-6349(07)70201-X PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000077 ER PT J AU Lipton, A Cook, RJ Major, P Smith, MR Coleman, RE AF Lipton, A. Cook, R. J. Major, P. Smith, M. R. Coleman, R. E. TI Early normalization of elevated baseline bone resorption marker levels by zoledronic acid and improved survival in patients with bone metastases from solid tumors SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Lipton, A.] Milton S Hershey Med Ctr, Penn State Canc Inst, Hershey, PA USA. [Cook, R. J.] Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. [Major, P.] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Boston, MA 02114 USA. [Coleman, R. E.] Univ Sheffield, Weston Pk Hosp, Canc Res Ctr, Sheffield, S Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 304 BP 58 EP 58 DI 10.1016/S1359-6349(07)70322-1 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000173 ER PT J AU Krop, IE Beeram, M Modi, S Rabbee, N Girish, S Tibbitts, J Holden, SN Lutzker, SG Burris, HA AF Krop, I. E. Beeram, M. Modi, S. Rabbee, N. Girish, S. Tibbitts, J. Holden, S. N. Lutzker, S. G. Burris, H. A. TI A phase I study of trastuzumab-DM1, a first-in-class HER2 antibody-drug conjugate, in patients with HER2+metastatic breast cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Krop, I. E.] Dana Farber Canc Inst, Boston, MA USA. [Beeram, M.] Int Drug Dev, San Antonio, TX USA. [Modi, S.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Rabbee, N.; Girish, S.; Tibbitts, J.; Holden, S. N.; Lutzker, S. G.] Genentech Inc, San Francisco, CA USA. [Burris, H. A.] Sarah Cannon Res Inst, Nashville, TN USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 2118 BP 219 EP 219 DI 10.1016/S1359-6349(07)70880-7 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000731 ER PT J AU Cappuzzo, F Finocchiaro, G Janne, PA Franklin, WA Bencardino, K Crino, L Roncalli, M Carnaghi, C Santoro, A Varella-Garcia, M AF Cappuzzo, F. Finocchiaro, G. Janne, P. A. Franklin, W. A. Bencardino, K. Crino, L. Roncalli, M. Carnaghi, C. Santoro, A. Varella-Garcia, M. TI Comprehensive assessment of molecular markers predicting response to cetuximab therapy in colorectal cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Cappuzzo, F.; Finocchiaro, G.; Roncalli, M.; Carnaghi, C.; Santoro, A.] Ist Clin Humanitas, IRCCS, Milan, Italy. [Janne, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Franklin, W. A.] Colorado Canc Ctr, Aurora, CO USA. [Bencardino, K.] Policlin San Matteo, I-27100 Pavia, Italy. [Crino, L.] Polyclin Monteluce, Perugia, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 3002 BP 235 EP 235 DI 10.1016/S1359-6349(07)70930-8 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000781 ER PT J AU Sternberg, C Sartor, O Petrylak, D Witjes, JA Bodrogi, I Harper, P Droz, JP James, N AF Sternberg, C. Sartor, O. Petrylak, D. Witjes, J. A. Bodrogi, I. Harper, P. Droz, J. P. James, N. TI Satraplatin increases progression-free survival (PFS) and delays pain progression in hormone refractory prostate cancer (HRPC): Results of SPARC, an international phase III trial with 950 patients SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Sternberg, C.] San Camillo & Forlanini Hosp, Rome, Italy. [Sartor, O.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA USA. [Petrylak, D.] Columbia Univ, Med Ctr, New York, NY USA. [Witjes, J. A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, Nijmegen, Netherlands. [Bodrogi, I.] Natl Inst Oncol Med Oncol & Clin Pharmacol, Budapest, Hungary. [Harper, P.] Guys & St Thomas NHS Trust, London, England. [Droz, J. P.] Ctr Leon Berard, Geriat Oncol Program, Lyon, France. [James, N.] Univ Birmingham, CRUK, Inst Canc Studies, Birmingham, W Midlands, England. RI Witjes, Fred/N-9665-2013 NR 0 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 4010 BP 282 EP 282 DI 10.1016/S1359-6349(07)71078-9 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000929 ER PT J AU Houk, BE Bello, CL Michaelson, MD Bukowski, RM Redman, B Hudes, GR Wilding, G Motzer, RJ AF Houk, B. E. Bello, C. L. Michaelson, M. D. Bukowski, R. M. Redman, B. Hudes, G. R. Wilding, G. Motzer, R. J. TI A population pharmacokinetic/pharmacodynamic (PK/PD) analysis of exposure-response for sunitinib in metastatic renal cell carcinoma (mRCC) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Houk, B. E.; Bello, C. L.] Pfizer Inc, La Jolla, CA USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bukowski, R. M.] Cleveland Clin Taussig Canc Ctr, Cleveland, OH USA. [Redman, B.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Hudes, G. R.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Wilding, G.] Univ Wisconsin, Comprehens Carbone Res Ctr, Madison, WI 53706 USA. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 4505 BP 300 EP 300 DI 10.1016/S1359-6349(07)71136-9 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000987 ER PT J AU Hutson, TE George, DJ Michaelson, MD Rosenberg, JE Bukowski, RM Sosman, JA Stadler, WM Margolin, K Rini, BI AF Hutson, T. E. George, D. J. Michaelson, M. D. Rosenberg, J. E. Bukowski, R. M. Sosman, J. A. Stadler, W. M. Margolin, K. Rini, B. I. TI A phase 2 trial of sunitinib in bevacizumab-refractory metastatic renal cell carcinoma (mRCC): updated results and analysis of circulating biomarkers SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [George, D. J.] Duke Univ, Ctr Med, Durham, NC 27706 USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenberg, J. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bukowski, R. M.; Rini, B. I.] Cleveland Clin Taussig Canc Ctr, Cleveland, OH USA. [Sosman, J. A.] Vanderbilt Univ, Nashville, TN USA. [Stadler, W. M.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 4510 BP 301 EP 301 DI 10.1016/S1359-6349(07)71141-2 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000992 ER PT J AU Motzer, RJ Michaelson, MD Hutson, TE Tomczak, P Bukowski, RM Rixe, O Negrier, S Kim, ST Chen, I Figlin, RA AF Motzer, R. J. Michaelson, M. D. Hutson, T. E. Tomczak, P. Bukowski, R. M. Rixe, O. Negrier, S. Kim, S. T. Chen, I. Figlin, R. A. TI Sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC): updated efficacy and safety results and further analysis of prognostic factors SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hutson, T. E.] Baylor Sammons Canc Ctr Texas Oncol, Dallas, TX USA. [Tomczak, P.] Klin Onkol Oddzial Chem, Poznan, Poland. [Bukowski, R. M.] Cleveland Clin Taussig Canc Ctr, Cleveland, OH USA. [Rixe, O.] Hop La Pitie Salpetriere, Paris, France. [Negrier, S.] Ctr Leon Berard, Lyon, France. [Kim, S. T.] Pfizer Inc, La Jolla, CA USA. [Figlin, R. A.] City Hope Comprehens Canc Ctr, Los Angeles, CA USA. NR 0 TC 11 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 4509 BP 301 EP 301 DI 10.1016/S1359-6349(07)71140-0 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000991 ER PT J AU George, DJ Michaelson, MD Rosenberg, JE Redman, BG Hudes, GR Bukowski, RM Kim, ST Chen, I Wilding, G Motzer, RJ AF George, D. J. Michaelson, M. D. Rosenberg, J. E. Redman, B. G. Hudes, G. R. Bukowski, R. M. Kim, S. T. Chen, I. Wilding, G. Motzer, R. J. TI Sunitinib in patients with cytokine-refiractory metastatic renal cell carcinoma (mRCC) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [George, D. J.] Duke Univ, Ctr Med, Durham, NC 27706 USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenberg, J. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Redman, B. G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Hudes, G. R.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Bukowski, R. M.] Cleveland Clin Taussig Canc Ctr, Cleveland, OH USA. [Kim, S. T.] Pfizer Inc, La Jolla, CA USA. [Wilding, G.] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53706 USA. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 4517 BP 304 EP 304 DI 10.1016/S1359-6349(07)71148-5 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204000999 ER PT J AU Makhija, S Glenn, D Ueland, F Dizon, D Paton, V Lin, CY Amler, L Sliwkowski, M Strauss, A Matulonis, U AF Makhija, S. Glenn, D. Ueland, F. Dizon, D. Paton, V. Lin, C. Y. Amler, L. Sliwkowski, M. Strauss, A. Matulonis, U. TI Results from a phase II randomized, placebo-controlled, double-blind trial suggest improved PFS with the addition of pertuzumab to gemcitabine in patients with platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Makhija, S.] Univ Alabama, Birmingham, AL USA. [Glenn, D.] Sharp Rees Stealy Med Grp, San Diego, CA USA. [Ueland, F.] UK Healthcare Markey Canc Ctr, Lexington, KY USA. [Dizon, D.] Women & Infants Hosp Rhode Isl, Program Womens Oncol, Providence, RI USA. [Paton, V.; Lin, C. Y.; Amler, L.; Sliwkowski, M.] Genentech Inc, San Francisco, CA 94080 USA. [Strauss, A.] Roche Diagnost GmbH, Penzberg, Germany. [Matulonis, U.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 5002 BP 311 EP 312 DI 10.1016/S1359-6349(07)71174-6 PG 2 WC Oncology SC Oncology GA 221CC UT WOS:000250204001025 ER PT J AU Solca, F Baum, A Krause, M Baumann, M Wong, KK Greulich, H Adolf, G AF Solca, F. Baum, A. Krause, M. Baumann, M. Wong, K. K. Greulich, H. Adolf, G. TI Efficacy of BIBW 2992, a potent irreversible inhibitor of EGFR and HER2, in models of head and neck cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Solca, F.; Baum, A.; Adolf, G.] Boehringer Ingelheim Austria GmbH, Vienna, Austria. [Baumann, M.] Tech Univ Dresden, Med Fac Carl Gustav Carus, D-8027 Dresden, Germany. [Wong, K. K.; Greulich, H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 5508 BP 326 EP 327 DI 10.1016/S1359-6349(07)71225-9 PG 2 WC Oncology SC Oncology GA 221CC UT WOS:000250204001076 ER PT J AU Crump, M Coiffier, B Jacobsen, ED Sun, L Ricker, JL Xie, H Frankel, SR Randolph, SS Cheson, BD AF Crump, M. Coiffier, B. Jacobsen, E. D. Sun, L. Ricker, J. L. Xie, H. Frankel, S. R. Randolph, S. S. Cheson, B. D. TI Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in relapsed diffuse large B-cell lymphoma (DLBCL) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Crump, M.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Coiffier, B.] Ctr Hosp Lyon Sud, Lyon, France. [Jacobsen, E. D.] Dana Faber Canc Inst, Boston, MA USA. [Cheson, B. D.] Georgetown Univ Hosp, Washington, DC 20007 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 6003 BP 346 EP 346 DI 10.1016/S1359-6349(07)71294-6 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001145 ER PT J AU Burris, H Krug, L Shapiro, G Fidias, R Crawford, J Reiman, T Michelson, G Young, D Adelman, D Ettinger, D AF Burris, H. Krug, L. Shapiro, G. Fidias, R. Crawford, J. Reiman, T. Michelson, G. Young, D. Adelman, D. Ettinger, D. TI SNS-595: Preliminary results of 2 phase 2 second line studies in lung cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Burris, H.] Sara Cannon Canc Ctr, Nashville, TN USA. [Krug, L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shapiro, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fidias, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Crawford, J.] Duke Univ, Ctr Canc, Durham, NC USA. [Reiman, T.] Cross Canc Ctr, Edmonton, AB, Canada. [Michelson, G.; Young, D.; Adelman, D.] Sunesis Pharmaceut Inc, San Francisco, CA USA. [Ettinger, D.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 6547 BP 371 EP 372 DI 10.1016/S1359-6349(07)71375-7 PG 2 WC Oncology SC Oncology GA 221CC UT WOS:000250204001226 ER PT J AU Abrey, L Johri, A Wen, PY Govindan, R Reimers, HJ Robins, HI de Bedout, S Hennan, L Ko, JL Rigas, JR AF Abrey, L. Johri, A. Wen, P. Y. Govindan, R. Reimers, H. J. Robins, H. I. de Bedout, S. Hennan, L. Ko, J. L. Rigas, J. R. TI Treatment of recurrent or progressive brain metastases with patupilone in patients with non-small cell lung cancer (NSCLC): results of a multicenter, open-label phase II study SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Abrey, L.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Johri, A.; de Bedout, S.; Hennan, L.; Ko, J. L.] Nova Pharmaceut Corp, E Hanover, NJ USA. [Wen, P. Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Govindan, R.] Washington Univ, Sch Med, St Louis, MO USA. [Reimers, H. J.] St Louis Univ, Sch Med, St Louis, MO 63103 USA. [Robins, H. I.] Univ Wisconsin, Hosp & Clin, Madison, WI 53792 USA. [Rigas, J. R.] Norris Cotton Canc Ctr, Dartmouth Med Sch, Lebanon, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 6549 BP 372 EP 372 DI 10.1016/S1359-6349(07)71377-0 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001228 ER PT J AU Allen, AM Othus, M Baldini, EH Mentzer, SJ Bueno, R Sugarbaker, DJ Colson, YL Marcoux, JP Johnson, BE Caglar, HB AF Allen, A. M. Othus, M. Baldini, E. H. Mentzer, S. J. Bueno, R. Sugarbaker, D. J. Colson, Y. L. Marcoux, J. P. Johnson, B. E. Caglar, H. B. TI Prognostic factors for radical treatment of stage IIINSCLC SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Allen, A. M.; Othus, M.; Baldini, E. H.] Brigham & Womens Hosp, Dana Faber Canc Inst, Boston, MA USA. [Mentzer, S. J.; Bueno, R.; Sugarbaker, D. J.; Colson, Y. L.] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA USA. [Marcoux, J. P.; Johnson, B. E.; Caglar, H. B.] Dana Faber Canc Inst, Dept Med Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 6613 BP 392 EP 392 DI 10.1016/S1359-6349(07)71441-6 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001292 ER PT J AU McDermott, D Sosman, JA Hodi, FS Gonzalez, R Linette, G Richards, J Jakub, JK Beeram, M Patel, K Hersch, E AF McDermott, D. Sosman, J. A. Hodi, F. S. Gonzalez, R. Linette, G. Richards, J. Jakub, J. K. Beeram, M. Patel, K. Hersch, E. TI Phase II randomized, placebo controlled study of sorafenib in combination with dacarbazine in subjects with unresectable Stage III or Stage IV melanoma SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [McDermott, D.] Beth Israel Deaconess Med Ctr, Dept Oncol, Boston, MA 02215 USA. [Sosman, J. A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Hodi, F. S.] Dana Faber Canc Inst, Boston, MA USA. [Gonzalez, R.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Linette, G.] Washington Univ, Sch Med, St Louis, MO USA. [Richards, J.] Lutheran Gen Canc Care Ctr, Park Ridge, IL USA. [Beeram, M.] Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. [Patel, K.] Onyx Pharmaceut, Emeryville, CA USA. [Hersch, E.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Jakub, J. K.] Reg Canc Ctr, Lakeland, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7004 BP 396 EP 396 DI 10.1016/S1359-6349(07)71458-1 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001309 ER PT J AU Hamid, O Urba, W Yellin, M Nichol, G Weber, J Hersh, E Tchekmedyian, S Hodi, S Weber, R O'Day, S AF Hamid, O. Urba, W. Yellin, M. Nichol, G. Weber, J. Hersh, E. Tchekmedyian, S. Hodi, S. Weber, R. O'Day, S. TI Ipilimumab (MDX-010) in patients with stage III/IV melanoma: kinetics and duration of response SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Hamid, O.; O'Day, S.] Angeles Clin & Res Inst, Santa Monica, CA USA. [Urba, W.] Earle A Chiles Res Inst, Providence Portland Med Ctr, Portland, OR USA. [Yellin, M.; Nichol, G.] Medarex Inc, Bloomsbury, NJ USA. [Weber, J.] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Hersh, E.] Arizona Canc Ctr, Tuscan, AZ USA. [Tchekmedyian, S.] Pacific Shores Med Grp, Long Beach, CA USA. [Hodi, S.] Dana Faber Canc Inst, Boston, MA USA. [Weber, R.] St Francis Mem Hosp, No Calif Melanoma Ctr, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7005 BP 397 EP 397 DI 10.1016/S1359-6349(07)71459-3 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001310 ER PT J AU Blay, JY George, S Casali, R Le Cesne, A Morgan, JA Pokela, J Quigley, MT Tasse, V Baum, CM Demetri, GD AF Blay, J. Y. George, S. Casali, P. G. Le Cesne, A. Morgan, J. A. Pokela, J. Quigley, M. T. Tasse, V. Baum, C. M. Demetri, G. D. TI Continuous daily dosing (CDD) study of sunitinib malate (SU) in patients (pts) with advanced GIST compares favorably with intermittent dosing SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Blay, J. Y.] Ctr Leon Berard, F-69373 Lyon, France. [George, S.; Morgan, J. A.; Pokela, J.; Quigley, M. T.; Demetri, G. D.] Dana Faber Canc Inst, Boston, MA USA. [Casali, P. G.] Inst Nazl Tumori, Milan, Italy. [Le Cesne, A.] Inst Gustave Roussy, Villejuif, France. [Tasse, V.; Baum, C. M.] Pfizer Res & Dev, La Jolla, CA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7501 BP 402 EP 402 DI 10.1016/S1359-6349(07)71478-7 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001329 ER PT J AU Demetri, GD Schuetze, S Le Cesne, A Chawia, S Casali, P Gomez, J Nieto, A Elsayed, Y Izquierdo, MA Blay, JY AF Demetri, G. D. Schuetze, S. Le Cesne, A. Chawia, S. Casali, Pg. Gomez, J. Nieto, A. Elsayed, Y. Izquierdo, M. A. Blay, J. Y. TI Impact of independent review on efficacy outcomes in a randomised multicenter trial of trabectedin given by two dosing regimens in patients (pts) with progressing leiomyosarcomas or liposarcomas (L-sarcomas) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Demetri, G. D.] Ludwig Ctr Dana Faber Harvard, Boston, MA USA. [Schuetze, S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Le Cesne, A.] Inst Gustave Roussy, Villejuif, France. [Chawia, S.] Century City Hosp, Los Angeles, CA USA. [Casali, Pg.] Ist Nazl Tumori, I-20133 Milan, Italy. [Gomez, J.; Nieto, A.; Izquierdo, M. A.] Pharma Mar, Madrid, Spain. [Elsayed, Y.] Johnson & Johnson Consumer Prod Inc, Raritan, NJ USA. [Blay, J. Y.] Ctr Leon Berard, F-69373 Lyon, France. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7500 BP 402 EP 402 DI 10.1016/S1359-6349(07)71477-5 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001328 ER PT J AU Schoffski, P Huang, X Demetri, GD Casali, R Garrett, CR Blackstein, M Shah, MH Verweij, J Baum, CM Deprimo, SE AF Schoffski, P. Huang, X. Demetri, G. D. Casali, Rg. Garrett, C. R. Blackstein, M. Shah, M. H. Verweij, J. Baum, C. M. Deprimo, S. E. TI Assessment of plasma levels of soluble KIT (sKIT) as a potential surrogate marker for TTP in patients (pts) with advanced gastrointestinal stromal tumor (GIST) treated with sunitinib SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Schoffski, P.] UZ Gasthuisberg, Louvain, Belgium. [Huang, X.; Baum, C. M.; Deprimo, S. E.] Pfizer Global Res & Dev, La Jolla, CA USA. [Demetri, G. D.] Ludwig Dana Farber Harvard Canc Ctr, Boston, MA USA. [Casali, Rg.] Inst Nazl Tumori, Milan, Italy. [Garrett, C. R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Blackstein, M.] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Shah, M. H.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Verweij, J.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7502 BP 402 EP 403 DI 10.1016/S1359-6349(07)71479-9 PG 2 WC Oncology SC Oncology GA 221CC UT WOS:000250204001330 ER PT J AU Fletcher, JA Corless, CL Liegl, B Fletcher, CD Raut, CP Donsky, R Bertagnolli, MM Harlow, A Demetri, GD Heinrich, MC AF Fletcher, J. A. Corless, C. L. Liegl, B. Fletcher, C. D. Raut, C. P. Donsky, R. Bertagnolli, M. M. Harlow, A. Demetri, G. D. Heinrich, M. C. TI KIT mutations and sunitinib resistance in gastrointestinal stromal tumors (GISTs) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Fletcher, J. A.; Liegl, B.; Fletcher, C. D.; Raut, C. P.; Donsky, R.; Bertagnolli, M. M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Corless, C. L.; Harlow, A.] OHSU, Inst Canc, Portland, OR USA. [Demetri, G. D.] Ludwig Dana Farber Harvard Ctr, Boston, MA USA. [Heinrich, M. C.] OHSU, Inst Canc, VAMC, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7503 BP 403 EP 403 DI 10.1016/S1359-6349(07)71480-5 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001331 ER PT J AU Joensuu, H Demetri, GD Heinrich, MC Eisenberg, BL Fletcher, JA Corless, CL Fletcher, CD Blanke, C Heintz, D von Mehren, M AF Joensuu, H. Demetri, G. D. Heinrich, M. C. Eisenberg, B. L. Fletcher, J. A. Corless, C. L. Fletcher, C. D. Blanke, C. Heintz, D. von Mehren, M. TI Up to 6 years follow-up of patients receiving imatinib mesylate (Glivec) to treat unresectable or metastatic gastrointestinal stromal tumors (GISTs) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Joensuu, H.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Demetri, G. D.; Fletcher, C. D.] Dana Farber Canc Inst, Boston, MA USA. [Heinrich, M. C.; Corless, C. L.; Blanke, C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Eisenberg, B. L.] Dartmouth Hitchcock Canc Ctr, Lebanon, NH USA. [Fletcher, J. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Heintz, D.] Nova Pharmaceut Corp, Basel, Switzerland. [von Mehren, M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7506 BP 404 EP 404 DI 10.1016/S1359-6349(07)71483-0 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001334 ER PT J AU Le Cesne, A von Mehren, M Chawla, S Blay, JY Schuetze, S Nieto, A Gomez, J Santabarbara, P Izquierdo, MA Demetri, GD AF Le Cesne, A. von Mehren, M. Chawla, S. Blay, J. Y. Schuetze, S. Nieto, A. Gomez, J. Santabarbara, P. Izquierdo, M. A. Demetri, G. D. CA Yondelis S S Grp TI Assessing the clinical impact of trabectedin in patients with leiomyosarcomas or liposarcomas (L-sarcomas) progressing despite prior conventional chemotherapy: clinical benefit rate, growth modulation index and tumor variation as parameters of treatment effect in a randomised international trial of two trabectedin dosing regimens SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Le Cesne, A.] Inst Gustave Roussy, Villejuif, France. [von Mehren, M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Chawla, S.] Century City Hosp, Los Angeles, CA USA. [Blay, J. Y.] Ctr Leon Berard, F-69373 Lyon, France. [Schuetze, S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nieto, A.; Gomez, J.; Santabarbara, P.; Izquierdo, M. A.] Pharma Mar, Madrid, Spain. [Demetri, G. D.; Yondelis S S Grp] Ludwig Ctr Dana Farber Harverd, Boston, MA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7512 BP 405 EP 406 DI 10.1016/S1359-6349(07)71489-1 PG 2 WC Oncology SC Oncology GA 221CC UT WOS:000250204001340 ER PT J AU Seddon, B Reichardt, P Ruka, W Kang, YK Baum, CM Demetri, GD AF Seddon, B. Reichardt, P. Ruka, W. Kang, Y. K. Baum, C. M. Demetri, G. D. TI Safety and efficacy results of sunitinib from a worldwide treatment. use trial of gastrointestinal stromal tumour (GIST) patients (pts) with resistance or intolerance to prior imatinib therapy SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Seddon, B.] Univ Coll Hosp NHS Trust, London, England. [Reichardt, P.] Charite Campus Buch, Berlin, Germany. [Ruka, W.] Maria Sklodowska Curie Mem Inst Oncol, Sarcoma & Melanoma Dept, Warsaw, Poland. [Kang, Y. K.] Asan Med Ctr, Div Oncol, Seoul, South Korea. [Baum, C. M.] Pfizer Global Res & Dev, La Jolla, CA USA. [Demetri, G. D.] Ludwig Ctr Dana Faber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7511 BP 405 EP 405 DI 10.1016/S1359-6349(07)71488-X PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001339 ER PT J AU Chawla, S Casali, PG von Mhren, M Le Cesne, A Blay, JY Lebedinsky, C Alfaro, V Elsayed, Y Michiels, B Demetri, GD AF Chawla, S. Casali, P. G. von Mhren, M. Le Cesne, A. Blay, J. Y. Lebedinsky, C. Alfaro, V. Elsayed, Y. Michiels, B. Demetri, G. D. CA Yondelis S S Grp TI Clinical tolerability of trabectedin administered by two different schedules (weekly for 3 of 4 weeks vs q3 weeks) in patients with advanced/metastatic liposarcoma or leiomyosarcoma (L-sarcomas) progressing despite prior treatment with at least anthracycline and ifosfamide SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Chawla, S.] Century City Hosp, Los Angeles, CA USA. [Casali, P. G.] Ist Nazl Tumori, I-20133 Milan, Italy. [von Mhren, M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Le Cesne, A.] Inst Gustave Roussy, Villejuif, France. [Blay, J. Y.] Ctr Leon Berard, F-69373 Lyon, France. [Lebedinsky, C.; Alfaro, V.] Pharma Mar, Madrid, Spain. [Elsayed, Y.; Michiels, B.; Demetri, G. D.] Johnson & Johnson Consumer Prod Inc, Raritan, NJ USA. [Demetri, G. D.] Ludwig Ctr Dana Farber Harvard, Boston, MA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7517 BP 407 EP 407 DI 10.1016/S1359-6349(07)71494-5 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001345 ER PT J AU Raut, C Morgan, JA Quigley, MT George, S Wagner, AJ Demetri, G Bertagnolli, MM AF Raut, C. Morgan, J. A. Quigley, M. T. George, S. Wagner, A. J. Demetri, G. Bertagnolli, M. M. TI Postoperative experience in patients with metastatic GIST are similar in patients while on sunitinib or imatinib SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org C1 [Raut, C.; Morgan, J. A.; Quigley, M. T.; George, S.; Wagner, A. J.; Demetri, G.; Bertagnolli, M. M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD SEP PY 2007 VL 5 IS 4 MA 7522 BP 409 EP 409 DI 10.1016/S1359-6349(07)71499-4 PG 1 WC Oncology SC Oncology GA 221CC UT WOS:000250204001350 ER PT J AU Kashiwagi, A DiGirolamo, CM Kanda, Y Niikura, Y Esmon, CT Hansen, TR Shioda, T Pru, JK AF Kashiwagi, Aki DiGirolamo, Carla M. Kanda, Yoshiaki Niikura, Yuichi Esmon, Charles T. Hansen, Thomas R. Shioda, Toshi Pru, James K. TI The Postimplantation embryo differentially regulates endometrial gene expression and decidualization SO ENDOCRINOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; BONE MORPHOGENETIC PROTEINS; RECURRENT PREGNANCY LOSS; CROSS-REACTIVE PROTEIN; MOUSE UTERUS; SERINE-PROTEASE; ACTIVIN-A; GROWTH-FACTORS; NK CELLS; IN-VITRO AB Transcriptomal changes in the uterine endometrium induced in response to the implanting embryo remain largely unknown. In this study, using Affymetrix mRNA expression microarray analysis, we identified genes differentially expressed in the murine endometrium in the presence or absence of the embryo. Compared with the pseudopregnant deciduoma induced by a mechanical stimulus in the absence of an embryo, approximately 1500 genes ( 753 up-regulated, 686 down-regulated; P < 0.05) were differentially expressed by at least 1.2-fold in the uterine decidua of pregnancy. Most of these genes fall into five major biological categories that include binding ( 45%), catalysis ( 24%), signal transduction ( 10%), transcriptional regulators ( 5%), and transporters ( 5%). This strong, embryo-induced transcriptomal impact represented approximately 10% of the total number of genes expressed in the decidualizing endometrium. Validation studies with mRNA and protein confirmed existence of the phylogenetically conserved, embryo-regulated genes involved in the following: 1) hemostasis and inflammation; 2) interferon signaling; 3) tissue growth and remodeling; and 4) natural killer cell function. Interestingly, whereas expression of many growth factors and their cognate receptors were not different between the decidual and deciduomal endometria, a number of proteases that degrade growth factors were selectively up-regulated in the decidual tissue. Increased expression of IGF and activin A neutralizing factors ( i.e. HtrA1 and Fstl3) correlated with reduced stromal cell mitosis, tissue growth, and mitogenic signaling in the decidual endometrium. These results support the hypothesis that the implanting murine embryo takes a proactive role in modulating endometrial gene expression and development during early gestation. C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Profiling Lab, Boston, MA 02114 USA. Oklahoma Med Res Fdn, Howard Hughes Med Inst, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA. Colorado State Univ, Anim Reprod & Biotechnol Lab, Ft Collins, CO 80523 USA. Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA. RP Pru, JK (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. EM jpru@partners.org FU NHLBI NIH HHS [P50 HL54502]; NICHD NIH HHS [HD032475]; NIEHS NIH HHS [ES012070] NR 75 TC 36 Z9 39 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2007 VL 148 IS 9 BP 4173 EP 4184 DI 10.1210/en.2007-0268 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 200UX UT WOS:000248789400010 PM 17510242 ER PT J AU Akingbemi, BT Braden, TD Kemppainen, BW Hancock, KD Sherrill, JD Cook, SJ He, XY Supko, JG AF Akingbemi, Benson T. Braden, Tim D. Kemppainen, Barbara W. Hancock, Karen D. Sherrill, Jessica D. Cook, Sarah J. He, Xiaoying Supko, Jeffrey G. TI Exposure to phytoestrogens in the perinatal period affects androgen secretion by testicular Leydig cells in the adult rat SO ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr ID ESTROGEN-RECEPTOR-ALPHA; SOY FORMULA MILK; DIETARY GENISTEIN; BISPHENOL-A; ENVIRONMENTAL ESTROGENS; NEONATAL EXPOSURE; MARMOSET MONKEYS; GENE-EXPRESSION; FETAL EXPOSURE; INFANT FORMULA AB The use of soy-based products in the diet of infants has raised concerns regarding the reproductive toxicity of genistein and daidzein, the predominant isoflavones in soybeans with estrogenic activity. Time-bred Long-Evans dams were fed diets containing 0, 5, 50, 500, or 1000 ppm of soy isoflavones from gestational d 12 until weaning at d 21 postpartum. Male rats in all groups were fed soy-free diets from postnatal d 21 until 90 d of age. The mean +/- SD concentration of unconjugated (i.e. biologically active) genistein and daidzein in serum from the group of dams maintained on the diet containing the highest amount of isoflavones ( 1000 ppm) were 17 +/- 27 and 56 +/- 30 nM, respectively, at d 21 postpartum. The concentrations were considerably greater in male offspring ( genistein: 73 +/- 46 nM; daidzein: 106 +/- 53 nM). Although steroidogenesis was decreased individual Leydig cells, male rats from the highest exposure group ( 1000 ppm diet) exhibited elevated serum levels of the sex steroid hormones androsterone at 21 d ( control: 15 +/- 1.5 vs. 28 +/- 3.5 ng/ml; P < 0.05) and testosterone at 90 d of age ( control: 7.5 +/- 1 vs. 17 +/- 2 ng/ml; P < 0.05). Testosterone secretion by immature Leydig cells, isolated from 35-d-old male rats, decreased on exposure to 0.1 nM genistein in vitro ( control: 175 +/- 5 vs. 117 +/- 3 ng/10(6) cells per 24 h; P < 0.05), indicative of direct phytoestrogen action. Thus, phytoestrogens have the ability to regulate Leydig cells, and additional studies to assess potential adverse effects of dietary soy-based products on reproductive tract development in neonates are warranted. C1 Auburn Univ, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Akingbemi, BT (reprint author), Auburn Univ, Dept Anat Physiol & Pharmacol, 109 Greene Hall, Auburn, AL 36849 USA. EM akingbt@auburn.edu NR 72 TC 42 Z9 46 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2007 VL 148 IS 9 BP 4475 EP 4488 DI 10.1210/en.2007-0327 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 200UX UT WOS:000248789400042 PM 17569756 ER PT J AU Sipp, JA Haver, KE Masek, BJ Hartnick, CJ AF Sipp, J. Andrew Haver, Kennan E. Masek, Bruce J. Hartnick, Christopher J. TI Botulinum toxin A: A novel adjunct treatment for debilitating habit cough in children SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Article ID PSYCHOGENIC COUGH; BEDSHEET; COMMON AB Vocal fold injection with botulinum toxin type A (BTX-A) may be used as an adjunct treatment for habit cough in children. We conducted a retrospective review of 3 cases involving children aged 11 to 13 years with habit cough treated with vocal fold injection of BTX-A. Injections of BTX-A to the thyroarytenoid muscles were effective in breaking the cough cycle in all 3 children. Their coughs recurred but were controlled with 4 to 8 sessions of behavioral therapy. Behavioral therapy remains the first-line treatment, but BTX-A may be a useful complement to behavioral therapy in patients who fail standard treatments or in those with severe cough who have limited or delayed access to mental health professionals. This is the first report, to our knowledge, on the use of BTX-A in the treatment of a habit cough. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Pulmonol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 15 TC 9 Z9 9 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0145-5613 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD SEP PY 2007 VL 86 IS 9 BP 570 EP 572 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 220PC UT WOS:000250167600014 PM 17970150 ER PT J AU Nelson, KM Reiber, G Kohler, T Boyko, EJ AF Nelson, Karin M. Reiber, Gayle Kohler, Ted Boyko, Edward J. TI Peripheral arterial disease in a multiethnic national sample: The role of conventional risk factors and allostatic load SO ETHNICITY & DISEASE LA English DT Article DE peripheral vascular disease; race/ethnicity ID ANKLE-BRACHIAL INDEX; NUTRITION EXAMINATION SURVEY; C-REACTIVE PROTEIN; UNITED-STATES; ARM INDEX; CARDIOVASCULAR-DISEASE; VASCULAR-DISEASE; PREVALENCE; HEALTH; POPULATION AB Background: Limited data exist on the prevalence of peripheral arterial disease (PAD) among ethnically diverse populations. Our objectives were to assess the prevalence of PAD in a multiethnic national sample and examine risk factor control and allostatic load (a marker of dysregulation of the inflammatory, metabolic, and cardiovascular systems) by race/ethnicity among individuals with PAD. Methods: We analyzed data from the 19992002 National Health and Nutrition Examination Surveyfor individuals aged >= 40 with a measured ankle brachial index (N=5,083). PAD was defined as an ankle brachial index <0.9. We performed bivariate and multivariate analyses to describe the association of race/ethnicity with PAD, controlling for sociodemographic factors, clinical risk factors and allostatic load. Results: Rates of PAD were higher among African Americans (7.8%) than Whites (3.4%) or Mexican Americans (5.1%) (P<.001). African Americans with PAD were more likely to be taking antihypertensive medications, were less likely to report vigorous physical activity, and had higher allostatic load scores than Whites. Although 95% of individuals with PAD report a routine place for care, almost half had a measured blood pressure >140/90 mm Hg, 28% were smokers, and 61% had a cholesterol value >= 200 mg/dL. Conclusions: Within this nationally representative sample, African Americans had the highest rates of PAD. Although conventional risk factor control, including control of hypertension and hyperlipidemia, were similar between racial groups, African Americans with PAD had higher allostatic load scores. Among all individuals with PAD, evidence showed suboptimal cardiovascular risk factor control. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Washington Univ, Dept Med, St Louis, MO 63130 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. Washington Univ, Dept Epidemiol & Hlth Serv, St Louis, MO 63130 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. RP Nelson, KM (reprint author), VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, 1660 S Columbian Way,S-111-GIMC, Seattle, WA 98108 USA. EM karin.nelson@va.gov NR 40 TC 16 Z9 16 U1 32 U2 35 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2007 VL 17 IS 4 BP 669 EP 675 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 233UK UT WOS:000251115600012 PM 18072377 ER PT J AU Scirica, BM Morrow, DA Hod, H Theroux, P Molhoek, P Karwatowska-Prokopczuk, E Qin, J Murhpy, S Mccabe, CH Braunwald, E AF Scirica, B. M. Morrow, D. A. Hod, H. Theroux, P. Molhoek, P. Karwatowska-Prokopczuk, E. Qin, J. Murhpy, S. Mccabe, C. H. Braunwald, E. CA MERLIN-TIMI 36 Investigators TI Clinical outcomes in patients with diabetes or the metabolic syndrome with non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 Trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Scirica, B. M.; Morrow, D. A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Karwatowska-Prokopczuk, E.; Qin, J.; Murhpy, S.; Mccabe, C. H.; Braunwald, E.] CV Therapeut, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 64 EP 65 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702200249 ER PT J AU Mckelvie, RS Komajda, M Mcmurray, J Zile, M Ptaszynska, A Bhaumik, A Carson, P Massie, B AF Mckelvie, R. S. Komajda, M. Mcmurray, J. Zile, M. Ptaszynska, A. Bhaumik, A. Carson, P. Massie, B. CA I-PRESERVE Investigators TI Baseline plasma NT-proBNP concentrations in relation to clinical characteristics: results from the irbesartan in heart failure with preserved systolic function trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Mckelvie, R. S.] Hamilton Hlth Sci, Hamilton, ON, Canada. [Komajda, M.] Hop La Pitie Salpetriere, Paris, France. [Mcmurray, J.; Bhaumik, A.] Univ Glasglow, Glasgow, Lanark, Scotland. [Zile, M.] Med Univ S Carolina, RHJ Dept VAMC, Charleston, SC USA. [Ptaszynska, A.] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. [Carson, P.] VAMC, Washington, DC USA. [Massie, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, B.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 145 EP 145 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702200569 ER PT J AU Giraldez, R Giugliano, RP Qie, J Murphy, SA Cannon, CP Braunwald, E AF Giraldez, R. Giugliano, R. P. Qie, J. Murphy, S. A. Cannon, C. P. Braunwald, E. CA PROVE IT-TIMI 22 Investigators TI Baseline LDL is an important predictor of the benefit of intensive statin therapy in PROVE IT-TIMI 22 SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Giraldez, R.; Giugliano, R. P.; Qie, J.; Murphy, S. A.; Cannon, C. P.; Braunwald, E.; PROVE IT-TIMI 22 Investigators] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 207 EP 207 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702201059 ER PT J AU Mieres, J Rodriguez, AE Grinfeld, L Fernandez-Pereira, C Berrocal, D Rodriguez-Granillo, AM Rodriguez-Granillo, GA Grinfeld, D Palacios, I AF Mieres, J. Rodriguez, A. E. Grinfeld, L. Fernandez-Pereira, C. Berrocal, D. Rodriguez-Granillo, A. M. Rodriguez-Granillo, G. A. Grinfeld, D. Palacios, I. CA ERACI Investigators TI Lack of advantage of DES compared to bare metal stents or coranary bypass surgery in diabetics patients: three years outcome of ERACI III trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Mieres, J.; Rodriguez, A. E.; Berrocal, D.; Grinfeld, D.] Otamendi Hosp, Buenos Aires, DF, Argentina. [Grinfeld, L.; Fernandez-Pereira, C.; Rodriguez-Granillo, A. M.; Rodriguez-Granillo, G. A.] Italian Hosp, Buenos Aires, DF, Argentina. [Palacios, I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 334 EP 334 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702201546 ER PT J AU Moselewski, F Kurtz, E Koenig, W Nichols, J Seneviratne, S Butler, J Achenbach, S Hoffmann, U AF Moselewski, F. Kurtz, E. Koenig, W. Nichols, J. Seneviratne, S. Butler, J. Achenbach, S. Hoffmann, U. TI Association between coronary plaque burden and inflammatory biomarkers in patients with acute chest pain SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Moselewski, F.; Kurtz, E.; Nichols, J.; Seneviratne, S.; Butler, J.; Hoffmann, U.] Massachusetts Gen Hosp, Cardiac Mr Pet Ct Program, Boston, MA 02114 USA. [Koenig, W.] Univ Ulm, D-89069 Ulm, Germany. [Achenbach, S.] Univ Erlangen Nurnberg, Erlangen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 371 EP 371 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702202043 ER PT J AU Rodriguez, AE Mieres, J Rodriguez-Granillo, AM Fernandez-Pereira, C Felssen, MR Curotto, V Tarragona, S Mauree, A Palacios, I AF Rodriguez, A. E. Mieres, J. Rodriguez-Granillo, A. M. Fernandez-Pereira, C. Felssen, M. R. Curotto, V. Tarragona, S. Mauree, A. Palacios, I. CA ORAR III Investigators TI Is oral rapamycin plus bare metal stents a feasible alternative to drug eluting stents to prevent restenosis? A cost effective follow up analysis from the randomized, controlled ORAR III study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Rodriguez, A. E.; Mieres, J.; Rodriguez-Granillo, A. M.; Fernandez-Pereira, C.; Felssen, M. R.; Curotto, V.; Tarragona, S.; Palacios, I.] Otamendi Hosp, Cardiovasc Res Ctr, Buenos Aires, DF, Argentina. [Mauree, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 396 EP 396 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702202139 ER PT J AU Cruz-Gonzalez, I Sanchez, PL Sanchez-Ledesma, M Maree, AO Martin-Moreiras, J Jneid, H Rengifo-Moreno, P Inglessis, I Palacios, IF AF Cruz-Gonzalez, I. Sanchez, P. L. Sanchez-Ledesma, M. Maree, A. O. Martin-Moreiras, J. Jneid, H. Rengifo-Moreno, P. Inglessis, I. Palacios, I. F. TI Impact of concomitant aortic regurgitation on percutaneous mitral valvuloplasty immediate results, short- and long-term outcome SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Cruz-Gonzalez, I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sanchez, P. L.; Sanchez-Ledesma, M.; Maree, A. O.] Gregorio Maranon, Madrid, Spain. [Martin-Moreiras, J.; Jneid, H.; Rengifo-Moreno, P.; Inglessis, I.; Palacios, I. F.] Univ Hosp, Salamanca, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 447 EP 448 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702202341 ER PT J AU Cruz-Gonzalez, I Sanchez-Ledesma, M Sanchez, PL Maree, AO Martin-Moreiras, J Jneid, H Rengifo-Moreno, P Inglessis, I Palacios, IF AF Cruz-Gonzalez, I. Sanchez-Ledesma, M. Sanchez, P. L. Maree, A. O. Martin-Moreiras, J. Jneid, H. Rengifo-Moreno, P. Inglessis, I. Palacios, I. F. TI Predicting success of mitral valvuloplasty: a multifactorial approach SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Cruz-Gonzalez, I.; Sanchez-Ledesma, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sanchez, P. L.; Maree, A. O.] Gregorio Maranon, Cardiol, Madrid, Spain. [Martin-Moreiras, J.; Jneid, H.; Rengifo-Moreno, P.; Inglessis, I.; Palacios, I. F.] Univ Hosp, Salamanca, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 449 EP 449 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702202347 ER PT J AU Moreiras, JM Awaida, JP Passeri, J Maree, A Jneid, H Cruz, I Pomerantsev, E Inglessis, I Yoerger, D Palacios, IF AF Martin Moreiras, J. Awaida, J. P. Passeri, J. Maree, A. Jneid, H. Cruz, I. Pomerantsev, E. Inglessis, I. Yoerger, D. Palacios, I. F. TI Transseptal and standard approaches to close long-tunnel patent foramen ovale are similar SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Martin Moreiras, J.; Cruz, I.] Hosp Univ Salamanca, Dept Cardiol, Salamanca, Spain. [Awaida, J. P.; Passeri, J.; Maree, A.; Jneid, H.; Pomerantsev, E.; Inglessis, I.; Yoerger, D.; Palacios, I. F.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 452 EP 453 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702202362 ER PT J AU Januzzi, J AF Januzzi, J. CA PRIDE Study Grp TI Measurement of soluble ST2 concentrations is useful for the evaluation of patients with acute dyspnea SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Januzzi, J.; PRIDE Study Grp] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 552 EP 552 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702202743 ER PT J AU Giraldez, R Sabatine, MS Morrow, DA Mohanavelu, S Mccabe, CH Antman, EM Braunwald, E AF Giraldez, R. Sabatine, M. S. Morrow, D. A. Mohanavelu, S. Mccabe, C. H. Antman, E. M. Braunwald, E. CA ExTRACT-TIMI 25 Investigators TI Combination of admission hemoglobin, white blood cell count and creatinine clearance in a laboratory index offers additional risk stratification in STEMI patients SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Giraldez, R.; Sabatine, M. S.; Morrow, D. A.; Mohanavelu, S.; Mccabe, C. H.; Antman, E. M.; Braunwald, E.; ExTRACT-TIMI 25 Investigators] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 761 EP 761 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702204135 ER PT J AU Lipskaia, L Lehoux, S Esposito, B Le Prince, P Bonnet, N Cantaloube, I Le Feuvre, C Hajjar, R Lompre, AM AF Lipskaia, L. Lehoux, S. Esposito, B. Le Prince, P. Bonnet, N. Cantaloube, I. Le Feuvre, C. Hajjar, R. Lompre, A. M. TI SERCA2a gene transfer reduces vascular smooth muscle proliferation and restenosis in human: a new target for drug-eluting stents? SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Lipskaia, L.; Esposito, B.] CHU Pitie Salpetriere, INSERM, UMR S 621, Paris 13, France. [Lehoux, S.; Cantaloube, I.] Hop Lariboisiere, INSERM, CRCIL UMR S 689, F-75475 Paris 10, France. [Le Prince, P.; Bonnet, N.; Le Feuvre, C.; Lompre, A. M.] Inst Cardiol Pitie Salpetriere, Paris 13, France. [Hajjar, R.] Massachusetts Gen Hosp, CVRC, Charlestown, MA USA. RI LOMPRE, Anne-Marie/H-2872-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 797 EP 797 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702204271 ER PT J AU Moselewski, F Dannemann, N Shapiro, MD Butler, J Koenig, W Nasir, K Achenbach, S Brady, T Hoffmann, U AF Moselewski, F. Dannemann, N. Shapiro, M. D. Butler, J. Koenig, W. Nasir, K. Achenbach, S. Brady, T. Hoffmann, U. TI Association between traditional risk factors and coronary atherosclerotic plaque burden as detected by multidetector computed tomography in men and women SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 [Moselewski, F.; Dannemann, N.; Shapiro, M. D.; Butler, J.; Nasir, K.; Brady, T.; Hoffmann, U.] Massachusetts Gen Hosp, Cardiac Mr Pet Ct Program, Boston, MA 02114 USA. [Koenig, W.] Univ Ulm, D-89069 Ulm, Germany. [Achenbach, S.] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 SU 1 BP 850 EP 850 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V28TD UT WOS:000208702204483 ER PT J AU Rodriguez, AE Maree, AO Mieres, J Berrocal, D Grinfeld, L Fernandez-Pereira, C Curotto, V Rodriguez-Granillo, A O'Neill, W Palacios, IF AF Rodriguez, Alfredo E. Maree, Andrew O. Mieres, Juan Berrocal, Daniel Grinfeld, Liliana Fernandez-Pereira, Carlos Curotto, Valeria Rodriguez-Granillo, Alfredo O'Neill, William Palacios, Igor F. TI Late loss of early benefit from drug-eluting stents when compared with bare-metal stents and coronary artery bypass surgery: 3 years follow-up of the ERACI III registry SO EUROPEAN HEART JOURNAL LA English DT Article DE drug-eluting stents; muttivesset disease; myocardial revascularization ID MULTIVESSEL DISEASE; RANDOMIZED-TRIAL; ANGIOPLASTY; THROMBOSIS; REVASCULARIZATION; INTERVENTION; OUTCOMES; DISCONTINUATION; IMPLANTATION; THERAPY AB Aims Long-term benefit from coronary revascularization with drug-etuting stents (DES) relative to bare metal stents (BMS) and coronary artery bypass grafting (CABG) has not been established. One year follow-up of the ERACI III registry study showed better outcome with DES. To compare major adverse cardiac and cerebrovascular event (MACCE) rates in patients with multivessel cardiovascular disease (CVD) who received DES with those patients treated with BMS or CABG in the ERACI 11 trial. Methods and results Patients with multivessel CVD who met the ERACI If trial, clinical and angiographic inclusion criteria were treated with DES and enrolled in the ERACI III registry. The primary endpoint was 3-year MACCE. ERACI III-DES patients (n = 225) Were compared with the BMS In = 225) and CABG (n = 225) arms of ERACI II. Patients treated with DES. were older, more often smokers, more often high risk by euroSCORE and less frequently had unstable angina. They also had higher incidence of type C lesions and received more stents than the BMS-treated cohort. Three year MACCE was tower in ERACI III-DES (22.7%) than in ERACI II-BMS (29.8%, P = 0.015), mainly reflecting less target vessel revascularization (14.2 vs. 24.4%, P = 0.009). MACCE rates at 3 years were similar in DES and CAB-Gtreated patients (22.7%, P = 1.0), in contrast to results at 1 year (12 vs. 19.6%, P = 0.038). MACCE rates in ERACI III-DES were higher in diabetics (RR 0.81, 0.66-0.99; P = 0.018). Death or non-fatal MI at 3 years trended higher in the DES (10.2%) than BMS cohort (6.2%, P = 0.08) and tower than in CABG patients (15.1 %, P = 0.07). Sub-acute late-stent thrombosis (LST) (> 30 days) occurred in nine DES patients and no BMS patients (P = 0.008). Conclusion In patients with multivessel CVD, the initial advantage for PCI with DES over CABG observed at 1 year was not apparent by 3 years. Furthermore, despite continued lower incidence of MACCE, initial advantage over BMS appeared to decrease with time. LST occurred more frequent in DES-treated patients. C1 Cardiovasc Res Ctr, CECI Sanatorio Otamendi, RA-1024 Buenos Aires, DF, Argentina. Dept Med, Sanatorio Otamendi, Buenos Aires, DF, Argentina. Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. RP Rodriguez, AE (reprint author), Cardiovasc Res Ctr, CECI Sanatorio Otamendi, Callao 1441,4B, RA-1024 Buenos Aires, DF, Argentina. EM rodrigueza@sanatorio-otamendi.com.ar NR 31 TC 49 Z9 58 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 IS 17 BP 2118 EP 2125 DI 10.1093/eurheartj/ehm297 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 214UN UT WOS:000249763800014 PM 17656352 ER PT J AU Poh, KK Wood, MJ Cury, RC AF Poh, Kian Keong Wood, Malissa J. Cury, Ricardo C. TI Prominent posterior mitral annular calcification causing embolic stroke and mimicking left atrial fibroma SO EUROPEAN HEART JOURNAL LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. Natl Univ Singapore, Dept Cardiac, Singapore 117548, Singapore. RP Poh, KK (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM doctorpoh@yahoo.com NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2007 VL 28 IS 18 BP 2216 EP 2216 DI 10.1093/eurheartj/ehm052 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 218YF UT WOS:000250051200011 PM 17409106 ER PT J AU Aliot, E Camm, AJ Hohnloser, SH Kowey, PR Prystowsky, EN Ruskin, J Singh, B AF Aliot, Etienne Camm, Alan John Hohnloser, Stefan H. Kowey, Peter R. Prystowsky, Eric N. Ruskin, Jeremy Singh, Bramah TI Introduction SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Editorial Material C1 Univ Nancy, Hop Brabois, Ctr Hosp, Vandoeuvre Les Nancy, France. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Univ Frankfurt, D-6000 Frankfurt, Germany. Lankenau Hosp, Main Line Hlth Heart Ctr, Wynnewood, PA USA. St Vincent Hosp, Indianapolis, IN USA. Hlth Ctr Program, Indianapolis, IN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Aliot, E (reprint author), Univ Nancy, Hop Brabois, Ctr Hosp, Vandoeuvre Les Nancy, France. 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 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD SEP PY 2007 VL 9 IS G BP G2 EP G2 DI 10.1093/eurheartj/sum046 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 225JW UT WOS:000250515200002 ER PT J AU Singh, BN Aliot, E AF Singh, Bramah N. Aliot, Etienne TI Newer antiarrhythmic agents for maintaining sinus rhythm in atrial fibrillation: simplicity or complexity? SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article; Proceedings Paper CT 1st Annual Advisory Meeting on Cardiac Rhythm/ Electrophysiology and Targeted Education CY OCT 10, 2006 CL Paris, FRANCE DE antiarrhythmic drug; atrial fibrillation; atrial selectivity; cardioversion; sinus rhythm ID CONGESTIVE-HEART-FAILURE; VENTRICULAR MYOCYTES; DOSE-RESPONSE; AMIODARONE; DRONEDARONE; EFFICACY; TRIAL; TEDISAMIL; FLUTTER; PREVENTION AB The morbidity and mortality associated with atrial fibrillation (AF), the most frequent cardiac arrhythmia, remain substantial. The efficacy and safety of current antiarrhythmic drugs continue to be less than optimal. The development of newer antiarrhythmic drugs has recently been made possible through a greater understanding of the pathophysiotogy of AF and knowledge of atrial electrophysiology relative to the properties of the congeners of known antiarrhythmic agents. Highly specific atrially acting drugs are currently being explored, their major merit concerning safety. In contrast, their rote may be somewhat limited in view of the etectrophysiological complexity of AF as an arrhythmia. The data suggest that complex antiarrhythmic agents with a multiplicity of actions may be preferable, although currently there are few data on the precise effectiveness of atrial.-specific agents in maintaining sinus rhythm in AF It is of interest that combining antiarrhythmic and non-antiarrhythmic agents, such as anti-inflammatory or antioxidant drugs, may increase the effectiveness of antifibrillatory actions in patients with AF, although these data have been obtained in uncontrolled, small or retrospective studies. Thus, at present, it is not certain whether it is preferable to target single antiarrhythmic drugs with antiadrenergic properties or to combine 'purely' antiarrhythmic drugs with other drugs devoid of anti-adrenergic effects. Controlled clinical trials are required to precisely define the effectiveness of single agents vs. various combinations of agents in maintaining sinus rhythm in patients with AF. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Nancy, Ctr Hosp, Hop Brabois, Vandoeuvre Les Nancy, France. RP Singh, BN (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Cardiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM b.singh@ucla.edu NR 52 TC 12 Z9 13 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD SEP PY 2007 VL 9 IS G BP G17 EP G25 DI 10.1093/eurheartj/sum049 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 225JW UT WOS:000250515200005 ER PT J AU Frahm, N Yusim, K Suscovich, TJ Adams, S Sidney, J Hraber, P Hewitt, HS Linde, CH Kavanagh, DG Woodberry, T Henry, LM Faircloth, K Listgarten, J Kadie, C Jojic, N Sango, K Brown, NV Pae, E Zaman, MT Bihl, F Khatri, A John, M Mallal, S Marincola, FM Walker, BD Sette, A Heckerman, D Korber, BT Brander, C AF Frahm, Nicole Yusim, Karina Suscovich, Todd J. Adams, Sharon Sidney, John Hraber, Peter Hewitt, Hannah S. Linde, Caitlyn H. Kavanagh, Daniel G. Woodberry, Tonia Henry, Leah M. Faircloth, Kellie Listgarten, Jennifer Kadie, Carl Jojic, Nebojsa Sango, Kaori Brown, Nancy V. Pae, Eunice Zaman, M. Tauheed Bihl, Florian Khatri, Ashok John, Mina Mallal, Simon Marincola, Francesco M. Walker, Bruce D. Sette, Alessandro Heckerman, David Korber, Bette T. Brander, Christian TI Extensive HLA class I allele promiscuity among viral CTL epitopes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antigen; bioinformatics; CD8 T cells; HIV; immune responses ID T-CELL EPITOPES; HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOCYTE EPITOPES; BIOINFORMATICS APPROACH; HIV POLYMORPHISMS; PEPTIDE BINDING; HEPATITIS-C; IDENTIFICATION; RECOGNITION; MOLECULES AB Promiscuous binding of T helper epitopes to MHC class 11 molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Los Alamos Natl Lab, Los Alamos, NM USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. La Jolla Inst Allergy & Immunol, La Jolla, CA USA. Microsoft Res, Redmond, WA USA. Fenway Community Hlth Ctr, Boston, MA USA. Lemuel Shattuck Hosp, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. Murdoch Univ, Perth, WA, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Brander, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, 149 13th St,Room 5239, Charlestown, MA 02129 USA. EM cbrander@partners.org OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897 FU NIAID NIH HHS [F32 AI058457, R01 AI067077-01, R01 AI067077-02, R01 AI067077-03, R21 AI055421, R21-AI-055421-01-A1]; PHS HHS [N01-AL-15422, R01-A1-067077] NR 58 TC 77 Z9 78 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2007 VL 37 IS 9 BP 2419 EP 2433 DI 10.1002/eji.200737365 PG 15 WC Immunology SC Immunology GA 214MV UT WOS:000249743200012 PM 17705138 ER PT J AU Niemann, S Kanki, H Fukui, Y Takao, K Fukaya, M Hynynen, MN Churchill, MJ Shefner, JM Bronson, RT Brown, RH Watanabe, M Miyakawa, T Itohara, S Hayashi, Y AF Niemann, Stephan Kanki, Hiroaki Fukui, Yasuyuki Takao, Keizo Fukaya, Masahiro Hynynen, Meri N. Churchill, Michael J. Shefner, Jeremy M. Bronson, Roderick T. Brown, Robert H., Jr. Watanabe, Masahiko Miyakawa, Tsuyoshi Itohara, Shigeyoshi Hayashi, Yasunori TI Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE excitatory synaptic transmission; gene targeting; motor neuron; mouse behaviour; NMDA type glutamate receptor subunit NR3B ID PSYCHIATRIC-DISORDERS; NERVOUS-SYSTEM; MESSENGER-RNA; AMINO-ACIDS; EXPRESSION; MICE; GLUTAMATE; STRESS; HIPPOCAMPUS; SCHIZOPHRENIA AB NR3B is a modulatory subunit of the NMDA receptor, abundantly expressed in both cranial and spinal somatic motoneurons and at lower levels in other regions of the brain as well. Recently, we found the human NR3B gene (GRIN3B) to be highly genetically heterogeneous, and that similar to 10% of the normal European-American population lacks NR3B due to homozygous occurrence of a null allele in the gene. Therefore, it is especially important to understand the phenotypic consequences of the genetic loss of NR3B in both humans and animal models. We here provide results of behavioral analysis of mice genetically lacking NR3B, which is an ideal animal model due to homogeneity in genetic and environmental background. The NR3B(-/-) mice are viable and fertile. Consistent with the expression of NR3B in somatic motoneurons, the NR3B(-/-) mice showed a moderate but significant impairment in motor learning or coordination, and decreased activity in their home cages. Remarkably, the NR3B(-/-) mice showed a highly increased social interaction with their familiar cage mates in their home cage but moderately increased anxiety-like behaviour and decreased social interaction in a novel environment, consistent with the inhibitory role of NR3B on the functions of NMDA receptors. This work is the first reporting of the functional significance of NR3B in vivo and may give insight into the contribution of genetic variability of NR3B in the phenotypic heterogeneity among human population. C1 MIT, RIKEN MIT Neurosci Res Ctr, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cecil B Day Lab Neuromuscular Res, Boston, MA 02129 USA. RIKEN, Lab Behav Genet, Brain Sci Inst, Wako, Saitama 3510198, Japan. Kyoto Univ, Genet Engn & Funct Genom Unit, Horizontal Med Res Org, Grad Sch Med, Kyoto 6068501, Japan. Fujita Hlth Univ, Div Syst Med Sci, Inst Comprehens Med Sci, Toyoake, Aichi 4701192, Japan. Hokkaido Univ, Sch Med, Dept Anat, Sapporo, Hokkaido 0608638, Japan. Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Niemann, S (reprint author), Epigenomics AG, Kleine Prasidentenstr 1, D-10178 Berlin, Germany. EM niste@mit.edu; yhayashi@mit.edu RI WATANABE, Masahiko/A-4055-2012; Itohara, Shigeyoshi/I-8769-2012; Hayashi, Yasunori/C-2249-2008; Takao, Keizo/B-9527-2008; Miyakawa, Tsuyoshi/A-7741-2008 OI Itohara, Shigeyoshi/0000-0002-2410-9989; Hayashi, Yasunori/0000-0002-7560-3004; Takao, Keizo/0000-0002-4734-3583; Miyakawa, Tsuyoshi/0000-0003-0137-8200 FU NIDA NIH HHS [R01DA17310]; NINDS NIH HHS [P01NS31248-02, R01NS37912, R21NS46421] NR 36 TC 27 Z9 30 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 2007 VL 26 IS 6 BP 1407 EP 1420 DI 10.1111/j.1460-9568.2007.05774.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 210WE UT WOS:000249485500003 PM 17880385 ER PT J AU Yeon, HB Weinberg, J Arlet, V Ouelett, JA Wood, KB AF Yeon, Howard B. Weinberg, Jacob Arlet, Vincent Ouelett, Jean A. Wood, Kirkham B. TI Anterior lumbar instrumentation improves correction of severe lumbar Lenke C curves in double major idiopathic scoliosis SO EUROPEAN SPINE JOURNAL LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Scoliosis-Research-Society CY OCT, 2005 CL Miami, FL SP Scoliosis Res DE anterior instrumentation; double major scoliosis; lenke C lumbar modifier ID COTREL-DUBOUSSET INSTRUMENTATION; SINGLE-ROD INSTRUMENTATION; TERM FOLLOW-UP; THORACIC SCOLIOSIS; SPINAL-FUSION; THORACOLUMBAR; SYSTEM; COMPLICATIONS; HARRINGTON; MANAGEMENT AB Fifteen skeletally immature patients with double major adolescent idiopathic scoliosis with large lumbar curves and notable L4 and L5 coronal plane obliquity were retrospectively studied. Seven patients who underwent anterior release and fusion of the lumbar curve with segmental anterior instrumentation and subsequent posterior instrumentation ending at L3 were compared with eight patients treated with anterior release and fusion without anterior instrumentation followed by posterior instrumentation to L3 or L4. At 4.5 years follow-up (range 2.5-7 years), curve correction, coronal balance and fusion rate were not statistically different between the two groups; however, the group with anterior instrumentation had improved coronal plane, near normalangulation in the distal unfused segment compared with the group without anterior instrumentation. In cases involving severe lumbar curvatures in the context of double major scoliosis, when as a first stage anterior release is chosen, the addition of instrumentation appears to restore normal coronal alignment of the distal unfused lumbar segment, and may in certain cases save a level compared with traditional fusions to L4. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr Outpatient Care, Spine Serv, Boston, MA 02114 USA. Texas Childrens Hosp, Dept Orthopaed Surg, Houston, TX 77030 USA. Univ Virginia, Dept Orthopaed Surg, Charlottesville, VA USA. McGill Univ, Ctr Hlth, Dept Orthopaed Surg, Montreal, PQ, Canada. RP Wood, KB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr Outpatient Care, Spine Serv, 55 Fruit St, Boston, MA 02114 USA. EM kbwood@partners.org NR 33 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0940-6719 J9 EUR SPINE J JI Eur. Spine J. PD SEP PY 2007 VL 16 IS 9 BP 1379 EP 1385 DI 10.1007/s00586-007-0370-6 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 209QX UT WOS:000249404200013 PM 17464517 ER PT J AU Heinrichs, S Kulkarni, RV Look, AT AF Heinrichs, S. Kulkarni, R. V. Look, A. T. TI HOXA9 is a required transcription factor for the proliferation of AML cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 28-30, 2007 CL Hamburg, GERMANY SP Int Soc Expt Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2007 VL 35 IS 9 SU 2 BP 66 EP 66 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 211PH UT WOS:000249535200180 ER PT J AU Santos, DD Ho, AW Tournilhac, O Hatjiharissi, E Leleu, X Xu, L Tassone, P Neri, P Hunter, ZR Chemaly, MAZ Branagan, AR Manning, RJ Patterson, CJ Moreau, AS Ciccarelli, B Adamia, S Kriangkum, J Kutok, JL Tai, YT Zhang, JW Pilarski, LM Anderson, KC Munshi, N Treon, SP AF Santos, Daniel Ditzel Ho, Allen W. Tournilhac, Olivier Hatjiharissi, Evdoxia Leleu, Xavier Xu, Lian Tassone, Pierfrancesco Neri, Paola Hunter, Zachary R. Chemaly, Mariana A. Z. Branagan, Andrew R. Manning, Robert J. Patterson, Christopher J. Moreau, Anne Sophie Ciccarelli, Bryan Adamia, Sophia Kriangkum, Jitra Kutok, Jeffery L. Tai, Yu-Tzu Zhang, Jiangwen Pilarski, Linda M. Anderson, Kenneth C. Munshi, Nikhil Treon, Steven P. TI Establishment of BCWM.1 cell line for Waldenstrom's macroglobulinemia with productive in vivo engraftment in SCID-hu mice SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MAST-CELLS; LYMPHOMA; EXPRESSION; GROWTH; CLASSIFICATION; TRANSLOCATIONS; EXPANSION; MYELOMA; APRIL; BAFF AB A significant impairment in understanding the biology and advancing therapeutics for Waldenstrom's macroglobulinemia (WM) has been the lack of a representative cell line and animal model. We, therefore, report on the establishment of the BCWM.1 cell line, which was derived from the long-term culture of CD19(+) selected bone marrow lymphoplasmacytic cells isolated from an untreated patient with WM. BCWM.1 cells morphologically resemble lymphoplasmacytic cells (LPC) and propagate in RPMI-1640 medium supplemented with 10% fetal bovine serum. Phenotypic characterization by flow cytometric analysis demonstrated typical WM LPC characteristics: CD5(-), CD10(-), CD19(+), CD20(+), CD23(+), CD27(-), CD38(+), CD138(+), CD40(+), CD52(+), CD70(+), CD117(+), cIgM(+), cIgG(-), cIgA(-), ck(-), c lambda(+), as well as the survival proteins APRIL and BLYS, and their receptors TACI, BCMA and BAFF-R. Enzyme-linked immunosorbent assay studies demonstrated secretion of IgM lambda and soluble CD27. Karyotypic and multicolor fluorescence in situ hybridization studies did not demonstrate cytogenetic abnormalities. Molecular analysis of BCWM.1 cells confirmed clonality by determination of IgH rearrangements. Inoculation of BCWM.1 cells in human bone marrow chips implanted in severe combined immunodeficient-hu mice led to rapid engraftment of tumor cells and serum detection of human IgM, lambda, and soluble CD27. These studies support the use of BCWM.1 cells as an appropriate model for the study of WM, which in conjunction with the severe combined immunodeficient-hu mouse model may be used as a convenient model for studies focused on both WM pathogenesis and development of targeted therapies for WM. (c) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglubulinemia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Univ Magna Graecia & Canc Ctr, Catanzaro, Italy. Univ Alberta, Dept Oncol, Cross Canc Inst, Edmonton, AB, Canada. Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglubulinemia, M547-8,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Ho, Allen/B-3017-2011; Zhang, Jiangwen/A-7654-2013; Hunter, Zachary/H-3018-2013; OI Hunter, Zachary/0000-0002-1689-1691; Branagan, Andrew/0000-0002-3868-9267 NR 32 TC 29 Z9 29 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2007 VL 35 IS 9 BP 1366 EP 1375 DI 10.1016/j.exphem.2007.05.022 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 210SI UT WOS:000249475500006 ER PT J AU Scirica, BM AF Scirica, Benjamin M. TI Ranolazine in patients with coronary artery disease SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE chronic angina; ischemia; pharmacotherapy; ranolazine ID STABLE ANGINA-PECTORIS; DOUBLE-BLIND; MICROVASCULAR DYSFUNCTION; EXERCISE TOLERANCE; ANTIANGINAL AGENT; RANDOMIZED-TRIAL; EFFICACY; TRIMETAZIDINE; INHIBITOR; METAANALYSIS AB Traditional anti-anginal agents such as beta-blockers and nitrates improve symptoms of cardiac ischemia by affecting either blood pressure or heart rates. Despite aggressive therapy, many patients suffer persistent angina, and optimal therapy is limited by intolerance to traditional agents. Ranolazine, a novel anti-anginal agent that is approved for use in the US, is felt to improve ischemic symptoms by reducing myocardial cellular sodium and calcium overload via inhibition of the late sodium current (I-Na) of the cardiac action potential. Several Phase-III trials in patients with chronic angina have demonstrated that ranolazine improves exercise tolerance and reduces ischemic symptoms as compared with placebo. In the largest evaluation of ranolazine, the MERLIN-TIMI 36 trial (Metabolic Efficiency with Ranolazine for Less Ischemia in non ST elevation acute coronary syndrome), ranolazine did not reduce the risk of death or recurrent myocardial infarction in patients with non-ST-elevation acute coronary syndromes, but it did improve ischemic symptoms over the subsequent year of therapy. Thus, ranolazine offers clinicians a new therapy in the long-term treatment of patients with chronic angina. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org NR 25 TC 4 Z9 4 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD SEP PY 2007 VL 8 IS 13 BP 2149 EP 2157 DI 10.1517/14656566.8.13.2149 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 211FL UT WOS:000249509600014 PM 17714067 ER PT J AU Esserman, LJ Shieh, Y Park, JW Ozanne, EM AF Esserman, Laura J. Shieh, Yiwey Park, John W. Ozanne, Elissa M. TI A role for biomarkers in the screening and diagnosis of breast cancer in younger women SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material DE biomarker; cancer susceptibility; early detection; prevention; regional cancer rate; screening ID SINGLE NUCLEOTIDE POLYMORPHISM; ACCELERATES TUMOR-FORMATION; GENOME-WIDE ASSOCIATION; GENE-EXPRESSION; RISK-ASSESSMENT; DUCTAL LAVAGE; UNITED-STATES; FOLLOW-UP; IN-SITU; PROMOTER HYPERMETHYLATION AB The widespread usage of screening mammography has resulted in an increase in the detection of early-stage disease, particularly in situ (stage 0) and early-stage (stage 1) cancers. However, incidence of stage 2 and 3 disease has not fallen commensurately, suggesting a bias in the detection of indolent cancers rather than aggressive cancers. Improved screening and diagnosis of a broader range of cancers is therefore an important need. Although MRI is a very sensitive breast cancer detection tool that has become standard for women at very high risk, it lacks sufficient specificity and cost-effectiveness for use as a general screen. The greatest opportunity for molecular tools to improve breast cancer outcomes is to better discern biologically aggressive cancers, especially in women under the age of 50 years. In this age group, presentation in stage 2 or 3 is more common and mammographic screening is less efficacious. We propose a multi-tiered triage strategy that uses emerging markers of susceptibility to segment the population for more focused screening with imaging. In particular, it would be helpful to identify a subset of at-risk, younger women who would benefit from intensive surveillance or preventive interventions. It is likely that tests for susceptibility, unless they are highly specific, will need to be combined with indicators of short-term risk. Although the combined sensitivity and specificity of screening must be high, each individual test does not require high specificity. It is important, however, for the susceptibility tests and short-term risk markers to be highly sensitive. If the majority of women under 50 years of age who develop breast cancer are captured with this strategy, then mammography screening for the general population can start at age 50 years. Finally, and perhaps most importantly, biomarkers of susceptibility and short-term risk are likely to provide insight into the biology of tumors that develop, leading to new interventions to support prevention. The most effective preventive strategies will be those where a marker predicts risk for the disease, as well as the benefit from preventive interventions. C1 Univ Calif San Francisco, Dept Surg & Radiol, San Francisco, CA 94115 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94115 USA. Univ Calif San Francisco, Div Hematol & Oncol, San Francisco, CA 94115 USA. Harvard Med Sch, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Esserman, LJ (reprint author), Univ Calif San Francisco, Dept Surg & Radiol, 1600 Div St,Box 1710, San Francisco, CA 94115 USA. EM laura.esserman@ucsfmedctr.org; yiwey.shieh@ucsfrnedctr.org; jpark@cc.ucsf.edu; elissa@mgh-ita.org NR 79 TC 12 Z9 13 U1 0 U2 1 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD SEP PY 2007 VL 7 IS 5 BP 533 EP 544 DI 10.1586/14737159.7.5.533 PG 12 WC Pathology SC Pathology GA 222TY UT WOS:000250321400010 PM 17892362 ER PT J AU Liu, CH Huang, SN Cui, JK Kim, YR Farrar, CT Moskowitz, MA Rosen, BR Liu, PK AF Liu, Christina H. Huang, Shuning Cui, Jiankun Kim, Young R. Farrar, Christian T. Moskowitz, Michael A. Rosen, Bruce R. Liu, Philip K. TI MR contrast probes that trace gene transcripts for cerebral ischemia in live animals SO FASEB JOURNAL LA English DT Article DE cardiac arrest; immediate early genes; oxidative stress; nanotechnology; signal transduction ID FOS MESSENGER-RNA; BLOOD-BRAIN-BARRIER; C-FOS; ANTISENSE OLIGONUCLEOTIDE; IN-VIVO; MOUSE-BRAIN; FOREBRAIN ISCHEMIA; CARDIAC-ARREST; EXPRESSION; PROTEIN AB The aim of this research was to validate transcription magnetic resonance (MR) imaging (MRI) for gene transcript targeting in acute neurological disorders in live subjects. We delivered three MR probe variants with superparamagnetic iron oxide nanoparticles (SPION, a T-2 susceptibility agent) linked to a phosphorothioate-modified oligodeoxynucleotide (sODN) complementary to c-fos mRNA (SPION-cfos) or beta-actin mRNA (SPION-beta-actin) and to sODN with random sequence (SPION-Ran). Each probe (1 mu g Fe in 2 mu l) was delivered via intracerebroventricular infusion to the left cerebral ventricle of male C57Black6 mice. We demonstrated SPION retention, measured as decreased T-2* signal or increased R-2* value (R-2* = 1/T-2*). Animals that received the SPION-beta-actin probe exhibited the highest R-2* values, followed ( in descending order) by SPION- cfos and SPION- Ran. SPION- cfos retention was localized in brain regions where SPION-cfos was present and where hybrids of SPION- cfos and its target c-fos mRNA were detected by in situ reverse transcription PCR. In animals that experienced cerebral ischemia, SPION- cfos retention was significantly increased in locations where c-fos mRNA increased in response to the ischemic insult; these elevations were not observed for SPION-beta-actin and SPION-Ran. This study should enable MR detection of mRNA alteration in disease models of the central nervous system.-Liu, C. H., Huang, S., Cui, J., Kim, Y. R., Farrar, C. T., Moskowitz, M. A., Rosen. B. R., Liu, P. K. MR contrast probes that trace gene transcripts for cerebral ischemia in live animals. C1 Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Liu, PK (reprint author), Massachusetts Gen Hosp, Dept Radiol, 149 13th St,Rm 2410, Charlestown, MA 02129 USA. EM philipl@nmr.mgh.harvard.edu OI Liu, Christina/0000-0002-5723-177X FU NCCIH NIH HHS [P01 AT002048, P01AT002048]; NCI NIH HHS [5T32CA009502, T32 CA009502]; NCRR NIH HHS [5P41RR14075, P41 RR014075]; NIA NIH HHS [K25 AG029415, K25 AG029415-01A1, K25 AG029415-02, K25 AG029415-03, K25 AG029415-04, K25 AG029415-05]; NIBIB NIH HHS [T32 EB001680]; NINDS NIH HHS [R01 NS045845, R01 NS045845-04, R01NS45845, R21 NS057556, R21 NS057556-01A1, R21 NS057556-01A1S1] NR 52 TC 22 Z9 23 U1 0 U2 4 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 SEP PY 2007 VL 21 IS 11 BP 3004 EP 3015 DI 10.1096/fj.07-8203com PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 207FR UT WOS:000249237500040 PM 17478745 ER PT J AU Lee, SA Jones, J Khalique, Z Kot, J Alba, M Bernardo, S Seghal, A Wong, B AF Lee, Samuel A. Jones, Jason Khalique, Zachary Kot, John Alba, Mercedes Bernardo, Stella Seghal, Alfica Wong, Brian TI A functional analysis of the Candida albicans homolog of Saccharomyces cerevisiae VPS4 SO FEMS YEAST RESEARCH LA English DT Article DE Candida albicans; protein secretion; vacuole; secreted aspartyl proteases; VPS ID SECRETED ASPARTYL PROTEINASES; DOMINANT-NEGATIVE ALLELE; PHOSPHATIDYLINOSITOL 3-KINASE; FILAMENTOUS GROWTH; INHIBITS GROWTH; GERM TUBE; YEAST; VIRULENCE; GENE; PATHOGENESIS AB To investigate the role of the prevacuolar secretion pathway in the trafficking of vacuolar proteins in Candida albicans, the C. albicans homolog of the Saccharomyces cerevisiae vacuolar protein sorting gene VPS4 was cloned and analyzed. Candida albicans VPS4 encodes a deduced AAA-type ATPase that is 75.6% similar to S. cerevisiae Vps4p, and plasmids bearing C. albicans VPS4 complemented the abnormal vacuolar morphology and carboxypeptidase missorting in S. cerevisiae vps4 null mutants. Candida albicans vps4 Delta null mutants displayed a characteristic class E vacuolar morphology and multilamellar structures consistent with an aberrant prevacuolar compartment. The C. albicans vps4 Delta mutant degraded more extracellular bovine serum albumin than did wild-type strains, which implied that this mutant secreted more extracellular protease activity. These phenotypes were complemented when a wild-type copy of VPS4 was reintroduced into its proper locus. Using a series of protease inhibitors, the origin of this extracellular protease activity was identified as a serine protease, and genetic analyses using a C. albicans vps4 Delta prc1 Delta mutant identified this missorted vacuolar protease as carboxypeptidase Y. Unexpectedly, C. albicans Sap2p was not detected in culture supernatants of the vps4 Delta mutants. These results indicate that C. albicans VPS4 is required for vacuolar biogenesis and proper sorting of vacuolar proteins. C1 S Texas Vet Healthcare Syst, Div Infect Dis, San Antonio, TX 78229 USA. Yale Univ, Sch Med, Infect Dis Sect, New Haven, CT USA. Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97201 USA. Univ Texas, Hlth Sci Ctr, Div Infect Dis, San Antonio, TX 78229 USA. RP Lee, SA (reprint author), S Texas Vet Healthcare Syst, Div Infect Dis, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA. EM lees7@uthscsa.edu FU NIAID NIH HHS [R01-AI64085, R01-AI47442] NR 33 TC 14 Z9 18 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1567-1356 J9 FEMS YEAST RES JI FEMS Yeast Res. PD SEP PY 2007 VL 7 IS 6 BP 973 EP 985 DI 10.1111/j.1567-1364.2007.00253.x PG 13 WC Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biotechnology & Applied Microbiology; Microbiology; Mycology GA 203FF UT WOS:000248959800022 PM 17506830 ER PT J AU Seifer, DB MacLaughlin, DT AF Seifer, David B. MacLaughlin, David T. TI Mullerian Inhibiting Substance is an ovarian growth factor of emerging clinical significance SO FERTILITY AND STERILITY LA English DT Article DE MIS; AMH; ovarian reserve; ovarian aging; IVF; PCOS; DHSS ID ASSISTED REPRODUCTIVE TECHNOLOGY; HORMONE SERUM CONCENTRATIONS; SPONTANEOUS MENSTRUAL-CYCLE; IN-VITRO FERTILIZATION; ANTRAL FOLLICLE COUNT; ANTIMULLERIAN-HORMONE; NORMAL WOMEN; MONOCLONAL-ANTIBODY; LEYDIG-CELLS; MOUSE OVARY AB Objective: To examine Mullerian Inhibiting Substance (MIS) as an emerging diagnostic marker of ovarian function. Design: Medlne review of published studies pertaining to the role of MIS in assessing ovarian aging, predicting response to ovulation induction in preparation for in vitro fertilization, assessing risk of developing ovarian hyperstimulation (OHSS) before ovulation induction, and diagnosis of polycystic ovarian disease (PCOS). Result(s): The majority of published studies to date support a role for MIS as a marker of ovarian reserve. Specific cut-off values are dependent upon the particular assay used. Mullerian Inhibiting Substance may offer value in assessing risk of DHSS and diagnosis of PCOS. Conclusion(s): Potential advantages of MIS compared with other conventional markers of ovarian reserve include: 1) MIS is the earliest marker to change with age; 2) it has the least intercycle variability; 3) it has the least intracycle variability; and 4) it may be informative if randomly obtained during the cycle. Widespread clinical use of MIS may await the availability of an international standard for MIS,so that results using different assays may be reliably compared. C1 Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11228 USA. Mt Sinai Sch Med, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA USA. RP Seifer, DB (reprint author), Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11228 USA. EM drseifer@genesisfertility.com OI Seifer, David/0000-0003-3950-9341 NR 65 TC 95 Z9 99 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 IS 3 BP 539 EP 546 DI 10.1016/j.fertnstert.2007.02.014 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 214PZ UT WOS:000249751900001 PM 17559842 ER PT J AU Kim, HH Bundorf, MK Behr, B McCallum, SW AF Kim, Howard H. Bundorf, M. Kate Behr, Barry McCallum, Stewart W. TI Use and outcomes of intracytoplasmic sperm injection for non-male factor infertility SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Urological-Association CY MAY 20-25, 2006 CL Atlanta, GA SP Amer Urol Assoc DE intracytoplasmic sperm injection; assisted reproductive technology; infertility; outcomes; in vitro fertilization; female factor ID IN-VITRO FERTILIZATION; INTRAUTERINE INSEMINATION; UNEXPLAINED INFERTILITY; CHILDREN BORN; HUMAN OOCYTES; ICSI; IVF; FAILURE; CONCEPTION; COUPLES AB Objective: To determine whether intracytoplasmic sperm injection (ICSI) is associated with improved outcomes for non-male factor infertility. Design: We examined the patient characteristics associated with treatment choice-ICSI and conventional in vitro fertilization (IVF)-among patients without a diagnosis of male factor infertility and compared outcomes between the two groups, adjusting for patient characteristics using multivariate regression models. Setting: Academic fertility center. Patient(s): We evaluated 696 consecutive assisted reproductive technology (ART) cycles performed for couples with normal semen analysis at the Stanford Reproductive Endocrinology and Infertility Center between 2002 and 2003. We compared patient characteristics, cycle details, and outcomes for ICSI and IVF. Main Outcome Measure(s): Fertilization, pregnancy, and live birth rates. Result(s): Patient characteristics were similar between the two groups, except the proportion of patients with unexplained infertility (IVF 15.1% vs. ICSI 23.5%), previous fertility (IVF 62.6% vs. ICSI45.5%), and previous ART cycle (IVF 41.2% vs. ICSI 67.7%). More oocytes were fertilized per cycle for the IVF group (6.6 oocytes versus 5.1 oocytes). Fertilization failure, pregnancy, and live birth rates did not differ between IVF and ICSI. Using logistic regressions, having had previous ART was found to be positively associated with ICSI. Treatment choice of ICSI was not associated with fertilization, pregnancy, or live birth rates. Conclusion(s): No clear evidence of improved outcomes with ICSI was demonstrated for non-male factor infertility. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Obstet & Gynecol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. RP Kim, HH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. EM hkim6@partners.org NR 27 TC 15 Z9 18 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 IS 3 BP 622 EP 628 DI 10.1016/j.fertnstert.2006.12.013 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 214PZ UT WOS:000249751900014 PM 17445809 ER PT J AU Chavarro, JE Sadie, SM Toth, TL Hauser, R AF Chavarro, J. E. Sadie, S. M. Toth, T. L. Hauser, R. TI Soy food and soy isoflavone intake in relation to semen quality parameters. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S22 EP S22 DI 10.1016/j.fertnstert.2007.07.089 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800059 ER PT J AU Doyle, JO Wright, DL Godfrey-Bailey, L Pearson, K Amarasiriwardena, C Hauser, RB AF Doyle, J. O. Wright, D. L. Godfrey-Bailey, L. Pearson, K. Amarasiriwardena, C. Hauser, R. B. TI Environniental exposure to mercury and early developmental endpoints among women undergoing IVF SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Massachusetts Gen Hosp, Div Reprod Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S306 EP S306 DI 10.1016/j.fertnstert.2007.07.1029 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800873 ER PT J AU Doyle, JO Pearson, K Kuleta, D Petrozza, JC AF Doyle, J. O. Pearson, K. Kuleta, D. Petrozza, J. C. TI Assessment of follicular number in controlled ovarian hyperstimulation (COH)/intrauterine insemination cycles (IUI) as predictors of success SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Reprod Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S155 EP S155 DI 10.1016/j.fertnstert.2007.07.538 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800424 ER PT J AU Gonzalez, RR Cherfils, S Ngugi, D Cipriani, P Olatinwo, M Rueda, BR AF Gonzalez, R. R. Cherfils, S. Ngugi, D. Cipriani, P. Olatinwo, M. Rueda, B. R. TI Emergency contraception potential of leptin signaling inhibition in a mouse model. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Morehouse Sch Med, Dept Obstet & Gynecol, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA. Morehouse Sch Med, Dept Physiol, Atlanta, GA 30310 USA. Boston Biomed Res Inst, Watertown, MA USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Spelman Coll, Dept Chem, Atlanta, GA 30314 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S52 EP S52 DI 10.1016/j.fertnstert.2007.07.182 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800139 ER PT J AU Klein, JU Kuleta, D Petrozza, JC AF Klein, J. U. Kuleta, D. Petrozza, J. C. TI Intrauterine insemination (IUI) outcomes in cases performed by nurses as compared with cases performed by physicians. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Harvard Univ, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Sch Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S9 EP S10 DI 10.1016/j.fertnstert.2007.07.052 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800026 ER PT J AU Luk, J Kuleta, D Petrozza, JC AF Luk, J. Kuleta, D. Petrozza, J. C. TI Comparison of pregnancy outcomes between follicle stimulating hormone or clomiphene citrate administration combined with intrauterine insemination for couples with unexplained infertility. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S289 EP S290 DI 10.1016/j.fertnstert.2007.07.977 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800825 ER PT J AU Olawaiye, AB Cipriani, P Cherfils, S Olatinwo, M Rueda, B AF Olawaiye, A. B. Cipriani, P. Cherfils, S. Olatinwo, M. Rueda, B. TI New insights into the molecular mechanisms of leptin actions in endometrial cells. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Dept Gynecol & Obst, Atlanta, GA 30310 USA. Boston Biomed Res Inst, Watertown, MA USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Spelman Coll, Dept Chem, Atlanta, GA 30314 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S335 EP S335 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800959 ER PT J AU Omurtag, KR Toth, TL AF Omurtag, K. R. Toth, T. L. TI The cost effectiveness and health outcomes of in vitro fertilization (IVF) as a mandated benefit. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S122 EP S122 DI 10.1016/j.fertnstert.2007.07.394 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800326 ER PT J AU Reindollar, RH Regan, MM Neumann, PJ Thornton, KL Alper, MM Goldman, MB AF Reindollar, R. H. Regan, M. M. Neumann, P. J. Thornton, K. L. Alper, M. M. Goldman, M. B. TI A randomized controlled trial of 503 couples assigned to conventional infertility treatment or an accelerated track to IVF: Preliminary results of the fast track and standard treatment (FASTT) trial. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. Boston IVF, Waltham, MA USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S41 EP S41 DI 10.1016/j.fertnstert.2007.07.145 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800108 ER PT J AU Sabatini, ME Rueda, BR Lee, HJ AF Sabatini, M. E. Rueda, B. R. Lee, H. -J. TI Effects of metformin on mouse oocyte maturation in vitro. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reproduct Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2007 VL 88 SU 1 BP S272 EP S273 DI 10.1016/j.fertnstert.2007.07.926 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 216PC UT WOS:000249889800777 ER PT J AU Mroz, P Pawlak, A Satti, M Lee, H Wharton, T Gali, H Sarna, T Hamblin, MR AF Mroz, Pawel Pawlak, Anna Satti, Minahil Lee, Haeryeon Wharton, Tim Gali, Hariprasad Sarna, Tadeusz Hamblin, Michael R. TI Functionalized fullerenes mediate photodynamic killing of cancer cells: Type I versus Type II photochemical mechanism SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nanotechnology; structure-function relationship; apoptosis; singlet oxygen; superoxide; phototoxicity; octanol-water partition coefficient; photochemical mechanism ID SINGLET OXYGEN; PHOTOSENSITIZED OXIDATION; BIOLOGICAL APPLICATIONS; LIPOPHILIC CATIONS; INDUCED APOPTOSIS; THERAPY; DERIVATIVES; C-60; MITOCHONDRIA; SUPEROXIDE AB Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers (PS) and harmless visible light to generate reactive oxygen species (ROS) and kill cells. Most clinically studied PS are based on the tetrapyrrole structure of porphyrins, chlorines, and related molecules, but new nontetrapyrrole PS are being sought. Fullerenes are soccer-ball shaped molecules composed of 60 or 70 carbon atoms and have attracted interest in connection with the search for biomedical applications of nanotechnology. Fullerenes are biologically inert unless derivatized with functional groups, whereupon they become soluble and can act as PS. We have compared the photodynamic activity of six functionalized fullerenes with 1, 2, or 3 hydrophilic or 1, 2, or 3 cationic groups. The octanol-water partition coefficients were determined and the relative contributions of Type I photochemistry (photogeneration of superoxide in the presence of NADH) and Type 11 photochemistry (photogeneration of singlet oxygen) were studied by measurement of oxygen consumption, 1270-nm luminescence and EPR spin trapping of the superoxide product. We studied three mouse cancer cell lines: (J774, LLC, and CT26) incubated for 24 h with fullerenes and illuminated with white light. The order of effectiveness as PS was inversely proportional to the degree of substitution of the fullerene nucleus for both the neutral and the cationic series. The monopyrrolidinium fullerene was the most active PS against all cell lines and induced apoptosis 4-6 h after illumination. It produced diffuse intracellular fluorescence when dichlorodihydrofluorescein was added as an ROS probe, suggesting a Type I mechanism for phototoxicity. We conclude that certain functionalized fullerenes have potential as novel PDT agents and phototoxicity may be mediated both by superoxide and by singlet oxygen. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Jagiellonian Univ, Dept Biophys, Krakow, Poland. Aga Khan Med Coll, Karachi, Pakistan. Lynntech Inc, College Stn, TX USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Pawlak, Anna/A-7904-2016; OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R43 CA103268, R43 CA103268-02, R43CA103268]; NIAID NIH HHS [R01 AI050875, R01 AI050875-04, R01AI050875, R01CA/AI838801, R44 AI068400, R44 AI068400-03A1, R44AI68400] NR 51 TC 118 Z9 123 U1 6 U2 50 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2007 VL 43 IS 5 BP 711 EP 719 DI 10.1016/j.freeradbiomed.2007.05.005 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 199ER UT WOS:000248679500007 PM 17664135 ER PT J AU Wei, GW Wang, DM Lu, HF Parmentier, S Wang, Q Panter, S Frey, WH Ying, WH AF Wei, Guangwei Wang, Dongmin Lu, Huafei Parmentier, Sophie Wang, Qing Panter, Scott Frey, William H., II Ying, Weihai TI Intranasal administration of a PARG inhibitor profoundly decreases ischemic brain injury SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE ischemia; brain injury; poly(ADP-ribose) polymerase; poly(ADP-ribose) glycohydrolase; neuronal death; oxidative damage ID APOPTOSIS-INDUCING FACTOR; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; OXYGEN-GLUCOSE DEPRIVATION; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; CELL-DEATH; NEURONAL DEATH; GLYCOHYDROLASE PARG; NAD(+) DEPLETION AB Cumulative evidence has indicated a critical role of poly(ADP-ribose) polymerase-1 activation in ischemic brain damage. Poly(ADP-ribose) glycohydrolase (PARG) is a key enzyme in poly(ADP-ribose) catabolism. Our previous studies showed that PARG inhibitors, gallotannin (GT) and nobotanin B, can profoundly decrease oxidative cell death in vitro. Here, we tested the hypothesis that intranasal delivery of GT can decrease ischemic brain damage by inhibiting PARG. Intranasal delivery of GT within 5 hours after the onset of focal brain ischemia markedly decreased the infarct formation and neurological deficits of rats. The GT administration also increased poly(ADP-ribose) in the ischemic brains, suggesting that GT acts as a PARG inhibitor in vivo. Furthermore, the GT treatment abolished nuclear translocation of apoptosis-inducing factor (AIF) in the ischemic brains, suggesting that prevention of AIF translocation may contribute to the protective effects of GT. In contrast, intravenous injection of GT, at 2 hours after ischemic onset, did not reduce ischemic brain damage. Collectively, our findings suggest that PARG inhibition can significantly decrease ischemic brain injury, possibly by blocking AIF translocation. This study also highlights distinct merits of intranasal drug delivery for treating CNS diseases. C1 [Wei, Guangwei; Wang, Dongmin; Lu, Huafei; Wang, Qing; Ying, Weihai] San Francisco VA Med Ctr, Dept Neurol 127, San Francisco, CA 94121 USA. [Wei, Guangwei; Wang, Dongmin; Lu, Huafei; Wang, Qing; Ying, Weihai] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Frey, William H., II] HealthPartners Res Fdn, Reg Hosp, Alzheimers Res Ctr, St Paul, MN 55101 USA. RP Ying, WH (reprint author), San Francisco VA Med Ctr, Dept Neurol 127, 4150 Clement St, San Francisco, CA 94121 USA. EM Weihai.Ying@ucsf.edu OI Frey II, William/0000-0002-6373-0794 NR 52 TC 20 Z9 20 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD SEP 1 PY 2007 VL 12 BP 4986 EP 4996 DI 10.2741/2443 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273PJ UT WOS:000253943900017 PM 17569625 ER PT J AU Johnson, FR Ozdemir, S Mansfield, C Hass, S Miller, DW Siegel, CA Sands, BE AF Johnson, F. Reed Oezdemir, Semra Mansfield, Carol Hass, Steven Miller, David W. Siegel, Corey A. Sands, Bruce E. TI Crohn's disease patients' risk-benefit preferences: Serious adverse event risks versus treatment efficacy SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/107th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2006 CL Los Angeles, CA SP Amer Gastroenterol Assoc ID INFLAMMATORY-BOWEL-DISEASE; QUALITY-OF-LIFE; WILLINGNESS-TO-PAY; HEALTH; 6-MERCAPTOPURINE; AZATHIOPRINE; NATALIZUMAB; INFLIXIMAB; VALUATION AB Background& Aims: Regulatory assessments of drug risks do not routinely consider patient preferences, despite evidence that some patients are willing to accept increased side-effect risk in exchange for therapeutic benefits. The aim of this study is to estimate the willingness of Crohn's disease (CD) patients to accept life-threatening adverse event risks in exchange for CD symptom relief. Methods: Patients with CD completed choice-format conjoint trade-off tasks involving hypothetical treatments with varying efficacy and risk levels. The treatment features included daily symptoms and activity limitations, serious complications (fistulas, abscesses, bowel obstructions), time between flare-ups, oral steroid use and risk of 3 serious adverse events (SAEs) known to be associated with CD treatment (progressive multifocal leukoencephalopathy (PML), serious infections, and lymphoma). The mean maximum acceptable annual risk (MAR) for each of the SAEs was calculated for various levels of clinical benefit. Results: Daily symptom severity was the most important factor in treatment preferences. Higher MAR was observed for trade-off tasks involving higher levels of clinical benefit. The MAR was similar across the 3 SAEs. For improvements from severe daily symptoms to remission and from moderate daily symptoms to remission, the MARs ranged from 0.69% to 0.81% and from 0.39% to 0.55%, respectively. Conclusions: Patients with CD have well-defined preferences among treatment attributes and are willing to accept tradeoffs among attributes. The patients indicated they are willing to accept elevated SAE risks in exchange for clinical efficacy. The perspective of the patients on the benefit versus risk balance can assist in making treatment and regulatory decisions. C1 Res Triangle Inst, RTI Int, Res Triangle Pk, NC 27709 USA. Elan Pharmaceut, San Diego, CA USA. Dartmouth Hitchcock Med Ctr, IBD Ctr, Sect Gastroenterol & Hepatol, Lebanon, NH USA. Massachusetts Gen Hosp, Harvard Med Sch, MGH Crohns & Colitis Ctr, Gastrointestinal Unit, Boston, MA USA. RP Johnson, FR (reprint author), RTI Hlth Solut, 200 Pk Dr,PO Box 12194, Res Triangle Pk, NC 27709 USA. EM frjohnson@rti.org OI Hass, Steven/0000-0002-1686-030X NR 26 TC 95 Z9 96 U1 2 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2007 VL 133 IS 3 BP 769 EP 779 DI 10.1053/j.gastro.2007.04.075 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 208NQ UT WOS:000249326900010 PM 17628557 ER PT J AU Videlock, EJ Chang, L AF Videlock, Elizabeth J. Chang, Lin TI Irritable bowel syndrome: Current approach to symptoms, evaluation, and treatment SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; FUNCTIONAL GASTROINTESTINAL DISORDERS; COGNITIVE-BEHAVIOR THERAPY; VISCERAL SENSITIVITY INDEX; PLACEBO-CONTROLLED TRIAL; RECEPTOR PARTIAL AGONIST; DOUBLE-BLIND; CONSTIPATION-PREDOMINANT; ABDOMINAL-PAIN AB There are frequent advances in knowledge about the clinical presentation, pathophysiology, and treatment of irritable bowel syndrome. It is important for clinicians to be aware of available therapies and the supporting evidence for those therapies to increase patient satisfaction. This is best achieved with a collaborative and long-term clinician-patient relationship and mutual commitment to modify therapy and try new modalities until the greatest relief of symptoms and improvement in health-related quality of life is achieved. This article reviews symptoms, comorbidities, gender differences, and measure of severity in irritable bowel syndrome and current and evidence-based approaches to evaluation and treatment, and the new symptom-based Rome III diagnostic criteria are reviewed and explained. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Chang, L (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Neurovisceral Sci & Womens Hlth, CURE Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM linchang@mednet.ucla.edu NR 101 TC 33 Z9 36 U1 6 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 2007 VL 36 IS 3 BP 665 EP + DI 10.1016/j.gtc.2007.07.002 PG 22 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 233BU UT WOS:000251066200011 PM 17950443 ER PT J AU Overholt, BF Wang, KK Burdick, JS Lightdale, CJ Kimmey, M Nava, HR Sivak, MV Nishioka, N Barr, H Marcon, N Pedrosa, M Bronner, MR Grace, M Depot, M AF Overholt, Bergein F. Wang, Kenneth K. Burdick, J. Steven Lightdale, Charles J. Kimmey, Michael Nava, Hector R. Sivak, Michael V., Jr. Nishioka, Norman Barr, Hugh Marcon, Norman Pedrosa, Marcos Bronner, Mary P. Grace, Michael Depot, Michelle CA Int Photodynamic Grp High-Grade Dy TI Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett's high-grade dysplasia SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ARGON PLASMA COAGULATION; TERM-FOLLOW-UP; LASER-ABLATION; EARLY CANCER; MULTIPOLAR ELECTROCOAGULATION; 5-AMINOLEVULINIC ACID; EARLY ADENOCARCINOMA; ANTIREFLUX SURGERY; CONTROLLED TRIAL; ESOPHAGUS AB Background: Barrett's esophagus (BE) with high-grade dysplasia (HGD) is a risk factor for development of esophageal carcinoma. Photodynamic therapy (PDT) with Photofrin (PHO) has been used to eliminate HGD in BE. Objective: Our purpose was to compare PHOPDT plus omeprazole with omeprazole only (OM). Design: Five-year follow-up of a randomized, multicenter, multinational, pathology-blinded HGD trial. Setting: 30 sites in 4 countries. Patients: 208. Interventions: Patients with BE and HGD were randomized (2:1) to PHOPDT (n = 138) or OM (n = 70) into a 2-year trial followed up for 3 more years. PHOPDT patients received 2 mg/kg PHO intravenously followed by endoscopic laser light exposure of Barrett's mucosa at a wavelength of 630 nm within 40 to 50 hours to a maximum of 3 courses at least 90 days apart. Both groups received 20 mg of OM twice daily. Pathologists at one center assessed biopsy specimens in a blinded fashion. Main Outcome Measurement: HGD ablation status over 5 years of follow-up. Results: At 5 years PHOPDTwas significantly more effective than OM in eliminating HGD (77% [106/138] vs 39% [27/70], P < .0001). A secondary outcome measure preventing progression to cancer showed a significant difference (P = .027) with about half the likelihood of cancer occurring in PHOPDT (21/138 [15%]) compared with OM (20/70 [29%]), with a significantly (P = .004) longer time to progression to cancer favoring PHOPDT Limitations: Not all patients were available for follow-up. Conclusions: This 5-year randomized trial of BE patients with HGD demonstrates that PHOPDT is a clinically and statistically effective therapy in producing long-term ablation of HGD and reducing the potential impact of cancer compared with OM. C1 Thompson Canc Survival Ctr, Knoxville, TN USA. Mayo Clin, Rochester, MN USA. Parkland Mem Hosp & Affiliated Inst, Dallas, TX USA. Columbia Univ, Presbyterian Hosp, New York, NY USA. Univ Washington, Seattle, WA 98195 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Case Western Reserve Univ Hosp, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Gloucester Royal Hosp, Gloucester, England. Univ Toronto, Wellesley Hosp, Toronto, ON M4Y 1J3, Canada. Boston Vet Adm Med Ctr, Boston, MA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Alberta, Edmonton, AB, Canada. Axcan Pharma Inc, Mt St Hilaire, PQ, Canada. RP Overholt, BF (reprint author), 801 Weisgarber Rd, Knoxville, TN 37909 USA. NR 43 TC 201 Z9 208 U1 2 U2 12 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 SEP PY 2007 VL 66 IS 3 BP 460 EP 468 DI 10.1016/j.gie.2007.12.037 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 211DE UT WOS:000249503700006 PM 17643436 ER PT J AU Egede, LE AF Egede, Leonard E. TI Major depression in individuals with chronic medical disorders: prevalence, correlates and association with health resource utilization, lost productivity and functional disability SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE major depression; chronic medical disorders; National Health Interview Survey ID OBSTRUCTIVE PULMONARY-DISEASE; PRIMARY-CARE PATIENTS; ANTIDEPRESSANT TREATMENT; HEART-FAILURE; UNITED-STATES; OLDER ADULTS; MORTALITY; RISK; POPULATION; SYMPTOMS AB Objective: The objective of this study was to determine the prevalence and odds of major depression and the incremental effect of major depression on utilization, lost productivity and functional disability in individuals with common chronic medical disorders. Method: Data on 30,801 adults from the 1999 National Health Interview Survey were analyzed. The 12-month prevalence and age/sex-adjusted odds of major depression were calculated for adults with hypertension (HTN), diabetes mellitus (DM), coronary artery disease (CAD), congestive heart failure (CHF), stroke or cerebrovascular accident (CVA), chronic obstructive pulmonary disease (COPD) and end-stage renal disease (ESRD). The association between chronic condition status (with and without major depression) and utilization, lost productivity and functional disability was determined by controlling for covariates. Results: The 12-month prevalence and age/sex-adjusted odds of major depression by chronic conditions were as follows: CHF, 7.9% [odds ratio (OR)=1.96]; HTN, 8.0% (OR=2.00); DM, 9.3% (OR=1.96); CAD, 9.3% (OR=2.30); CVA, 11.4% (OR=3.15); COPD, 15.4% (OR=3.21); ESRD, 17.0% (OR=3.56); any chronic condition, 8.8% (OR=2.61). Compared to adults without chronic conditions, those with chronic conditions plus major depression had greater odds of >= 1 ambulatory visit [OR=1.50; 95% confidence interval (95% CI)=1.28, 1.77]; >= 1 emergency room visit (OR=1.94; 95% CI=1.55, 2.45); and >= 1 day in bed due to illness (OR=1.60; 95% CI=1.28, 2.00); and functional disability (OR=2.48; 95% CI=1.96, 3.15). Conclusion: The 12-month prevalence and odds of major depression are high in individuals with chronic medical conditions, and major depression is associated with significant increases in utilization, lost productivity and functional disability. (C) 2007 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Ctr Hlth Disparities Res, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston VA TREP, Charleston, SC 29403 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Disparities Res, Charleston, SC 29425 USA. EM egedel@musc.edu NR 51 TC 225 Z9 229 U1 1 U2 15 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 SEP-OCT PY 2007 VL 29 IS 5 BP 409 EP 416 DI 10.1016/j.genhosppsych.2007.06.002 PG 8 WC Psychiatry SC Psychiatry GA 217VS UT WOS:000249976000005 PM 17888807 ER PT J AU Smolen, GA Schott, BJ Stewart, RA Diederichs, S Muir, B Provencher, HL Look, AT Sgroi, DC Peterson, RT Haber, DA AF Smolen, Gromoslaw A. Schott, Benjamin J. Stewart, Rodney A. Diederichs, Sven Muir, Beth Provencher, Heather L. Look, A. Thomas Sgroi, Dennis C. Peterson, Randall T. Haber, Daniel A. TI A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors SO GENES & DEVELOPMENT LA English DT Article DE neural crest; migration; adhesion; Rap; development; zebrafish ID CELL-ADHESION; HIRSCHSPRUNG-DISEASE; CANDIDATE EFFECTOR; ZEBRAFISH FOXD3; PROTEIN; GASTRULATION; DERIVATIVES; MUTATIONS; SURVIVAL; ENCODES AB The neural crest (NC) is a highly motile cell population that gives rise to multiple tissue lineages during vertebrate embryogenesis. Here, we identify a novel effector of the small GTPase Rap, called RADIL, and show that it is required for cell adhesion and migration. Knockdown of radii in the zebrafish model results in multiple defects in NC-derived lineages such as cartilage, pigment cells, and enteric neurons. We specifically show that these defects are primarily due to the diminished migratory capacity of NC cells. The identification of RADIL as a regulator of NC migration defines a role for the Rap pathway in this process. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Mol Pathol Res Unit, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. EM haber@helix.mgh.harvard.edu RI Diederichs, Sven/J-6237-2012; OI Diederichs, Sven/0000-0001-7901-4752; Stewart, Rodney/0000-0003-1220-1830 FU NCI NIH HHS [CA104605, CA117737, F32 CA117737, R01 CA104605]; NHLBI NIH HHS [HL079267, R01 HL079267]; NINDS NIH HHS [R00 NS058608, K99 NS058608, K99 NS058608-01, K99 NS058608-02, K99NS058608, R00 NS058608-03]; PHS HHS [P01 95281] NR 34 TC 24 Z9 28 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 2007 VL 21 IS 17 BP 2131 EP 2136 DI 10.1101/gad.1561507 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 207HW UT WOS:000249243200003 PM 17704304 ER PT J AU Salinas, LS Maldonado, E Macias-Silva, M Blackwell, TK Navarro, RE AF Salinas, L. Silvia Maldonado, Ernesto Macias-Silva, Marina Blackwell, T. Keith Navarro, Rosa E. TI The DEAD box RNA helicase VBH-1 is required for germ cell function in C-elegans SO GENESIS LA English DT Article DE germline; DEAD box RNA helicase; sperm/oocyte switch ID SEX-DETERMINATION GENE; P GRANULE COMPONENTS; CAENORHABDITIS-ELEGANS; MEIOTIC MATURATION; SACCHAROMYCES-CEREVISIAE; PROTEIN; DROSOPHILA; VASA; LINE; TRANSLATION AB Vasa and Belle are conserved DEAD box RNA helicases required for germ cell function. Homologs of this group of proteins in several species, including mammals, are able to complement a mutation in yeast (DED1) suggesting that their function is highly conserved. It has been proposed that these proteins are required for mRNA translation regulation, but their specific mechanism of action is still unknown. Here we describe functions of VBH-1, a C. elegans protein closely related to Belle and Vasa. VBH-1 is expressed specifically in the C. elegans germline, where it is associated with P granules, the C. elegans germ plasm counterpart. vbh-1(RNAi) animals produce fewer offspring than wild type because of defects in oocyte and sperm production, and embryonic lethality. We also find that VBH-1 participates in the sperm/oocyte switch in the hermaphrodite gonad. We conclude that VBH-1 and its orthologs may perform conserved roles in fertility and development. C1 Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular, Mexico City 04510, DF, Mexico. Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Mol Genet, Mexico City 04510, DF, Mexico. Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dept Pathol, Boston, MA 02215 USA. RP Navarro, RE (reprint author), Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular, Circuito Exterior S-N, Mexico City 04510, DF, Mexico. EM mavarro@ifc.unam.mx NR 56 TC 22 Z9 25 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-968X J9 GENESIS JI Genesis PD SEP PY 2007 VL 45 IS 9 BP 533 EP 546 DI 10.1002/dvg.20323 PG 14 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 223JG UT WOS:000250365600001 PM 17868112 ER PT J AU Tercyak, KP Peshkin, BN Demarco, TA Patenaude, AF Schneider, KA Garber, JE Valdimarsdottir, HB Schwartz, MD AF Tercyak, Kenneth P. Peshkin, Beth N. Demarco, Tiffani A. Patenaude, Andrea Farkas Schneider, Katherine A. Garber, Judy E. Valdimarsdottir, Heiddis B. Schwartz, Marc D. TI Information needs of mothers regarding communicating BRCA1/2 cancer genetic test results to their children SO GENETIC TESTING LA English DT Article ID HEREDITARY BREAST-CANCER; DECISION-MAKING; OVARIAN-CANCER; INTERRATER RELIABILITY; FAMILY; SUSCEPTIBILITY; ADOLESCENTS; PREFERENCES; RISK; PERCEPTIONS AB Mothers who participate in genetic testing for hereditary breast/ovarian cancer risk must decide if, when, and how to ultimately share their BRCA1 and BRCA2 (BRCA1/2) test results with their minor-age children. One of the primary aides for mothers in making this decision is cancer genetic counseling. However, counseling is limited in how well it can educate mothers about such decisions without the availability of resources that are specific to family communication and genetic testing per se. In an effort to fill this gap and identify mothers most likely to benefit from such resources, surveys were conducted with 187 mothers undergoing BRCA1/2 testing who had children 8-21 years old. Data were collected weeks after genetic testing but prior to mothers' learning of their test results; quantitative assessments of informational resource needs (i. e., speaking with previous BRCA1/2 testing participants who are parents regarding their experiences, reading educational literature about options and what to expect, speaking with a family counselor, attending a family support group, and self-nominated other resources), testing motivations, decision making vigilance, and decisional conflict regarding communicating test results to children were included. Mothers' most-to-least frequently cited information resource needs were: literature (93.4%), family counseling (85.8%), prior participants (79.0%), support groups (53.9%), and other (28.9%; e. g., pediatricians and psychologists). Seventy-eight percent of mothers were interested in accessing three or more resources. In multivariate regression analyses, testing motivations (beta = 0.35, p = 0.03), decision-making vigilance (beta = 0.16, p = 0.00), and decisional conflict (beta = 0.10, p = 0.00) were associated with mothers' need level; mothers with a greater interest in testing to learn about their children's risks, those with more vigilant decision-making styles, and those with higher decisional conflict had the greatest need. In conjunction with enhanced genetic counseling focusing on family disclosure, educational literature, and psychosocial support may promote improved outcomes. C1 Georgetown Univ, Med Ctr, Canc Control Program, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Sch Med, New York, NY USA. RP Tercyak, KP (reprint author), Georgetown Univ, Med Ctr, Canc Control Program, Lombardi Comprehens Canc Ctr, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. FU NCI NIH HHS [CA091831, R01 CA108933, CA108933, K07 CA091831, R01 CA082346, CA082346]; NHGRI NIH HHS [R01 HG002686, HG002686, R01 HG002686-04] NR 57 TC 32 Z9 32 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2007 VL 11 IS 3 BP 249 EP 255 DI 10.1089/gte.2006.0534 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 224KD UT WOS:000250445000008 PM 17949286 ER PT J AU Hims, MM Shetty, RS Pickel, J Mull, J Leyne, M Liu, LJ Gusella, JF Slaugenhaupt, SA AF Hims, Matthew M. Shetty, Ranjit S. Pickel, James Mull, James Leyne, Maire Liu, Lijuan Gusella, James F. Slaugenhaupt, Susan A. TI A humanized IKBKAP transgenic mouse models a tissue-specific human splicing defect SO GENOMICS LA English DT Article DE familial dysautonomia; mRNA splicing; transgenic model ID FAMILIAL DYSAUTONOMIA; MESSENGER-RNA; ARTIFICIAL CHROMOSOMES; HUMAN-DISEASE; MUTATION; ISRAEL; CELLS; GENE AB Familial dysautonomia (FD) is a severe hereditary sensory and autonomic neuropathy, and all patients with FD have a splice mutation in the IKBKAP gene. The FD splice mutation results in variable, tissue-specific skipping of exon 20 in IKBKAP rnRNA, which leads to reduced IKAP protein levels. The development of therapies for FD will require suitable mouse models for preclinical studies. In this study, we report the generation and characterization of a mouse model carrying the complete human IKBKAP locus with the FD IVS20+6T -> C splice mutation. We show that the mutant IKBKAP transgene is misspliced in this model in a tissue-specific manner that replicates the pattern seen in FD patient tissues. Creation of this humanized mouse is the first step toward development of a complex phenotypic model of FD. These transgenic mice are an ideal model system for testing the effectiveness of therapeutic agents that target the missplicing defect. Last, these mice will permit direct studies of tissue-specific splicing and the identification of regulatory factors that play a role in complex gene expression. (c) 2007 Elsevier Inc. All rights reserved. C1 Natl Inst Hlth, NIMH, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Slaugenhaupt, SA (reprint author), Natl Inst Hlth, NIMH, Boston, MA 02114 USA. EM slaugenhaupt@chgr.mgh.harvard.edu FU Intramural NIH HHS; NINDS NIH HHS [R01 NS036326, R01 NS036326-07A1, R01 NS036326-08, R01 NS036326-09, R01 NS036326-10] NR 26 TC 22 Z9 23 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2007 VL 90 IS 3 BP 389 EP 396 DI 10.1016/j.ygeno.2007.05.012 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 199SQ UT WOS:000248715900012 PM 17644305 ER PT J AU Moss, AC Anton, P Savidge, T Newman, P Cheifetz, AS Gay, J Paraschos, S Winter, MW Moyer, MP Karalis, K Kokkotou, E Pothoulakis, C AF Moss, Alan C. Anton, Pauline Savidge, Tor Newman, Paul Cheifetz, Adam S. Gay, Jerome Paraschos, Sophia Winter, Michael Weinstein Moyer, Mary P. Karalis, Katia Kokkotou, Efi Pothoulakis, Charalabos TI Urocortin II mediates pro-inflammatory effects in human colonocytes via corticotropin-releasing hormone receptor 2 alpha SO GUT LA English DT Article ID CLOSTRIDIUM-DIFFICILE TOXIN; NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; EPITHELIAL-CELL LINE; COLON-CANCER CELLS; FACTOR CRF; INTESTINAL INFLAMMATION; ULCERATIVE-COLITIS; INDUCED ENTERITIS; HORMONE-RECEPTOR AB Background/Aims: Urocortin II (UcnII) is a neuropeptide that binds with high affinity to the corticotropin-releasing hormone receptor 2 (CRHR2) in peripheral tissues. UcnII is synthesised in the intestine, but its role in human intestinal inflammation is largely unknown. Methods: Responses of human colonic epithelial cells expressing CRHR2 to stimulation by UcnII were measured using ELISA, western blot analysis, real-time reverse transcription-PCR (RT-PCR) and interleukin (IL)8 promoter activity. Expression levels of CRHR2 and UcnII in human colitis were determined by immunofluorescence and real-time RT-PCR in mucosal biopsies from patients with Crohn's and ulcerative colitis, and in human intestinal xenografts after exposure to Clostridium difficile toxin A. Results: It is reported here that expression of CRHR2 mRNA and protein in human colonic epithelial cells (HT-29) are increased by exposure to C difficile toxin A or tumour necrosis factor (TNF)alpha. Stimulation of nontransformed NCM460 colonocytes overexpressing CRHR2 alpha receptor with UcnII resulted in a time- and concentration-dependent increase in IL8 production. UcnII stimulation also led to activation of nuclear factor-kappa B (NF-kappa B) and mitogen-acivated protein (MAP) kinase in these cells, as evidenced by degradation of I kappa B alpha and phosphorylation of the p65 subunit of NF-kappa B and extracellularly regulated kinase (ERK) 1/2. Furthermore, expression of UcnII and CRHR2 mRNA was increased in mucosal samples of patients with inflammatory bowel disease, and after exposure of human intestinal xenografts to C difficile toxin A. Conclusions: These results suggest that UcnII has pro-inflammatory effects in human intestinal cells via the CRHR2 alpha receptor and may play an important role in the pathophysiology of colitis in humans. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastrointestinal Neuropeptide C, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Ctr Inflammatory Bowel Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Gastroenterol & Nutr, Boston, MA USA. Harvard Univ, Sch Med, Div Endocrinol, Childrens Hosp, Boston, MA USA. INCELL Corp, San Antonio, TX USA. RP Pothoulakis, C (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastrointestinal Neuropeptide C, Dana 601,330 Brookline Ave, Boston, MA 02215 USA. EM cpothoul@bidmc.harvard.edu FU NIDDK NIH HHS [P0-1 DK 33506, P01 DK033506] NR 49 TC 48 Z9 49 U1 0 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 SEP PY 2007 VL 56 IS 9 BP 1210 EP 1217 DI 10.1136/gut.2006.110668 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 199WJ UT WOS:000248725600010 PM 17412781 ER PT J AU Olawaiye, A Lee, LM Krasner, C Horowitz, N AF Olawaiye, Alexander Lee, Lisa M. Krasner, Carolyn Horowitz, Nell TI Treatment of squamous cell vulvar cancer with the anti-EGFR tyrosine kinase inhibitor Tarceva SO GYNECOLOGIC ONCOLOGY LA English DT Article DE vulvar cancer; EGFR; erlotinib ID GROWTH-FACTOR RECEPTOR; LUNG-CANCER; MUTATIONS; GEFITINIB AB Background. The purpose of this case report is to describe the first experience with erlotinib (Tarceva) in the treatment of locally advanced vulvar cancer. Case. Two elderly patients presented with locally advanced vulvar cancer. surgery was not a suitable method of treatment for either of them because of multiple medical co-morbidities and stage of disease. One patient had disease progression on standard chemoradiation. Erlotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, was tried in both cases and dramatic responses were observed. Conclusion. Therapy targeted to EGFR may be effective in the treatment of locally advanced vulvar cancer. This new therapeutic approach deserves further evaluation in carefully designed studies. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet Gynecol & Reprod Biol,Div Gyn, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol Oncol, Boston, MA 02114 USA. RP Olawaiye, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet Gynecol & Reprod Biol,Div Gyn, 55 Fruits St, Boston, MA 02114 USA. EM aolawaiye@partners.org NR 10 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2007 VL 106 IS 3 BP 628 EP 630 DI 10.1016/j.ygyno.2007.05.006 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 209AS UT WOS:000249361100031 PM 17561233 ER PT J AU Freudenreich, O Holt, DJ Cather, C Goff, DC AF Freudenreich, Oliver Holt, Daphne J. Cather, Corinne Goff, Donald C. TI The evaluation and management of patients with first-episode schizophrenia: A selective, clinical review of diagnosis, treatment, and prognosis SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE diagnosis; first-episode psychosis; prognosis; schizophrenia; treatment ID RANDOMIZED CONTROLLED-TRIAL; CONVENTIONAL ANTIPSYCHOTIC-DRUGS; TRANSIENT PSYCHOTIC DISORDERS; FIRST-EPISODE PSYCHOSIS; INDUCED WEIGHT-GAIN; NEW-ONSET PSYCHOSIS; 1966 BIRTH COHORT; QUALITY-OF-LIFE; 1ST EPISODE; NEGATIVE SYMPTOMS AB Patients who present with a first episode of psychosis pose many challenges to psychiatry. While some morbidity from schizophrenia is probably not modifiable once acute psychosis has occurred, the best management of this stage of illness nevertheless holds the promise of improving long-term outcomes. We review the clinical literature on first-episode psychosis to derive clinical guidance with regard to timely diagnosis and optimal pharmacological and nonpharmacological treatment. We describe the illness course and the prognosis for this acute phase of illness and the immediate, postpsychotic period. C1 Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Freudenreich, O (reprint author), Freedom Trail clin, MGH Episode & Early Psychosis Program 1, 25 Staniford St,2nd Fl, Boston, MA 02114 USA. EM ofreudenreich@partners.org NR 186 TC 15 Z9 15 U1 9 U2 16 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 SEP-OCT PY 2007 VL 15 IS 5 BP 189 EP 211 DI 10.1080/10673220701679804 PG 23 WC Psychiatry SC Psychiatry GA 229KZ UT WOS:000250803200002 PM 17924256 ER PT J AU Manschreck, TC Boshes, RA AF Manschreck, Theo C. Boshes, Roger A. TI The CATIE schizophrenia trial: Results, impact, controversy SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE antipsychotic drugs; cognition; cost-effectiveness; metabolic syndrome; schizophrenia ID CLINICAL ANTIPSYCHOTIC TRIALS; BASE-LINE; 2ND-GENERATION ANTIPSYCHOTICS; COST-EFFECTIVENESS; SUBSTANCE USE; NIMH CATIE; DRUGS; PREVALENCE; 1ST-GENERATION; MEDICATIONS AB The CATIE (Clinical Antipsychotic Trials for Intervention Effectiveness) Schizophrenia Trial was designed to examine fundamental issues about second-generation antipsychotic (SGA) medications (olanzapine, risperidone, quetiapine, and ziprasidone)-their relative effectiveness and their effectiveness compared to a first-generation antipsychotic (FGA), perphenazine. This article reviews these and other findings from this important trial and offers a perspective regarding their meaning for practice and their significance for the advancement of research in psychiatry. The primary outcome measure, time to discontinuation, served as an index of effectiveness and was remarkably short; only 26% of subjects completed the 18-month trial on the medicine to which they were initially randomized. Subjects receiving olanzapine experienced a slightly longer time to discontinuation. Based on this single criterion, olanzapine showed greater effectiveness than the other agents despite its association with significant metabolic disturbance, especially weight gain. Perphenazine unexpectedly showed comparable levels of effectiveness and produced no more extrapyramidal side effects than the other agents. Despite modest prolactin elevation, risperidone was the best-tolerated medication. Ziprasidone was associated with weight loss and with positive impact on lipids and blood glucose. In Phase 2, clozapine demonstrated better effectiveness compared to other SGAs for subjects who discontinued their Phase 1 medication because of efficacy. Olanzapine and risperidone showed greater effectiveness in the tolerability pathway. CATIE secondary outcomes are currently being examined. Improvements in cognition were modest among all the agents in Phase 1, and perphenazine was no less effective in improving cognitive performance than the SGAs. Cost-effectiveness analysis revealed a significant advantage for perphenazine, due to the impact of the high-priced, brand-name SGAs on overall health care costs. C1 John C Corrigan Mental Hlth Ctr, Fall River, MA 02720 USA. Harvard Univ, Sch Med, Lab Clin & Expt Psychopathol,Dept Psychiat, Harvard Commonwealth Massachusetts Res Ctr, Cambridge, MA 02138 USA. Brockton VA Med Ctr, Psychiat Serv, Brockton, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Manschreck, TC (reprint author), John C Corrigan Mental Hlth Ctr, 49 Hillside St, Fall River, MA 02720 USA. EM Theo.Manschreck@dmh.state.ma.us NR 36 TC 63 Z9 68 U1 4 U2 7 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 SEP-OCT PY 2007 VL 15 IS 5 BP 245 EP 258 DI 10.1080/10673220701679838 PG 14 WC Psychiatry SC Psychiatry GA 229KZ UT WOS:000250803200005 PM 17924259 ER PT J AU Mendez, E Fan, W Choi, P Agoff, SN Whipple, M Farwell, DG Futran, ND Weymuller, EA Zhao, LP Chen, C AF Mendez, Eduardo Fan, Wenhong Choi, Peter Agoff, S. Nicholas Whipple, Mark Farwell, D. Gregory Futran, Neal D. Weymuller, Ernest A., Jr. Zhao, Lue-Ping Chen, Chu TI Tumor-specific genetic expression profile of metastatic oral squamous cell carcinoma SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE oral squamous cell carcinoma; metastasis; genetic profiles; oral cancer; lymph nodes ID NECK-CANCER; MICROARRAY ANALYSIS; BREAST-CANCER; HEAD; IDENTIFICATION; SIGNATURE; TRANSGLUTAMINASE-3; DISCOVERY; DISEASE; MODEL AB Background. Metastasis is the most important predictor of survival in patients with oral squamous cell carcinoma (OSCC). We tested the hypothesis that there is a genetic expression profile associated with OSCC metastasis. Methods. We obtained samples from 6 OSCC node-positive primary tumors and their matched metastatic lymph nodes, and 5 OSCC node-negative primary tumors. Using laser capture microdissection, we isolated OSCC cells from metastatic lymph nodes and compared them with those from matched primary tumors and unmatched node-negative primary tumors using Affymetrix Human Genome Focus arrays. Results. Comparison of tumor cells from the lymph nodes with those from the unmatched, node-negative primary tumors revealed differential expression of 160 genes. Hierarchical clustering and principal component analysis using this 160-gene set showed that the node-negative samples were distinguishable from both, node-positive primary tumors and tumors in the lymph nodes. Many of the expression changes found in the metastatic cells from the lymph nodes were also found in the node-positive primary tumors. Immunohistochemical analysis for transglutaminase-3 and keratin 16 confirmed the differential genetic expression for these genes. C1 Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA 98108 USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Program Biostat, Seattle, WA 98109 USA. Virginia Mason Med Ctr, Dept Pathol, Seattle, WA 98111 USA. Univ Calif Davis, Dept Otolaryngol Head & Neck Surg, Sacramento, CA 95817 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Chen, C (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. EM cchen@fbcrc.org FU NCI NIH HHS [R01 CA 095419]; NCRR NIH HHS [5 K12 RR023265-03]; NIDCD NIH HHS [T32 DC00018] NR 35 TC 25 Z9 27 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD SEP PY 2007 VL 29 IS 9 BP 803 EP 814 DI 10.1002/hed PG 12 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 207YZ UT WOS:000249288300001 PM 17573689 ER PT J AU Eikermann-Haerter, K Kudo, C Moskowitz, MA AF Eikermann-Haerter, Katharina Kudo, Chiho Moskowitz, Michael A. TI Cortical spreading depression and estrogen SO HEADACHE LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Headache-Society CY JUN, 2006 CL Los Angeles, CA SP Amer Headache Soc DE cortical spreading depression; familial hemiplegic migraine; estrogen ID FAMILIAL HEMIPLEGIC MIGRAINE; STEROID-HORMONES; MECHANISMS; BRAIN; POPULATION; HEADACHE; DENSITY; CELLS; RATS AB Cortical spreading depression (CSD) is an electrophysiological phenomenon characterized by a wave of excitation followed by inhibition. The aura phase that precedes migraine headache in about 20-30% of migraineurs shares overlapping characteristics with CSD. Studies of rare autosomal-dominant forms of migraine with aura provide strong evidence that the threshold for evoking CSD and aura are related to neuronal excitability. Although the relationship between CSD and migraine without aura is not completely understood, the molecular abnormalities that predispose to migraine with aura illustrate the importance of physiologic events associated with neuronal hyperexcitability, and provide a basis for understanding a more generalized view of migraine. C1 Massachusetts Gen Hosp, Ctr Neurosci, Harvard Med Sch, Harvard MIT Div Hlth & Sci Technol, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Harvard Med Sch, Harvard MIT Div Hlth & Sci Technol, Charlestown, MA 02129 USA. NR 27 TC 19 Z9 19 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-8748 J9 HEADACHE JI Headache PD SEP PY 2007 VL 47 SU 2 BP S79 EP S85 DI 10.1111/j.1526-2007.00818.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 213VW UT WOS:000249696400003 PM 17850538 ER PT J AU Weinick, RM Caglia, JM Friedman, E Flaherty, K AF Weinick, Robin M. Caglia, Jacquelyn M. Friedman, Elisa Flaherty, Katherine TI Measuring racial and ethnic health care disparities in Massachusetts SO HEALTH AFFAIRS LA English DT Article AB Reducing racial and ethnic disparities in the quality of health care is a national policy priority; collecting race and ethnicity data from patients is a necessary first step in identifying and addressing these disparities. Recognizing this, Boston and Massachusetts recently enacted race and ethnicity data collection regulations affecting all acute care hospitals in the city and state. This paper describes the regulations and early lessons learned from implementing these data collection efforts in three areas: the design of data collection tools, uses of the data for eliminating disparities, and the role of the policy process in such efforts. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Cambridge Hlth Alliance, Dept Community Affairs, Cambridge, MA USA. Inst Community Hlth, Cambridge, MA USA. RP Weinick, RM (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. EM rweinick@partners.org NR 19 TC 17 Z9 17 U1 1 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SEP-OCT PY 2007 VL 26 IS 5 BP 1293 EP 1302 DI 10.1377/hlthaff.26.5.1293 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 209WZ UT WOS:000249420000013 PM 17848439 ER PT J AU Shields, AE Shin, P Leu, MG Levy, DE Betancourt, RM Hawkins, D Proser, M AF Shields, Alexandra E. Shin, Peter Leu, Michael G. Levy, Douglas E. Betancourt, Rene Marie Hawkins, Dan Proser, Michelle TI Adoption of health information technology in community health centers: Results of a national survey SO HEALTH AFFAIRS LA English DT Article ID PRIMARY-CARE; RECORDS; SYSTEMS; DISPARITIES; DIFFUSION; SAFETY AB To the extent that health information technology (IT) improves health care quality, differential adoption among providers that serve vulnerable populations may exacerbate health disparities. This first national survey of federally funded community health centers (CHCs) shows that although 26 percent reported some electronic health record (EHR) capacity and 13 percent have the minimal set of EHR functionalities, CHCs serving the most poor and uninsured patients were less likely to have a functional EHR. CHCs cited lack of capital as the top barrier to adoption. Ensuring comparable health IT capacity among providers that disproportionately serve disadvantaged patients will have increasing relevance for disparities; thus, monitoring adoption among such providers should be a priority. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Genom Vulnerable Populat & Hlth Dispar, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners Healthcare Inst Hlth Policy, Boston, MA 02114 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. Natl Assoc Community Hlth Ctr, Washington, DC USA. RP Shields, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Genom Vulnerable Populat & Hlth Dispar, Boston, MA 02115 USA. EM ashields@partners.org FU NHGRI NIH HHS [HG003400] NR 27 TC 59 Z9 59 U1 1 U2 11 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SEP-OCT PY 2007 VL 26 IS 5 BP 1373 EP 1383 DI 10.1377/hlthaff.26.5.1373 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 209WZ UT WOS:000249420000022 PM 17848448 ER PT J AU Levy, AG Maselko, J Bauer, M Richman, L Kubzansky, L AF Levy, Andrea Gurmankin Maselko, Joanna Bauer, Mark Richman, Laura Kubzansky, Laura TI Why do people with an anxiety disorder utilize more nonmental health care than those without? SO HEALTH PSYCHOLOGY LA English DT Article DE health care utilization; anxiety; psychological disorder; health care services ID CHRONIC DISEASE SCORE; AUTOMATED PHARMACY DATA; CORONARY-HEART-DISEASE; MAINTENANCE ORGANIZATION; DEPRESSIVE SYMPTOMS; COMORBID DEPRESSION; SERVICE UTILIZATION; MEDICAL UTILIZATION; SOMATIC COMPLAINTS; NEGATIVE AFFECT AB Objective: It is unclear why nonmental healthcare utilization is greater among those with psychological problems. The authors examined healthcare utilization in HMO patients to determine whether greater utilization in anxiety disorder (AD) patients was explained by anxiety symptoms (increasing sensitivity to physical symptoms) or comorbid illness (causing greater need for services). Design: Patients were randomly selected from the database of a multi-specialty practice and 1,041 completed a survey assessing psychological symptoms, health behaviors, and demographics. Anxiety symptoms were assessed by questionnaire and the presence of an AD was determined from the medical chart. Healthcare encounters and medication use were abstracted from medical charts and HMO claims data. Main Outcome Measures: Healthcare utilization. Results: Both AD and anxiety symptoms predicted utilization, but symptoms were not associated with utilization in a model that also included AD. Comorbid illness was significantly associated with utilization independent of AD and somewhat reduced the strength of the AD-utilization association. The results were replicated in comparison of those with any psychiatric disorder to those without. Conclusion: Among those with AD, greater utilization is not explained by anxiety symptoms but is partly explained by greater comorbid illness. Further study is needed to understand excess healthcare utilization among AD patients. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Harvard Vanguard Med Associates, Wellesley, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Duke Univ, Durham, NC 27706 USA. RP Levy, AG (reprint author), Dana Farber Canc Inst, 44 Binney St,LW 618, Boston, MA 02115 USA. EM andrea_gurmankin@dfci.harvard.edu NR 75 TC 7 Z9 7 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2007 VL 26 IS 5 BP 545 EP 553 DI 10.1037/0278-6133.26.5.545 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 209AW UT WOS:000249361500008 ER PT J AU O'Toole, TP Conde-Martel, A Gibbon, JL Hanusa, BH Freyder, PJ Fine, MJ AF O'Toole, Thomas P. Conde-Martel, Alicia Gibbon, Jeanette L. Hanusa, Barbara H. Freyder, Paul J. Fine, Michael J. TI Where do people go when they first become homeless? A survey of homeless adults in the USA SO HEALTH & SOCIAL CARE IN THE COMMUNITY LA English DT Article DE access to care; homelessness; help-seeking; substance abuse ID SOUP KITCHEN POPULATION; URBAN HOMELESS; MENTALLY-ILL; MEDICAL-CARE; HOUSED POOR; DRUG; SERVICES; ALCOHOL; HEALTH; READINESS AB The longer a person is homeless, the more likely he or she is to experience poor health and be placed at higher risk for premature death. This makes interventions early in one's homelessness an important prevention strategy. However, little is known about where someone goes for help when they first become homeless and how well those sites are prepared to address the multitude of issues facing a homeless person. In order to address this question, we conducted a cross-sectional community-based survey in two US cities in 1997 using population proportionate sampling of homeless persons identified at 91 sites to identify 'first-stop' access sites and reasons for seeking help at those sites. A total of 230 persons participated in the face-to-face interview (93% response rate). From a list of 20 possible 'first-stop' sites, 105 (45.7%) reported going to a soup kitchen, 71 (30.9%) went to a welfare office, 64 (27.8%) sought admission to a detoxification centre, 60 (26.1 %) met with a homeless outreach team, 57 (24.8%) went to a family member, and 54 (23.5%) went to an emergency room. Individuals with a chronic medical or mental health condition were significantly more likely to access a healthcare site (medical: 62.6% vs. 47.6%, P = 0.02; mental health: 62.4% vs. 38.8%, P < 0.01) or social service agency (medical: 64.0% vs. 43.3 %, P = 0.02; mental health: 59.1 % vs. 40.7%, P < 0.01). Those persons reporting a need for alcohol treatment were significantly more likely to first go to a healthcare site (46.4% vs. 29.1 %, P < 0.01) and those with alcohol abuse/dependence were less likely to seek help from family or friends (66.7% vs. 81.9%, P < 0.01). Most respondents sought assistance for concerns directly associated with an immediate need as opposed to seeking care for issues causing their actual homelessness. These findings suggest the need to expand and integrate the availability of services at 'first-stop' access sites that facilitate early exits from homelessness. C1 Providence VA Med Ctr, Providence, RI 02908 USA. Brown Med Sch, Providence, RI 02912 USA. Hosp Univ Gran Canaria, Las Palmas Gran Canaria, Spain. Maricopa Cty Dept Publ Hlth, Phoenix, AZ USA. Univ Pittsburgh, Womens Behav Healthcare Program, Dept Psychiat, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Salvat Army Publ Inebriate Program, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP O'Toole, TP (reprint author), Providence VA Med Ctr, 830 Chalkstone Ave, Providence, RI 02908 USA. EM thomas.o'toole@va.gov FU NIDA NIH HHS [K23 DA13988-01] NR 30 TC 22 Z9 22 U1 1 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0966-0410 J9 HEALTH SOC CARE COMM JI Health Soc. Care Community PD SEP PY 2007 VL 15 IS 5 BP 446 EP 453 PG 8 WC Public, Environmental & Occupational Health; Social Work SC Public, Environmental & Occupational Health; Social Work GA 207HY UT WOS:000249243400006 PM 17685990 ER PT J AU Blendea, D Shah, RV Auricchio, A Nandigam, V Orencole, M Heist, K Reddy, VY McPherson, CA Ruskin, JN Singh, JP AF Blendea, Dan Shah, Ravi V. Auricchio, Angelo Nandigam, Veena Orencole, Mary Heist, Kevin Reddy, Vivek Y. McPherson, Craig A. Ruskin, Jeremy N. Singh, Jagmeet P. TI Variability of coronary venous anatomy in patients undergoing cardiac resynchronization therapy: A high-speed rotational venography study SO HEART RHYTHM LA English DT Article DE coronary venous anatomy; left atrial veins; cardiac resynchronization therapy; heart failure; coronary venous angiography ID CHRONIC HEART-FAILURE; COMPUTED-TOMOGRAPHY; INTRAVASCULAR ULTRASOUND; DILATED CARDIOMYOPATHY; ATRIAL-FIBRILLATION; ARTERY SIZE; SINUS; ANGIOGRAPHY; GENDER; SYSTEM AB BACKGROUND Imaging the coronary venous (CV) tree to delineate the coronary sinus and its tributaries can facilitate electro-physiological procedures, such as cardiac resynchronization therapy (CRT) and catheter ablation. Venography also allows visualization of the left atrial (LA) veins, which may be a potential conduit for ablative or pacing strategies given their proximity to foci that can trigger atrial fibrillation. OBJECTIVE The aim of this study was to provide a detailed description of CV anatomy using rotational venography in patients undergoing CRT. METHODS Coronary sinus (CS) size and the presence, size, and angutation of its tributaries were determined from the analysis of rotational CV angiograms from 51 patients (age 68 +/- 11 years; n = 12 women) undergoing CRT. RESULTS The CS, posterior veins, and lateral veins were identified in 100%, 76%, and 91% of patients. Lateral. veins were less prevalent in patients with a history of lateral myocardial infarction than in patients without such a history (33% vs. 96%; P =.014). The diameters of the CS and its tributaries were fairly variable (7.3-18.9 mm for CS, 1.3-10.5 mm for CS tributaries). The CS was larger in men than in women and in cases of ischemic than in cases of nonischernic cardiomyopathy (all P <.05). The vein of Marshall, the most constant LA vein, was identified in 37 patients; its diameter is 1.7 +/- 0.5 mm, and its takeoff angle is 154 degrees +/- 15 degrees, making the vein potentially accessible for cannulation. CONCLUSIONS Differences in CV anatomy that are related to either gender or coronary artery disease could have important practical implications during the left ventricular lead implantation. The anatomical features of the vein of Marshall make it a feasible potential conduit for epicardial LA pacing. C1 Yale Univ, Sch Med, Bridgeport Hosp, Div Cardiol, Bridgeport, CT USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arryhthmia Serv,Dept Med, Boston, MA 02115 USA. Fdn Carioctr Ticino, Div Cardiol, Lugano, Switzerland. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arryhthmia Serv,Ctr Heart, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org NR 38 TC 40 Z9 43 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD SEP PY 2007 VL 4 IS 9 BP 1155 EP 1162 DI 10.1016/j.hrthm.2007.05.023 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 210IB UT WOS:000249448800006 PM 17765613 ER PT J AU El-Serag, HB AF El-Serag, Hashem B. TI Epidemiology of hepatocellular carcinoma in USA SO HEPATOLOGY RESEARCH LA English DT Article; Proceedings Paper CT 4th Single Topic Conference on HCC CY DEC 02-03, 2005 CL Awaji Isl, JAPAN SP Japan Soc Hepatol DE epidemiology; hepatitis B; hepatitis C; nonalcoholic steatohepatitis ID HEPATITIS-C VIRUS; CHRONIC LIVER-DISEASE; UNITED-STATES; RISK-FACTORS; VIRAL-HEPATITIS; MORTALITY; JAPAN; POPULATION; PREVALENCE; INFECTION AB Hepatocellular carcinoma (HCC) is increasing in frequency the USA. Age-adjusted incidence, hospitalization, and mortality rates have doubled over the past two decades. There are striking differences in the incidence of HCC related to age, gender, race, and geographic region. Although it remains an affliction of the elderly (mean age 65), there has been a considerable shift toward younger cases. There is a birth cohort effect with those born after 1945. Men are affected three times more frequently than women, Asians two times more than African American and Hispanic people, who are affected two times more often than Caucasians. However, the recent increase has disproportionately affected Caucasian (and Hispanic) men between ages 45 and 65. Hepatitis C virus (HCV) infection acquired 2-4 decades ago explains at least half of the observed increase in HCC; HCV-related HCC is likely to continue to increase for the next decade. A variable but significant proportion of cases (15-50%) do not have evidence for the risk factors of either viral hepatitis or heavy alcohol consumption. Insulin resistance syndrome manifesting as obesity and diabetes is emerging as a risk factor for HCC in the USA and may operate through the formation of non-alcoholic fatty liver disease (NAFLD); however, its effect on the current trend in HCC remains unclear. While there has been a small recent improvement in survival, it remains generally dismal (median 8 months). Population-based data in the USA indicate low application rate of HCC potentially curative therapy and marked regional differences. C1 Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 28 TC 190 Z9 196 U1 0 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD SEP PY 2007 VL 37 SU 2 BP S88 EP S94 DI 10.1111/j.1872-034X.2007.00168.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 228UP UT WOS:000250758400002 PM 17877502 ER PT J AU Bischoff-Grethe, A Ozyurt, IB Busa, E Quinn, BT Fennema-Notestine, C Clark, CP Morris, S Bondi, MW Jernigan, TL Dale, AM Brown, GG Fischl, B AF Bischoff-Grethe, Amanda Ozyurt, I. Burak Busa, Evelina Quinn, Brian T. Fennema-Notestine, Christine Clark, Camellia P. Morris, Shaunna Bondi, Mark W. Jernigan, Terry L. Dale, Anders M. Brown, Gregory G. Fischl, Bruce TI A technique for the deidentification of structural brain MR images SO HUMAN BRAIN MAPPING LA English DT Article DE MRI; image processing; statistics; HIPAA; algorithms; humans ID SKULL STRIPPING PROBLEM; INTENSITY NONUNIFORMITY; QUANTITATIVE-EVALUATION; SEGMENTATION; EXTRACTION; VIDEO AB Due to the increasing need for subject privacy, the ability to deidentify structural MR images so that they do not provide full facial detail is desirable. A program was developed that uses models of nonbrain structures for removing potentially identifying facial features. When a novel image is presented, the optimal linear transform is computed for the input volume (Fischl et al. [20021: Neuron 33:341-355; Fischl et al. [20041: Neuroimage 23 (Suppl 1):S69-S84). A brain mask is constructed by forming the union of all voxels with nonzero probability of being brain and then morphologically dilated. All voxels outside the mask with a nonzero probability of being a facial feature are set to 0. The algorithm was applied to 342 datasets that included two different T1-weighted pulse sequences and four different diagnoses (depressed, Alzheimer's, and elderly and young control groups). Visual inspection showed none had brain tissue removed. In a detailed analysis of the impact of defacing on skull-stripping, 16 datasets were bias corrected with N3 (Sled et al. [1998]: IEEE Trans Med Imaging 17:87-97), defaced, and then skull-stripped using either a hybrid watershed algorithm (Segonne et al. [2004]: Neuroimage 22:1060-1075, in FreeSurfer) or Brain Surface Extractor (Sandor and Leahy [1997]: IEEE Trans Med Imaging 16:41-54; Shattuck et al. [20011: Neuroimage 13:856-876); defacing did not appreciably influence the outcome of skull-stripping. Results suggested that the automatic defacing algorithm is robust, efficiently removes nonbrain tissue, and does not unduly influence the outcome of the processing methods utilized; in some cases, skull-stripping was improved. Analyses support this algorithm as a viable method to allow data sharing with minimal data alteration within large-scale multisite projects. (c) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr, NMR Ctr, Boston, MA 02129 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, Dept Psychiat, Lab Cognit Imaging, La Jolla, CA 92093 USA. RP Fischl, B (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr, NMR Ctr, 149 13th St,Rm 2301, Boston, MA 02129 USA. EM fischl@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; OI Fennema-Notestine, Christine/0000-0002-6527-6361 FU NCRR NIH HHS [M01 RR000827, M01 RR000827-328412, M01RR00827, P41 RR014075, P41-RR14075, R01 RR016594, R01 RR16594-01A1, U24 RR021382]; NIA NIH HHS [AG04085, AG12674, P50 AG005131, P50 AG05131, R01 AG004085, R01 AG006849, R01 AG012674, R29 AG012674, R56 AG012674]; NIDA NIH HHS [5K01DA015499, K01 DA015499]; NIMH NIH HHS [5K08MH01642, K08 MH001642, K08 MH001642-05, P50 MH045294, R01MH42575] NR 19 TC 25 Z9 26 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2007 VL 28 IS 9 BP 892 EP 903 DI 10.1002/hbm.20312 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 209XC UT WOS:000249420300008 PM 17295313 ER PT J AU Pohl, KM Bouix, S Nakamura, M Rohlfing, T McCarley, RW Kikinis, R Grimson, WEL Shenton, ME Wells, WM AF Pohl, Kilian M. Bouix, Sylvain Nakamura, Motoaki Rohlfing, Torsten McCarley, Robert W. Kikinis, Ron Grimson, W. Eric L. Shenton, Martha E. Wells, William M. TI A hierarchical algorithm for MR brain image parcellation SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE automatic segmentation; data tree; expectation-maximization; MRI; parcellation; statistical group comparison study ID EXPECTATION-MAXIMIZATION ALGORITHM; LEFT TEMPORAL-LOBE; 1ST-EPISODE SCHIZOPHRENIA; NONRIGID REGISTRATION; SEGMENTATION; MODEL; DISORDER; CLASSIFICATION; ABNORMALITIES; VALIDATION AB We introduce an algorithm for segmenting brain magnetic resonance (MR) images into anatomical compartments such as the major tissue classes and neuro-anatomical structures of the gray matter. The algorithm is guided by prior information represented within a tree structure. The tree mirrors the hierarchy of anatomical structures and the subtrees correspond to limited segmentation problems. The solution to each problem is estimated via a conventional classifier. Our algorithm can be adapted to a wide range of segmentation problems by modifying the tree structure or replacing the classifier. We evaluate the performance of our new segmentation approach by revisiting a previously published statistical group comparison between first-episode schizophrenia patients, first-episode affective psychosis patients, and comparison subjects. The original study is based on 50 MR volumes in which an expert identified the brain tissue classes as well as the superior temporal gyrus, amygdala, and hippocampus. We generate analogous segmentations using our new method and repeat the statistical group comparison. The results of our analysis are similar to the original findings, except for one structure (the left superior temporal gyrus) in which a trend-level statistical significance (p = 0.07) was observed instead of statistical significance. C1 Harvard Univ, Sch Med, Surg Planning Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat,Psychiat Neuro Imaging Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Neurosci Lab, Clin Neurosci Div, Brockton, MA 02301 USA. SRI Int, Program Neurosci, Menlo Pk, CA 94025 USA. RP Pohl, KM (reprint author), Harvard Univ, Sch Med, Surg Planning Lab, Boston, MA 02115 USA. EM pohl@csail.mit.edu RI Rohlfing, Torsten/A-1146-2007; McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Bouix, Sylvain/0000-0003-1326-6054 FU NCRR NIH HHS [P41 RR013218, P41-RR13218, U24 RR021382, U24-RR021382]; NIAAA NIH HHS [AA13521, AA05965, R01 AA005965, R01 AA016748, R01 AA016748-01, R37 AA005965, U01 AA013521]; NIBIB NIH HHS [U54 EB005149]; NIMH NIH HHS [K02 MH 01110, K02 MH001110, K02 MH001110-10, K05 MH 01110, R01 MH 40799, R01 MH 50747, R01 MH040799]; NINDS NIH HHS [R01 NS051826, R01-NS051826] NR 48 TC 55 Z9 56 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD SEP PY 2007 VL 26 IS 9 BP 1201 EP 1212 DI 10.1109/TMI.2007.901433 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 206WL UT WOS:000249213500007 PM 17896593 ER PT J AU Deeks, SG Walker, BD AF Deeks, Steven G. Walker, Bruce D. TI Human immunodeficiency virus controllers: Mechanisms of durable virus control in the absence of antiretroviral therapy SO IMMUNITY LA English DT Review ID T-CELL RESPONSES; LONG-TERM NONPROGRESSORS; PLASMACYTOID DENDRITIC CELLS; ACUTE HIV-1 INFECTION; VIRAL LOAD; DISEASE PROGRESSION; ELITE SUPPRESSORS; TYPE-1 INFECTION; RNA LEVELS; HLA-B AB Chronic viral infections can appear in two very different forms: those that are typically immunologically contained after acute symptomatic infection, such as Epstein-Barr virus (EBV), and those that predictably lead to persistent viremia and progressive clinical disease. Human immunodeficiency virus (HIV) infection is typical of the latter and has resulted in more than 20 million deaths worldwide. Here we review a remarkable subset of persons infected with HIV who are able to achieve long-term control of viremia and avoid immunodeficiency without the need for antiviral therapy. We review the contributing role of host genetic factors, innate and adaptive immune responses, and viral factors that may contribute to this phenotype. These individuals indicate that as with other potentially pathogenic chronic viral infections, the human immune system is able to fully control HIV and prevent HIV-associated disease, at least in some individuals. Further understanding of the mechanisms whereby this occurs should yield critical insights for prophylactic and therapeutic antiviral interventions. C1 Univ Calif San Francisco, San Francisco, CA 94110 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Walker, BD (reprint author), Univ Calif San Francisco, San Francisco, CA 94110 USA. EM bwalker@partners.org FU NIAID NIH HHS [K24 AI69994, R01 AI052745, R01 AI060354-03]; NIMH NIH HHS [P30 MH59037] NR 102 TC 381 Z9 393 U1 5 U2 29 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2007 VL 27 IS 3 BP 406 EP 416 DI 10.1016/j.immuni.2007.08.010 PG 11 WC Immunology SC Immunology GA 215XX UT WOS:000249843400006 PM 17892849 ER PT J AU Jia, YH Subramanian, KK Erneux, C Pouillon, V Hattori, H Jo, HY You, J Zhu, D Schurmans, S Luo, HBR AF Jia, Yonghui Subramanian, Kulandayan K. Erneux, Christophe Pouillon, Valerie Hattori, Hidenori Jo, Hakryul You, Jian Zhu, Daocheng Schurmans, Stephane Luo, Hongbo R. TI Inositol 1,3,4,5-tetrakisphosphate negatively regulates phosphatidylinositol-3,4,5-trisphosphate signaling in neutrophils SO IMMUNITY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; TUMOR-SUPPRESSOR PTEN; HEXAKISPHOSPHATE KINASE; CELL-DEATH; STRUCTURAL BASIS; 1,4,5-TRISPHOSPHATE; CHEMOTAXIS; 3-KINASE; PHOSPHORYLATION; EXPRESSION AB Many neutrophil functions are regulated by phosphatidylinositol-3,4,5-trisphosphate (Ptdlns(3,4,5)P3) that mediates protein membrane translocation via binding to pleckstrin homolog (PH) domains within target proteins. Here we show that inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), a cytosolic small molecule, bound the same PH domain of target proteins and competed for binding to Ptdlns(3,4,5)P3. In neutrophils, chemoattractant stimulation triggered rapid elevation in lns(1,3,4,5)P4 concentration. Depletion of lns(1,3,4,5)P4 by deleting the gene encoding lnsP3KB, which converts Ins(1,4,5)P3 to Ins(1,3,4,5)P4, enhanced membrane translocation of the Ptdins(3,4,5)P3specific PH domain. This led to enhanced sensitivity to chemoattractant stimulation, elevated superoxide production, and enhanced neutrophil recruitment to inflamed peritoneal cavity. On the contrary, augmentation of intracellular Ins(1,3,4,5)P4 concentration blocked PH domainmediated membrane translocation of target proteins and dramatically decreased the sensitivity of neutrophils to chemoattractant stimulation. These findings establish a role for lns(1,3,4,5)P4 in cellular signal transduction pathways and provide another mechanism for modulating Ptdlns(3,4,5)P3 signaling in neutrophils. C1 Harvard Univ, Sch Med, Dept Pathol,Childrens Hosp, Dana Farber Canc Ctr,Dept Lab Med, Boston, MA 02115 USA. Univ Libre Bruxelles, IRIBHM, B-6041 Gosselies, Belgium. RP Luo, HBR (reprint author), Harvard Univ, Sch Med, Dept Pathol,Childrens Hosp, Dana Farber Canc Ctr,Dept Lab Med, Karp Family Res Bldg,Room 10214, Boston, MA 02115 USA. EM hongbo.luo@childrens.harvard.edu FU NHLBI NIH HHS [HL066987, R01 HL085100, HL085100, T32 HL066987, R01 HL085100-01A1]; NIGMS NIH HHS [GM076084, R01 GM076084, R01 GM076084-01A1, R01 GM076084-02]; NINDS NIH HHS [NS052200, R21 NS052200] NR 69 TC 41 Z9 45 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD SEP PY 2007 VL 27 IS 3 BP 453 EP 467 DI 10.1016/j.immuni.2007.07.016 PG 15 WC Immunology SC Immunology GA 215XX UT WOS:000249843400012 PM 17825589 ER PT J AU Montoya, CJ Pollard, D Martinson, J Kumari, K Wasserfall, C Mulder, CB Rugeles, MT Atkinson, MA Landay, AL Wilson, SB AF Montoya, Carlos J. Pollard, David Martinson, Jeffrey Kumari, Kumud Wasserfall, Clive Mulder, Candice B. Rugeles, Maria T. Atkinson, Mark A. Landay, Alan L. Wilson, S. Brian TI Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11 SO IMMUNOLOGY LA English DT Article DE invariant NKT cells; 6B11 clone; LAG-3; IFN-gamma; IL-4 ID NKT CELLS; ALPHA-GALACTOSYLCERAMIDE; CUTTING EDGE; CD1D-RESTRICTED RECOGNITION; MULTIPLE-SCLEROSIS; DISTINCT SUBSETS; ANTIGEN RECEPTOR; GENE-EXPRESSION; DENDRITIC CELLS; VIRUS-INFECTION AB Identification of human CD1d-restricted T-cell receptor (TCR)-invariant natural killer T (iNKT) cells has been dependent on utilizing combinations of monoclonal antibodies or CD1d tetramers, which do not allow for the most specific analysis of this T-cell subpopulation. A novel monoclonal antibody (clone 6B11), specific for the invariant CDR3 loop of human canonical V alpha 24J alpha 18 TCR alpha chain, was developed and used to specifically characterize iNKT cells. In healthy individuals studied for up to 1 year, a wide but stable frequency of circulating iNKT cells (range: 0.01-0.92%) was observed, with no differences in frequency by gender. Four stable iNKT cell subsets were characterized in peripheral blood based on the expression of CD4 and CD8, with CD8(+) iNKT cells being a phenotypic and functionally different subset from CD4(+) and double negative iNKT cells; in particular, LAG-3 was preferentially expressed on CD8(+) iNKT cells. In addition, a strong negative linear correlation between the frequency of total iNKT cells and percentage of the CD4(+) subset was observed. In terms of their potential association with disease, patients at risk for type 1 diabetes had significantly expanded frequencies of double negative iNKT cells when compared to matched controls and first-degree relatives. Moreover, peripheral blood CD4(+) iNKT cells were the highest producers of interleukin-4, while the production of interferon-gamma and tumour necrosis factor-alpha was similar amongst all iNKT cell subsets. These differences in iNKT cell subsets suggest that in humans the relative ratio of iNKT cell subsets may influence susceptibility vs. resistance to immune-mediated diseases. C1 Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. Univ Antioquia, Grp Immunol Biogenesis, Medellin, Colombia. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. RP Montoya, CJ (reprint author), Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. EM cjmonto@epm.net.co; bwilson@rics.bwh.harvard.edu RI wasserfall, clive/J-9078-2012 OI wasserfall, clive/0000-0002-3522-8932 FU NIAID NIH HHS [P01 AI055793, R01 AI045051, R01 AI45051] NR 69 TC 91 Z9 95 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2007 VL 122 IS 1 BP 1 EP 14 DI 10.1111/j.1365-2567.2007.02647.x PG 14 WC Immunology SC Immunology GA 204JU UT WOS:000249040700001 PM 17662044 ER PT J AU Mullegger, RR Means, TK Shin, JJ Lee, M Jones, KL Glickstein, LJ Luster, AD Steere, AC AF Muellegger, Robert R. Means, Terry K. Shin, Junghee J. Lee, Marshall Jones, Kathryn L. Glickstein, Lisa J. Luster, Andrew D. Steere, Allen C. TI Chemokine signatures in the skin disorders of Lyme Borreliosis in Europe: Predominance of CXCL9 and CXCLIO in erythema migrans and acrodermatitis and CXCL13 in lymphocytoma SO INFECTION AND IMMUNITY LA English DT Article ID BURGDORFERI-SENSU-STRICTO; ECTOPIC GERMINAL CENTER; TUMOR-NECROSIS-FACTOR; CHRONICA ATROPHICANS; CEREBROSPINAL-FLUID; INTERLEUKIN-8 IL-8; ENDOTHELIAL-CELLS; HOMING CHEMOKINES; GENE-EXPRESSION; DENDRITIC CELLS AB The three skin disorders of Lyme borreliosis in Europe include erythema migrans, an acute, self-limited lesion; borrelial lymphocytoma, a subacute lesion; and acrodermatitis chronica atrophicans, a chronic lesion. Using quantitative reverse transcription-PCR, we determined mRNA expression of selected chemokines, cytokines, and leukocyte markers in skin samples from 100 patients with erythema migrans, borrelial lymphocytoma, or acrodermatitis chronica atrophicans and from 25 control subjects. Chemokine patterns in lesional skin in each of the three skin disorders included low but significant mRNA levels of the neutrophil chemoattractant CXCLI and the dendritic cell chemoattractant CCL20 and intermediate levels of the macrophage chemoattractant CCL2. Erythema migrans and particularly acrodermatitis lesions had high mRNA expression of the T-cell-active chemokines CXCL9 and CXCLIO and low levels of the B-cell-active chemokine CXCL13, whereas lymphocytoma lesions had hi, gh levels of CXCL13 and lower levels of CXCL9 and CXCLIO. This pattern of chemokine expression was consistent with leukocyte marker mRNA in lesional skin. Moreover, using immunohistologic methods, CD3(+) T cells and CXCL9 were visualized in erythema migrans and acrodermatitis lesions, and CD20(+) B cells and CXCL13 were seen in lymphocytorna lesions. Thus, erythema migrans and acrodermatitis chronica atrophicans have high levels of the T-cell-active chemokines CXCL9 and CXCLIO, whereas borrelial lymphocytoma has high levels of the B-cell-active chemokine CXCL13. C1 Med Univ Graz, Dept Dermatol, A-8036 Graz, Austria. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA USA. RP Mullegger, RR (reprint author), Med Univ Graz, Dept Dermatol, Auenbruggerpl 8, A-8036 Graz, Austria. EM robert.muellegger@kh-wrn.ac.at FU NCI NIH HHS [CA-69212, R01 CA069212]; NIAMS NIH HHS [T32 AR-07258]; PHS HHS [C1000157] NR 43 TC 35 Z9 38 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2007 VL 75 IS 9 BP 4621 EP 4628 DI 10.1128/IAI.00263-07 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 205RG UT WOS:000249131700050 PM 17606602 ER PT J AU Kotton, CN AF Kotton, Camille Nelson TI Nailing down the shingles in IBD SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; HERPES-ZOSTER; COLITIS; VACCINE C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St Cox 5, Boston, MA 02114 USA. NR 6 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2007 VL 13 IS 9 BP 1178 EP 1179 DI 10.1002/ibd.20161 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 205JJ UT WOS:000249109500018 PM 17476676 ER PT J AU Ring, D AF Ring, David TI Current concepts in plate and screw fixation of osteoporotic proximal humerus fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE open reduction and internal fixation; proximal humerus fractures; osteoporosis; plate and screw fixation; angular stable screws ID PROSTHETIC REPLACEMENT; UNSTABLE FRACTURES; LOCKING PLATE; RISK-FACTORS; CLASSIFICATION; EPIDEMIOLOGY; HEAD; NEER; HEMIARTHROPLASTY; REPRODUCIBILITY AB Most surgeons feel that angular stable implants have improve the ability to obtain reliable fixation of an osteoporotic fracture of the proximal humerus fracture, but complications such as varus fracture collapse and screw penetration of the articular surface remain problematic. The use of limited drilling, blunt tipped locking bolts and routine incorporation of the rotator cuff into the internal fixation construct may help limit these complications. It may be of benefit to replace the concept of standard screw fixation of the osteoporotic proximal humerus with a concept of an angular stable scaffold support of the subchondral bone combined with fixation that does not rely on bone quality and utilizes the more predictable fixation of sutures through the rotator cuff attachments. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dring@partners.org NR 42 TC 30 Z9 31 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD SEP PY 2007 VL 38 SU 3 BP 59 EP 68 DI 10.1016/j.injury.2007.08.013 PG 10 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 221LT UT WOS:000250230000010 ER PT J AU Barrocas, AM Eskey, CJ Hirsch, JA AF Barrocas, Alex M. Eskey, Clifford J. Hirsch, Joshua A. TI Vertebral augmentation in osteoporotic fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE osteoporosis; spine; fracture; vertebral compression fracture; vertebroplasty; kyphoplasty; vertebral augmentation ID PERCUTANEOUS POLYMETHYLMETHACRYLATE VERTEBROPLASTY; COMPRESSION FRACTURES; ACRYLIC CEMENT; PULMONARY-EMBOLISM; BALLOON KYPHOPLASTY; RARE COMPLICATION; CLINICAL-OUTCOMES; ORAL ALENDRONATE; BODY FRACTURE; FAT-EMBOLISM AB Osteoporotic vertebral compression fractures result in an enormous medical, social and economic burden to society. Here, we review osteoporotic vertebral compression fractures, focusing on both their diagnosis and the treatment options, particularly vertebral augmentation. C1 Massachusetts Gen Hosp, Intervent Neuroradiol Serv, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, Intervent Neuroradiol Serv, Boston, MA 02114 USA. EM jahirsch@partners.org NR 85 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD SEP PY 2007 VL 38 SU 3 BP 88 EP 96 DI 10.1016/j.injury.2007.08.016 PG 9 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 221LT UT WOS:000250230000013 ER PT J AU Keuthen, NJ Jameson, M Loh, R Deckersbach, T Wilhelm, S Dougherty, DD AF Keuthen, Nancy J. Jameson, Mariko Loh, Rebecca Deckersbach, Thilo Wilhelm, Sabine Dougherty, Darin D. TI Open-label escitalopram treatment for pathological skin picking SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE dermatillomania; escitalopram; neurotic excoriations; pathological skin picking; self-injurious skin picking ID OBSESSIVE-COMPULSIVE DISORDER; BODY DYSMORPHIC DISORDER; PSYCHOGENIC EXCORIATION; NEUROTIC EXCORIATIONS; CITALOPRAM; FLUOXETINE; SCALE; FLUVOXAMINE; DEPRESSION; INVENTORY AB Pathological skin picking is characterized by dysfunctional, repetitive and excessive manipulation of the skin resulting in noticeable tissue damage. This study sought to assess the effectiveness of escitalopram in treating pathological skin picking. Twenty-nine individuals with pathological skin picking were enrolled in an 18-week, open-label trial of escitalopram. Study measures assessing skin picking severity and impact, anxiety, depression, and quality of life were given at baseline and weeks 2, 4, 6, 10, 14, and 18. The mean maximally tolerated dose was 25.0 mg (standard deviation = 8.4). For the 19 study completers, pre-post-treatment analyses revealed significant improvements (P<0.05) on measures of skin picking severity and impact, quality of life, and self-rated anxiety and depression. Completer as well as intent-to-treat analyses indicated that approximately half of the sample satisfied full medication response criteria and one-quarter were partial medication responders. Correlational analyses indicated that changes in depression, anxiety, and quality of life co-occurred with reductions in skin picking severity but not impact. A high percentage of variance in severity, however, remained unexplained. These results suggest that escitalopram can be an effective agent in reducing pathological skin picking. The lack of medication response in a subset of our sample suggests the possibility of pathological skin picking subtypes. Int Clin Psychopharmacol 22:268-274 (c) 2007 Lippincott Williams & Wilkins. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp, OCD Clin, Simches Res Bldg,Fl 2,185 Cambridge St, Boston, MA 02114 USA. EM nkeuthen@partners.org NR 34 TC 24 Z9 25 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD SEP PY 2007 VL 22 IS 5 BP 268 EP 274 DI 10.1097/YIC.0b013e32809913b6 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 206CH UT WOS:000249161000002 PM 17690595 ER PT J AU Darouiche, R AF Darouiche, R. TI Antimicrobial coating of devices for prevention of infection: Principles and protection SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Review DE antimicrobial coating; device; infection; prevention ID CENTRAL VENOUS CATHETERS; BLOOD-STREAM INFECTION; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE-CARE UNIT; SURGICAL IMPLANTS; COATED CATHETERS; CLINICAL-TRIAL; EXCESS LENGTH; DOUBLE-BLIND; EFFICACY AB Device-associated infections are responsible for about half of nosocomial infections and can cause major medical and economical sequelae. Despite adherence to basic infection control measures, which constitute the mainstay for preventing infection, infections associated with certain devices continue to exist at unacceptably high rates. Potentially-preventive, antimicrobial-utilizing strategies include systemic antibiotic prophylaxis and local administration of antimicrobial agents (antibiotics or antiseptics), which includes antimicrobial irrigation of the surgical field, placement of antimicrobial carriers, antiseptic cleansing of the skin, dipping of surgical implants in antimicrobial solutions, and inserting antimicrobial-coated implants. Since bacterial colonization of the indwelling device is a prelude to infection, prevention of device colonization may lead to a lower rate of clinical infection. Different approaches for antimicrobial coating of devices have been variably successful in preventing device-associated infections. Optimal characteristics of antimicrobial coating can help predict the likelihood and degree of clinical protection against infection. This review addresses the impact of device-related infection, antimicrobial-utilizing approaches for preventing infection, clinical protection afforded by different types of antimicrobial coating, characteristics that predict the ability of antimicrobial coating of devices to prevent clinical infection, and future directions of antimicrobial coating. C1 Baylor Coll Med, Michael E Debakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Darouiche, R (reprint author), Baylor Coll Med, Ctr Prostheses Infect, 1333 Moursund Ave,Suite A221, Houston, TX 77030 USA. EM rdarouiche@aol.com NR 45 TC 22 Z9 22 U1 2 U2 16 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD SEP PY 2007 VL 30 IS 9 BP 820 EP 827 PG 8 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 228LK UT WOS:000250731200011 PM 17918128 ER PT J AU Duraisamy, S Kufe, T Ramasamy, S Kufe, D AF Duraisamy, Sekhar Kufe, Turner Ramasamy, Selvi Kufe, Donald TI Evolution of the human MUC1 oncoprotein SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE secreted mucins; membrane-bound mucins; MUC1; transformation; MUC5B; MUC2; MUC6 ID CARCINOMA-ASSOCIATED ANTIGEN; GEL-FORMING MUCINS; BETA-CATENIN; APOPTOTIC RESPONSE; GENE-TRANSCRIPTION; SURVIVAL RESPONSE; OXIDATIVE STRESS; SEA MODULE; C-SRC; PROTEIN AB The mucin (MUC) family consists of secreted and membrane-bound forms. The transmembrane mucin 1 (MUC1) is a heterodimer that is aberrantly overexpressed by diverse human carcinomas and certain hematologic malignancies. The MUC1 N-terminal (MUC1-N) and C-terminal (MUC1-C) subunits are generated by autocleavage within a SEA domain. The MUC1 cytoplasmic domain (MUC1-CD) located downstream of the SEA domain is sufficient for the induction of anchorage-independent growth and tumorigenicity; however, no information is available regarding the origin of these transforming sequences. Previous work demonstrated that, except for the SEA domain, MUC1 has no sequence homology with other membrane-bound mucins. The present results demonstrate that MUC1-CD evolved from repeat regions in the MUC5B secreted mucin. We also show that MUC1 sequences upstream to the SEA domain emerged from MUC5B. These findings indicate that both the MUC1-N and MUC1-C subunits evolved from secreted gel-forming mucins and that the MUC1-CD oncogenic function emerged by diversification after evolution from MUC5B. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA97098] NR 49 TC 17 Z9 17 U1 0 U2 3 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 2007 VL 31 IS 3 BP 671 EP 677 PG 7 WC Oncology SC Oncology GA 199KX UT WOS:000248695800025 PM 17671696 ER PT J AU Roach, M De Silvio, M Rebbick, T Grignon, D Rotman, M Wolkov, H Fisher, B Hanks, G Shipley, WU Pollack, A Sandler, H Watkins-Bruner, D AF Roach, Mack, III De Silvio, Michelle Rebbick, Timothy Grignon, David Rotman, Marvin Wolkov, Harvey Fisher, Barbara Hanks, Gerald Shipley, William U. Pollack, Alan Sandler, Howard Watkins-Bruner, Deborah TI Racial differences in cyp3a4 genotype and survival among men treated on radiation therapy oncology group (rtog) 9202: A phase III randomized trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; radiotherapy; race; genetic polymorphisms ID PROSTATE-CANCER; GENETIC VARIANT; CLINICAL PRESENTATION; ASSOCIATION; RISK; POLYMORPHISMS; RADIOTHERAPY; HAPLOTYPES; LONG AB Purpose: Inherited genotypes may explain the inferior outcomes of African American (AA) men with prostate cancer. To understand how variation in CYP3A4 correlated with outcomes, a retrospective examination of the CYP3A4*1B genotype was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02. Methods and Materials: From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54 (4.3%) of 1,274 European American (EA) -patients. All patients received goserelin and flutamide for 2 months before and during RT (STAD-RT) +/- 24 months of goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events studied included overall survival and biochemical progression using American Society for Therapeutic Radiology and Oncology consensus guidelines. Results: There were no differences in outcome in patients in with or without CYP3A4 data. There was an association between race and CYP3A4 polymorphisms with 75% of EAs having the Wild Type compared to only 25% of AA men (p <0.0001). There was no association between CYP3A4 classification or race and survival or progression. Conclusions: The samples analyzed support previously reported observations about the distribution of CYP3A4*1B genotype by race, but race was not associated with poorer outcome. However, patient numbers were limited, and selection bias cannot be completely ruled out. (c) 2007 Elsevier Inc. C1 Univ Calif San Francisco, Ctr Comprehens Canc, Dept Radiat Oncol, San Francisco, CA 94143 USA. RTOG Statist Headquaters, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Wayne State Univ, Detroit, MI USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Radiol Associates Sacramento, Sacramento, CA USA. Univ Western Ontario, London, ON, Canada. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Roach, M (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, Dept Radiat Oncol, 1600 Divisadero St,Suite H 1031, San Francisco, CA 94143 USA. EM mroach@radonc.ucsf.edu FU NCI NIH HHS [U10 CA37422, P50-CA105641, U10 CA 32115, U10 CA21661] NR 19 TC 10 Z9 10 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 SEP 1 PY 2007 VL 69 IS 1 BP 79 EP 87 DI 10.1016/j.ijrobp.2007.03.008 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 203MI UT WOS:000248978300012 PM 17498886 ER PT J AU Berbeco, RI Hacker, F Ionascu, D Mamon, HJ AF Berbeco, Ross I. Hacker, Fred Ionascu, Dan Mamon, Harvey J. TI Clinical feasibility of using an epid in cine mode for image-guided verification of stereotactic body radiotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE SBRT; respiratory motion; organ motion; EPID ID RADIATION-THERAPY; LIVER METASTASES; TUMOR MOTION; REAL-TIME; TRACKING; RADIOSURGERY; LUNG AB Purpose: To introduce a novel method for monitoring tumor location during stereotactic body radiotherapy (SBRT) while the treatment beam is on by using a conventional electronic portal imaging device (EPID). Methods and Materials: In our clinic, selected patients were treated under a phase I institutional review boardapproved SBRT proto, I for limited hepatic metastases from solid tumors. Before treatment planning multiple gold fiducial markers were implanted on the periphery of the tumor. During treatment the EPID was used in cine mode to collect the exit radiation and produce a sequence of images for each field. An in-house program was developed for calculating the location of the fiducials and their relative distance to the planned locations. Results: Three case studies illustrate the utility of the technique. Patient A exhibited a systematic shift of 4 mm during one of the treatment beams. Patient B showed an inferior drift of the target of approximately 1 cm from the time of setup to the end of the fraction. Patient C had a poor setup on the first day of treatment that was quantified and accounted for on subsequent treatment days. Conclusions: Target localization throughout each treatment beam can be quickly assessed with the presented technique. Treatment monitoring with an EPID in cine mode is shown to be a clinically feasible and useful tool. (c) 2007 Elsevier Inc. C1 Brigham & Womens Hosp, Ctr Canc, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Berbeco, RI (reprint author), Brigham & Womens Hosp, Ctr Canc, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. EM rberbeco@lroc.harvard.edu OI Hacker, Fred/0000-0001-7535-7598 NR 19 TC 42 Z9 42 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2007 VL 69 IS 1 BP 258 EP 266 DI 10.1016/j.ijrobp.2007.04.051 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 203MI UT WOS:000248978300034 PM 17707280 ER PT J AU Mori, S Chen, GTY Endo, M AF Mori, Shinichiro Chen, George T. Y. Endo, Masahiro TI Effects of intrafractional motion on water equivalent pathlength in respiratory-gated heavy charged particle beam radiotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE computed tomography; charged particle radiotherapy; cardiac motion; respiratory motion; water equivalent length (WEL) ID CORRELATED IMAGE-RECONSTRUCTION; ROW COMPUTED-TOMOGRAPHY; 256-SLICE CT-SCANNER; PERFORMANCE EVALUATION; INITIAL-EXPERIENCE; HEART; ALGORITHM; CANCER; MODEL AB Purpose: To analyze the water equivalent pathlength (WEL) fluctuations resulting from cardiac motion and display these variations on a beam's-eye-view image; the analysis provides insight into the accuracy of lung tumor irradiation with heavy charged particle beams. Materials and Methods: Volumetric cine computed tomography (CT) images were obtained on 7 lung cancer patients under free-breathing conditions with a 256-multislice CT scanner. Cardiac phase was determined by selecting systole and diastole. A WEL difference image (A WEL) was calculated by subtracting the WEL image at end-systole from that at end-diastole at respiratory exhalation phase. Two calculation regions were defined: Region I was limited to the volume defined by planes bounding the heart; Region 2 included the entire body thickness for a given beam's-eye-view angle. Results: The A WEL values observed in Region 1 showed fluctuations at the periphery of the heart that varied from 20.4 (SD), 5.2) mm WEL to -15.6 (3.2) turn WEL. The areas over which these range perturbation values were observed were 36.8 (32.4) mm(2) and 6.0 (2.8) mm(2) for positive and negative WEL, respectively. The WEL fluctuations in Region 2 increased by approximately 3-4 mm WEL, whereas negative WEL fluctuations changed by approximately -4 to -5 mm WEL, compared with WEL for Region 1; areas over 20 mm WEL changes in Region 2 increased by 9 mm 2 for positive triangle WEL and 2 mm(2) for negative triangle WEL. Conclusions: Cine CT with a 256-multislice CT scanner captures both volumetric cardiac and respiratory motion with a-temporal resolution sufficient to estimate range fluctuations by these motions. This information can be used to assess the range perturbations that charged particle beams may experience in irradiation of lung or esophageal tumors adjacent to the heart. (c) 2007 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Natl Inst Radiol Sci, Dept Planning & Management, Chiba 260, Japan. RP Mori, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 317, Boston, MA 02114 USA. EM shinshin@nirs.go.jp OI Mori, Shinichiro/0000-0002-0412-4399 FU NCI NIH HHS [P01 CA19138] NR 34 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2007 VL 69 IS 1 BP 308 EP 317 DI 10.1016/j.ijrobp.2007.05.018 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 203MI UT WOS:000248978300040 PM 17707286 ER PT J AU Shoeb, M Weinstein, H Mollica, R AF Shoeb, Marwa Weinstein, Harvey Mollica, Richard TI The Harvard trauma questionnaire: Adapting a cross-cultural instrument for measuring torture, trauma and posttraumatic stress disorder in Iraqi refugees SO INTERNATIONAL JOURNAL OF SOCIAL PSYCHIATRY LA English DT Article DE posttraumatic stress disorder (PTSD); Harvard trauma questionnaire (HTQ); mental helath assessment; Iraq; refugees ID DECONSTRUCTING CRITIQUES; ASYLUM SEEKERS; DSM-IV; DEPRESSION; PTSD; INTERNATIONALIZATION; RECONCILIATION; CLASSIFICATION; PSYCHIATRY; INTERVIEW AB Background: Mental health assessments in post-conflict zones have relied heavily on Western psychiatric scales. Yet, a strict dependence on the paradigms of Western psychiatry risks inappropriately prioritizing syndromes, such as PTSD, which, however important, are eclipsed by local concerns. Material and discussion: In Dearborn, Michigan, home to the largest population of Iraqi refugees in the United States, 60 Iraqi refugee life stories were collected in order to adapt the Harvard Trauma Questionnaire (HTQ) to the Iraqi context. Conclusion: The methodology described proved to be a useful approach to developing a trauma measure that is culturally grounded in a multi-dimensional model of mental health. C1 Univ Calif San Francisco, San Francisco Sch Med, San Francisco, CA 94143 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Massachusetts Gen Hosp, Dept Psychiat, Harvard Program Refugee Trauma, Cambridge, MA 02139 USA. RP Shoeb, M (reprint author), Univ Calif San Francisco, San Francisco Sch Med, San Francisco, CA 94143 USA. EM marwa.shoeb@ucsf.edu NR 52 TC 55 Z9 55 U1 2 U2 16 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0020-7640 J9 INT J SOC PSYCHIATR JI Int. J. Soc. Psychiatr. PD SEP PY 2007 VL 53 IS 5 BP 447 EP 463 DI 10.1177/0020764007078362 PG 17 WC Psychiatry SC Psychiatry GA 231OV UT WOS:000250959800007 PM 18018666 ER PT J AU Sanda, T AF Sanda, Takaomi TI Transcription factors as therapeutic targets in lymphoid malignancies SO INTERNATIONAL REVIEWS OF IMMUNOLOGY LA English DT Review DE factor-kappa B; hisotone deacetylace; NOTCH1; retinoid; transcription factor ID NF-KAPPA-B; ACUTE LYMPHOBLASTIC-LEUKEMIA; HISTONE DEACETYLASE INHIBITOR; TRANS-RETINOIC ACID; T-CELL LYMPHOMA; SUBEROYLANILIDE HYDROXAMIC ACID; MULTIPLE-MYELOMA CELLS; TUMOR-NECROSIS-FACTOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; GENE-EXPRESSION SIGNATURES AB Abet-rant activation of transcription factors is frequently observed in lymphoid malignancies. Chromosomal abnormalities, genetic mutations, and/or activation of upstream molecules induce ectopic activation of transcription factors, which can remodel intracellular states by deregulating gene expression. A number of studies have shown that aberrant activity of transcription factors plays a crucial role in oncogenesis. Recent reports on specific inhibitors suggest that transcription factors could be feasible therapeutic targets. In this review, I describe the implications of transcription factors in oncogenesis as well as novel therapeutic approaches based on our previous findings including nuclear factor-kappa B inhibitor, synthetic retinoid, and histone deacetylase inhibitor. C1 [Sanda, Takaomi] Nagoya City Univ, Grad Sch Med Sci, Dept Internal Med & Mol Sci, Nagoya, Aichi 4678601, Japan. [Sanda, Takaomi] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. RP Sanda, T (reprint author), Nagoya City Univ, Grad Sch Med Sci, Dept Internal Med & Mol Sci, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 4678601, Japan. EM tsanda@med.nagoya-cu.ac.jp NR 181 TC 2 Z9 2 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0883-0185 J9 INT REV IMMUNOL JI Int. Rev. Immunol. PD SEP-DEC PY 2007 VL 26 IS 5-6 BP 305 EP 332 DI 10.1080/08830180701655945 PG 28 WC Immunology SC Immunology GA 240AM UT WOS:000251559400004 PM 18027203 ER PT J AU Connolly, TJ Litman, HJ Tennstedt, SL Link, CL McKinlay, JB AF Connolly, Thomas J. Litman, Heather J. Tennstedt, Sharon L. Link, Carol L. McKinlay, John B. TI The effect of mode of delivery, parity, and birth weight on risk of urinary incontinence SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE urinary incontinence; reproductive risk factors ID PELVIC FLOOR DISORDERS; MIDDLE-AGED WOMEN; VAGINAL DELIVERY; CESAREAN-SECTION; NORWEGIAN EPINCONT; MEDICAL RECORDS; PREVALENCE; PREGNANCY; CHILDBIRTH; HISTORY AB To examine the relationship between symptoms of urinary incontinence (UI) and mode of delivery, parity, and birth weight, data were obtained from a population-based random sample of 3,205 black, Hispanic, and white women age 30-79 in the Boston Area Community Health Survey. Measures include UI symptoms [>= 3 (moderate/severe) Sandvik's severity index]; reproductive history [live birth(s), no live births, never pregnant]; mode of delivery for live births (>= 1 vaginal birth, cesarean delivery only); parity (1, 2, >= 3); and maximum birth weight of live births (< 4,000 g, >= 4,000 g). Using logistic regression, women having >= 1 vaginal delivery had twice the odds of UI compared to women with no pregnancies (P=0.002) or only cesarean deliveries (P=0.032). There was no difference in odds of UI between cesarean delivery only and never pregnant, by parity or birth weight. Vaginal delivery contributes to risk of UI for black, Hispanic, and white women. C1 New England Res Inst, Watertown, MA 02472 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Litman, HJ (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM hlitman@neriscience.com FU NIDDK NIH HHS [DK 56842] NR 55 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD SEP PY 2007 VL 18 IS 9 BP 1033 EP 1042 DI 10.1007/s00192-006-0286-4 PG 10 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 195LL UT WOS:000248413600010 PM 17219253 ER PT J AU Pryor, J D'Arceuil, H Phil, M Liu, J He, J Gonzalez, RG Duggan, M De Crespigny, A AF Pryor, J. D'Arceuil, H. Phil, M. Liu, J. He, J. Gonzalez, R. G. Duggan, M. De Crespigny, A. TI Superselective intracerebral catheterization of a branch of the internal carotid artery coupled with magnetic resonance Imaging SO INTERVENTIONAL NEURORADIOLOGY LA English DT Article DE MRI; stroke; cerebral perfusion; intravascular devices ID ACUTE ISCHEMIC-STROKE; SYSTEM; EXPERIENCE; OCCLUSION; RETEPLASE; CT AB We used fluoroscopic guidance and over-the-wire techniques to superselectively place a microcatheter into a branch of the MCA of three macaques and MRI bolus tracking techniques to measure perfusion within the selected brain region. Such techniques are likely to be useful in the assessment and treatment of ischemic infarction, cerebral vasospasm, and monitoring local delivery of drugs into the brain. C1 Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr, NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurosurg, Endovasc Neuroradiol Sect, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Comparat Med, Charlestown, MA USA. RP De Crespigny, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr, NMR Ctr, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM alexdec@nmr.mgh.harvard.edu FU NINDS NIH HHS [R01 NS041285] NR 18 TC 1 Z9 1 U1 0 U2 1 PU EDIZIONI CENTAURO PI BOLOGNA PA VIA DEL PRATELLO, 8, 40122 BOLOGNA, ITALY SN 1123-9344 J9 INTERV NEURORADIOL JI Interv. Neuroradiol. PD SEP PY 2007 VL 13 IS 3 BP 277 EP 280 PG 4 WC Clinical Neurology; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 237MD UT WOS:000251377200007 PM 20566119 ER PT J AU Khani, SC Pawlyk, BS Bulgakov, OV Kasperek, E Young, JE Adamian, M Sun, X Smith, AJ Ali, RR Li, T AF Khani, Shahrokh C. Pawlyk, Basil S. Bulgakov, Oleg V. Kasperek, Eileen Young, Joyce E. Adamian, Michael Sun, Xun Smith, Alexander J. Ali, Robin R. Li, Tiansen TI AAV-Mediated expression targeting of rod and cone photoreceptors with a human rhodopsin kinase promoter SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; REPORTER GENE-EXPRESSION; RETINOID-BINDING PROTEIN; TRANSGENIC MICE; RETINITIS-PIGMENTOSA; RIBOZYME RESCUE; MOUSE RETINA; RAT MODEL; THERAPY; DEGENERATION AB PURPOSE. Gene therapy for retinal degeneration requires well-defined promoters that drive expression in rod and cone photoreceptors. This study was undertaken to develop short, active derivatives of the human rhodopsin kinase (RK) gene promoter for targeting transgene expression in rods and cones. RK, also known as G protein-coupled receptor kinase 1 (GRK1), is a component of the light adaptation pathway expressed in rods and cones. METHODS. Human RK (hRK) promoter and its concatemers or derivatives extending into the conserved 5' untranslated region (5'-UTR) were assayed for promoter activity in WERI retinoblastoma or Crx/Sp1-supplemented HEK-293 cells. The derivative displaying the highest activity was linked to a GFP reporter and packaged in a pseudotyped adenoassociated viral vector (AAV2/5). The AAV vector was tested in vivo by sub-retinal injections in wild-type mice, in the all-cone Nrl(-/-) mice, and in the cone-rich diurnal Nile grass rat (Arvicanthis niloticus). Control eyes received a similar AAV2/5 vector carrying a mouse rod opsin (mOps) promoter-controlled GFP reporter. RESULTS. The hRK promoter with the full 5' untranslated sequence (-112 to +180) was the most active in cell culture. Delivered by the AAV2/5 vector, RK promoter drove GFP expression specifically in photoreceptors. In rods, hRK promoter-mediated expression was as efficient as, but appeared more uniform than, mOps promoter-mediated expression. In cones, the hRK promoter drove expression, whereas the mOps promoter did not. CONCLUSIONS. The hRK promoter is active and specific for rod and cone photoreceptors. Because of its small size and proven activity in cones, it is a promoter of choice for somatic gene transfer and gene therapy targeting rods and cones. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Berman Gund Lab Study Retinal Deg, Boston, MA 02114 USA. SUNY Buffalo, Dept Ophthalmol, Buffalo, NY 14260 USA. SUNY Buffalo, Dept Biochem, Buffalo, NY 14260 USA. SUNY Buffalo, Ross Eye Inst, Buffalo, NY 14260 USA. UCL, Inst Ophthalmol, Div Mol Therapy, London, England. RP Khani, SC (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Berman Gund Lab Study Retinal Deg, 243 Charles St, Boston, MA 02114 USA. EM skhani@buffalo.edu RI Smith, Alexander/A-5142-2009 FU NEI NIH HHS [EY13600, EY10581] NR 43 TC 56 Z9 58 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2007 VL 48 IS 9 BP 3954 EP 3961 DI 10.1167/iovs.07-0257 PG 8 WC Ophthalmology SC Ophthalmology GA 204RO UT WOS:000249061900007 PM 17724172 ER PT J AU Huang, W Fileta, JB Filippopoulos, T Ray, A Dobberfuhl, A Grosskreutz, CL AF Huang, Wei Fileta, John B. Filippopoulos, Theodoros Ray, Arjun Dobberfuhl, Adam Grosskreutz, Cynthia L. TI Hsp27 phosphorylation in experimental glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HEAT-SHOCK PROTEINS; FIBRILLARY ACIDIC PROTEIN; OPTIC-NERVE HEAD; CELL-DEATH; UP-REGULATION; MULLER CELLS; RAT RETINA; INTRAOCULAR-PRESSURE; MEDIATED APOPTOSIS; OXIDATIVE STRESS AB PURPOSE. The role of heat shock proteins (Hsp) in injury response has been well established, but it is now becoming apparent that the phosphorylation state of Hsp27 may be a critical determinant of its ability to act in a protective capacity. In this study, the expression of Hsp27 and its phosphorylation were evaluated in an experimental glaucoma model in Brown Norway rats and in a spontaneous model of glaucoma in the DBA/2J mouse. METHODS. The intraocular pressure (IOP) of one eye was elevated by injecting 1.9 M saline into the episcleral vein, as previously described in Brown Norway rats. IOP was measured in awake Brown Norway rats before surgery and every other day after saline injection. After 10 days of elevated IOP, the retinas were either removed for Western blot analysis or fixed for immunohistochemistry (IHC). IOP measurement in 7-month-old female DBA/2J mice was performed by direct cannulation. Retinas of eyes with and without elevated IOP were collected for Western blot analysis. RESULTS. Western blot results showed a significant increase in total Hsp27 (3.9-fold; P < 0.05; n = 8) and phosphorylated Hsp27 ( pHsp27) (2.1-fold; P < 0.05; n = 6) in high IOP eyes in the experimental rat glaucoma model, and similar increases were observed in DBA/2J mice with elevated IOP (3.1-fold and 2.2-fold for Hsp27 and pHsp27, respectively; P < 0.05; n = 5). In rats, increased Hsp27 and pHsp27 immunoreactivity were observed in the nerve fiber layer of elevated IOP eyes and colocalized with glial fibrillary acidic protein (GFAP) and with vimentin staining, suggesting that glial cells contribute to the increase in Hsp27 and pHsp27 seen in experimental glaucoma. No change in Hsp70 or Hsp90 was observed. CONCLUSIONS. These results confirm previous reports of elevated Hsp27 in experimental glaucoma and extend them to the DBA/2J mouse. In addition, a significant increase occurred in Hsp27 phosphorylation with elevated IOP in both models of glaucoma. IHC studies show that the increases in Hsp27 and pHsp27 occur primarily in glial cells. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Howe Lab Ophthalmol, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Howe Lab Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu NR 58 TC 28 Z9 34 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2007 VL 48 IS 9 BP 4129 EP 4135 DI 10.1167/iovs.06-0606 PG 7 WC Ophthalmology SC Ophthalmology GA 204RO UT WOS:000249061900032 PM 17724197 ER PT J AU Tyer-Viola, LA AF Tyer-Viola, Lynda A. TI Obstetric nurses' attitudes and nursing care intentions regarding care of HIV-positive pregnant women SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE attitudes; care; intentions; HIV; pregnancy; prejudice; theory of reasoned action; vignettes ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INFECTED WOMEN; AIDS; PEOPLE; KNOWLEDGE; HIV/AIDS; PATIENT; SCALE AB Objective: To define attitudes toward pregnant women with HIV and how these attitudes correlate with and affect prejudice and nursing care intentions. Design: Cross-sectionaldescriptivecorrelational study of obstetric nurses. Setting: Eight hundred (800) mailed surveys in the United States (N = 350). Participants: A random sample of nurses certified in inpatient obstetrics. Main Outcome Measures: Background information tool, the Pregnant Women with HIV Attitude Scale, the Prejudice Interaction Scale in response to four vignettes, and the Marlowe-Crowne Social Desirability Scale-Form C. Results: Obstetric nurses had more positive Mothering-Choice attitudes than Sympathy-Rights attitudes (p=.000). Nurses who knew more than four people affected by HIV/AIDS had more positive attitudes (p <= .05). Nurses with more positive attitudes were less prejudiced and more willing to care for pregnant women with HIV (p = .05). Nurses were significantly more prejudiced and less willing to care for women with than without HIV (p <= .0001). Conclusions: Nurses' clinical care may be influenced by their attitudes and prejudice toward pregnant women with HIV. Nursing education should include how prejudice can affect our clinical decision making and behaviors. Research is needed to explicate the effects on patient outcomes. C1 Massachusetts Gen Hosp, Dept Patient Care Serv, Boston, MA 02114 USA. RP Tyer-Viola, LA (reprint author), Massachusetts Gen Hosp, Dept Patient Care Serv, 55 Fruit St,Blake 1473, Boston, MA 02114 USA. EM ltyerviola@partners.org NR 35 TC 14 Z9 14 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD SEP-OCT PY 2007 VL 36 IS 5 BP 398 EP 409 DI 10.1111/J.1552-6909.2007.00172.x PG 12 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 220ZZ UT WOS:000250197400002 PM 17880310 ER PT J AU Tebes, JK Feinn, R Vanderploeg, JJ Chinman, MJ Shepard, J Brabham, T Genovese, M Connell, C AF Tebes, Jacob Kraemer Feinn, Richard Vanderploeg, Jeffrey J. Chinman, Matthew J. Shepard, Jane Brabham, Tamika Genovese, Maegan Connell, Christian TI Impact of a positive youth development program in urban after-school settings on the prevention of adolescent substance use SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE youth development; after school; urban; substance use; resilience; propensity scores; HLM ID RISK; COMPETENCE; ADJUSTMENT; PATTERNS; CHILDREN; STUDENTS; ABUSE; CARE AB Purpose: Positive youth development (PYD) emphasizes a strengths-based approach to the promotion of positive outcomes for adolescents. After-school programs provide a unique opportunity to implement PYD approaches and to address adolescent risk factors for negative outcomes, such as unsupervised out-of-school time. This study examines the effectiveness of an after-school program delivered in urban settings on the prevention of adolescent substance use. Methods: A total of 304 adolescents participated in the study: 149 in the intervention group and 155 in a control group. A comprehensive PYD intervention that included delivery of an 18-session curriculum previously found to be effective in preventing substance use in school settings was adapted for use in urban after-school settings. The intervention emphasizes adolescents' use of effective decision-making skills to prevent drug use. Assessments of substance use attitudes and behaviors were conducted at program entry, program completion, and at the 1-year follow-up to program entry. Propensity scores were computed and entered in the analyses to control for any pretest differences between intervention and control groups. Hierarchical linear modeling (HLM) analyses were conducted to assess program effectiveness. Results: The results demonstrate that adolescents receiving the intervention were significantly more likely to view drugs as harmful at program exit, and exhibited significantly lower increases in alcohol, marijuana, other drug use, and any drug use I year after beginning the program. Conclusions: A PYD intervention developed for use in an urban after-school setting is effective in preventing adolescent substance use. (c) 2007 Society for Adolescent Medicine. All rights reserved. C1 Yale Univ, Div Prevent & Community Res, New Haven, CT 06511 USA. Yale Univ, Consultat Ctr, New Haven, CT 06511 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RAND Corp, Santa Monica, CA USA. W Losangeles VA Healthcare Ctr, Santa Monica, CA USA. RP Tebes, JK (reprint author), Yale Univ, Div Prevent & Community Res, 389 Whitey Ave, New Haven, CT 06511 USA. EM jacob.tebes@yale.edu FU CSAP SAMHSA HHS [KD1 SP09280] NR 40 TC 44 Z9 44 U1 2 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2007 VL 41 IS 3 BP 239 EP 247 DI 10.1016/j.jadohealth.2007.02.016 PG 9 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 204OS UT WOS:000249054500005 PM 17707293 ER PT J AU Chang, BH Boehmer, U Zhao, Y Sommers, E AF Chang, Bei-Hung Boehmer, Ulrike Zhao, Yue Sommers, Elizabeth TI Relaxation response with acupuncture trial in patients with HIV: Feasibility and participant experiences SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID THERAPIES AB Objectives: The study of complementary and alternative medicine ( CAM) using a randomized, controlled trial ( RCT) design poses challenges, such as treatment standardization and blinding. We designed an RCT, which avoided these two common challenges, to evaluate the effect of adding the relaxation response (RR) to usual acupuncture treatment. In this paper, we report on the feasibility and patients' experience from the study participation. Design, setting, and subjects: Our study was a two-arm, double-blind RCT conducted in an acupuncture clinic in Boston. Study subjects were patients with human immunodeficiency virus/autoimmunodeficiency syndrome (HIV/AIDS), who reported having at least one of the highly prevalent HIV-related symptoms, and were receiving acupuncture treatment. Intervention: The intervention group wore earphones to listen to tapes with instructions to elicit the RR and also soft music while receiving acupuncture treatment, while the control group only listened to soft music. The intervention group was also required to listen to the RR tapes at home daily. Outcome measures: A study evaluation was completed upon termination of the 12-week study ( 36 intervention and 44 control patients). Results: A majority of participants in both groups reported: no discomfort wearing earphones (82.9%, 81.8%); the study met their expectations ( 87.1%, 85.4%); and they would recommend the study to others ( 91.1%, 90.5%). Intervention participants reported better experiences with the tapes than the control group ( p = 0.056) ( 72.4% versus 52.8% felt better with tapes; 3.5% versus 16.7% felt better without tapes; and 24.1% versus 30.6% felt no difference). Intervention participants were also more likely than the control group ( p = 0.02) to report positive emotional/ physical/ spiritual changes ( 45.5% vs. 20.9%) and relaxed/ peaceful/ calm feelings ( 30.3% vs. 25.6%) from the study participation. Conclusions: We demonstrated the feasibility of conducting a unique trial that examined the synergistic effects of two types of CAM practices. The intervention group reported more positive study-related experiences than the control group. C1 Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. VA Boston Hlth Care Syst, Boston, MA USA. Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Pathways Wellness AIDS Care Project, Boston, MA USA. RP Chang, BH (reprint author), Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. EM bhchang@bu.edu OI Boehmer, Ulrike/0000-0003-0097-5927 FU NCCIH NIH HHS [R21 AT001276-02, R21 AT001276] NR 15 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD SEP PY 2007 VL 13 IS 7 BP 719 EP 724 DI 10.1089/acm.2007.7025 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 220XT UT WOS:000250191300008 PM 17931064 ER PT J AU Page, ST Kalhorn, TF Bremner, WJ Anawalt, BD Matsumoto, AM Amory, JK AF Page, Stephanie T. Kalhorn, Thomas F. Bremner, William J. Anawalt, Bradley D. Matsumoto, Alvin M. Amory, John K. TI Intratesticular androgens and spermatogenesis during severe gonadotropin suppression induced by male hormonal contraceptive treatment SO JOURNAL OF ANDROLOGY LA English DT Article DE testosterone; dihydrotestosterone; INSL3; LH; FSH ID INSULIN-LIKE FACTOR-3; EXOGENOUSLY ADMINISTERED TESTOSTERONE; DEFICIENT HPG MICE; NORMAL MEN; LUTEINIZING-HORMONE; CIRCULATING HORMONE; INDUCED AZOOSPERMIA; HUMAN TESTIS; SERUM-LEVELS; MAINTENANCE AB Male hormonal contraceptive regimens function by suppressing gonadotropin secretion, resulting in a dramatic decrease in testicular androgen biosynthesis and spermatogenesis. Animal studies suggest that persistent intratesticular (iT)-androgen production has a stimulatory effect on spermatogenesis in the setting of gonadotropin suppression. We hypothesized that men with incompletely suppressed spermatogenesis (> 1 000 000 sperm/mL) during male hormonal contraceptive treatment would have higher iT-androgen concentrations than men who achieved severe oligospermia (: l 000 000 sperm/mL). Twenty healthy men ages 18-55 years enrolled in a 6-month male contraceptive study of transdermal testosterone (T) gel (100 mg/d) plus depomedroxyprogesterone acetate (300 mg intramuscularly every 12 weeks) with or without the gonaclotropin releasing hormone (GnRH) antagonist acyline (300 mu g/kg subcutaneously every 2 weeks for 12 weeks) were studied. During the 24th week of treatment, subjects underwent fine needle aspirations of the testes and iT-T and iT-dihydrotestosterone (iT-DHT) were measured in testicular fluid by liquid chromatography-tandem mass spectrometry. All men dramatically suppressed spermatogenesis; 15 of 20 men were severely oligospermic, and 5 of 20 suppressed to 1.5 million-3.2 million sperm per milliliter. In all subjects, mean iT-T and iT-DHT concentrations were 35 +/- 8 and 5.1 +/- 0.8 nmol/L. IT-androgen concentrations did not significantly differ in men who did and did not achieve severe oligospermia (P = .41 for iT-T; P = .18 for iT-DHT). Furthermore, there was no significant correlation between iT-T or iT-DHT and sperm concentration after 24 weeks of treatment. In this study of prolonged gonadotropin suppression induced by male hormonal contraceptive treatment, differences in iT-androgens did not explain differences in spermatogenesis. Additional studies to identify factors involved in persistent spermatogenesis despite gonaclotropin suppression are warranted. C1 Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Page, ST (reprint author), Box 357138,1959 NE Pacific, Seattle, WA 98195 USA. EM page@u.washington.edu FU NIA NIH HHS [K23 AG027238-04, K23 AG027238]; NICHD NIH HHS [K23 HD45386, U54 HD-42454, U54-HD-12629] NR 40 TC 22 Z9 23 U1 0 U2 1 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD SEP-OCT PY 2007 VL 28 IS 5 BP 734 EP 741 DI 10.2164/jandrol.107.002790 PG 8 WC Andrology SC Endocrinology & Metabolism GA 207BG UT WOS:000249226000016 PM 17494097 ER PT J AU Kellogg, DL Hodges, GJ Orozco, CR Phillips, TM Zhao, JL Johnson, JM AF Kellogg, D. L., Jr. Hodges, G. J. Orozco, C. R. Phillips, T. M. Zhao, J. L. Johnson, J. M. TI Cholinergic mechanisms of cutaneous active vasodilation during heat stress in cystic fibrosis SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; SKIN BLOOD-FLOW; GENE-RELATED PEPTIDE; HUMAN SWEAT GLANDS; NITRIC-OXIDE; HUMAN FOREARM; VASCULAR-RESPONSES; SUBSTANCE-P; HUMANS; NERVES AB To test the hypothesis that cutaneous active vasodilation in heat stress is mediated by a redundant cholinergic cotransmitter system, we examined the effects of atropine on skin blood flow (SkBF) increases during heat stress in persons with (CF) and without cystic fibrosis (non-CF). Vasoactive intestinal peptide (VIP) has been implicated as a mediator of cutaneous vasodilation in heat stress. VIP-containing cutaneous neurons are sparse in CF, yet SkBF increases during heat stress are normal. In CF, augmented ACh release or muscarinic receptor sensitivity could compensate for decreased VIP; if so, active vasodilation would be attenuated by atropine in CF relative to non-CF. Atropine was administered into skin by iontophoresis in seven CF and seven matched non-CF subjects. SkBF was monitored by laser-Doppler flowmetry (LDF) at atropine treated and untreated sites. Blood pressure [mean arterial pressure (MAP)] was monitored (Finapres), and cutaneous vascular conductance was calculated (CVC = LDF/MAP). The protocol began with a normothermic period followed by a 3-min cold stress and 30 -45 min of heat stress. Finally, LDF sites were warmed to 42 C to effect maximal vasodilation. CVC was normalized to its site-specific maximum. During heat stress, CVC increased in both CF and non-CF (P < 0.01). CVC increases were attenuated by atropine in both groups (P < 0.01); however, the responses did not differ between groups (P = 0.99). We conclude that in CF there is not greater dependence on redundant cholinergic mechanisms for cutaneous active vasodilation than in non-CF. C1 Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, Dept Med, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Christ Santa Rosa Hosp, Adult Cyst Fibrosis Clin, San Antonio, TX USA. RP Kellogg, DL (reprint author), Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kelloggd@uthscsa.edu FU NHLBI NIH HHS [HL-065599, HL-059166] NR 47 TC 6 Z9 6 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2007 VL 103 IS 3 BP 963 EP 968 DI 10.1152/japplphysiol.00278.2007 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 204OU UT WOS:000249054700032 PM 17600158 ER PT J AU Parvataneni, HK Shah, VP Howard, H Cole, N Ranawat, AS Ranawat, CS AF Parvataneni, Hari K. Shah, Vineet P. Howard, Holly Cole, Naida Ranawat, Amar S. Ranawat, Chitranjan S. TI Controlling pain after total hip and knee arthroplasty using a Multimodal protocol with local periarticular injections - A prospective randomized study SO JOURNAL OF ARTHROPLASTY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Association-of-Hip-and-Knee-Surgeons CY NOV, 2006 CL Dallas, TX SP Amer Assoc Hip & Knee Surg DE total knee arthroplasty; total hip arthroplasty; periarticular injection; pain; functional recovery ID POSTOPERATIVE ANALGESIA; AMBULATORY SURGERY; CONTROLLED-TRIAL; INCISION; COMPLICATIONS; BUPIVACAINE; COMBINATION; CLONIDINE; MORPHINE AB In this prospective randomized study, patients undergoing total hip (THA) or knee arthroplasty (TKA) were randomized to either a study group receiving periarticular injections or a control group receiving patient-controlled analgesia with or without femoral nerve block (TKA patients). All patients received a comprehensive multimodal perioperative protocol. Pain, recovery of functional milestones, and overall satisfaction were assessed. The THA study group demonstrated significantly lower average pain scores and higher overall satisfaction than the control group. There was no significant difference in pain scores between the study and control groups in the TKA cohort. Both study groups demonstrated lower narcotic usage and side effects as well as improved early functional recovery. Periarticular injection with a multimodal protocol was shown to safely provide excellent pain control and functional recovery and an be substituted for conventional pain control modalities. C1 Lenox Hill Hosp, Ranawat Orthopaed Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Parvataneni, HK (reprint author), Lenox Hill Hosp, Ranawat Orthopaed Ctr, 100 E 77th St, New York, NY 10021 USA. RI teng, yj/C-4440-2011 NR 25 TC 108 Z9 124 U1 0 U2 8 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2007 VL 22 IS 6 SU 2 BP 33 EP 38 DI 10.1016/j.arth.2007.03.034 PG 6 WC Orthopedics SC Orthopedics GA 220ZV UT WOS:000250196900009 PM 17823012 ER PT J AU Bragdon, CR Greene, ME Freiberg, AA Harris, WH Malchau, H AF Bragdon, Charles R. Greene, Meridith E. Freiberg, Andrew A. Harris, William H. Malchau, Henrik TI Radiostereometric analysis comparison of wear of highly cross-linked polyethylene against 36-vs 28-mm femoral heads SO JOURNAL OF ARTHROPLASTY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Association-of-Hip-and-Knee-Surgeons CY NOV, 2006 CL Dallas, TX SP Amer Assoc Hip & Knee Surg DE RSA; total hip arthroplasty; wear; hip; outcomes; polyethylene ID TOTAL HIP-ARTHROPLASTY; MOLECULAR-WEIGHT POLYETHYLENE; RADIO STEREOMETRIC ANALYSIS; 3RD-BODY WEAR; IN-VITRO; REPLACEMENT; PENETRATION; LARGER; DISLOCATIONS; SIZES AB This study used radiostereometric analysis (RSA) to compare the femoral head penetration of 28- vs 36-mm-diameter femoral heads into highly cross-linked polyethylene in 2 groups of total hip arthroplasty patients. Thirty patients were enrolled in this RSA study using highly cross-linked polyethylene (Longevity, Zimmer Inc, Warsaw, Idaho) against either 28- or 36-mm-diameter cobalt chrome femoral heads. At 3-year follow-up, there was no significant difference in the total average femoral head penetration, including both creep and wear, using 3 methods of RSA measurement between the 2 groups. Importantly, after bedding-in, there was no further significant increase in the amount of femoral head penetration (ie, wear) with either head size between years 1 and 3. There were no radiographic signs of lysis or radiolucencies at a minimum 3-year follow-up. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Orthopaed Biomech & Biomat Lab, Boston, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Orthopaed Surg, Boston, MA USA. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Jackson 1126, Boston, MA 02114 USA. NR 23 TC 48 Z9 51 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2007 VL 22 IS 6 SU 2 BP 125 EP 129 DI 10.1016/i.arth.2007.03.009 PG 5 WC Orthopedics SC Orthopedics GA 220ZV UT WOS:000250196900027 PM 17823030 ER PT J AU Korpilahti, P Jansson-Verkasalo, E Mattila, ML Kuusikko, S Suominen, K Rytky, S Pauls, DL Moilanen, I AF Korpilahti, Pirjo Jansson-Verkasalo, Eira Mattila, Marja-Leena Kuusikko, Sanna Suominen, Kalervo Rytky, Seppo Pauls, David L. Moilanen, Irma TI Processing of affective speech prosody is impaired in Asperger syndrome SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Asperger syndrome; auditory perception; affective prosody; familial pattern; ERP ID HIGH-FUNCTIONING AUTISM; EVENT-RELATED POTENTIALS; MISMATCH NEGATIVITY; SPECTRUM DISORDERS; EVOKED-POTENTIALS; N1 WAVE; TOTAL POPULATION; MIND HYPOTHESIS; CHILDREN; INDIVIDUALS AB Many people with the diagnosis of Asperger syndrome (AS) show poorly developed skills in understanding emotional messages. The present study addressed discrimination of speech prosody in children with AS at neurophysiological level. Detection of affective prosody was investigated in one-word utterances as indexed by the N1 and the mismatch negativity (MMN) of auditory event-related potentials (ERPs). Data from fourteen boys with AS were compared with those for thirteen typically developed boys. These results suggest atypical neural responses to affective prosody in children with AS and their fathers, especially over the RH, and that this impairment can already be seen at low-level information processes. Our results provide evidence for familial patterns of abnormal auditory brain reactions to prosodic features of speech. C1 Univ Turku, Sch Finnish & Gen Linguist, Turku, Finland. Oulu Univ Hosp, Cognit Lab, Oulu, Finland. Univ Oulu, Dept Finnish Informat Studies & Logoped, Oulu, Finland. Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, Helsinki, Finland. Oulu Univ Hosp, Dept Child Psychiat, Oulu, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Unit,Psychiat & Neurodev Genet Un, Charlestown, MA USA. RP Korpilahti, P (reprint author), Univ Turku, Sch Finnish & Gen Linguist, Turku, Finland. EM pirjo.korpilahti@utu.fi NR 75 TC 49 Z9 51 U1 5 U2 16 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 SEP PY 2007 VL 37 IS 8 BP 1539 EP 1549 DI 10.1007/s10803-006-0271-2 PG 11 WC Psychology, Developmental SC Psychology GA 201GD UT WOS:000248818600012 PM 17086440 ER PT J AU Tomer, Y Menconi, F Davies, TF Barbesino, G Rocchi, R Pinchera, A Concepcion, E Greenberg, DA AF Tomer, Yaron Menconi, Francesca Davies, Terry F. Barbesino, Giuseppe Rocchi, Roberto Pinchera, Aldo Concepcion, Erlinda Greenberg, David A. TI Dissecting genetic heterogeneity in autoimmune thyroid diseases by subset analysis SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Graves' disease; Hashimoto's disease; thyroiditis; genes genetics; linkage; association ID X-CHROMOSOME INACTIVATION; LINKAGE ANALYSIS; GRAVES-DISEASE; HASHIMOTOS-THYROIDITIS; THYROGLOBULIN GENE; TURNERS-SYNDROME; FEMALE PREDISPOSITION; ITALIAN POPULATION; COMPUTER-PROGRAM; WHICKHAM SURVEY AB Abundant epidemiological data point to a strong genetic susceptibility to the development of autoimmune thyroid diseases (AITD), Graves' disease (GD) and Hashimoto's thyroiditis (HT). However, identifying the AITD susceptibility genes has been confounded by significant genetic heterogeneity that exists in AITD. The goals of the present study were to dissect the genetic heterogeneity in AITD in order to identify novel AITD genes. We studied a dataset of 102 multiplex Caucasian AITD families (540 individuals) and divided them into three subsets: (1) families with young age of onset (AO <= 30), (2) families with females-only affected, and (3) Italian families. These subsets were analyzed separately for linkage with AITD in a whole genome screen. Four subset-specific loci were mapped: analyzing the families with AO <= 30, we identified a locus on 10q (linked with AITD) and a locus on Xp containing the FOXP3 gene (linked with GD); analysis of markers flanking the FOXP3 gene demonstrated association of one of the FOXP3 markers with juvenile GD in females (p = 0.02); in the subset of families with females-only affected the thyroglobulin (T-g) gene locus was linked with AITD; and in the Italian subset, a novel locus on 3q was linked with GD. Finally, applying the predivided-sample test confirmed that all four loci were specific to the subsets. We conclude that distinct genes predispose to AITD in different subsets of patients. We have identified four subset-specific AITD loci, and two putative subset-specific AITD susceptibility genes; the FOXP3 gene in juvenile GD and the thyroglobulin gene in females with AITD. In view of the significant genetic heterogeneity observed in AITD, analyzing subsets is an efficient way to resolve heterogeneity and identify novel genes. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Cincinnati, Coll Med, Vontz Ctr, Div Endocrinol, Cincinnati, OH 45267 USA. Univ Cincinnati, Coll Med, Div Endocrinol, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Cincinnati VA Med Ctr, Cincinnati, OH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Pisa, Dept Endocrinol, Pisa, Italy. Columbia Univ, Div Stat Genet, New York, NY USA. Mt Sinai Sch Med, James J Peters VA Med Ctr, Div Endocrinol, New York, NY USA. RP Tomer, Y (reprint author), Univ Cincinnati, Coll Med, Vontz Ctr, Div Endocrinol, 3125 Eden Ave, Cincinnati, OH 45267 USA. EM yaron.tomer@uc.edu FU NIDDK NIH HHS [DK067555, DK052464, DK073681, DK31775, DK61659]; NIMH NIH HHS [MH48858]; NINDS NIH HHS [NS27941] NR 57 TC 34 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD SEP-NOV PY 2007 VL 29 IS 2-3 BP 69 EP 77 DI 10.1016/j.jaut.2007.05.006 PG 9 WC Immunology SC Immunology GA 215NS UT WOS:000249816900002 PM 17644307 ER PT J AU Sah, AP Scott, RD AF Sah, Alexander P. Scott, Richard D. TI Lateral unicompartmental knee arthroplasty through a medial approach - Study with an average five-year follow-up SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID UNICONDYLAR ARTHROPLASTY; POSTTRAUMATIC ARTHROSIS; CLINICAL-EXPERIENCE; REPLACEMENT; SURVIVORSHIP; GONARTHROSIS; ARTHRITIS; FRACTURE; MINIMUM; WEAR AB Background: Unicompartmental knee arthroplasty of the medial compartment has excellent long-term clinical outcomes. Arthritis isolated to the lateral compartment is much less common; subsequently, the clinical outcomes of the treatment of that condition are less frequently reported. Most commonly, the lateral compartment is approached through a lateral arthrotomy. The purpose of this study was to determine the mid-term results of lateral unicondylar replacement through a medial arthrotomy in patients with primary osteoarthritis or posttraumatic arthritis. Methods: From 1991 to 2004, forty-nine lateral unicompartmental knee arthroplasties were performed in forty-five patients by a single surgeon. One patient was excluded from the study because of a severe underlying neurologic condition. Lateral unicompartmental replacement was performed in thirty-eight knees with primary osteoarthritis and in ten knees with posttraumatic arthritis secondary to a tibial plateau fracture. Retrospective chart reviews and radiographic evaluations were performed, and Knee Society scores were determined. Results: The average Knee Society knee and function scores improved from 39 and 45 points, respectively, preoperatively to 89 and 80 points at an average of 5.2 years postoperatively. Preoperative alignment averaged 10 degrees of valgus, which was corrected to an average of 6.2 degrees of valgus postoperatively. There were no revisions and no notable soft-tissue complications. The mean postoperative knee and function scores were significantly better for patients with primary osteoarthritis (95 and 86 points, respectively) than they were for those with posttraumatic arthritis (74 and 65 points). Conclusions: Lateral unicompartmental knee replacement through a medial approach provided durable and reliable short to mid-term results. This approach is safe, effective, and extensile, making it a viable alternative to a lateral approach. The outcomes of lateral unicompartmental replacement in patients with posttraurnatic arthritis can be expected to be inferior to those in patients with primary osteoarthritis. C1 Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Sah, AP (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,GRB 624, Boston, MA 02114 USA. EM asah07@gmail.com NR 33 TC 45 Z9 47 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 2007 VL 89A IS 9 BP 1948 EP 1954 DI 10.2106/JBJS.F.01457 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 208VH UT WOS:000249346800009 PM 17768191 ER PT J AU Chen, NC Jupiter, JB AF Chen, Neal C. Jupiter, Jesse B. TI Management of distal radial fractures SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID DISPLACED INTRAARTICULAR FRACTURES; FRAGMENT-SPECIFIC FIXATION; PRONATOR QUADRATUS COMPARTMENT; AUGMENTED EXTERNAL FIXATION; PHYSICAL-ACTIVITY SCALE; VOLAR PLATE FIXATION; FIXED-ANGLE PLATE; INTERNAL-FIXATION; RADIOULNAR JOINT; COMPUTED-TOMOGRAPHY AB The older population continues to grow and, at the same time, live more active lives; as a consequence, the incidence of distal radial fractures can be expected to increase. There is no Level-I clinical evidence suggesting a superior modality for treatment of distal radial fractures. The lunate facet has a considerable volar extension at the distal extent of the pronator quadratus and subsequently has an important role in fracture pathomechanics and stability. Application of a volar plate with angular stable fixation has been used successfully in a number of cohort studies but needs to be examined in stringent trials to determine if there is any benefit when compared with other treatment modalities. Irritation of the flexor pollicis longus and irritation of extensor tendons are possible complications of fixation with a locked volar plate. C1 Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. RP Chen, NC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 89 TC 86 Z9 95 U1 0 U2 7 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 2007 VL 89A IS 9 BP 2051 EP 2062 DI 10.2106/JBJS.G.00020 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 208VH UT WOS:000249346800025 PM 17768207 ER PT J AU Ahmad, OM Ramamurthi, K Thrall, E Karasik, D Bouxsein, M Wilson, KE Engelke, K Taylor, RH AF Ahmad, O. M. Ramamurthi, K. Thrall, E. Karasik, D. Bouxsein, M. Wilson, K. E. Engelke, K. Taylor, R. H. TI Hip geometry and density parameters derived from volumetric DXA (VXA) correlate strongly with 3D QCT SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Ahmad, O. M.; Taylor, R. H.] Johns Hopkins Univ, CISST, Baltimore, MD USA. [Ramamurthi, K.; Wilson, K. E.] Holog Inc, Bedford, MA USA. [Thrall, E.; Karasik, D.; Bouxsein, M.] BIDMC, Orthopaed Biomech Lab, Boston, MA USA. [Engelke, K.] Univ Erlangen Nurnberg, Inst Med Phys, Erlangen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W224 BP S418 EP S418 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102311 ER PT J AU Araujo, AB Travison, TG Leder, BZ Esche, GR McKinlay, JB AF Araujo, A. B. Travison, T. G. Leder, B. Z. Esche, G. R. McKinlay, J. B. TI Presence of symptoms in men with low testosterone levels improves prediction of low BMD SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Araujo, A. B.; Travison, T. G.; Esche, G. R.; McKinlay, J. B.] New England Res Inst, Watertown, MA USA. [Leder, B. Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RI Travison, Thomas/C-7098-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA M337 BP S196 EP S196 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101094 ER PT J AU Aydin, C Frohlich, LF Ozturk, D Bastepe, M AF Aydin, C. Frohlich, L. F. Ozturk, D. Bastepe, M. TI Ability of XL alpha s to mimic Gs alpha in mediating parathyroid hormone signaling in vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Aydin, C.; Ozturk, D.; Bastepe, M.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Endocrine Unit, Boston, MA USA. [Frohlich, L. F.] Univ Med Med, Inst Pathophysiol, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA M218 BP S174 EP S174 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101015 ER PT J AU Banerjee, S Shaheen, S Harris, SE Bringhurst, FR Divieti, P AF Banerjee, S. Shaheen, S. Harris, S. E. Bringhurst, F. R. Divieti, P. TI Effects of PTH(1-34) on primary osteocytes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Banerjee, S.; Shaheen, S.; Bringhurst, F. R.; Divieti, P.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Harris, S. E.] Univ Texas Hlth Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 BP S96 EP S96 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100350 ER PT J AU Bischoff, MPS Sakamoto, T Makhijani, NS Gruber, HE Yamayuchi, DT AF Bischoff, Mice. P. S. Sakamoto, T. Makhijani, N. S. Gruber, H. E. Yamayuchi, D. T. TI Analysis of cranial defect healing in CXC receptor2 knock-out (CXCR2(-/-)) mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Bischoff, Mice. P. S.; Sakamoto, T.; Makhijani, N. S.; Yamayuchi, D. T.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gruber, H. E.] Carolinas Med Ctr, Charlotte, NC 28203 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA M276 BP S185 EP S185 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101053 ER PT J AU Cho, YK Demissie, S Livshits, G Meigs, JB Cupples, LA Florez, JC McAteer, J Kiel, DP Karasik, D AF Cho, Y. K. Demissie, S. Livshits, G. Meigs, J. B. Cupples, L. A. Florez, J. C. McAteer, J. Kiel, D. P. Karasik, D. TI ENPP1 as a candidate gene for femoral bone geometry SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Cho, Y. K.; Demissie, S.; Cupples, L. A.] BU Sch Publ Hlth, Boston, MA USA. [Livshits, G.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Meigs, J. B.; Florez, J. C.; McAteer, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kiel, D. P.; Karasik, D.] Hebrew SrLife & Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 BP S285 EP S285 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101440 ER PT J AU Conen, KL Nishimori, S Provot, S Kronenberg, HM AF Conen, K. L. Nishimori, S. Provot, S. Kronenberg, H. M. TI Role of the transcription factor Lbh in endochondral bone formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Conen, K. L.; Nishimori, S.; Kronenberg, H. M.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. [Provot, S.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA M122 BP S157 EP S157 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100584 ER PT J AU Divieti, PP Powell, WF Kobayashi, T Harris, SE Bringhurst, F AF Divieti, P. P. Powell, W. F. Kobayashi, T. Harris, S. E. Bringhurst, F. TI Target ablation of PTH/PTHrP receptor in osteocytes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Divieti, P. P.; Powell, W. F.; Kobayashi, T.; Bringhurst, F.] Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. [Harris, S. E.] Univ Texas Hlth Sci Ctr, Dept Periodont, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1047 BP S14 EP S14 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100048 ER PT J AU Ferrandon, S Castro, M Okasaki, M Potts, JT Gardella, TJ Vilardaga, J AF Ferrandon, S. Castro, M. Okasaki, M. Potts, J. T. Gardella, T. J. Vilardaga, J. TI Fluorescence resonance energy transfer analysis reveals selective binding of long- and short-acting PTH(1-28) analogs to distinct PTH receptor conformations SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Ferrandon, S.; Potts, J. T.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. [Castro, M.; Okasaki, M.; Gardella, T. J.; Vilardaga, J.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W144 BP S398 EP S398 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102231 ER PT J AU Gensure, RC Bastepe, M AF Gensure, R. C. Bastepe, M. TI Hyperparathyroid bone disease in two sisters with parathyroid hormone resistance (pseudohypopoarathyroidism 1b) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Gensure, R. C.] Ochsner Clin Fdn, New Orleans, LA USA. [Bastepe, M.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W429 BP S471 EP S471 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102515 ER PT J AU Gori, F Zhu, E Demay, MB AF Gori, F. Zhu, E. Demay, M. B. TI Wdr5 is essential for osteoblast differentiation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Gori, F.; Zhu, E.; Demay, M. B.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W032 BP S370 EP S370 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102119 ER PT J AU Guo, J Liu, M Thomas, CC Yang, D Bouxsein, ML Schipani, E Bringhurst, FR Kronenberg, HM AF Guo, J. Liu, M. Thomas, C. C. Yang, D. Bouxsein, M. L. Schipani, E. Bringhurst, F. R. Kronenberg, H. M. TI Phospholipase C signaling via the PTH/PTHrP receptor is essential for normal full response to PTH in both bone and kidney SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Guo, J.; Liu, M.; Thomas, C. C.; Yang, D.; Schipani, E.; Bringhurst, F. R.; Kronenberg, H. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Bouxsein, M. L.] Harvard Univ, Sch Med, Beth Israel Hosp, Orthopaed Biomech Lab, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1119 BP S35 EP S35 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100120 ER PT J AU Hidalgo, A Florea, J Roodman, GD Kurihara, N Onate, S AF Hidalgo, A. Florea, J. Roodman, G. D. Kurihara, N. Onate, S. TI Changes in VDR coregulator recruitment result in 1 alpha,25(OH)(2)D-3 hypersensitivity in MVNP expressing cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Hidalgo, A.; Florea, J.; Onate, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Roodman, G. D.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Kurihara, N.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W152 BP S399 EP S399 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102239 ER PT J AU Hiruma, Y Kurihara, N Subler, MA Zhou, H Dempster, DW Ishizuka, S Roodman, GD Windle, JJ AF Hiruma, Y. Kurihara, N. Subler, M. A. Zhou, H. Dempster, D. W. Ishizuka, S. Roodman, G. D. Windle, J. J. TI Mutations in p62 linked to Paget's disease make the bone microenvironment highly osteoclastogenic. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Hiruma, Y.; Kurihara, N.] Univ Pittsburgh, Pittsburgh, PA USA. [Subler, M. A.; Windle, J. J.] Virginia Commonwealth Univ, Richmond, VA USA. [Zhou, H.; Dempster, D. W.] Helen Hayes Hosp, Reg Bone Ctr, New York, NY USA. [Ishizuka, S.] Teijin Biomed Res, Tokyo, Japan. [Roodman, G. D.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 BP S132 EP S132 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100484 ER PT J AU Huston, A Leleu, X Jia, X Anderson, J Vallet, S Roccaro, A Moreau, A Runnels, J Ngo, H Hatiiharissi, E Roodman, GD Tai, Y Sportelli, P Hideshima, T Richardson, P Anderson, K Ghobrial, I AF Huston, A. Leleu, X. Jia, X. Anderson, J. Vallet, S. Roccaro, A. Moreau, A. Runnels, J. Ngo, H. Hatiiharissi, E. Roodman, G. D. Tai, Y. Sportelli, P. Hideshima, T. Richardson, P. Anderson, K. Ghobrial, I. TI Activity of the akt inhibitor perifosine and heat shock protein (HSP)-90 inhibitor 17-(Dimethylaminoethylamino)-17-Demetboxygeldanamycin (17-DMAG) in modulating osteoclastogenesis and the bone marrow microenviromment (BMM) in multiple myeloma (MM) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Huston, A.] James P Wilmot Canc Ctr, Rochester, NY USA. [Leleu, X.; Jia, X.; Vallet, S.; Roccaro, A.; Moreau, A.; Runnels, J.; Ngo, H.; Hatiiharissi, E.; Tai, Y.; Hideshima, T.; Richardson, P.; Anderson, K.; Ghobrial, I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, J.; Roodman, G. D.] Univ Pittsburgh, Pittsburgh, PA USA. [Sportelli, P.] Keryx Biopharmaceut, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W195 BP S411 EP S411 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102282 ER PT J AU Jaureguiberry, G Carpenter, TO Forman, S Juppner, H Bergwitz, C AF Jaureguiberry, G. Carpenter, T. O. Forman, S. Juppner, H. Bergwitz, C. TI Threonine 137 is an important determinant of sodium-phosphate co-transport in human NaPi-IIc SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Jaureguiberry, G.; Juppner, H.; Bergwitz, C.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Carpenter, T. O.] Yale Univ, Sch Med, Dept Pediat, Endocrine Unit, New Haven, CT 06520 USA. [Forman, S.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1264 BP S74 EP S74 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100265 ER PT J AU Kamiya, N Ye, L Kobayashi, T Mochida, Y Yamauchi, M Kronenberg, H Feng, J Mishina, Y AF Kamiya, N. Ye, L. Kobayashi, T. Mochida, Y. Yamauchi, M. Kronenberg, H. Feng, J. Mishina, Y. TI BMP signaling in osteoblasts negatively regulates canonical Wnt signaling to reduce bone mass during embryonic bone development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Kamiya, N.; Mishina, Y.] NIEHS, NIH, LRDT, Res Triangle Pk, NC 27709 USA. [Ye, L.; Feng, J.] Univ Missouri, Kansas City, MO 64110 USA. [Kobayashi, T.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. [Mochida, Y.; Yamauchi, M.] Univ N Carolina, Dent Res Ctr, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA S270 BP S110 EP S110 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100409 ER PT J AU Kim, W Meliton, V Amantea, CM Hahn, TJ Parhami, F AF Kim, W. Meliton, V. Amantea, C. M. Hahn, T. J. Parhami, F. TI Hairy enhancer of split 1 (HES-1) is an anti-adipogenic mediator of osteogenic oxysterols and hedgehog signaling SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Kim, W.; Meliton, V.; Amantea, C. M.; Parhami, F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. [Hahn, T. J.] VA Greater Los Angeles Healthcare Syst & Geriatr, Ctr Clin, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W043 BP S373 EP S373 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102130 ER PT J AU Kong, L Zhang, Y Jiang, B Xie, Y Feng, JO Kobayashi, T Kronenberg, HM Liu, C AF Kong, L. Zhang, Y. Jiang, B. Xie, Y. Feng, J. O. Kobayashi, T. Kronenberg, H. M. Liu, C. TI ECM1, a direct targeting molecule of PTHrP, is a novel potent mediator of chondrogenesis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Kong, L.; Zhang, Y.; Liu, C.] NYU, Dept Orthopaed Surg, New York, NY USA. [Jiang, B.; Xie, Y.; Feng, J. O.] Texas A&M Univ Syst, Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, Dallas, TX USA. [Kobayashi, T.; Kronenberg, H. M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1062 BP S18 EP S18 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100063 ER PT J AU Kurihara, N Hiruma, Y Yamana, K Rousseau, C Morissette, J Brown, JP Roodman, GD AF Kurihara, N. Hiruma, Y. Yamana, K. Rousseau, C. Morissette, J. Brown, J. P. Roodman, G. D. TI Measles virus nucleocapsid gene expression is required for abnormal osteoclast activity in Paget's disease of bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Kurihara, N.; Hiruma, Y.] Univ Pittsburgh, Pittsburgh, PA USA. [Yamana, K.] Biomed Res, Tokyo, Japan. [Rousseau, C.; Morissette, J.; Brown, J. P.] Univ Laval, CHUL Res Ctr, Quebec City, PQ, Canada. [Roodman, G. D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1152 BP S43 EP S43 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100153 ER PT J AU Lu, G Patrene, K Garcia-Palacios, V Anderson, J Boykin, C Del Prete, D Windle, JJ Roodman, GD AF Lu, G. Patrene, K. Garcia-Palacios, V. Anderson, J. Boykin, C. Del Prete, D. Windle, J. J. Roodman, G. D. TI ADAM8 binds alpha(9)beta(1) to increase OCL formation and function by interacting with pyk2 and activating paxillin SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Lu, G.; Patrene, K.; Garcia-Palacios, V.; Anderson, J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Boykin, C.; Windle, J. J.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Del Prete, D.] Univ Bari, Sch Med, Bari, Italy. [Roodman, G. D.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1099 BP S29 EP S29 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100100 ER PT J AU Luisella, C Demay, MB AF Luisella, C. Demay, M. B. TI The nuclear interactions of the VDR and lef1 are ligand independent SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Luisella, C.; Demay, M. B.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W148 BP S398 EP S398 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102235 ER PT J AU Maeda, Y Erben, RG Schipani, E Lanske, B AF Maeda, Y. Erben, R. G. Schipani, E. Lanske, B. TI Indian hedgehog is essential for postnatal bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Maeda, Y.; Lanske, B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Erben, R. G.] Univ Vet Med, Dept Nat Sci, Vienna, Austria. [Schipani, E.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Schipani, E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA T011 BP S234 EP S235 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101234 ER PT J AU Mannstadt, M Bertrand, G Grandchamp, B Jueppner, H Silve, C AF Mannstadt, M. Bertrand, G. Grandchamp, B. Jueppner, H. Silve, C. TI Dominant-negative GCMB mutations cause hypoparathyroidism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Mannstadt, M.; Jueppner, H.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bertrand, G.; Grandchamp, B.; Silve, C.] Hop Xavier Bichat, Fac Med, Paris, France. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1031 BP S9 EP S9 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100032 ER PT J AU Nagai, S Okazaki, M Potts, JT Jueppner, H Gardella, TJ AF Nagai, S. Okazaki, M. Potts, J. T. Jueppner, H. Gardella, T. J. TI Dissection of the mechanisms of PTH-mediated inhibition of sodium-dependent phosphate transport using a long-acting PTH(1-28) analog SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Nagai, S.; Okazaki, M.; Potts, J. T.; Jueppner, H.; Gardella, T. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1189 BP S53 EP S53 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100190 ER PT J AU Napierala, D Sam, K Morello, R Bertin, T Zheng, O Sibai, T Shivdasani, R Lee, B AF Napierala, D. Sam, K. Morello, R. Bertin, T. Zheng, O. Sibai, T. Shivdasani, R. Lee, B. TI Trps1 transcription factor regulates chondrocyte hypertrophy and perichondrial mineralization through repression of Runx2 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Napierala, D.; Sam, K.; Morello, R.; Bertin, T.; Zheng, O.; Sibai, T.; Lee, B.] Baylor Coll Med, Houston, TX 77030 USA. [Shivdasani, R.] 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 BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1184 BP S52 EP S52 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100185 ER PT J AU Ohishi, M Purton, LE Stanford, WL Scadden, DT Kronenberg, HM Schipani, E AF Ohishi, M. Purton, L. E. Stanford, W. L. Scadden, D. T. Kronenberg, H. M. Schipani, E. TI The PTH/PTHrP receptor modulates the pool of bone marrow stromal cells: Implications for the anabolic action of PTH SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Ohishi, M.; Kronenberg, H. M.; Schipani, E.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Purton, L. E.; Scadden, D. T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Stanford, W. L.] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W138 BP S396 EP S396 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102225 ER PT J AU Okazaki, M Nagai, S Dean, T Potts, JT Gardella, TJ AF Okazaki, M. Nagai, S. Dean, T. Potts, J. T. Gardella, T. J. TI Analysis of PTH-PTH receptor interaction mechanisms using a new, long-acting PTH(1-28) analog reveals selective binding to distinct PTH receptor conformations and biological consequences in vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Okazaki, M.; Nagai, S.; Dean, T.; Potts, J. T.; Gardella, T. J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1190 BP S54 EP S54 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100191 ER PT J AU Sarmasik, A Hiruma, Y Okumura, S Brown, JP Windle, JJ Roodman, GD Kurihara, N Galson, DL AF Sarmasik, A. Hiruma, Y. Okumura, S. Brown, J. P. Windle, J. J. Roodman, G. D. Kurihara, N. Galson, D. L. TI Measles virus nucleoprotein (MVNP) enhances NFATc1 activation during osteoclastogenesis in Paget's disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Sarmasik, A.; Hiruma, Y.; Okumura, S.; Kurihara, N.; Galson, D. L.] Univ Pittsburgh, Ctr Bone Biol, Dept Med, Pittsburgh, PA 15260 USA. [Brown, J. P.] Univ Laval, CHUL Res Ctr, Quebec City, PQ G1K 7P4, Canada. [Windle, J. J.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Roodman, G. D.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 BP S221 EP S221 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101184 ER PT J AU Shimada, M Greer, PA McMahon, AP Schipani, E AF Shimada, M. Greer, P. A. McMahon, A. P. Schipani, E. TI Characterization of osteoblast-specific capn4 knockout mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Shimada, M.; Schipani, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Greer, P. A.] Queens Univ, Kingston, ON, Canada. [McMahon, A. P.] Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1024 BP S8 EP S8 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100025 ER PT J AU Sitara, D Bergwitz, C Kim, S Erben, R Juppner, H Lanske, B AF Sitara, D. Bergwitz, C. Kim, S. Erben, R. Juppner, H. Lanske, B. TI Phosphate-independent effects of Fgf-23 on skeletogenesis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Sitara, D.; Kim, S.; Lanske, B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Bergwitz, C.; Juppner, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Erben, R.] Univ Vet Med, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1114 BP S33 EP S33 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100115 ER PT J AU Turan, S Bastepe, M Bereket, A Akcay, T Guran, T Makitie, O Juppner, H AF Turan, S. Bastepe, M. Bereket, A. Akcay, T. Guran, T. Makitie, O. Juppner, H. TI Identification of novel dentin matrix protein-1 (DMP1) mutations in two unrelated kindreds with autosomal recessive hypophosphatemia SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Turan, S.; Bastepe, M.; Juppner, H.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. [Bereket, A.; Akcay, T.; Guran, T.] Marmara Univ, Istanbul, Turkey. [Makitie, O.] Univ Helsinki, Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W165 BP S403 EP S403 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102252 ER PT J AU Uveges, TE Cabral, WA Bergwitz, C Legard, F Collin-Osdoby, P Forlino, A Osdoby, P Gronowitz, GA Marini, JC AF Uveges, T. E. Cabral, W. A. Bergwitz, C. Legard, F. Collin-Osdoby, P. Forlino, A. Osdoby, P. Gronowitz, G. A. Marini, J. C. TI Bone formation rate falls after puberty in Brtl OI mouse due to cellular uncoupling SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Uveges, T. E.; Cabral, W. A.; Marini, J. C.] NIH, NICHD, BEMB, Bethesda, MD USA. [Bergwitz, C.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA 02114 USA. [Legard, F.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Collin-Osdoby, P.; Osdoby, P.] Washington Univ, Dept Biol Bone & Min Metab, St Louis, MO USA. [Forlino, A.] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA W166 BP S403 EP S403 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509102253 ER PT J AU Wu, JY Rodda, S Sims, NA Poulton, IJ Chen, M Weinstein, LS McMahon, AP Kronenberg, HM AF Wu, J. Y. Rodda, S. Sims, N. A. Poulton, I. J. Chen, M. Weinstein, L. S. McMahon, A. P. Kronenberg, H. M. TI Impaired bone formation in mice lacking the G protein subunit Gs alpha in early osteoblasts leads to marked bone fragility SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Wu, J. Y.; Kronenberg, H. M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Rodda, S.; McMahon, A. P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Sims, N. A.; Poulton, I. J.] St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. [Chen, M.; Weinstein, L. S.] Natl Inst Diabet & Digest & Kidney Dis, Metab Dis Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA 1020 BP S7 EP S7 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100021 ER PT J AU Yan, D Guo, J Bringhurst, R AF Yan, D. Guo, J. Bringhurst, R. TI CITED1 ablation impairs endochondral bone formation during embryonic development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Yan, D.; Guo, J.; Bringhurst, R.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 BP S100 EP S100 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100370 ER PT J AU Yang, D Guo, J Bringhurst, R AF Yang, D. Guo, J. Bringhurst, R. TI CITED1 ablation impairs endochondral bone formation during embryonic development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Yang, D.; Guo, J.; Bringhurst, R.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA O142 BP S85 EP S85 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509100306 ER PT J AU Zhu, S Gori, F AF Zhu, S. Gori, F. TI Using replication competent avian virus system to delivery short hairpin SiRNA to silence gene expression of Wdr5 in chicken limb bud during embryogenesis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Zhu, S.; Gori, F.] Massachusetts Gen Hosp, Harvard Med Sch, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA T141 BP S265 EP S265 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101362 ER PT J AU Fagenholz, PJ Sheridan, RL Harris, NS Pelletier, AJ Carnargo, CA AF Fagenholz, Peter J. Sheridan, Robert L. Harris, N. Stuart Pelletier, Andrea J. Carnargo, Carlos A., Jr. TI National study of emergency department visits for burn injuries, 1993 to 2004 SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID RACIAL DISPARITIES; CARE; ANALGESIA; EPIDEMIOLOGY; MORTALITY; PATTERNS; OUTCOMES; GENDER; IMPACT AB No studies have examined U.S. burn epidemiology from the perspective of the Emergency Department. We sought to describe patient characteristics, injury types, and Emergency Department practice patterns. Data were collected from the National Hospital Ambulatory Medical Care Survey between 1993 and 2004. Emergency Department visit rates for burn injury decreased from 1993 to 2004 with a peak of 2.8 (95% confidence interval [CI] 2.1-3.4) per 1000 U.S. population in 1995 and a nadir of 1.6 (95% CI 1.2-2.0) per 1000 in 2004. The Emergency Department visit rate for burn injuries was greater for men than women (2.7 [95% CI 2.4-3.0] vs 1.8 [95% CI 1.6-2.0] per 1000) and for black than white subjects (3.4 [95% CI 2.8-3.9] vs 2.1 [95%CI 1.9-2.3] per 1000), though all these groups showed decreases. Emergency Department visit rates for burns were greatest in the first and third decades (3.3 [95% CI 2.8-3.7] and 3.5 [95% CI 3.0-4.0] per 1000, respectively) and decreased thereafter. The upper extremity was the most commonly burned part of the body (37% of total) and most burns of specified depth were partial thickness (48% of total). Less than half of patients received analgesics (47%) or topical antibiotics (38%). Emergency Department visits for burns are declining, but rates remain high in men, black individuals, and children. Burn-prevention efforts should target these groups. Upper-extremity and partial-thickness injuries are common, and less than half of patients receive analgesics or topical antibiotics. Collaboration between burn specialists and Emergency Department personnel should focus on the care of these types of injuries. C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. RP Carnargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, 326 Cambridge St, Boston, MA 02114 USA. NR 45 TC 33 Z9 33 U1 0 U2 4 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 SEP-OCT PY 2007 VL 28 IS 5 BP 681 EP 690 PG 10 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 208WS UT WOS:000249350500007 PM 17762387 ER PT J AU Leaf, A AF Leaf, Alexander TI Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids SO JOURNAL OF CARDIOVASCULAR MEDICINE LA English DT Article; Proceedings Paper CT 1st International Forum on n-3 Polyunsaturated Fatty Acids CY JAN, 2006 CL Rome, ITALY DE arrhythmia; fish oils; n-3 polyunsaturated fatty acids; sudden cardiac death ID RAT VENTRICULAR MYOCYTES; NA+ CHANNELS; LONG-CHAIN; FISH; ARRHYTHMIAS; TRIAL AB There were already several epidemiologic studies that showed eating fish frequently seemed to reduce deaths from coronary heart disease. There were also observational and clinical trials that more specifically showed that the reduction in cardiovascular deaths from eating fish was largely the result of the prevention of sudden cardiac death by n-3 polyunsaturated fatty acids in fish oil.This led me to perform a clinical trial in which all subjects had an implanted cardioverter-defibrillator and were at very high risk of sudden cardiac death. The results of this study and the mechanisms by which n-3 fish oil fatty acids prevent fatal cardiac arrhythmias will be the subject of this review. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, E Bldg 149,Rm 4001,13th St, Charlestown, MA 02129 USA. EM aleaf@partners.org NR 14 TC 15 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1558-2027 J9 J CARDIOVASC MED JI J. Cardiovasc. Med. PD SEP PY 2007 VL 8 SU 1 BP S27 EP S29 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 222XX UT WOS:000250332900007 PM 17876194 ER PT J AU Shah, AP Ichiuji, AM Han, JK Traina, M El-Bialy, A Meymandi, SK Wachsner, RY AF Shah, Atman Prabodh Ichiuji, Anne Marie Han, Janet K. Traina, Mahmoud El-Bialy, Adel Meymandi, Sheba Kamal Wachsner, Robin Yvonne TI Cardiovascular and endothelial effects of fish oil supplementation in healthy volunteers SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE endothelium; fish oil; hemodynamics ID POLYUNSATURATED FATTY-ACIDS; FLOW-MEDIATED VASODILATION; MYOCARDIAL-INFARCTION; DIETARY SUPPLEMENTATION; EICOSAPENTAENOIC ACID; SUDDEN-DEATH; DOUBLE-BLIND; HEART-RATE; DOCOSAHEXAENOIC ACID; CONTROLLED TRIAL AB Consumption of fish oil (FO) is associated with reduced adverse cardiovascular events. In a randomized, blinded, placebo-controlled trial, 26 subjects (17 men and 9 women; mean age [ +/- SD] 31 +/- 3.7 years) received 1 g FO capsule (n = 14) or placebo (1 g of corn oil, n = 12) for 14 days. At day 0 and day 14, heart rate (HR), blood pressure, endothelium-dependent brachial artery flow-mediated vasodilation (EDV), and endothelium-independent nitroglycerin-mediated vasodilation (EIDV) were assessed with ultrasound. FO supplementation resulted in a significant increase in EDV (20.4% +/- 13.2% vs 9.9% +/- 5.4%; P = .036) and EIDV (32.6% +/- 16.8% vs 18.0% +/- 14.9%; P = .043 ). Resting HR decreased by a mean of 5.9 +/- 9.4 bpm (FO) compared with placebo (mean increase of 0.73 +/- 4.8 bpm [P = .05]). FO supplementation in healthy subjects is associated with improved endothelial function and decreased resting HR. C1 Univ Calif Los Angeles, David Geffen Sch Med, Harbor UCLA Med Ctr, St Johns Cardiovasc Res Ctr, Torrance, CA 90502 USA. Univ Calif Los Angeles, Olive View Med Ctr Sylmar, Los Angeles, CA USA. Greater Los Angeles VA Healthcare, Los Angeles, CA USA. Kaiser Permanente Med Ctr, Div Cardiol, Los Angeles, CA 90034 USA. RP Shah, AP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Harbor UCLA Med Ctr, St Johns Cardiovasc Res Ctr, 1124 W Carson Ave,3rd Floor, Torrance, CA 90502 USA. EM apshah73@yahoo.com NR 40 TC 32 Z9 33 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD SEP PY 2007 VL 12 IS 3 BP 213 EP 219 DI 10.1177/1074248407304749 PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 203EV UT WOS:000248958800005 PM 17875948 ER PT J AU Henderson, BA Kim, JY Ament, CS Ferrufino-Ponce, ZK Grabowska, A Cremers, SL AF Henderson, Bonnie A. Kim, Jae Yong Ament, Christine S. Ferrufino-Ponce, Zandra K. Grabowska, Anna Cremers, Sandra L. TI Clinical pseudophakic cystoid macular edema - Risk factors for development and duration after treatment SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID EXTRACAPSULAR CATARACT-EXTRACTION; INTRAOCULAR-LENS IMPLANTATION; BLOOD-AQUEOUS BARRIER; VITREOUS LOSS; KETOROLAC TROMETHAMINE; VISUAL-ACUITY; SURGERY; PHACOEMULSIFICATION; THERAPY; INDOMETHACIN AB PURPOSE: To characterize the incidence, duration, and risk factors for and outcome of cystoid macular edema (CME) after cataract surgery and investigate the effects of treatment regimens on visual outcome and duration. SETTING: University-based comprehensive ophthalmology practice. METHODS: This study included 1659 consecutive cataract surgeries performed by residents between 2001 and 2006. Cases were classified according to the presence of CME. Subset analysis excluded patients with diabetes mellitus (DM). The CME groups were analyzed according to type of treatment to compare duration of CME and final best corrected visual acuity. RESULTS: The incidence of postoperative CME was 2.35% (39/1659), and history of retinal vein occlusion (RVO) was predictive of postoperative CME (odds ratio [OR], 47.12; P<.001). When patients with DM were excluded, the incidence of CME was 2.14% (29/1357) and history of RVO (OR, 31.75; P<.001), epiretinal membrane (ERM) (OR, 4.93; P<.03), and preoperative prostaglandin use (OR, 12.45; P<.04) were predictive of postoperative CME. Patients with DM and/or intraoperative complications did not have an increased risk for CME when treated with prophylactic postoperative nonsteroidal antiinflammatory drugs (NSAIDs) for 3 months. Groups treated with NSAIDs plus a steroid had significantly shorter resolution times than the untreated group (P =.004). CONCLUSIONS: A history of RVO, ERM, and preoperative prostaglandin use were associated with an increased risk for pseudophakic CME. Treatment with NSAIDs plus steroids was associated with faster resolution of CME than no treatment. Treating high-risk patients with NSAIDs after cataract surgery decreases the incidence of postoperative CME to that of patients who are not at high risk. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Henderson, BA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. EM bahenderson@eyeboston.com NR 50 TC 72 Z9 78 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD SEP PY 2007 VL 33 IS 9 BP 1550 EP 1558 DI 10.1016/j.jcrs.2007.05.013 PG 9 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 208IJ UT WOS:000249312700013 PM 17720069 ER PT J AU Hofer, AM AF Hofer, Aldebaran M. TI Review series on the extracellular Ca2+-Sensing receptor SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Editorial Material C1 Vet Adm Med Ctr W Roxbury, Harvard Univ, Sch Med, Brigham & Womens Hosp, W Roxbury, MA 02132 USA. Vet Adm Med Ctr W Roxbury, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. RP Hofer, AM (reprint author), Vet Adm Med Ctr W Roxbury, Harvard Univ, Sch Med, Brigham & Womens Hosp, 1400 VFW Pkwy Room 2B111, W Roxbury, MA 02132 USA. EM ahofer@rics.bwh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD SEP-OCT PY 2007 VL 11 IS 5 BP 906 EP 907 DI 10.1111/j.1582-4934.2007.00116.x PG 2 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 226KI UT WOS:000250587500002 PM 17979872 ER PT J AU Schulze-Spate, U Battaglino, R Fu, J Sharma, A Vokes, M Stashenko, P AF Schulze-Spaete, Ulrike Battaglino, Ricardo Fu, Jia Sharma, Anupriya Vokes, Martha Stashenko, Philip TI Brn3 transcription factors control terminal osteoclastogenesis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE bone; osteoclast; transcription factor; differentiation; RANKL ID NF-KAPPA-B; RETINAL GANGLION-CELLS; POU-DOMAIN FACTORS; RECEPTOR ACTIVATOR; NERVOUS-SYSTEM; FACTORS BRN-3A; FAMILY; DIFFERENTIATION; EXPRESSION; NEURONS AB Osteoclastic bone resorption is a central mechanism in skeletal development, remodeling and pathology. RANKL is a mandatory factor controlling osteoclastogenesis; however, the underlying signaling pathways are only partially characterized. Using a screening array for the investigation of differential transcription factor activation, we identified activation of the Brn3 transcription factor family as a downstream event of RANKL signaling during terminal osteoclastogenesis. RANKL stimulation induces expression of Brn3a and b and maximal transcriptional activity of Brn3 family members concurrent with osteoclastic giant cell formation. Immunohistochemical analysis revealed both nuclear and cytoplasmic localization of Brn3a and b in mature osteoclasts. Functional inhibition of Brn3 transcription factors resulted in inhibition of pre-osteoclast fusion and reduction in bone resorbing activity of mature osteoclasts. Furthermore, we identified synaptotagmin-1, a regulator of membrane and vesicular fusion, as downstream target of Brn3 with a role in osteoclast function. We conclude that Brn-3 represents a novel molecular differentiation factor that controls osteoclast maturation and function, suggesting an important role in bone metabolism. J. Cell. Biochem. 102: 1-12, 2007. 0 2007 Wiley-Liss, Inc.(C) C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pstashianko@forsyth.org RI battaglino, ricardo/D-2892-2015 FU NIDCR NIH HHS [DE-07378] NR 37 TC 1 Z9 1 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP 1 PY 2007 VL 102 IS 1 BP 1 EP 12 DI 10.1002/jcb.21257 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 207PM UT WOS:000249263100001 PM 17668438 ER PT J AU Gragnoli, C Cronsell, J AF Gragnoli, C. Cronsell, J. TI PSMD9 gene variants within NIDDM2 may rarely contribute to type 2 diabetes SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GENOMEWIDE SEARCH; FINNISH FAMILIES; COACTIVATOR; BRIDGE-1; MELLITUS; LINKAGE; DISEASE AB Multiple genome-wide scans in different populations have linked the chromosome 12q24 region, known as NIDDM2 (non-insulindependent-diabetes, locus 2), to type 2 diabetes. Within NIDDM2 we examined the PSMD9 (proteasome modulator 9/Bridge- 1) genethat encodes a PDZ-domain transcriptional coactivator of insulin production. Our goal was to identify a potential contribution of the PSMD9 gene to type 2 diabetes in Italians. We directly sequenced the entire gene PSMD9 in Italian type 2 diabetes patients (n = 237) and controls subjects (n = 2 15) and performed an association study with the identified gene variants. We found five single nucleotide polymorphisms (SNPs), A 17V, IVSI +nt29, IVS3+nt460, IVS3+nt437, and E 197G, which are not associated with disease in our case-control study. Furthermore, we identified two PSMD9 gene variants in type 2 diabetes patients, which produced nonconservative amino acid substitutions S 143G and N 166S within the PDZ domain and two other gene variants. Three out of four of these variants are absent from the control subjects screened. We propose that the three PSMD9 gene variants (S 143G, N 166S and IS > A at IVS3+nt 102), absent in control subjects, contribute rarely to late-onset type 2 diabetes in Italians. In fact, the frequency rate of such variants in unrelated cases equals 0.016. We may not exclude that PSMD9 gene variants may contribute, either commonly or rarely, to an increased risk of type 2 diabetes in other populations. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Roma Tor Vergata, Dipartimento Med, Rome, Italy. Bios Multi Diagnost Biotech & Res Fdn, Rome, Italy. RP Gragnoli, C (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Div Endocrinol Diabet & Metab, H044,500 Univ Dr, Hershey, PA 17033 USA. EM claudia.gragnoli@gmail.com FU NIDDK NIH HHS [DK07028] NR 17 TC 15 Z9 15 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2007 VL 212 IS 3 BP 568 EP 571 DI 10.1002/jcp.21127 PG 4 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 200NQ UT WOS:000248770500002 PM 17516568 ER PT J AU Jeanne, BH Oberley, TD AF Bourdeau-Heller, Jeanne Oberley, Terry D. TI Prostate carcinoma cells selected by long-term exposure to reduce oxygen tension show remarkable biochemical plasticity via modulation of superoxide, HIF-l alpha levels, and energy metabolism SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; OXIDATIVE-PHOSPHORYLATION; CANCER-CELLS; COMPLEX-III; MITOCHONDRIA; INHIBITION; GLYCOLYSIS; PATHWAY; ADAPTATION; DISMUTASE AB Cancer cells are able to tolerate levels Of O-2 that are damaging or lethal to normal cells; we hypothesize that this tolerance is the result of biochemical plasticity which maintains cellular homeostasis of both energy levels and oxidation state. In order to examine this hypothesis, we used different 02 levels as a selective agent during long-term culture of DU 145 prostate cancer cells to develop three isogenic cell lines that grow in normoxic (4%), hyperoxic (2 1 %), or hypoxic (I %) 02 conditions. Growth characteristics and 02 consumption differed significantly between these cell lines without changes in ATP levels or altered sensitivity to 2-deoxy-D-glucose, an inhibitor of glycolysis. 02 consumption was significantly higher in the hyperoxic line as was the level of endogenous superoxide. The hypoxic cell line regulated the chemical gradient of the proton motive force (PMF) independent of the electrical component without O-2-dependent changes in Hif- I a levels. In contrast, the normoxic line regulated Hif- I alpha without tight regulation of the chemical component of the PMF noted in the hypoxic cell line. From these studies, we conclude that selection of prostate cancer cells by long-term exposure to low ambient levels Of 02 resulted in cells with unique biochemical properties in which energy metabolism, reactive oxygen species (ROS), and HIF- I alpha levels are modulated to allow cell survival and growth. Thus, cancer cells exhibit remarkable biochemical plasticity in response to various O-2 levels. C1 Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Pathol, 2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@wisc.edu NR 50 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2007 VL 212 IS 3 BP 744 EP 752 DI 10.1002/jcp.21069 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 200NQ UT WOS:000248770500022 ER PT J AU Zhu, A Wang, X Yu, M Wang, JQ Brownell, AL AF Zhu, Aijun Wang, Xukui Yu, Meixiang Wang, Ji-Quan Brownell, Anna-Lisa TI Evaluation of four pyridine analogs to characterize 6-OHDA-induced modulation of mGluR5 function in rat brain using microPET studies SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE distribution volume; dopamine transporter; metabotropic glutamate receptor; Parkinson's disease; positron emission tomography; striaturn ID METABOTROPIC GLUTAMATE-RECEPTOR; PARKINSONS-DISEASE; GRAPHICAL ANALYSIS; PET DATA; 6-HYDROXYDOPAMINE; DEGENERATION; DEFICITS; NEURONS; COCAINE; MODEL AB Micro-positron emission tomography imaging studies were conducted to characterize modulation of metabotropic glutamate subtype-5 receptor (mGluR5) function in a 6-hydroxydopamine (6-OHDA)induced rat model of Parkinson's disease using four analogical PET ligands: 2-[C-11]methyl-6-(2phenylethynyl) pyridine ([C-11]MPEP), 2-(2-(3-[C-11]methoxyphenyl)ethynyl)pyridine ([C-11]M-MPEP), 2(2-(5-[C-11]methoxypyridin-3-yl)ethynyl)pyridine ([(CIM)-C-11-PEPy), and 3-[(2-[8 F]methyl-1,3-thiazol-4yl)ethynyl]pyridine ([F-18]M-TEP). A total of 45 positron emission tomography (PET) imaging studies were conducted on nine male Sprague-Dawley rats within 4 to 6 weeks after unilateral 6-OHDA lesioning into the right medial forebrain bundle. The severity of the lesion was determined with [C-11]CFT ([C-11]2-fl-carbomethoxy-3-p-(4-fluorophenyl)tropane), a specific and sensitive ligand for imaging dopamine transporter function. The binding potential (BP) images were processed on pixelby-pixel basis by using a method of the distribution volume ratio with cerebellum as a reference tissue. The values for BP were determined on striatum, hippocampus, and cortex. [11C]CFT binding was decreased on the lesioned (right) striatum by 35.4% +/- 13.4% compared with the intact left striatum, indicating corresponding loss of presynaptic dopamine terminals. On the same areas of the lesioned striatum, three of the four tested mGluR5 ligands showed enhanced binding characteristics. The average differences between the right and left striatum were 4.4%.+/- 6.5% (P<0.05) with [C-11]MPEP, -0.1% +/- 1.7% (P>0.05) with [C-11]M-MPEP, 3.9% +/- 4.6% (P<0.05) with [C-11]M-PEPy, and 6.6% +/- 2.7% (P>0.05) with [F-18]M-TEP. The enhanced binding was also observed in the right hippocampus and cortex. These studies showed that glutamatergic neurotransmission might have a complementary role in dopaminergic degeneration, which can be evaluated by in vivo PET imaging. C1 Massachusetts Gen Hosp, Dept Radiol, Expt PET Lab, Boston, MA 02114 USA. RP Brownell, AL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Expt PET Lab, Boston, MA 02114 USA. EM abrownnell@partners.org FU NIBIB NIH HHS [EB001850] NR 36 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2007 VL 27 IS 9 BP 1623 EP 1631 DI 10.1038/sj.jcbfm.9600461 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 202ZY UT WOS:000248946100010 PM 17299451 ER PT J AU Peterfreund, RA Wargo, JA AF Peterfreund, Robert A. Wargo, Jennifer A. TI Errant central line placement SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material DE cannulation; central venous catheterization; internal jugular vein ID CENTRAL VENOUS CANNULATION; INTERNAL JUGULAR-VEIN; CATHETERIZATION; ULTRASOUND; COMPLICATIONS; ARTERIAL; PUNCTURE AB Clinicians use several tests to confirm proper placement of catheters in central veins. This report describes errant insertion of a catheter intended for the central venous circulation, despite the reassuring results of initial tests to evaluate the insertion procedure. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Peterfreund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM rpeterfreund@partners.org; jennifer_wargo@nih.gov NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP PY 2007 VL 19 IS 6 BP 479 EP 481 DI 10.1016/j.jclinane.2007.06.003 PG 3 WC Anesthesiology SC Anesthesiology GA 229PX UT WOS:000250817600018 PM 17967683 ER PT J AU Moore, AF Grinspoon, SK AF Moore, Allan F. Grinspoon, Steven K. TI Image in endocrinology: A dural tale SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID ENHANCED MR IMAGES; MENINGIOMAS C1 Massachusetts Gen Hosp, Endocrine Div AFM, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit SKG, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Endocrine Div AFM, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 5 TC 1 Z9 1 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2007 VL 92 IS 9 BP 3367 EP 3368 DI 10.1210/jc.2007-0957 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 207VS UT WOS:000249279800001 PM 17823272 ER PT J AU Leder, BZ Araujo, AB Travison, TG McKinlay, JB AF Leder, Benjamin Z. Araujo, Andre B. Travison, Thomas G. McKinlay, John B. TI Racial and ethnic differences in bone turnover markers in men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HIP FRACTURE INCIDENCE; D-RECEPTOR GENE; MINERAL DENSITY; OSTEOPOROTIC FRACTURES; LIFE-STYLE; BIOCHEMICAL MARKERS; RISK-FACTORS; BLACK-WOMEN; ELDERLY-MEN; AXIS LENGTH AB Context: Whereas racial and ethnic differences in fracture risk and bone mineral density ( BMD) in men have been well described, the influence of race and ethnicity on biochemical markers of bone turnover is less clear. Methods: To examine the relationship between bone turnover, BMD, and race and ethnicity in men, we measured BMD, serum intact osteocalcin ( OC), and serum C-terminal telopeptides of type 1 collagen ( CTx) in 1029 men ( aged 30-79 yr) enrolled in the Boston Area Community Health/Bone Survey, a population-based random sample of Black, Hispanic, and White. Men with diseases or on medications known to affect bone metabolism were excluded from the analysis. Mean serum levels of OC and CTx were adjusted for age, month and time of blood sample, and 25-hydroxyvitamin D. Results: Compared with Black men, adjusted mean OC levels were 17.6 and 20.5% higher in Hispanic ( P = 0.02) and White men ( P < 0.01), respectively. There was no significant difference between White and Hispanic men. Adjusted mean CTx levels were 14.3% higher in White men, compared with Black men ( P = 0.04), but no other differences were significant. OC declined by 0.4%/ yr from age 30 to 65 yr and increased thereafter by 2.1%/yr. The age trend in CTx appeared to follow a pattern consistent with a quadratic function of age. Model-estimated annual percent changes within age decade were as follows: 30-39 yr, -2.5%; 40 - 49 yr, - 1.4%; 50 - 59 yr, - 0.3%; 60 - 69 yr, + 0.9%; 70 - 79 yr, + 1.7%. There was no variation in the shape of the age trend in OC or CTx by race or ethnic group. Correlations between bone turnover markers and BMD ( adjusted for age, height, weight, serum 25-hydroxyvitamin D, and PTH and month and time of blood sample) were generally weak. Conclusions: Bone turnover markers are lower in Black men, compared with White and Hispanic men. Age trends in bone turnover markers are not influenced by race or ethnicity. Future studies in this cohort and others are needed to explore further these reported differences in bone metabolism among Black, Hispanic, and White men. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. New England Res Inst, Watertown, MA 02472 USA. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Thier 1047,50 Blossom St, Boston, MA 02114 USA. EM bzleder@partners.org RI Travison, Thomas/C-7098-2011 FU NCRR NIH HHS [K23-RR16310]; NIA NIH HHS [AG 20727, R01 AG020727, R01 AG020727-05A1]; NIDDK NIH HHS [DK 56842] NR 49 TC 25 Z9 25 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2007 VL 92 IS 9 BP 3453 EP 3457 DI 10.1210/jc.2006-2695 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 207VS UT WOS:000249279800018 PM 17579203 ER PT J AU Cheng, I Henderson, KD Haiman, CA Kolonel, LN Henderson, BE Freedman, ML Le Marchand, L AF Cheng, Iona Henderson, Katherine DeLellis Haiman, Christopher A. Kolonel, Laurence N. Henderson, Brian E. Freedman, Matthew L. Le Marchand, Loic TI Genetic determinants of circulating insulin-like growth factor (IGF)-I, IGF binding protein (BP)-1, and IGFBP-3 levels in a multiethnic population SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BREAST-CANCER RISK; FACTOR-I; PROSTATE-CANCER; COLORECTAL-CANCER; SERUM-LEVELS; COHORT; WOMEN; POLYMORPHISMS; ASSOCIATION; LOCUS AB Context: Both circulating levels and genetic variation of IGFs have been associated with cancer risk, yet the relationship between the two is not well understood. Objective: To investigate whether common genetic variation in IGF1, IGF binding protein 1 (IGFBP1), and IGFBP3 influences circulating levels of IGF-I, IGFBP-1, and IGFBP-3, we conducted a cross-sectional study of African-American, Native Hawaiian, Japanese-American, Latino, and white men and women in the Multiethnic Cohort. Design: Plasma levels of IGF-I, IGFBP- 1, and IGBFP-3 were measured by ELISA in a random sample of 837 Multiethnic Cohort participants. Previously identified tag single nucleotide polymorphisms ( SNPs) for IGF1 (29 tag SNPs) and IGFBP1/ IGFBP3 ( 23 tag SNPs) were genotyped among the 837 participants. Analysis of covariance was conducted to test for differences in mean IGF-I, IGFBP- 1, and IGFBP- 3 levels across respective IGF1, IGFBP1, and IGFBP3 genotypes, adjusting for previously identified dietary and lifestyle correlates. Results: Five highly correlated IGFBP3 SNPs (rs3110697, rs2854747, rs2854746, rs2854744, and rs2132570) demonstrated strongly significant associations with IGFBP- 3 levels when conservatively adjusted for multiple hypothesis testing (Bonferroni adjusted P trends = 7.75 X 10(-8) to 1.44 X 10(-5)). Patterns of associations were consistent across the five racial/ethnic groups. Conclusion: In summary, our study suggests that common genetic variation in IGFBP3 influences circulating levels of IGFBP- 3 among African-Americans, Native Hawaiians, Japanese-Americans, Latinos, and whites. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Broad Inst Massachusetts Inst Technol & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA. RP Cheng, I (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. FU NCI NIH HHS [CA 54281, CA 63464, R25T CA 112355-01A1] NR 26 TC 35 Z9 36 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2007 VL 92 IS 9 BP 3660 EP 3666 DI 10.1210/jc.2007-0790 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 207VS UT WOS:000249279800051 PM 17566087 ER PT J AU Hennessy, S Bilker, WB Leonard, CE Chittams, J Palumbo, CM Karlawish, JH Yang, YX Lautenbach, E Baine, WB Metlay, JP AF Hennessy, Sean Bilker, Warren B. Leonard, Charles E. Chittams, Jesse Palumbo, Cristin M. Karlawish, Jason H. Yang, Yu-Xiao Lautenbach, Ebbing Baine, William B. Metlay, Joshua P. TI Observed association between antidepressant use and pneumonia risk was confounded by comorbidity measures SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE aged; antidepressive agents; pneumonia; pneumonia; aspiration; pharmacoepidemiology; confounding factors ID COMMUNITY-ACQUIRED PNEUMONIA; ASPIRATION PNEUMONIA; TRENDS; ADULTS; OLDER AB Objective: A prior study suggested that antidepressants might increase the risk of hospitalization for pneumonia in the elderly. This study sought to confirm or refute this hypothesis. Study Design and Setting: Case-control study of persons aged 65 and above nested in the UK General Practice Research Database. Results: We identified 12,044 cases of the hospitalization for pneumonia (the primary outcome) and 48,176 controls. The odds ratio (OR) for any antidepressant use, adjusting for age, sex, and calendar year was 1.61 (95% confidence interval 1.46-1.78). After further adjustment for comorbidity measures, the OR was 0.89 (0.79-1.00). We also identified 159 cases of hospitalization for aspiration pneumonia (the secondary outcome) and 636 controls. The OR for any antidepressant use, adjusted for age, sex, and calendar year was 1.45 (0.65-3.24). After further adjustment for comorbidity measures, the OR was 0.63 (0.23-1.71). Conclusion: These findings refute the prior hypothesis that use of antidepressants by elderly patients increases the risk of hospitalization for pneumonia or for aspiration pneumonia. Decisions regarding use of antidepressants in elderly persons should not be affected by concern about pneumonia risk. Data-derived hypotheses should be independently confirmed before being acted upon. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Developing Evidence Inform Decis Effectiveness Ct, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. US Dept HHS, Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD 20852 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Hennessy, S (reprint author), 824 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM shenness@cceb.med.upenn.edu RI CPRD, CPRD/B-9594-2017; Leonard, Charles/K-3447-2012; Research Datalink, Clinical Practice/H-2477-2013 FU NIA NIH HHS [K23 AG000987-01A1, K23 AG000987, K23 AG000987-02, K23 AG000987-03, K23 AG000987-04, K23 AG000987-05, K23AG000987]; NIDDK NIH HHS [K08 DK062978, K08 DK062978-01A1, K08 DK062978-02, K08 DK062978-03, K08 DK062978-04, K08 DK062978-05, K08DK062978] NR 17 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 2007 VL 60 IS 9 BP 911 EP 918 DI 10.1016/j.jclinepi.2006.11.022 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 202VI UT WOS:000248931700007 PM 17689807 ER PT J AU Singal, AK Anand, BS AF Singal, Ashwani K. Anand, Bhupinder S. TI Mechanisms of synergy between alcohol and hepatitis C virus SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE hepatitis C virus; alcohol; synergism; oxidative stress; abstinence ID SYMPTOMATIC LIVER-CIRRHOSIS; INJECTION-DRUG USERS; HEPATOCELLULAR-CARCINOMA; RISK-FACTORS; INTERFERON THERAPY; INFECTED PATIENTS; OXIDATIVE STRESS; CLINICAL-SIGNIFICANCE; FIBROSIS PROGRESSION; HIV-INFECTION AB Background: Since the discovery of the hepatitis C virus (HCV), extensive literature has emerged on alcohol and HCV interaction. Goal: To understand the impact of alcohol and HCV infection on the severity of liver disease and the mechanisms of interaction between the two. Study: Of 1269 articles (1991 to 2006) searched through MEDLINE and cited cross references, 133 were thoroughly reviewed to assess: (a) prevalence of combined alcohol use and HCV, (b) severity of liver disease (c) treatment response, and (d) mechanisms of interaction between HCV and alcohol. Data on study design, patient demographics, diagnostic tests used, and study outcomes were extracted for critical analysis. Results: Prevalence of HCV is Mold to 30-fold higher in alcoholics compared with the general population. Patients with HCV infection and alcohol abuse develop more severe fibrosis with higher rate of cirrhosis and hepatocellular cancer compared with nondrinkers. Increased oxidative stress seems to be the dominant mechanism for this synergism between alcohol and the HCV. Abstinence is the key to the management of liver disease due to HCV and alcohol. Data have shown that lower response rates to interferon in alcoholics with HCV infection are likely due to noncompliance. Conclusions: Alcoholics with HCV infection have more severe liver disease compared with nondrinkers. Patients should be encouraged to enroll in rehabilitation programs so as to improve treatment adherence and response. C1 James J Peters VA Med Ctr, Dept Med, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, James J Peters Bronx Vet Affairs Med CTr, New York, NY 10029 USA. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Singal, AK (reprint author), James J Peters VA Med Ctr, Dept Med, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ashwanisingal.com@gmail.com NR 131 TC 63 Z9 64 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD SEP PY 2007 VL 41 IS 8 BP 761 EP 772 DI 10.1097/MCG.0b013e3180381584 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 205SN UT WOS:000249135000007 PM 17700425 ER PT J AU Davila, JA Weston, A Smalley, W El-Serag, HB AF Davila, Jessica A. Weston, Allan Smalley, Walter El-Serag, Hashem B. TI Utilization of screening for hepatocellular carcinoma in the United States SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE tomography; hepatocelluar carcinoma ID CIRRHOTIC-PATIENTS; PATIENT SURVIVAL; SURVEILLANCE; CANCER; EXPERIENCE; MANAGEMENT; HEPATITIS AB Background: Screening for hepatocellular carcinoma (HCC) has been recommended for patients at high-risk of developing HCC. Yet, the utilization and determinants of screening remain unclear. Methods: All patients diagnosed with HCC at 3 medical centers during 1998 to 2003 were identified. Information regarding receipt of HCC screening, demographics, risk factors, liver disease severity, number of HCC lesions, therapy, and date of death was abstracted from medical records. Multivariable logistic regression models were conducted to evaluate determinants of HCC screening and therapy. Cox proportional hazards models were developed to assess the effect of screening on risk of mortality. Results: We identified 157 patients diagnosed with HCC. The majority of patients were < 65 years (62%), white (59%), had a single mass (42%), and a Child-Pugh-Turcotte score B (41%). Approximately, 28% (n = 44) received at least one possible screening test (36% alpha-fetoprotein only, 23% abdominal ultrasound only. 7% computed tomography only; 34% had more than one test). Screened patients were younger [odds ratio (OR) = 2.70; 95% confidence interval (CI): 1.22-5.99) and were more likely to have underlying HCV (OR = 2.91; 95% CI: 1.36-6.23), or alcoholic liver disease (OR = 4.20; 95% CI: 1.89-9.35). The only predictors of receipt of therapy were presentation at tumor board conference (OR = 2.85; 95% CI: 1.42-5.72) and documented referral to oncology (OR = 2.33; 95% CI: 1.10-4.94). Conclusions: Less than one-third of patients who were diagnosed with HCC received screening before their diagnosis, and of those a large proportion received ail alpha-fetoprotein test only. In this study. the use of screening was too suboptimal to be expected to affect outcomes. C1 Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Kansas City Vet Affairs Med Ctr, Gastroenterol Sect, Kansas City, KS USA. Tennessee Valley Vet Affairs Med Ctr, Gastroenterol Sect, Nashville, TN USA. Vanderbilt Univ, Nashville, TN USA. RP Davila, JA (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM jdavila@bcm.tmc.edu NR 18 TC 64 Z9 64 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD SEP PY 2007 VL 41 IS 8 BP 777 EP 782 DI 10.1097/MCG.0b013e3180381560 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 205SN UT WOS:000249135000009 PM 17700427 ER PT J AU Kitamura, T Kitamura, YI Funahashi, Y Shawber, CJ Castrillon, DH Kollipara, R DePinho, RA Kitajewski, J Accili, D AF Kitamura, Tadahiro Kitamura, Yukari Ido Funahashi, Yasuhiro Shawber, Carrie J. Castrillon, Diego H. Kollipara, Ramya DePinho, Ronald A. Kitajewski, Jan Accili, Domenico TI A Foxo/Notch pathway controls myogenic differentiation and fiber type specification SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SKELETAL-MUSCLE; TRANSCRIPTION FACTORS; SIGNALING PATHWAYS; NOTCH; ACTIVATION; PROTEIN; TARGET; GAMMA; GENE; MYOD AB Forkhead box O (Foxo) transcription factors govern metabolism and cellular differentiation. Unlike Foxo-dependent metabolic pathways and target genes, the mechanisms by which these proteins regulate differentiation have not been explored. Activation of Notch signaling mimics the effects of Foxo gain of function on cellular differentiation. Using muscle differentiation as a model system, we show that Foxo physically and functionally interacts with Notch by promoting corepressor clearance from the Notch effector Csl, leading to activation of Notch target genes. Inhibition of myoblast differentiation by constitutively active Foxo1 is partly rescued by inhibition of Notch signaling while Foxo1 loss of function precludes Notch inhibition of myogenesis and increases myogenic determination gene (MyoD) expression. Accordingly, conditional Foxo1 ablation in skeletal muscle results in increased formation of MyoD-containing (fast-twitch) muscle fibers and altered fiber type distribution at the expense of myogenin-containing (slow-twitch) fibers. Notch/Foxo1 cooperation may integrate environmental cues through Notch with metabolic cues through Foxo1 to regulate progenitor cell maintenance and differentiation. C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Gunma Univ, Metab Signal Res Ctr, Inst Mol & Cellular Regulat, Maebashi, Gumma 371, Japan. Columbia Univ, Coll Phys & Surg, Dept Pathol & Obstet Gynecol, New York, NY 10027 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci,Dept Genet, Boston, MA 02115 USA. RP Accili, D (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, 1150 St Nicholas Ave, New York, NY 10032 USA. EM da230@columbia.edu FU NHLBI NIH HHS [R01 HL062454, 5 R01 HL062454]; NIDDK NIH HHS [DK64819, DK63608, K01 DK074629, P30 DK063608, DK57539, R01 DK057539, R01 DK064819] NR 53 TC 147 Z9 159 U1 3 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2007 VL 117 IS 9 BP 2477 EP 2485 DI 10.1172/JC132054 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 209JK UT WOS:000249384600019 PM 17717603 ER PT J AU Park, EJ Mora, JR Carman, CV Chen, J Sasaki, Y Cheng, G von Andrian, UH Shimaoka, M AF Park, Eun Jeong Mora, J. Rodrigo Carman, Christopher V. Chen, JianFeng Sasaki, Yoshiteru Cheng, Guiying von Andrian, Ulrich H. Shimaoka, Motornu TI Aberrant activation of integrin alpha(4)beta(7) suppresses lymphocyte migration to the gut SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID T-CELLS; IN-VIVO; HOMING SPECIFICITY; STRUCTURAL BASIS; ADHESION; BINDING; EXPRESSION; MADCAM-1; RECEPTOR; LIGAND AB Integrin adhesion molecules mediate lymphocyte migration and homing to normal and inflamed tissues. While the ligand-binding activity of integrins is known to be modulated by conformational changes, little is known about how the appropriate balance of integrin adhesiveness is maintained in order to optimize the migratory capacity of lymphocytes in vivo. In this study we examined the regulation of the gut homing receptor (alpha(4)beta(7) integrin by manipulating at the germline level an integrin regulatory domain known as adjacent to metal ion-dependent adhesion site (ADMIDAS). ADMIDAS normally serves to raise the activation threshold of alpha(4)beta(7)(, thereby stabilizing it in the default nonadhesive state. Lymphocytes from knockin beta(7) (D146A) mice, which harbor a disrupted ADMIDAS, not only expressed an alpha(4)beta(7) integrin that persistently adhered to mucosal addressin cell adhesion molecule-1 (MAWAM-1), but also exhibited perturbed cell migration along MAdCAM-1 substrates resulting from improper de-adhesion of the lymphocyte trailing edge. In vivo, aberrantly activated alpha(4)beta(7) enhanced adhesion to Peyer's patch venules, but suppressed lymphocyte homing to the gut, diminishing the capacity of T cells to induce colitis. Our results underscore the importance of a proper balance in the adhesion and de-adhesion of the alpha(4)beta(7) integrin, both for lymphocyte trafficking to the gut and for colitis progression. C1 Inst Biomed Res, CBR, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. RP Shimaoka, M (reprint author), Inst Biomed Res, CBR, 200 Longwood Ave,Room 253, Boston, MA 02115 USA. EM shimaoka@cbrinstitute.org RI von Andrian, Ulrich/A-5775-2008; Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU NHLBI NIH HHS [P01 HL048675, HL048675]; NIAID NIH HHS [AI061663, AI063421, R01 AI061663, R01 AI063421] NR 54 TC 40 Z9 43 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2007 VL 117 IS 9 BP 2526 EP 2538 DI 10.1172/JC131570 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 209JK UT WOS:000249384600024 PM 17786243 ER PT J AU Lang, JD Teng, X Churnley, P Crawford, JH Isbell, TS Chacko, BK Liu, Y Jhala, N Crowe, DR Smith, AB Cross, RC Frenette, L Kelley, EE Wilhite, DW Hall, CR Page, GP Fallon, MB Bynon, JS Eckhoff, DE Patel, RP AF Lang, John D., Jr. Teng, Xinjun Churnley, Phillip Crawford, Jack H. Isbell, T. Scott Chacko, Balu K. Liu, Yuliang Jhala, Nirag Crowe, D. Ralph Smith, Alvin B. Cross, Richard C. Frenette, Luc Kelley, Eric E. Wilhite, Diana W. Hall, Cheryl R. Page, Grier P. Fallon, Michael B. Bynon, J. Steven Eckhoff, Devin E. Patel, Rakesh P. TI Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE GENERATION; ISCHEMIA/REPERFUSION INJURY; ANOXIC TISSUES; BLOOD-FLOW; IN-VIVO; CELL; HEMOGLOBIN; REDUCTION; KINETICS AB Ischemia/reperfusion (IR) injury in transplanted livers contributes to organ dysfunction and failure and is characterized in part by loss of NO bioavailability. Inhalation of NO is nontoxic and at high concentrations (80 ppm) inhibits IR injury in extrapulmonary tissues. In this prospective, blinded, placebo-controned study, we evaluated the hypothesis that administration of inhaled NO (iNO; 80 ppm) to patients undergoing orthotopic liver transplantation inhibits hepatic IR injury, resulting in improved liver function. Patients were randomized to receive either placebo or iNO (n = 10 per group) during the operative period only. When results were adjusted for cold ischemia time and sex, iNO significantly decreased hospital length of stay, and evaluation of serum transaminases (alanine transaminase, aspartate aminotransferase) and coagulation times (prothrombin time, partial thromboplastin time) indicated that iNO improved the rate at which liver function was restored after transplantation. iNO did not significantly affect changes in inflammatory markers in liver tissue 1 hour after reperfusion but significantly lowered hepatocyte apoptosis. Evaluation of circulating NO metabolites indicated that the most likely candidate transducer of extrapulmonary effects of iNO was nitrite. In summary, this study supports the clinical use of iNO as an extrapulmonary therapeutic to improve organ function following transplantation. C1 Univ Washington, Sch Med, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Birmingham, Dept Pathol, Birmingham, AL USA. Univ Birmingham, Dept Anesthesiol, Birmingham, AL USA. Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15260 USA. Univ Alabama, Dept Biostat, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL USA. Univ Alabama, Dept Surg, Birmingham, AL USA. Univ Alabama, Ctr Free Rad Biol, Birmingham, AL USA. RP Patel, RP (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Anesthesiol, 1660 S Columbian Way, Seattle, WA 98108 USA. EM rakeshp@uab.edu OI Isbell, Timothy/0000-0003-0979-0582; Patel, Rakesh/0000-0002-1526-4303 NR 41 TC 124 Z9 127 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2007 VL 117 IS 9 BP 2583 EP 2591 DI 10.1172/JCI31892 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 209JK UT WOS:000249384600029 PM 17717604 ER PT J AU Citron, DM Goldstein, EJC Merriam, CV Lipsky, BA Abramson, MA AF Citron, Diane M. Goldstein, Ellie J. C. Merriam, C. Vreni Lipsky, Benjamin A. Abramson, Murray A. TI Bacteriology of moderate-to-severe diabetic foot infections and in vitro activity of antimicrobial agents SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; VERTEBRAL OSTEOMYELITIS; SWAB CULTURES; RISK-FACTORS; SUSCEPTIBILITY; ULCERS; LUGDUNENSIS; PREVALENCE; MANAGEMENT; RESISTANCE AB As part of a United States-based multicenter clinical trial, conducted from 2001 to 2004, that compared ertapenern to piperacillin-tazobactam for the treatment of moderate-to-severe diabetic foot infections (DFIs), we obtained 454 pretreatment specimens from 433 patients. After debridement, the investigators collected wound specimens, mostly by curettage or biopsy, and sent them to the R. M. Alden Research Laboratory for aerobic and anaerobic culture. Among the 427 positive cultures, 83.8% were polymicrobial, 48% grew only aerobes, 43.7% had both aerobes and anaerobes, and 1.3% had only anaerobes. Cultures yielded a total of 1,145 aerobic strains and 462 anaerobic strains, with an average of 2.7 organisms per culture (range, I to 8) for aerobes and 2.3 organisms per culture (range, I to 9) for anaerobes. The predominant aerobic organisms were oxacillin-susceptible Staphylococcus aureus (14.3%), oxacillin-resistant Staphylococcus aureus (4.4%), coagulase-negative Staphylococcus species (15.3%), Streptococcus species (15.5%), Enterococcus species (13.5%), Corynebacterium species (10.1%), members of the family Enterobacteriaceae (12.8%), and Pseudonumas aeruginosa (3.5%). The predominant anaerobes were gram-positive cocci (45.2%), Prevotella species (13.6%), Porphyromonas species (11.3%), and the Bacteroides fragilis group (10.2%). Pure cultures were noted for 20% of oxacillin-resistant Staphylococcus aureus cultures, 9.2% of Staphylococcus epidermidis cultures, and 2.5% of P. aeruginosa cultures. Two or more species of Staphylococcus were present in 13.1% of the patients. Ertapenem and piperacillin-tazobactam were each active against > 98% of the enteric gram-negative rods, methicillin-sensitive S. aureus, and anaerobes. Among the fluoroquinolones, 24% of anaerobes, especially the gram-positive cocci, were resistant to moxifloxacin; 27% of the gram-positive aerobes but only 6% of the members of the family Enterobacteriaceae were resistant to levofloxacin. Moderate-to-severe DFIs are typically polymicrobial, and almost half include anaerobes. Our antibiotic susceptibility results can help to inform therapeutic choices. C1 RM Alden Res Lab, Santa Monica, CA 90404 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Washington, Sch Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Merck & Co Inc, Merck Res Labs, West Point, PA USA. RP Citron, DM (reprint author), RM Alden Res Lab, 2001 Santa Monica Blvd,Suite 685W, Santa Monica, CA 90404 USA. EM d.m.citron@verizon.net RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 56 TC 118 Z9 128 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2007 VL 45 IS 9 BP 2819 EP 2828 DI 10.1128/JCM.00551-07 PG 10 WC Microbiology SC Microbiology GA 211EK UT WOS:000249506900011 PM 17609322 ER PT J AU Brito, LCN Teles, FR Teles, RP Franca, EC Ribeiro-Sobrinho, AP Haffajee, AD Socransky, SS AF Brito, L. C. N. Teles, F. R. Teles, R. P. Franca, E. C. Ribeiro-Sobrinho, A. P. Haffajee, A. D. Socransky, S. S. TI Use of multiple-displacement amplification and checkerboard DNA-DNA hybridization to examine the microbiota of endodontic infections SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; ROOT-CANAL INFECTIONS; ACINETOBACTER-BAUMANNII; PORPHYROMONAS-GINGIVALIS; FUSOBACTERIUM-NUCLEATUM; TREPONEMA-DENTICOLA; RESISTANT ACINETOBACTER; DIALISTER-PNEUMOSINTES; MOLECULAR EPIDEMIOLOGY; GEOGRAPHIC LOCATIONS AB Multiple-displacement amplification (MDA) has been used to uniformly amplify bacterial genomes present in small samples, providing abundant targets for molecular analysis. The purpose of this investigation was to combine MDA and checkerboard DNA-DNA hybridization to examine the microbiota of endodontic infections. Sixty-six samples were collected from teeth with endodontic infections. Nonamplified and amplified samples were analyzed by checkerboard DNA-DNA hybridization for levels and proportions of 77 bacterial taxa. Counts, percentages of DNA probe counts, and percentages of teeth colonized for each species in amplified and nonamplified samples were computed. Significance of differences for each species between amplified and nonamplified samples was sought mith Wilcoxon signed-rank test and adjusted for multiple comparisons. The amount of DNA in the samples ranged from 6.80 ( +/- 5.2) ng before to 6.26 ( +/- 1.73) mu g after MDA. Seventy of the 77 DNA probes hybridized with one or more of the nonamplified samples. All probes hybridized with at least one sample after amplification. Most commonly detected species at levels of > 10(4) in both amplified and nonamplified samples were Prevotella tannerae and Acinetobacter baumannii at frequencies between 89 and 100% of samples. The mean number of species at counts of > 10(4) in amplified samples was 51.2 +/- 2.2 and in nonamplified samples was 14.5 +/- 1.7. The endodontic microbiota was far more complex than previously shown, although microbial profiles at teeth with or without periradicular lesions did not differ significantly. Species commonly detected in endodontic samples included P. tannerae, Prevotella oris, and A. baumannii. C1 Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Brito, LCN (reprint author), Univ Fed Minas Gerais, Gerais Sch Dent, Av Antonio Carlos 6627 Sl,3310 Bairro, BR-31270901 Belo Horizonte, MG, Brazil. EM luitauna@yahoo.com.br RI Sobrinho, Antonio/H-3245-2012 FU NIDCR NIH HHS [T32-DE-07327, R01 DE014242, DE-12108, DE-14242, T32 DE007327, R01 DE012108] NR 64 TC 31 Z9 31 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2007 VL 45 IS 9 BP 3039 EP 3049 DI 10.1128/JCM.02618-06 PG 11 WC Microbiology SC Microbiology GA 211EK UT WOS:000249506900043 PM 17634304 ER PT J AU Burstein, HJ Winer, EP AF Burstein, Harold J. Winer, Eric P. TI Aromatase inhibitors and arthralgias: A new frontier in symptom management for breast cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; AMERICAN-SOCIETY; BONE HEALTH; TRIAL; TAMOXIFEN; LETROZOLE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. NR 14 TC 41 Z9 42 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2007 VL 25 IS 25 BP 3797 EP 3799 DI 10.1200/JCO.2007.11.9529 PG 3 WC Oncology SC Oncology GA 209VL UT WOS:000249416000003 PM 17761968 ER PT J AU Earle, CC AF Earle, Craig C. TI Cancer survivorship research and guidelines: Maybe the cart should be beside the horse SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. RP Earle, CC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 4 TC 14 Z9 14 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2007 VL 25 IS 25 BP 3800 EP 3801 DI 10.1200/JCO.2007.12.2325 PG 2 WC Oncology SC Oncology GA 209VL UT WOS:000249416000004 PM 17646665 ER PT J AU Viale, G Regan, MM Maiorano, E Mastropasqua, MG Dell'Orto, P Rasmussen, BB Raffoul, J Neven, P Orosz, Z Braye, S Oehlschlegel, C Thurlimann, B Gelber, RD Castiglione-Gertsch, M Price, KN Goldhirsch, A Gusterson, BA Coates, AS AF Viale, Giuseppe Regan, Meredith M. Maiorano, Eugenio Mastropasqua, Mauro G. Dell'Orto, Patrizia Rasmussen, Birgitte Bruun Raffoul, Johnny Neven, Patrick Orosz, Zsolt Braye, Stephen Oehlschlegel, Christian Thuerlimann, Beat Gelber, Richard D. Castiglione-Gertsch, Monica Price, Karen N. Goldhirsch, Aron Gusterson, Barry A. Coates, Alan S. TI Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 28th Annual San Antonio Breast Cancer Symposium CY DEC 08-11, 2005 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas, San Antonio, Hlth Sci Ctr ID IMMUNOHISTOCHEMICAL ANALYSIS; ENDOCRINE THERAPY; WOMEN; ANASTROZOLE; COMBINATION; TIME AB Purpose To evaluate locally versus centrally assessed estrogen ( ER) and progesterone ( PgR) receptor status and the impact of PgR on letrozole adjuvant therapy compared with tamoxifen in postmenopausal women with early breast cancer. Patients and Methods Breast International Group ( BIG) 1- 98 randomly assigned 8,010 patients to four arms comparing letrozole and tamoxifen with sequences of each agent. The Central Pathology Office received material for 6,549 patients ( 82%), of which 79% were assessable ( 6,291 patients). Prognostic and predictive value of both local and central hormone receptor expression on disease- free survival ( DFS) were evaluated among 3,650 assessable patients assigned to the monotherapy arms. Prognostic value and the treatment effect were estimated for centrally assessed ER and PgR expression levels using the Subpopulation Treatment Effect Pattern Plot. Results Central review confirmed 97% of tumors as hormone receptor - positive ( ER and/ or PgR >= 10%). Of 105 tumors locally ER- negative, 73 were found to have more than 10% positive cells, and eight had 1% to 9%. Of 6,100 tumors locally ER positive, 66 were found to have no staining, and 54 had only 1% to 9%. Discordance was more marked for PgR than ER. Patients with tumors reclassified centrally as ER- negative, or as hormone receptor - negative, had poor DFS. Centrally assessed ER and PgR showed prognostic value. Among patients with centrally assessed ER- expressing tumors, letrozole showed better DFS than tamoxifen, irrespective of PgR expression level. Conclusion Central review changed the assessment of receptor status in a substantial proportion of patients, and should be performed whenever possible in similar trials. PgR expression did not affect the relative efficacy of letrozole over tamoxifen. C1 Univ Milan, European Inst Oncol, Dept Pathol, Lab Med, Milan, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Int Breast Canc Study Grp, Boston, MA 02115 USA. Univ Bari, Dept Pathol Anat, Bari, Italy. European Inst Oncol, Div Pathol, Lab Med, Milan, Italy. Nordsjaellands Hosp, Dept Pathol, Hillerod, Denmark. Ctr Hosp Belfort Montbeliard, Serv Anat & Cytol Pathol, Montbeliard, France. UZ KU Leuven, Multidisciplinary Breast Ctr, Dept Gynecol Oncol, Louvain, Belgium. Natl Inst Oncol, Dept Pathol, Budapest, Hungary. Univ Newcastle, John Hunter Hosp, Australian new Zealand Breast Canc trials Grp, Hunter Area Pathol Serv, New Lambton Heights, NSW, Australia. Kantonsspital, Swiss Grp Clin Canc Res, Bern, Switzerland. Kantonsspital, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. Harvard Univ, Sch Med, Dana Farber Canc Inst, Frontier Sci & Technol Res Fdn, Boston, MA 02115 USA. Harvard Univ, Sch Med, IBCSG Stat Ctr, Swiss Grp Clin Canc Res, Boston, MA 02115 USA. IBCSG Coordinating Ctr, Bern, Switzerland. IBCSG Stat Ctr, Frontier Sci & Technol Res Fdn, Boston, MA USA. European Inst Oncol, Milan, Italy. Oncol Inst So, Bellinzona, Switzerland. Univ Glasgow, Western Infirm, Div Canc Sci & Mol Pathol, Glasgow G11 6NT, Lanark, Scotland. Int Breast Canc Study Grp, Bern, Switzerland. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. RP Viale, G (reprint author), Ist Europeo Oncol, Div Anat Patol, Med Lab, Via Ripamonti,435, I-20141 Milan, Italy. EM giuseppe.viale@ieo.it RI gusterson, barry/D-3752-2009; Maiorano, Eugenio/F-1382-2015 FU NCI NIH HHS [CA-75362] NR 27 TC 226 Z9 230 U1 1 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2007 VL 25 IS 25 BP 3846 EP 3852 DI 10.1200/JCO.2007.11.9453 PG 7 WC Oncology SC Oncology GA 209VL UT WOS:000249416000011 PM 17679725 ER PT J AU Suter, TM Procter, M van Veldhuisen, DJ Muscholl, M Bergh, J Carlomagno, C Perren, T Passalacqua, R Bighin, C Klijn, JGM Ageev, FT Hitre, E Groetz, J Iwata, H Knap, M Gnant, M Muehlbauer, S Spence, A Gelber, RD Piccart-Gebhart, MJ AF Suter, Thomas M. Procter, Marion van Veldhuisen, Dirk J. Muscholl, Michael Bergh, Jonas Carlomagno, Chiara Perren, Timothy Passalacqua, Rodolfo Bighin, Claudia Klijn, Jan G. M. Ageev, Fail T. Hitre, Erika Groetz, Juergen Iwata, Hiroji Knap, Malgorzata Gnant, Michael Muehlbauer, Susanne Spence, Alison Gelber, Richard D. Piccart-Gebhart, Martine J. TI Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID HER2-POSITIVE BREAST-CANCER; VENTRICULAR MYOCYTES; CHEMOTHERAPY; CARDIOTOXICITY; NEUREGULIN-1-BETA; DYSFUNCTION; DOXORUBICIN; THERAPY; GROWTH; ERBB2 AB Purpose The purpose of this analysis was to investigate trastuzumab- associated cardiac adverse effects in breast cancer patients after completion of ( neo) adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant ( HERA) trial is a three- group, multicenter, open- label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer. Only patients who after completion of ( neo) adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction ( LVEF >= 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low ( 4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation ( severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin ( 287 mg/m(2) v 257 mg/m(2)) or epirubicin ( 480 mg/m(2) v 422 mg/m(2)) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria. C1 Univ Hosp Bern, Swiss Cardiovasc Ctr, Basel, Switzerland. F Hoffmann La Roche, Basel, Switzerland. Frontier Sci, Kingussie, Scotland. Univ Groningen, Dept Cardiol, Groningen, Netherlands. Dr Daniel Den Hoed Canc Ctr, Erasmus MC, Rotterdam, Netherlands. Kardiol Praxis, Munich, Germany. Krakenhaus Gerresheim, Cardiol Wilhelm Marx Haus, Dusseldorf, Germany. Univ Hamburg Hosp, Dept Cardiol, D-2000 Hamburg, Germany. Univ Hosp Stockholm, Karolinska Inst, Dept Cardiol, Stockholm, Sweden. Univ Naples Federico 2, Dept Mol & Clin Endocrinol, Naples, Italy. Ist Ospitalieri, Div Med Oncol, Cremona, Italy. Natl Canc Inst, Genoa, Italy. UK Clin Ctr, Natl Canc Inst, Leeds, W Yorkshire, England. St James Univ Hosp, Leeds, W Yorkshire, England. Cardiol Res Complex, Moscow, Russia. Natl Inst Oncol, Budapest, Hungary. Aichi Canc Ctr Hosp, Nagoya, Aichi 464, Japan. Med Univ Vienna, Vienna, Austria. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Univ Libre Bruxelles, Inst Jules Bordet, Dept Med & Breast Int Grp, Brussels, Belgium. RP Suter, TM (reprint author), Univ Hosp Bern, Swiss Cardiovasc Ctr, Inselspital, CH-3010 Bern, Switzerland. EM thomas.suter@insel.ch RI van Veldhuisen, Dirk Jan/E-8967-2014; OI Perren, Timothy/0000-0001-8472-8856; Gnant, Michael/0000-0003-1002-2118 NR 14 TC 268 Z9 278 U1 2 U2 18 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2007 VL 25 IS 25 BP 3859 EP 3865 DI 10.1200/JCO.2006.09.1611 PG 7 WC Oncology SC Oncology GA 209VL UT WOS:000249416000013 PM 17646669 ER PT J AU Janne, PA von Pawel, J Cohen, RB Crino, L Butts, CA Olson, SS Eiseman, IA Chiappori, AA Yeap, BY Lenehan, PF Dasse, K Sheeran, M Bonomi, PD AF Jaenne, Pasi A. von Pawel, Joachim Cohen, Roger B. Crino, Lucio Butts, Charles A. Olson, Steven S. Eiseman, Irene A. Chiappori, Alberto A. Yeap, Beow Y. Lenehan, Peter F. Dasse, Kathy Sheeran, Meredith Bonomi, Philip D. TI Multicenter, randomized, phase II trial of CI-1033, an irreversible pan-ERBB inhibitor, for previously treated advanced non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; COOPERATIVE-ONCOLOGY-GROUP; TYROSINE KINASE INHIBITOR; GENE COPY NUMBER; PROTEIN EXPRESSION; GEFITINIB THERAPY; FAMILY-MEMBERS; EGF RECEPTOR; SURVIVAL; SENSITIVITY AB Purpose To evaluate the efficacy of the pan-ERBB inhibitor, CI- 1033, in platinum- refractory or recurrent advanced-stage non-small-cell lung cancer ( NSCLC). Patients and Methods This open-label, randomized phase II trial evaluated CI- 1033 in patients with advanced- stage NSCLC who experienced treatment failure after or were refractory to platinum- based chemotherapy. Three oral CI- 1033 doses were evaluated in 21- day dosing cycles: 50 mg daily for 21 consecutive days, 150 mg daily for 21 consecutive days, and 450 mg daily for 14 consecutive days followed by 7 days of no treatment. The primary efficacy end point was the 1- year survival rate. Results One hundred sixty-six patients were randomly assigned to treatment. Baseline patient demographics were well balanced. The most common drug- related adverse events were rash and diarrhea. The 450- mg arm ( 14 days on/ 7 days off) was closed early due to an excessive rate of adverse events. The 1- year survival rates were 29%, 26%, and 29%, respectively, in the three arms. The response rates were 2%, 2%, and 4%, and stable disease was confirmed in 16%, 23%, and 18% of patients, respectively, in the three study arms. Exploratory analyses demonstrated a prolonged survival in patients who developed a rash and in those with baseline tumor ERBB-2 expression. Conclusion CI- 1033 had modest activity in unselected NSCLC patients but did not meet its primary end point. Future studies should focus on identifying methods of patient selection. C1 Lowe Ctr Thorac Oncol, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Asklepios Fach Klin Fuer Lungenkrankheiten, Gauting, Germany. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Osped Silvestini, Perugia, Italy. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Pfizer Global Res & Dev, Ann Arbor, MI USA. H Lee Moffitt Canc Ctr & Res Inst, Res Inst, Tampa, FL USA. Rush Canc Inst, Sect Oncol, Chicago, IL USA. RP Janne, PA (reprint author), Lowe Ctr Thorac Oncol, Dana Farber Canc Inst, Dept Med Oncol, 820A,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org NR 39 TC 75 Z9 77 U1 2 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2007 VL 25 IS 25 BP 3936 EP 3944 DI 10.1200/JCO.2007.11.1336 PG 9 WC Oncology SC Oncology GA 209VL UT WOS:000249416000024 PM 17761977 ER PT J AU Cmelak, AJ Li, SG Goldwasser, MA Murphy, B Cannon, M Pinto, H Rosenthal, DI Gillison, M Forastiere, AA AF Cmelak, Anthony J. Li, Sigui Goldwasser, Meredith A. Murphy, Barbara Cannon, Michael Pinto, Harlan Rosenthal, David I. Gillison, Maura Forastiere, Arlene A. TI Phase II trial of chemoradiation for organ preservation in resectable stage III or IV squamous cell carcinomas of the larynx or oropharynx: Results of Eastern Cooperative Oncology Group study E2399 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID PERFORMANCE STATUS SCALE; LOCALLY ADVANCED HEAD; NECK-CANCER PATIENTS; RADIATION-THERAPY; CONCURRENT CHEMORADIATION; FUNCTIONAL ASSESSMENT; TUMOR OXYGENATION; CISPLATIN; RADIOTHERAPY; ERYTHROPOIETIN AB Purpose Taxane- based concurrent chemoradiotherapy ( CCR) for head and neck cancers has proven to have a favorable toxicity profile compared with cisplatin and radiation. This phase II multi- institutional trial evaluates taxane- based induction chemotherapy followed by CCR for organ preservation in resectable stage III/IVA and IVB larynx and oropharynx ( OP) cancer patients. Patients and Methods Eligibility required resectable stage T2N+, or T3-T4N0-3M0 biopsy- proven squamous carcinoma, age at least 18 years, PS 0 to 2, good organ function, and no prior chemotherapy or radiation. Treatment was induction paclitaxel 175 mg/m(2) and carboplatin area under the concentration-time curve ( AUC) 6 for two cycles every 21 days followed by concurrent paclitaxel 30 mg/m(2) every 7 days with 70 Gy if no evidence of tumor progression. Weekly erythropoietin alpha 40 kU was used for suboptimal hemoglobin (< 14 gm/dL men, < 13 gm/dL women). The primary end point was organ preservation ( freedom from primary site salvage surgery or primary tumor recurrence). Results One hundred five of 111 patients ( 36 larynx, 69 OP) were eligible. Median follow- up was 36.7 months. Ninety- four percent received full- dose radiotherapy and 91% received at least five cycles of concurrent paclitaxel. No patient progressed while receiving chemotherapy. Organ preservation was 81% at 2 years after completion of therapy ( larynx 74%, OP 84%). Thirteen patients required primary-site salvage surgery ( seven larynx, six OP), and six of these have progressed and died ( three larynx, three OP). Thirteen patients developed distant metastases ( seven larynx, six OP; P =.02) and 10 of 36 larynx and 11 of 69 OP patients have died as a result of their disease. Two- year survival is 76% ( 63% larynx v 83% OP). Conclusion A high organ preservation rate was obtained with this regimen for OP but not for larynx patients. Toxicity was low, and induction chemotherapy did not preclude delivery of concurrent chemoradiotherapy. C1 Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Canc, Wichita, KS USA. Stanford Univ, Ctr Med, Stanford, CA 94305 USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Cmelak, AJ (reprint author), Vanderbilt Univ, Med Ctr, B-902 TVC,22nd Ave at Pierce, Nashville, TN 37232 USA. EM Anthony.cmelak@vanderbilt.edu NR 33 TC 85 Z9 87 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2007 VL 25 IS 25 BP 3971 EP 3977 DI 10.1200/JCO.2007.10.8951 PG 7 WC Oncology SC Oncology GA 209VL UT WOS:000249416000029 PM 17761982 ER PT J AU Callahan, MJ Crum, CP Medeiros, F Kindelberger, DW Elvin, JA Garber, JE Feltmate, CM Berkowitz, RS Muto, MG AF Callahan, Michael J. Crum, Christopher P. Medeiros, Fabiola Kindelberger, David W. Elvin, Julia A. Garber, Judy E. Feltmate, Colleen M. Berkowitz, Ross S. Muto, Michael G. TI Primary Fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-of-Gynecologic-Oncologists CY MAR 22-26, 2006 CL Palm Springs, CA SP Soc Gynecol Oncologists ID PROPHYLACTIC OOPHORECTOMY SPECIMENS; REDUCING SALPINGO-OOPHORECTOMY; MUTATION CARRIERS; INTRAEPITHELIAL CARCINOMA; PATHOLOGICAL FINDINGS; SEROUS CARCINOMA; OCCULT CANCER; BREAST; PENETRANCE; FAMILIES AB Purpose To review the frequency and location of malignancies detected after prophylactic salpingo-oophorectomy in women with BRCA mutations. Methods Medical records and pathology findings were reviewed from BRCA-positive women undergoing prophylactic surgery for ovarian cancer risk reduction who underwent complete examination of the adnexa. Patients undergoing this procedure between January 1999 and January 2007 were identified. Results From January 1999 to January 2007, 122 BRCA-positive patients underwent prophylactic surgery in the Division of Gynecologic Oncology at Brigham and Women's Hospital. The median age was 46.5 years (range, 33 to 76 years). Seven (5.7%) were found to have an early malignancy in the upper genital tract and all patients were age >= 44 years at diagnosis. Of seven consecutive cancers culled between January 1999 and January 2007, all (100%) originated in the fimbrial or ampullary region of the tube; six had an early (intraepithelial) component. Two were associated with surface implants on the ovary and two required repeated sectioning to detect microscopic carcinomas in the fimbria. Conclusion The distal fallopian tube seems to be the dominant site of origin for early malignancies detected in approximately 6% of women undergoing ovarian cancer risk-reduction surgery. The greatest proportion of serous cancer risk in BRCA mutation-positive women should be assigned to the fimbria rather than the ovary, and future clinical and research protocols should employ thorough examination of the fimbria, including multiple sections from each tissue block, to maximize detection of early malignancies in this population. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Canc Risk & Prevent Program, Boston, MA 02115 USA. RP Callahan, MJ (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mmuto@partners.org NR 29 TC 242 Z9 252 U1 1 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2007 VL 25 IS 25 BP 3985 EP 3990 DI 10.1200/JCO.2007.12.2622 PG 6 WC Oncology SC Oncology GA 209VL UT WOS:000249416000031 PM 17761984 ER PT J AU Morris, DW Rush, AJ Jain, S Fava, M Wisniewski, SR Balasubramani, GK Khan, AY Trivedi, MH AF Morris, David W. Rush, A. John Jain, Shailesh Fava, Maurizio Wisniewski, Stephen R. Balasubramani, G. K. Khan, Ahsan Y. Trivedi, Madhukar H. TI Diurnal mood variation in outpatients with major depressive disorder: Implications for DSM-V from an analysis of the sequenced treatment alternatives to relieve depression study data SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; DIAGNOSTIC SCREENING QUESTIONNAIRE; INTERACTIVE VOICE RESPONSE; REPORT QIDS-SR; SLEEP-DEPRIVATION; QUICK INVENTORY; RATING-SCALE; PSYCHOMETRIC EVALUATION; ENDOGENOUS-DEPRESSION; CORTISOL SECRETION AB Objective: Diurnal mood variation (DMV) with early morning worsening is considered a classic symptom of melancholic features in The Diagnostic and Statistical Manual of Mental Disorders (DSM) as well as The International Classification of Diseases (ICD) criteria for so-matic major depressive disorder (MDD). Using the unique opportunity afforded by the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study data, we examined whether DMV with afternoon or evening worsening, in addition to classic early morning worsening, was related to other symptom constructs to determine whether the exclusive reliance on morning worsening is justified in defining melancholic features. Method: Baseline demographic and clinical characteristics. as well as depressive symptoms, including DMV. were evaluated in 3744 outpatients with nonpsychotic MDD enrolled in the STAR*D study. Results: DMV in at least one of the time periods was reported by 22.4% (N = 837) of the sample. Only 3.3% (N = 28) of these 837 patients with DMV attributed it to environmental factors. Of the 809 participants (96.7%) with DMV unrelated to environmental events, only 31.9% (N = 258) reported morning worsening, while 19.5%, (N = 158) and 48.6% (N = 393) reported afternoon and evening worsening, respectively. Minimal distinctions in demographic characteristics. clinical features, and depressive symptoms were found between participants with morning worsening and those with either afternoon or evening worsening. More importantly, other melancholic symptom features were associated with DMV regardless of time of worsening. Conclusion: DMV was meaningfully related to other melancholia criteria regardless of when the DMV occurred. If replicated, these findings suggest that DMV as a component of melancholic features might be expanded to include any DMV not simply early morning worsening. C1 Univ Texas, SW Med Ctr, Mood Disorders Program & Clin, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Clin Sci, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Kansas, Wichita, KS USA. Clin Res Inst, Wichita, KS USA. RP Trivedi, MH (reprint author), Univ Texas, SW Med Ctr, Mood Disorders Program & Clin, Exchange Pk Express,Amer Gen Tower,6363 Forest Pk, Dallas, TX 75390 USA. EM madhukar.trivedi@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 46 TC 15 Z9 15 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2007 VL 68 IS 9 BP 1339 EP 1347 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 214NP UT WOS:000249745500003 PM 17915971 ER PT J AU Sachs, GS Gaulin, BD Gutierrez-Esteinou, R McQuade, RD Pikalov, A Pultz, JA Sanchez, R Marcus, RN Crandall, DI AF Sachs, Gary S. Gaulin, Bruce D. Gutierrez-Esteinou, Rolando McQuade, Robert D. Pikalov, Andrei, III Pultz, Joseph A. Sanchez, Raymond Marcus, Ronald N. Crandall, David I. TI Antimanic response to aripiprazole in bipolar I disorder patients is independent of the agitation level at baseline SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; INTRAMUSCULAR HALOPERIDOL; ACUTE MANIA; RANDOMIZED-TRIAL; PARTIAL AGONIST; OLANZAPINE; EFFICACY; SCHIZOPHRENIA; ZIPRASIDONE AB Objective: To examine the antimanic efficacy of the relatively nonsedating antipsychotic aripiprazole in patients with bipolar I disorder and high or low baseline levels of agitation. Method: Data were pooled for this post hoc analysis from two 3-week, placebo-controlled trials of aripiprazole in acute mania (DSM-IV). Patients randomly assigned to aripiprazole 30 mg/day (N = 259) or placebo (N = 254) were Classified as having either high (Positive and Negative Syndrome Scale [PANSS] Excited Component [PEC] score of >= 14 and a score of >= 4 on at least one PEC item) or low (PEC < 14) levels of agitation at baseline. Efficacy measures were changes in Young Mania Rating Scale (YMRS) scores, Clinical Global Impressions-Bipolar (CGI-BP) scores, and PEC scores. Efficacy and agitation measurements were assessed by analysis of covariance. Results: From the first week of therapy onward, aripiprazole-treated subjects had significantly greater reduction from baseline in YMRS total scores than placebo-treated subjects in both the high- and low-agitation groups (p <.05 for both groups) and significantly improved CGI-BP scores vs. placebo at end point (p <.05 for both). In highly agitated patients receiving aripiprazole, PEC scores were significantly decreased versus placebo at end point (p <.05). In patients with low agitation receiving aripiprazole, no increases in PE scores were seen, and a significant reduction in agitation symptoms was apparent after adjustment for baseline PEC scores. Conclusions: Aripiprazole was superior to placebo in reducing the severity of both mania and agitation in highly agitated patients with bipolar I disorder and showed significant antimanic activity in patients with low levels of agitation without increasing agitation. These findings suggest that aripiprazole's antimanic effect is specific and not limited to control of agitation through sedation. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Bristol Myers Squibb Co, Plainsboro, NJ USA. Bristol Myers Squibb Co, Lawrenceville, NJ USA. Otsuka Amer Pharmaceut Inc, Princeton, NJ USA. Otsuka Amer Pharmaceut Inc, Rockville, MD USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, 50 Stanford St, Boston, MA 02114 USA. EM sachsg@aol.com RI Piper, Walter/B-7908-2009 NR 43 TC 18 Z9 19 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2007 VL 68 IS 9 BP 1377 EP 1383 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 214NP UT WOS:000249745500008 PM 17915976 ER PT J AU Gelenberg, AJ de Leon, J Evins, AE Parks, JJ Rigotti, NA AF Gelenberg, Alan J. de Leon, Jose Evins, A. Eden Parks, Joseph J. Rigotti, Nancy A. TI Smoking cessation in patients with psychiatric disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID FAGERSTROM TOLERANCE QUESTIONNAIRE; PLACEBO-CONTROLLED TRIAL; PURSUIT EYE-MOVEMENT; 2-YEAR FOLLOW-UP; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; MAJOR DEPRESSION; SMOOTH-PURSUIT; TOBACCO DEPENDENCE; GENETIC-VARIATION C1 Univ Arizona, Dept Psychiat, Tucson, AZ 85721 USA. Univ Kentucky, Eastern State Hosp, Mental Hlth Res Ctr, Lexington, KY USA. Univ Kentucky, Dept Psychiat, Lexington, KY USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Freedom Trail Clin, Boston, MA USA. State Missouri, Dept Mental Hlth, Jefferson City, MO USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gelenberg, AJ (reprint author), Univ Arizona, Dept Psychiat, Tucson, AZ 85721 USA. RI de Leon, Jose/F-2709-2013 OI de Leon, Jose/0000-0002-7756-2314 NR 76 TC 7 Z9 7 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2007 VL 68 IS 9 BP 1404 EP 1410 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 214NP UT WOS:000249745500012 PM 17915980 ER PT J AU Marcus, DS Wang, TH Parker, J Csernansky, JG Morris, JC Buckner, RL AF Marcus, Daniel S. Wang, Tracy H. Parker, Jamie Csernansky, John G. Morris, John C. Buckner, Randy L. TI Open access series of imaging studies (OASIS): Cross-sectional MRI data in young, middle aged, nondemented, and demented older adults SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; CEREBRAL-CORTEX; BRAIN MR; VULNERABILITY; SEGMENTATION; DIAGNOSIS; REGIONS; ATROPHY; MATTER AB The Open Access Series of Imaging Studies is a series of magnetic resonance imaging data sets that is publicly available for study and analysis. The initial data set consists of a cross-sectional collection of 416 subjects aged 18 to 96 years. One hundred of the included subjects older than 60 years have been clinically diagnosed with very mild to moderate Alzheimer's disease. The subjects are all right-handed and include both men and women. For each subject, three or four individual TI-weighted magnetic resonance imaging scans obtained in single imaging sessions are included. Multiple within-session acquisitions provide extremely high contrast-to-noise ratio, making the data amenable to a wide range of analytic approaches including automated computational analysis. Additionally, a reliability data set is included containing 20 subjects without dementia imaged on a subsequent visit within 90 days of their initial session. Automated calculation of whole-brain volume and estimated total intracranial volume are presented to demonstrate use of the data for measuring differences associated with normal aging and Alzheimer's disease. C1 Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Marcus, DS (reprint author), Washington Univ, Sch Med, Dept Radiol, Campsu Box 8225,4525 Scott Ave, St Louis, MO 63110 USA. EM dmarcus@wustl.edu RI Morris, John/A-1686-2012 FU NCRR NIH HHS [RR 16594, RR14075]; NIA NIH HHS [R01 AG021910-04, P01 AG03991, P50 AG05681, R01 AG021910, R01 AG021910-03]; NIMH NIH HHS [P20 MH071616] NR 41 TC 380 Z9 384 U1 1 U2 20 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 2007 VL 19 IS 9 BP 1498 EP 1507 DI 10.1162/jocn.2007.19.9.1498 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 207KX UT WOS:000249251100007 PM 17714011 ER PT J AU Akpinar, E Koroglu, M Ptak, T AF Akpinar, Erhan Koroglu, Mert Ptak, Thomas TI Diffusion tensor MR imaging in pediatric head trauma SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE DTL; head trauma; pediatric ID WHITE-MATTER INJURY; GLASGOW COMA SCALE; AXONAL INJURY; BRAIN-INJURY; CHILDREN; ABNORMALITIES; SCORE; CT AB Purpose: We propose to investigate the fractional anisotropy (FA) values in pediatric patients with closed head trauma and correlate them with the initial Glasgow Coma Scale (GCS). Materials and Methods: A retrospective evaluation of 24 pediatric patients (15 men, 9 women; mean age, 13 years; range, 2-18 years) who underwent both unenhanced head computed tomography and cerebral magnetic resonance imaging (MRI), including the tenser diffusion sequence, within 30 days of the incident. Twenty-two atraumatic control patients (9 men, 13 women; mean age, 9 years; range, 4-17 years) were randomly selected from the records of the radiology department within the same period. Fractional anisotropy measurements were taken from each of 6 major white matter volumes. Data extracted from the record of each subject included GCS, initial head computed tomographic results, and length of hospital stay. Kruskal-Wallis and t tests were used for statistical evaluation. Results: The mean acute score on the GCS was 9.7 +/- 5. Mean duration of hospitalization days was 8.7 +/- 10. Statistically significant differences in mean FA values between trauma and control subjects were noted in corpus callosum. Trauma patients with positive findings on MRI and with GCS less than 10 also had lower FA values than patients with GCS greater than 10 and patients who had normal MRI findings. There was a negative correlation between time to discharge and FA values. Conclusions: In pediatric head trauma, MRI diffusion FA measurements can show abnormalities despite normal-appearing brain MRI findings. Larger investigations are required to verify the stability of correlations. C1 Hacettepe Univ, Fac Med, Dept Radiol, Ankara, Turkey. Massachusetts Gen Hosp, Harvard Med Sch, Div Emergency Radiol, Boston, MA USA. Suleyman Demirel Univ, Fac Med, Dept Radiol, Isparta, Turkey. RP Akpinar, E (reprint author), Hacettepe Univ, Fac Med, Dept Radiol, Ankara, Turkey. EM erhan.akpinar@gmail.com NR 28 TC 13 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2007 VL 31 IS 5 BP 657 EP 661 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 217RK UT WOS:000249964800001 PM 17895772 ER PT J AU Prasad, SR Sahani, DV Mino-Kenudson, M Narra, VR Humphrey, PA Menias, CO Chintapalli, KN AF Prasad, Srinivasa R. Sahani, Dushyant V. Mino-Kenudson, Mari Narra, Vamsi R. Humphrey, Peter A. Menias, Christine O. Chintapalli, Kedar N. TI Neoplasms of the perivascular epithelioid cell involving the abdomen and the pelvis: Cross-sectional imaging findings SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE PEComa; abdomen; pelvis; CT scan; magnetic; resonance imaging ID OF-THE-LITERATURE; RADIOLOGIC-PATHOLOGICAL CORRELATION; SARCOMA MALIGNANT PECOMA; RENAL ANGIOMYOLIPOMA; TUBEROUS SCLEROSIS; HEPATIC ANGIOMYOLIPOMA; MYOMELANOCYTIC TUMOR; SUGAR TUMOR; MINIMAL FAT; ADRENAL ANGIOMYOLIPOMA AB Neoplasms of the perivascular epithelioid cell (PEComas) represent a recently described heterogeneous group of mesenchymal tumors characterized by the presence of specific histological, immunohistochemical, and ultrastructural findings. The PEComas encompass a family of neoplasms that include angiomyolipomas, clear cell sugar tumors, and lymphangioleiomyomatosis. The PEComas demonstrate a wide spectrum of clinicobiological behavior and imaging findings. Perivascular epithelioid cell, as the name implies, is a unique cell that is characterized by perivascular distribution and epithelioid morphology. Perivascular epithelioid cell consistently shows immunoreactivity to melanocytic and smooth muscle markers including HMB-45 and actin. Abdominopelvic PEComas are found at a variety of somatic and visceral locations including kidney, liver, pancreas, gastrointestinal tract, genitourinary tract, peritoneum, and retroperitoneum. A subset of patients with abdominopelvic PEComas manifests tuberous sclerosis complex. In this paper, we review the histological spectrum and discuss the imaging findings of the PEComas that involve the abdomen and pelvis. C1 Univ Texas, Hlth Sci Ctr, Abdomin Radiol, San Antonio, TX 78229 USA. Univ Texas, Ctr Hearing Sci, Dept Radiol, San Antonio, TX USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Washington Univ, Dept Pathol, Dept Radiol, Mallinckrodt Inst Radiol, St Louis, MO USA. RP Prasad, SR (reprint author), Univ Texas, Hlth Sci Ctr, Abdomin Radiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM prasads@uthscsa.edu NR 71 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2007 VL 31 IS 5 BP 688 EP 696 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 217RK UT WOS:000249964800007 PM 17895778 ER PT J AU Singh, AK Levenson, RB Gervais, DA Hahn, PF Kandarpa, K Mueller, PR AF Singh, Ajay K. Levenson, Robin B. Gervais, Debra A. Hahn, Peter F. Kandarpa, Krishna Mueller, Peter R. TI Dropped gallstones and surgical clips after cholecystectomy: CT assessment SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE dropped gallstones; cholecystectomy ID RETAINED ABDOMINAL GALLSTONES; LAPAROSCOPIC CHOLECYSTECTOMY; LATE COMPLICATION; ABSCESS FORMATION; FEATURES AB Aim: To describe the spectrum of computed tomographic (CT) findings in patients with dropped gallstones or dropped surgical clips after cholecystectomy. Materials and Methods: Seventeen patients diagnosed with dropped gallstones and 26 patients with dropped surgical clips on computed tomography after cholecystectomies were included in this study. The CT scans were evaluated for the number, location, size, and density of dropped gallstones or surgical clips and for the presence of an abscess. The cases were evaluated for the outcome on clinical and/or CT follow-up. Results: The location for dropped gallstones and dropped surgical clips after cholecystectomy was the Morrison's pouch in 17 and 12 patients, respectively. There were 9 abscesses in the study, all located in the Morrison's pouch. Duration from surgery to observation of abscess on computed tomography ranged from 5 days to more than 4.7 years. None of the patients with a dropped surgical clip from cholecystectomy developed an associated abscess. Conclusions: Subhepatic location was the most common location for dropped gallstones with associated abscess and for dropped surgical clips. Dropped cholecystectomy clips are not associated with increased risk of abscess formation and therefore do not need screening follow-up or operative removal. Abscess formation around dropped gallstone is a more common complication and requires surgical treatment in most when associated with an abscess. C1 Univ Massachusetts, Mem Med Ctr, Worcester, MA USA. Massachusetts Gen Hosp, Div Abdomin Imaging & Intervent Radiol, Boston, MA USA. RP Singh, AK (reprint author), 10 Museum Way,524, Boston, MA 02141 USA. EM asingh1@partners.org NR 20 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2007 VL 31 IS 5 BP 758 EP 762 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 217RK UT WOS:000249964800017 PM 17895788 ER PT J AU Yeung, A Overstreet, KM Albert, EV AF Yeung, Albert Overstreet, Karen M. Albert, Elizabeth V. TI Current practices in depression care SO JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS LA English DT Article DE best practices; CME; current practices; depression; depression practices; disparities; practice guidelines; quality of care ID CASE-FINDING INSTRUMENTS; MAJOR DEPRESSION; ANTIDEPRESSANT TREATMENT; SEROTONIN TRANSPORTER; MENTAL-DISORDERS; GLOBAL BURDEN; HEALTH; ADULTS; DISEASE; RISK AB Despite improved awareness among the medical community concerning common mental health disorders, the high prevalence of depression in the United States remains unchanged(1) and has been compounded by increasing evidence of gaps in mental health care for ethnic and racial minorities.(1,2) Thus, there is a strong need for the timely creation of comprehensive educational initiatives aimed at improving the quality of care provided by mental health professionals and primary care physicians. Fundamental to this process is the examination of current treatment standards, as well as identification of practices that require improved physician education. Consistent use of appropriate screening tools, diagnostic accuracy and timeliness, continual assessment of illness severity, adherence to practice guidelines, and individualized patient care need heightened attention to improve outcomes. This article describes the most prevalent types of depression and summarizes current practices in depression care, with an emphasis on treatment standards and opportunities for improved performance. C1 [Yeung, Albert] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Overstreet, Karen M.; Albert, Elizabeth V.] Indicia Med Educ LLC, N Wales, PA USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM ayeung@partners.org NR 76 TC 3 Z9 3 U1 4 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1912 J9 J CONTIN EDUC HEALTH JI J. Contin. Educ. Health Prof. PD FAL PY 2007 VL 27 SU 1 BP S9 EP S17 DI 10.1002/chp.130 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 256AH UT WOS:000252699600003 PM 18085581 ER PT J AU Shah, AP Rubin, SA AF Shah, Atman P. Rubin, Stanley A. TI Errors in the computerized electrocardiogram interpretation of cardiac rhythm SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article ID ATRIAL-FIBRILLATION; MISDIAGNOSIS; ARRHYTHMIA; DIAGNOSIS; ECG AB Background: More than 100 million computer-interpreted electrocardiograms (ECG-C) are obtained annually. However, there are few contemporary published data on the accuracy of cardiac rhythm interpretation by this method. Purpose: The purpose of this study is to determine the accuracy of ECG-C rhythm interpretation in a typical patient population. Methods: We compared the ECG-C rhythm interpretation to that of 2 expert overreaders in 2112 randomly selected standard 12-lead ECGs. Results: The ECG-C Correctly interpreted the rhythm in 1858 and incorrectly identified the rhythm in 254 (overall accuracy, 88.0%). Sinus rhythm was correctly interpreted in 95.0% of the ECGs (1666/1753) with this rhythm, whereas nonsinus rhythms were correctly interpreted with an accuracy of only 53.5% (192/359) (P < .0001). The ECG-C interpreted sinus rhythm with a sensitivity of 95% (confidence interval, 93.8-96.7), specificity of 66.3%, and positive predictive value of 93.2%. The ECG-C interpreted nonsinus rhythms with a sensitivity of 72%, (confidence interval, 68.7-73.7), a specificity of 93%, and a positive predictive value of 59.3%. Of the 254 ECGs that had incorrect rhythm interpretation, additional major errors were noted in 137 (54%). Conclusions: The ECG-C demonstrates frequent errors in the interpretation of nonsinus rhythms. In addition, incorrect rhythm interpretation by the ECG-C was frequently further compounded by additional major inaccuracies. Expert overreading of the ECG remains important in clinical settings with a high percentage of nonsinus rhythms. Published by Elsevier Inc. C1 Univ Calif Los Angeles, Sch Med, Div Cardiol 111 E, VA Greater Los Angeles, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Rubin, SA (reprint author), Univ Calif Los Angeles, Sch Med, Div Cardiol 111 E, VA Greater Los Angeles, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sarubin@ucla.edu NR 21 TC 10 Z9 10 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD SEP-OCT PY 2007 VL 40 IS 5 BP 385 EP 390 DI 10.1016/j.jelectrocard.2007.03.008 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 211EU UT WOS:000249507900001 PM 17531257 ER PT J AU Morse, CR Fernando, HC Ferson, PF Landreneau, RJ Luketich, JD AF Morse, Christopher R. Fernando, Hiran C. Ferson, Peter F. Landreneau, Rodney J. Luketich, James D. TI Preliminary experience by a thoracic service with endoscopic transoral stapling of cervical (Zenker's) diverticulum SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Society-for-Surgery-of the Alimentary-Tract CY MAY 20-24, 2006 CL Los Angeles, CA SP Soc Surg Alimentary Tract DE cenoical (Zenker's) diverticulum; transoral stapling; cricopharyngeal myotomy ID CO2-LASER; OPERATION; MYOTOMY AB Recently endoscopic transoral stapling (ES) of cervical (Zenker's) diverticulum (ZD) has been reported. In a 10-year retrospective review, we identified 47 patients undergoing ES or open surgery (OS) for ZD. ES was attempted in 28 patients and OS in 19. Using an intention to treat analysis, outcomes examined included operative time, length of stay, and dyspbagia severity using a scale from I (no dyspbagia) to 5 (severe dysphagia). ES was completed in 24/28 patients with four conversions to OS. The mean age was 75 years for the ES group and 70 years for the OS group (p=0.079). Mean operative time (1.57 versus 2.35 h.) was less (p < 0.03) in the ES group. Length of stay (2.12 versus 2.44 days) was shorter for ES but not significant (P=0.49). Mean follow up was 17 (1-103) months for both groups. Dysphagia scores were comparable between the two groups preoperatively (2.78 ES versus 2.79 OS; p=0.98) and improved significantly (P=0.001) to 1.1 after ES and 1.0 after OS. The time to oral intake was 1.38 days in the ES group and 1.29 days in the OS group (p=0.80). We conclude that ES is feasible and can be performed with shorter operative times and comparable short-term results to OS. C1 Univ Pittsburgh, Med Ctr Hlth Syst, Div Thorac & Foregut Surg, Pittsburgh, PA 15213 USA. Boston Univ, Med Ctr, Dept Cardiothorac Surg, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Luketich, JD (reprint author), Univ Pittsburgh, Med Ctr Hlth Syst, Div Thorac & Foregut Surg, 200 Lothrop St,Suite C-800, Pittsburgh, PA 15213 USA. EM luketichjd@upmc.edu OI Fernando, Hiran/0000-0002-5330-7036 NR 12 TC 7 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP PY 2007 VL 11 IS 9 BP 1091 EP 1094 DI 10.1007/s11605-007-0191-2 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 207RE UT WOS:000249268000003 PM 17623265 ER PT J AU Green, AR Carney, DR Pallin, DJ Ngo, LH Raymond, KL Iezzoni, LI Banaji, MR AF Green, Alexander R. Carney, Dana R. Pallin, Daniel J. Ngo, Long H. Raymond, Kristal L. Iezzoni, Lisa I. Banaji, Mahzarin R. TI Implicit bias among physicians and its prediction of thrombolysis decisions for black and white patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE unconscious bias; thrombolysis; race; clinical decisions; disparities ID ACUTE MYOCARDIAL-INFARCTION; RACIAL-DIFFERENCES; ASSOCIATION TEST; RACE; ATTITUDES; STEREOTYPES; DISPARITIES; MANAGEMENT; COGNITION; GENDER AB Cotext: Studies documenting racial/ethnic disparities in health care frequently implicate physicians' unconscious biases. No study to date has measured physicians' unconscious racial bias to test whether this predicts physicians' clinical decisions. Objective: To test whether physicians show implicit race bias and whether the magnitude of such bias predicts thrombolysis recommendations for black and white patients with acute coronary syndromes. Design, Setting, and participants: An internet-based tool comprising a clinical vignette of a patient presenting to the emergency department with an acute coronary syndrome, followed by a questionnaire and three Implicit Association Tests (IATs). Study invitations were e-mailed to all internal medicine and emergency medicine residents at four academic medical centers in Atlanta and Boston; 287 completed the study, met inclusion criteria, and were randomized to either a black or white vignette patient. Main outcome measurements: IAT scores (normal continuous variable) measuring physicians' implicit race preference and perceptions of cooperativeness. Physicians' attribution of symptoms to coronary artery disease for vignette patients with randomly assigned race, and their decisions about thrombolysis. Assessment of physicians' explicit racial biases by questionnaire. Results: Physicians reported no explicit preference for white versus black patients or differences in perceived cooperativeness. In contrast, IATs revealed implicit preference favoring white Americans (mean IAT score=0.36, P <.001, one-sample t test) and implicit stereotypes of black Americans as less cooperative with medical procedures (mean IAT score 0.22, Pe <.001), and less cooperative generally (mean IAT score 0.30, P <.001). As physicians' prowhite implicit bias increased, so did their likelihood of treating white patients and not treating black patients with thrombolysis (P=.009). Conclusions: This study represents the first evidence of unconscious (implicit) race bias among physicians, its dissociation from conscious (explicit) bias, and its predictive validity. Results suggest that physicians' unconscious biases may contribute to racial/ethnic disparities in use of medical procedures such as thrombolysis for myocardial infarction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Disparities Solut Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Univ N Carolina, Chapel Hill, NC USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Inst Hlth Policy, Boston, MA 02115 USA. RP Green, AR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Disparities Solut Ctr, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM argreen@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU NHLBI NIH HHS [HL-0000013]; PHS HHS [T32HP11001-15] NR 28 TC 331 Z9 333 U1 16 U2 55 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2007 VL 22 IS 9 BP 1231 EP 1238 DI 10.1007/s11606-007-0258-5 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 201EQ UT WOS:000248814700002 PM 17594129 ER PT J AU Parker, CS Chen, Z Price, M Gross, R Metlay, JP Christie, JD Brensinger, CM Newcomb, CW Samaha, FF Kimmel, SE AF Parker, Catherine S. Chen, Zhen Price, Maureen Gross, Robert Metlay, Joshua P. Christie, Jason D. Brensinger, Colleen M. Newcomb, Craig W. Samaha, Frederick F. Kimmel, Stephen E. TI Adherence to warfarin assessed by electronic pill caps, clinician assessment, and patient reports: Results from the IN-RANGE study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient adherence; warfarin; medication event monitoring system ID ANTICOAGULATION-CONTROL; ORAL ANTICOAGULANTS; ATRIAL-FIBRILLATION; DRUG-THERAPY; MEDICATION; PHYSICIANS; MANAGEMENT; OUTCOMES; TRIAL AB Background: Patient adherence to warfarin may influence anticoagulation control; yet, adherence among warfarin users has not been rigorously studied. Objective: Our goal was to quantify warfarin adherence over time and to compare electronic medication event monitoring systems (MEMS) cap measurements with both self-report and clinician assessment of patient adherence. Design: We performed a prospective cohort study of warfarin users at 3 Pennsylvania-based anticoagulation clinics and assessed pill-taking behaviors using MEMS caps, patient reports, and clinician assessments. Results: Among 145 participants, the mean percent of days of nonadherence by MEMS was 21.8% (standard deviation +/- 21.1%). Participants were about 6 times more likely to take too few pills than to take extra pills (18.8 vs. 3.3%). Adherence changed over time, initially worsening over the first 6 months of monitoring, which was followed by improvement beyond 6 months. Although clinicians were statistically better than chance at correctly labeling a participant's adherence (odds ratio=2.05, p=0.015), their estimates often did not correlate with MEMS-cap data; clinicians judged participants to be "adherent" at 82.8% of visits that were categorized as moderately nonadherent using MEMS-cap data (>= 20% nonadherence days). Similarly, at visits when participants were moderately nonadherent by MEMS, they self-reported perfect adherence 77.9% of the time. Conclusions: These results suggest that patients may benefit from adherence counseling even when they claim to be taking their warfarin or the clinician feels they are doing so, particularly several months into their course of therapy. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. Vet Affairs Med Ctr, Div Cardiovasc, Philadelphia, PA USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Kimmel, SE (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 717 Blockley Hall,432 Guardian Dr, Philadelphia, PA 19104 USA. EM skimmel@cceb.med.upenn.edu FU AHRQ HHS [P01 HS011530, P01-HS11530]; NCRR NIH HHS [P20 RR020741, P20RR020741]; NHLBI NIH HHS [R01 HL066176, R01-HL66176] NR 19 TC 55 Z9 55 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2007 VL 22 IS 9 BP 1254 EP 1259 DI 10.1007/s11606-007-0233-1 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 201EQ UT WOS:000248814700005 PM 17587092 ER PT J AU Vig, EK Starks, H Taylor, JS Hopley, EK Fryer-Edwards, K AF Vig, Elizabeth K. Starks, Helene Taylor, Janelle S. Hopley, Elizabeth K. Fryer-Edwards, Kelly TI Surviving surrogate decision-making: What helps and hampers the experience of making medical decisions for others SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 27-29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med DE surrogate decision-making; advance care planning; substituted judgment; qualitative research ID OF-LIFE DECISIONS; MENTAL STATUS QUESTIONNAIRE; INTENSIVE-CARE-UNIT; SUBSTITUTED JUDGMENT; ADVANCE DIRECTIVES; INFORMATION NEEDS; ELDERLY PATIENTS; FAMILY-MEMBERS; HEALTH-CARE; END AB Background: A majority of end-of-life medical decisions are made by surrogate decision-makers who have varying degrees of preparation and comfort with their role. Having a seriously ill family member is stressful for surrogates. Moreover, most clinicians have had little training in working effectively with surrogates. Objectives:To better understand the challenges of decision-making from the surrogate's perspective. Design: Semistructured telephone interview study of the experience of surrogate decision-making. Participants: Fifty designated surrogates with previous decision-making experience. Approach: We asked surrogates to describe and reflect on their experience of making medical decisions for others. After coding transcripts, we conducted a content analysis to identify and categorize factors that made decision-making more or less difficult for surrogates. Results: Surrogates identified four types of factors: (1) surrogate characteristics and life circumstances (such as coping strategies and competing responsibilities), (2) surrogates' social networks (such as intrafamily discord about the "right" decision), (3) surrogate-patient relationships and communication (such as difficulties with honoring known preferences), and (4) surrogate-clinician communication and relationship (such as interacting with a single physician whom the surrogate recognizes as the clinical spokesperson vs. many clinicians). Conclusions: These data provide insights into the challenges that surrogates encounter when making decisions for loved ones and indicate areas where clinicians could intervene to facilitate the process of surrogate decision-making. Clinicians may want to include surrogates in advance care planning prior to decision-making, identify and address surrogate stressors during decision-making, and designate one person to communicate information about the patient's condition, prognosis, and treatment options. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Div Gerontol & Geriatr, Seattle, WA 98195 USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Vig, EK (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way S-182 Eth, Seattle, WA 98108 USA. EM vigster@u.washington.edu FU NIA NIH HHS [K23 AG019635, K23 AG19635] NR 39 TC 83 Z9 83 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2007 VL 22 IS 9 BP 1274 EP 1279 DI 10.1007/s11606-007-0252-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 201EQ UT WOS:000248814700008 PM 17619223 ER PT J AU Givens, JL Katz, IR Bellamy, S Holmes, WC AF Givens, Jane L. Katz, Ira R. Bellamy, Scarlett Holmes, William C. TI Stigma and the acceptability of depression treatments among African Americans and whites SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 27-29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med DE stigma; depression treatment; patient preferences; ethnicity ID PRIMARY-CARE PATIENTS; MENTAL-HEALTH-SERVICES; TREATMENT PREFERENCES; PERCEIVED STIGMA; DISORDERS; REJECTION; ATTITUDES; SEVERITY; ILLNESS; HELP AB Background: Stigma is associated with depression treatment, however, whether stigma differs between depression treatment modalities is not known, nor have racial differences in depression treatment stigma been fully explored. Objective: To measure stigma for four depression treatments and estimate its association with treatment acceptability for African Americans and whites. Design: Cross-sectional, anonymous mailed survey. Pariticpants: Four hundred and ninety African-American and white primary care patients. Measurements: The acceptability of four depression treatments (prescription medication, mental health counseling, herbal remedy, and spiritual counseling) was assessed using a vignette. Treatment-specific stigma was evaluated by asking whether participants would: (1) feel ashamed; (2) feel comfortable telling friends and family; (3) feel okay if people in their community knew; and (4) not want people at work to know about each depression treatment. Sociodemographics, depression history, and current depressive symptoms were measured. Results: Treatment-specific stigma was lower for herbal remedy than prescription medication or mental health counseling (p <.01). Whites had higher stigma than African Americans for all treatment modalities. In adjusted analyses, stigma relating to self [AOR 0.43 (0.20-0.95)] and friends and family [AOR 0.42 (0.21-0.88)] was associated with lower acceptability of mental health counseling. Stigma did not account for the lower acceptability of prescription medication among African Americans. COnclusions: Treatment associated stigma significantly affects the acceptability of mental health counseling but not prescription medication. Efforts to improve depression treatment utilization might benefit from addressing concerns about stigma of mental health counseling. C1 Boston Univ, Med Ctr, Geriat Sect, Boston, MA 02118 USA. Univ Penn, Dept Psychiat, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Adm Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Givens, JL (reprint author), 88 E Newton St,Robinson 2,Room 2702, Boston, MA 02118 USA. EM jane.givens@bmc.org NR 34 TC 49 Z9 51 U1 4 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2007 VL 22 IS 9 BP 1292 EP 1297 DI 10.1007/s11606-007-0276-3 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 201EQ UT WOS:000248814700011 PM 17610120 ER PT J AU Shrank, WH Stedman, M Ettner, SL DeLapp, D Dirstine, J Brookhart, MA Fischer, MA Avorn, J Asch, SM AF Shrank, William H. Stedman, Margaret Ettner, Susan L. DeLapp, Dee Dirstine, June Brookhart, M. Alan Fischer, Michael A. Avorn, Jerry Asch, Steven M. TI Patient, physician, pharmacy, and pharmacy benefit design factors related to generic medication use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 27-29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med DE patient; physician; pharmacy; pharmacy benefit; design; generic medications; medication costs ID INCENTIVE-BASED FORMULARIES; POTENTIAL SAVINGS; DRUG UTILIZATION; HYPERTENSION; ADHERENCE; SAMPLES; COSTS; PROXY; CARE AB Background: Increased use of generic medications conserves insurer and patient financial resources and may increase patient adherence. Objective: The objective of the study is to evaluate whether physician, patient, pharmacy benefit design, or pharmacy characteristics influence the likelihood that patients will use generic drugs Design, setting, and participants: Observational analysis of 2001-2003 pharmacy claims from a large health plan in the Western United States. We evaluated claims for 5,399 patients who filled a new prescription in at least 1 of 5 classes of chronic medications with generic alternatives. We identified patients initiated on generic drugs and those started on branded medications who switched to generic drugs in the subsequent year. We used generalized estimating equations to perform separate analyses assessing the relationship between independent variables and the probability that patients were initiated on or switched to generic drugs. Results: Of the 5,399 new prescriptions filled, 1,262 (23.4%) were generics. Of those initiated on branded medications, 606 (14.9%) switched to a generic drug in the same class in the subsequent year. After regression adjustment, patients residing in high-income zip codes were more likely to initiate treatment with a generic than patients in low-income regions (RR=1.29; 95% C.I. 1.04-1.60); medical subspecialists (RR=0.82; 0.69-0.95) and obstetrician/gynecologists (RR=0.81; 0.69-0.98) were less likely than generalist physicians to initiate generics. Pharmacy benefit design and pharmacy type were not associated with initiation of generic medications. However, patients were over 2.5 times more likely to switch from branded to generic medications if they were enrolled in 3-tier pharmacy plans (95% C.I. 1.12-6.09), and patients who used mail-order pharmacies were 60% more likely to switch to a generic (95% C.I. 1.18-2.30) after initiating treatment with a branded drug. Conclustions: Physician and patient factors have an important influence on generic drug initiation, with the patients who live in the poorest zip codes paradoxically receiving generic drugs least often. While tiered pharmacy benefit designs and mail-order pharmacies helped steer patients towards generic medications once the first prescription has been filled, they had little effect on initial prescriptions. Providing patients and physicians with information about generic alternatives may reduce costs and lead to more equitable care. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Hlth, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Anthern Blue Cross Blue Shield, N Haven, CT USA. Anthem Prescript Management, N Haven, CT USA. RP Shrank, WH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM wshrank@partners.org OI Stedman, Margaret/0000-0001-9271-8332 NR 31 TC 36 Z9 36 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2007 VL 22 IS 9 BP 1298 EP 1304 DI 10.1007/s11606-007-0284-3 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 201EQ UT WOS:000248814700012 PM 17647066 ER PT J AU Gerrity, MS Corson, K Dobscha, SK AF Gerrity, Martha S. Corson, Kathryn Dobscha, Steven K. TI Screening for posttraumatic stress disorder in VA primary care patients with depression symptoms SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE posttraumatic stress disorder; depression; screening; primary care; veterans ID MENTAL-HEALTH PROBLEMS; PTSD CHECKLIST; VALIDATION; VETERANS; IRAQ; AFGHANISTAN; PREVALENCE; VALIDITY; UTILITY; SCALE AB Background: Unrecognized posttraumatic stress disorder (PTSD) is common and may be an important factor in treatment-resistant depression. Brief screens for PTSD have not been evaluated for patients with depression. Objective: The objective was to evaluate a 4-item screen for PTSD in patients with depression. Design: Baseline data from a depression study were used to evaluate sensitivity, specificity, and likelihood ratios (LRs) using the PTSD checklist (PCL-17) as the reference standard. Subjects: Subjects are 398 depressed patients seen in Veterans Affairs (VA) primary care clinics. Measures: The Patient Health Questionnaire (PHQ) for depression, PCL-17, and 4-item screen for PTSD were used. Results: Patients had a mean PHQ score of 14.8 (SD 3.7). Using a conservative PCL-17 cut point "(> 50)", the prevalence of PTSD was 37%. PCL-17 scores were strongly associated with PHQ scores (r=0.59, P < 0.001). Among the 342 (86%) patients endorsing trauma, a score of 0 on the remaining 3 symptom items had a LR=0.21, score of 1 a L=.62, score of 2 a LR=1.36, and score of 3 a LR=4.38. Conclusions: Most depressed VA primary care patients report a history of trauma, and one third may have comorbid PTSD. Our 4-item screen has useful LRs for scores of 0 and 3. Modifying item rating options may improve screening characteristics. C1 Portland VA Med Ctr, Columbia Ctr Study Chron Comorbid Mental & Phys, Portland, OR 97207 USA. Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Columbia Ctr Study Chron Comorbid Mental & Phys, POB 1034 R&D-66, Portland, OR 97207 USA. EM steven.dobscha@va.gov NR 26 TC 16 Z9 16 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2007 VL 22 IS 9 BP 1321 EP 1324 DI 10.1007/s11606-007-0290-5 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 201EQ UT WOS:000248814700016 PM 17634781 ER PT J AU Chen, P Kales, HC Weintraub, D Blow, FC Jiang, L Mellow, AM AF Chen, Peijun Kales, Helen C. Weintraub, Daniel Blow, Frederic C. Jiang, Lan Mellow, Alan M. TI Antidepressant treatment of veterans with Parkinson's disease and depression: Analysis of a national sample SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 03-06, 2005 CL San Diego, CA SP Amer Assoc Geriatr Psychiat DE Parkinson's disease; depression; antidepressants ID PRIMARY-CARE; SEROTONIN; MANAGEMENT; SYMPTOMS; RISK; LIFE AB We examined the impact of comorbid Parkinson's disease (PD) on depression treatment. Using national Veterans Affairs (VA) databases, fiscal year 2002 data were examined for 283 273 elderly males seen for depression. We compared 2 matched depression groups, one with (N = 7868) and one without (N = 7868) PD. In the 12-month period following a depression-related clinic visit, PD and non-PD patients were equally likely to fill an antidepressant prescription (77.8% vs. 77.4%), most commonly for a selective serotonin re-uptake inhibitor (SSRI) (62.9% vs 62.6%). Depressed PD patients had slightly higher rates of newer non-SSRI use (20.6% vs 19.2%, P <.05) and lower rates of tricyclic antidepressant use (7.4% vs 8.9%, P <.001). The presence of a PD diagnosis appears to have little impact on the frequency and type of antidepressant treatment. Efforts to improve the care of depressed PD patients should focus instead on improving recognition, ensuring adequacy of treatment, and evaluating the efficacy of existing antidepressants. C1 Case Western Reserve Univ, Cleveland VA Med Ctr, Psychiat Serv, Dept Psychiat, Brecksville, OH 44141 USA. Univ Michigan, Dept Psychiat, Div Geriatr Psychiat, Ann Arbor, MI 48109 USA. VA Natl Serious Mental Illness Treatment Res & Ev, Ann Arbor, MI USA. VA Ann Arbor Healthcare Syst, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. Univ Penn, Dept Psychiat, Philadelphia VA Med Ctr, Parkinsons Dis & Mental Illness Res,Educ & Clin C, Philadelphia, PA 19104 USA. Dept Vet Affairs, VISN Mental Hlth Serv Line 11, Cleveland, OH USA. RP Chen, P (reprint author), Case Western Reserve Univ, Cleveland VA Med Ctr, Psychiat Serv, Dept Psychiat, 116A B,1000 Breckville Rd, Brecksville, OH 44141 USA. EM Peijun.chen@med.va.gov FU NIMH NIH HHS [K23 MH067894, K23 MH067894-04] NR 17 TC 21 Z9 22 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2007 VL 20 IS 3 BP 161 EP 165 DI 10.1177/0891988707301866 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 201SD UT WOS:000248852000005 PM 17712099 ER PT J AU Lozano-Calderon, S Moore, M Liebman, M Jupiter, JB AF Lozano-Calderon, Santiago Moore, Michael Liebman, Matthew Jupiter, Jesse B. TI Distal radius osteotomy in the elderly patient using angular stable implants and Norian bone cement SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE angle stable implants; corrective osteotomy; distal radius; malunion; Norian cement ID DONOR-SITE MORBIDITY; INJECTABLE CALCIUM-PHOSPHATE; CORRECTIVE OSTEOTOMY; INTERNAL-FIXATION; PLATE FIXATION; ILIAC BONE; FRACTURES; COMPLICATIONS; GRAFT; REPAIR AB Purpose: To report our results after testing the combination of two technologies-angular-stable locking screw implants and Norian SRS cement-in corrective osteotomies of the distal radius in the elderly. This technique eliminates donor site bone-graft morbidity and expands the indications of corrective osteotomies to older patients with osteoporotic bone. Methods: Our retrospective series include 6 patients (5 women and 1 man) with an average age of 60 years. Three patients had corrections through a dorsal approach, 1 through a volar approach, and 2 through a combined approach. Two corrections included an intraarticular osteotomy. We used 2.4-mm volar T plates in patients approached volarly and 2.4-mm L and T plates for those approached dorsally; the osseous defect was, filled with bone cement (Norian SRS). Range of motion and grip strength were measured at 16 months average follow-up. Standard wrist radiographs were taken to evaluate alignment and determine improvement. At final follow-up, patients completed the Modified Mayo Wrist score, the Modified Gartland and Werley score, and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Results: There were no perioperative complications. All corrective osteotomies healed. One patient required a Darrach procedure at 6 months. The average wrist and forearm motion was 77% of the opposite side and grip strength 88% of the opposite side. The average total correction in the sagittal plane was 22 degrees with all patients returning to neutral or better alignment. The average ulnar variance improvement was 2 mm. Average postoperative DASH was 28 points; average Modified Mayo Wrist score was 68; and the Modified Gartland and Werley score averaged 9 points. Conclusions: We believe that corrective osteotomy of the distal radius in the elderly using angular stable implants and Norian calcium phosphate cement is a safe and predictable surgical technique, even in patients with underlying osteoporosis. It eliminates donor site morbidity, and patient-rated outcome measures demonstrated acceptable daily living function return. C1 Harvard Univ, Hand & Upper Extrem Serv, Sch Med, Massachusetts Gen Hosp,Dept Orthopaed Surg, Boston, MA 02114 USA. Arkansas Specialty, Hand & Upper Extrem Ctr, Little Rock, AR USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand Surg Serv, Boston, MA 02115 USA. RP Lozano-Calderon, S (reprint author), Harvard Univ, Hand & Upper Extrem Serv, Sch Med, Massachusetts Gen Hosp,Dept Orthopaed Surg, YAW 2100,55 Fruit St, Boston, MA 02114 USA. EM slozanocalderon@partners.org NR 40 TC 16 Z9 18 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2007 VL 32A IS 7 BP 976 EP 983 DI 10.1016/j.jhsa.2007.05.005 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 211RD UT WOS:000249540100006 PM 17826549 ER PT J AU Cooke, CR Sheffield, JVL Hirschmann, JV AF Cooke, Colin R. Sheffield, John V. L. Hirschmann, Jan V. TI Fishing for a diagnosis SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID ESOPHAGEAL-PERFORATION; PULMONARY-EMBOLISM; PATIENT; MANAGEMENT; MISDIAGNOSIS; MEDICINE; TIME AB A 54-year-old man with hypertension and type 2 diabetes A mellitus entered the Chest Pain Evaluation Unit of a teaching hospital after 12 hours of intermittent thoracic discomfort. The pain began during dinner and was sharp, bandlike, and located beneath the sternum and across the entire chest. He had dyspnea but no diaphoresis or nausea. A recumbent position relieved the pain after dinner, but it recurred during the night and again the following morning. He did not smoke and had no family history of coronary artery disease. C1 [Cooke, Colin R.] Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. [Sheffield, John V. L.] Univ Washington, Harborview Med Ctr, Div Gen Med, Seattle, WA 98104 USA. [Hirschmann, Jan V.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Gen Med, Seattle, WA 98195 USA. RP Cooke, CR (reprint author), Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, 325 9th Ave,Box 359762, Seattle, WA 98104 USA. EM crcooke@u.washington.edu OI Cooke, Colin/0000-0001-9713-5371 FU NHLBI NIH HHS [T32 HL007287] NR 27 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD SEP-OCT PY 2007 VL 2 IS 5 BP 345 EP 351 DI 10.1002/jhm.243 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 292HY UT WOS:000255258300010 PM 17935255 ER PT J AU Sykes, M AF Sykes, M. TI Immune tolerance: mechanisms and application in clinical transplantation SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE bone marrow transplantation; immunity; immunology; immunosuppressive treatment; transplantation immunology ID REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; DONOR-SPECIFIC TOLERANCE; GROWTH-FACTOR-BETA; ANTI-CD154 MONOCLONAL-ANTIBODY; MIXED HEMATOPOIETIC CHIMERISM; TOTAL LYMPHOID IRRADIATION; RENAL-ALLOGRAFT REJECTION; LONG-TERM SURVIVAL AB Sykes M (Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA). Immune tolerance: mechanisms and application in clinical transplantation (Review). J Intern Med 2007; 262: 288-310. The achievement of immune tolerance, a state of specific unresponsiveness to the donor graft, has the potential to overcome the current major limitations to progress in organ transplantation, namely late graft loss, organ shortage and the toxicities of chronic nonspecific immumnosuppressive therapy. Advances in our understanding of immunological processes, mechanisms of rejection and tolerance have led to encouraging developments in animal models, which are just beginning to be translated into clinical pilot studies. These advances are reviewed here and the appropriate timing for clinical trials is discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sec, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sec, MGH E bldg 149-5102,13St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NCI NIH HHS [P01 CA11159, R01 CA79989]; NHLBI NIH HHS [P01 HL018646, R01 HL49915]; NIAID NIH HHS [P01 P01 AI39755] NR 260 TC 44 Z9 45 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD SEP PY 2007 VL 262 IS 3 BP 288 EP 310 DI 10.1111/j.1365-2796.2007.01855.x PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA 207QZ UT WOS:000249267500002 PM 17697153 ER PT J AU Luo, F Li, ZX Treistman, SN Kim, YR King, JA Fox, GB Ferris, CF AF Luo, Feng Li, Zhixin Treistman, Steven N. Kim, Young Ro King, Jean A. Fox, Gerard B. Ferris, Craig F. TI Confounding effects of volatile Anesthesia on CBV assessment in rodent Forebrain following ethanol challenge SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE ethanol; anesthesia; awake; cerebral blood; volume; pharmacological MRI ID CEREBRAL-BLOOD-FLOW; FUNCTIONAL MRI; RAT-BRAIN; PHARMACOLOGICAL MRI; CONSCIOUS RATS; AWAKE RATS; ISOFLURANE; COCAINE; HALOTHANE; ACTIVATION AB Purpose: To compare and contrast the pattern and characteristics of the cerebral blood volume (CBV) response to ethanol (EtOH) in rats under awake and anesthetized conditions. Materials and Methods: Acute EtOH (0.75 g/kg) challenge-induced CBV changes were measured using a contrast-enhanced functional MRI CBV method in 15 male Sprague Dawley rats under three experimental conditions: 1.0% to 1.2% isoflurane (N = 5); 0.8% halothane (N = 5); and awake with no anesthetic (N = 5). Physiological parameters were collected from bench settings in nine rats from the above different conditions. Four parameters: 1) area under the curve (AUC%); 2) the maximum signal change (Maxo%); 3) EtOH absorption rate (alpha(2)); and 4) EtOH elimination rate (alpha(1)) were employed to compare EtOH-induced MRI signals between the awake and anesthetized groups. Results: Both awake and anesthetized animals responded with an increase in CBV to EtOH challenge. However, the presence of anesthesia promoted a significant preferential flow to subcortical areas not seen in the awake condition. Conclusion: Unclear mechanisms of anesthesia add a layer of uncertainty to the already complex interpretation of EtOH's influence on neuronal activity, cellular metabolism, and C1 Expt Imagin Abbott Labs, Abbott Pk, IL 60064 USA. Univ Massachusetts, Sch Med, Ctr Comparat Neuroimaging, Worcester, MA USA. Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Worcester, MA USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Luo, F (reprint author), Expt Imagin Abbott Labs, 100 Abbott Pk, Abbott Pk, IL 60064 USA. EM Feng.Luo@abbott.com FU NIAAA NIH HHS [AA08003]; NIDA NIH HHS [DA13517] NR 41 TC 13 Z9 14 U1 0 U2 0 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 SEP PY 2007 VL 26 IS 3 BP 557 EP 563 DI 10.1002/jmri.21083 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 207NH UT WOS:000249257300012 PM 17729349 ER PT J AU Gaige, TA Benner, T Wang, R Wedeen, VJ Gilbert, RJ AF Gaige, Terry A. Benner, Thomas Wang, Ruopeng Wedeen, Van J. Gilbert, Richard J. TI Three dimensional myoarchitecture of the human tongue determined in vivo by diffusion tensor imaging with tractography SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE muscular anatomy; diffusion imaging; human; tongue; tractography ID MAGNETIC-RESONANCE; FIBER ARCHITECTURE; SKELETAL-MUSCLE; BOVINE TONGUE; RESTRICTED DIFFUSION; WEIGHTED MRI; HUMAN CALF; WATER; SENSITIVITY; VALIDATION AB Purpose: To study the anatomical relationships involving the intrinsic and extrinsic myofiber populations of the human tongue employing diffusion tensor imaging (DTI) with tractography. Materials and Methods: Images of the human tongue In vivo were obtained using a twice-refocused spin echo DTI pulse sequence at 1.5T, isotropic 3 x 3 x 3 mm(3) voxels, b-value 500 seconds/mm(2), and 90 different diffusion sensitizing gradient directions. Multivoxel tracts were generated along the vectors of maximal diffusion in each voxel. The data was visualized using custom fiber tracking software and images compared with known anatomy. Results: DTI tractography depicts the complete three-dimensional (3D) myoarchitecture of the human tongue, specifically demonstrating the geometric relationships between the intrinsic and extrinsic myofiber populations. These results define the manner in which key extrinsic fiber populations merge with the longitudinally-, transversely-, and vertically-aligned intrinsic fibers. Conclusion: The current results display for the first time the use of DTI tractography in vivo to visualize the complete structural anatomy of the human tongue and allow us to consider fundamental structure-function relationships. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Gilbert, RJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rgilbert@mit.edu NR 36 TC 26 Z9 26 U1 0 U2 4 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 SEP PY 2007 VL 26 IS 3 BP 654 EP 661 DI 10.1002/jmri.21022 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 207NH UT WOS:000249257300024 PM 17685446 ER PT J AU Vepsalainen, S Parkinson, M Helisalmi, S Mannermaa, A Soininen, H Tanzi, RE Bertram, L Hiltunen, M AF Vepsalainen, Saila Parkinson, Michele Helisalmi, Seppo Mannermaa, Arto Soininen, Hilkka Tanzi, Rudolph E. Bertram, Lars Hiltunen, Mikko TI Insulin-degrading enzyme is genetically associated with Alzheimer's disease in the Finnish population SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID AMYLOID BETA-PROTEIN; CHROMOSOME-10; DEGRADATION; LINKAGE; LOCUS AB The gene for insulin-degrading enzyme (IDE), which is located at chromosome 10q24, has been previously proposed as a candidate gene for late-onset Alzheimer's disease (AD) based on its ability to degrade amyloid beta-protein. Genotyping of single nucleotide polymorphisms (SNPs) in the IDE gene in Finnish patients with AD and controls revealed SNPs rs4646953 and rs4646955 to be associated with AD, conferring an approximately two-fold increased risk. Single locus findings were corroborated by the results obtained from haplotype analyses. This suggests that genetic alterations in or near the IDE gene may increase the risk for developing AD. C1 Univ Kuopio, Dept Neurol & Neurosci, FIN-70211 Kuopio, Finland. Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland. Univ Kuopio, Clin Res Ctr Mediteknia, Brain Res Unit, FIN-70211 Kuopio, Finland. Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA USA. Kuopio Univ Hosp, Dept Pathol, SF-70210 Kuopio, Finland. RP Hiltunen, M (reprint author), Univ Kuopio, Dept Neurol & Neurosci, POB 1627, FIN-70211 Kuopio, Finland. EM mikko.hiltunen@uku.fi RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 10 TC 31 Z9 31 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2007 VL 44 IS 9 AR 606 DI 10.1136/jmg.2006.048470 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 207FH UT WOS:000249236500010 PM 17496198 ER PT J AU Moser, M Yu, QM Bode, C Xiong, JW Patterson, C AF Moser, Martin Yu, Qingming Bode, Christoph Xiong, Jing-Wei Patterson, Cam TI BMPER is a conserved regulator of hematopoietic and vascular development in zebrafish SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE developmental biology; gene expression; blood vessel formation; hematopoiesis; zebrafish; bone morphogenetic protein; BMPER ID DORSOVENTRAL PATTERN-FORMATION; BONE MORPHOGENETIC PROTEINS; ENDOTHELIAL-CELLS; EXPRESSION; DIFFERENTIATION; ANGIOGENESIS; CHORDIN; MICE; CROSSVEINLESS-2; VASCULOGENESIS AB For the proper development of vertebrate embryos as well as for survival of the adult organism, it is essential to form a functional vascular system. Molecules involved in this process are members of highly conserved families of proteins that exert conserved functions across species. Bone morphogenetic proteins (BMP) are extracellular factors that are regulated by extracellular modulators and bind to BMP receptors, which in turn activate intracellular signaling cascades. BMPs are necessary not only for induction of endothelial and hematopoietic lineages but also for further endothelial and hematopoietic cell differentiation. Previously, we identified BMPER (BMP endothelial cell precursor derived regulator) and demonstrated its spatiotemporal expression at sites of vasculogenesis and direct modulation of BMP activity. To directly investigate the role of BMPER in vascular development, we cloned the BMPER ortholog in zebrafish (zbmper). It is expressed at sites of high BMP activity, including vascular precursor cells located in the aortic arches and the intermediate cell mass during zebrafish embryonic development. Knockdown of zbmper results in a dorsalized phenotype, a reduced number of gatal expressing hematopoietic precursor cells and of circulating blood cells as well as in a vascular phenotype. The generation of the caudal vein is compromised and the pattern guiding of the intersomitic vessels is disturbed, indicating that zbmper is required for early steps in vascular pattern formation and hematopoiesis in zebrafish. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Freiburg, D-79106 Freiburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02115 USA. Univ N Carolina, Carolina Cardiovasc Biol Ctr, Div Cardiol, Chapel Hill, NC 27599 USA. RP Moser, M (reprint author), Univ Freiburg, Hugstetter Str 55, D-79106 Freiburg, Germany. EM Martin.Moser@uniklinik-freiburg.de; cpatters@med.unc.edu RI Xiong, Jing-Wei/A-7113-2011 FU NHLBI NIH HHS [HL61656, HL65619, R01 HL061656, R01 HL061656-09, R01 HL065619, R01 HL072347, HL072347, R37 HL065619]; NIA NIH HHS [AG 19676, AG024282, K01 AG019676, K01 AG019676-04, P01 AG024282] NR 42 TC 33 Z9 33 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2007 VL 43 IS 3 BP 243 EP 253 DI 10.1016/j.yjmcc.2007.05.008 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 212QG UT WOS:000249611300002 PM 17618647 ER PT J AU Wang, FF Wang, LL Briggs, C Sicinska, E Gaston, SM Mamon, H Kulke, MH Zamponi, R Loda, M Maher, E Ogino, S Fuchs, CS Li, J Hader, C Makrigiorgos, GM AF Wang, Fengfei Wang, Lilin Briggs, Christine Sicinska, Ewa Gaston, Sandra M. Mamon, Harvey Kulke, Matthew H. Zamponi, Raffaella Loda, Massimo Maher, Elizabeth Ogino, Shuji Fuchs, Charles S. Li, Jin Hader, Carlos Makrigiorgos, G. Mike TI DNA degradation test predicts success in whole-genome amplification from diverse clinical samples SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID MULTIPLE DISPLACEMENT AMPLIFICATION; SINGLE NUCLEOTIDE POLYMORPHISM; PARAFFIN-EMBEDDED TISSUES; REAL-TIME PCR; CANCER-PATIENTS; PLASMA DNA; ARRAY-CGH; ALLELIC IMBALANCE; CIRCULATING DNA; CELL AB The need to apply modern technologies to analyze DNA from diverse clinical samples often stumbles on suboptimal sample quality. We developed a simple approach to assess DNA fragmentation in minute clinical samples of widely different origin and the likelihood of success of degradation-tolerant whole genome amplification (restriction and circularization-aided rolling circle amplification, RCA-RCA) and subsequent polymerase chain reaction (PCR). A multiplex PCR amplification of four glyceraldehyde-3-phosphate dehydrogenase amplicons of varying sizes was performed using genomic DNA from clinical samples, followed by size discrimination on agarose gel or fluorescent denaturing high-performance liquid chromatography (dHPLC). RCA-RCA followed by real-time PCR was also performed, for correlation. Even minimal quantities of longer PCR fragments (similar to 300 to 400 bp), visible via high-sensitivity fluorescent dHPLC or agarose gel, were essential for the success of RCA-RCA and subsequent PCR-based assays. dHPLC gave a more accurate correlation between DNA fragmentation and sample quality than agarose gel electrophoresis. Multiplex-PCR-dHPLC predicted correctly the likelihood of assay success in formalin-fixed, paraffin-embedded samples fixed under controlled conditions and of different ages, in laser capture microdissection samples, in tissue print micropeels, and plasma-circulating DNA. Estimates of the percent information retained relative to snap-frozen DNA are derived for real-time PCR analysis. The assay is rapid and convenient and can be used widely to characterize DNA from any clinical sample of unknown quality. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Mol Genet Core Facil, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Div Genom Stabil & DNA Repair, 75 Francis St,Level L2, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NCI NIH HHS [R21 CA115439, R21 CA111994, P50 CA090381, 5T32 CA09078, T32 CA009078, 1R21 CA111994-01, 1R21 CA115439-01A1, 5P50 CA90381, P01 CA089021] NR 39 TC 24 Z9 24 U1 1 U2 8 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 SEP PY 2007 VL 9 IS 4 BP 441 EP 451 DI 10.2353/jmoldx.2007.070004 PG 11 WC Pathology SC Pathology GA 210QT UT WOS:000249471400004 PM 17690213 ER PT J AU Candrian, M Farabaugh, A Pizzagalli, DA Baer, L Fava, M AF Candrian, Michele Farabaugh, Amy Pizzagalli, Diego A. Baer, Lee Fava, Maurizio TI Perceived stress and cognitive vulnerability mediate the effects of personality disorder comorbidity on treatment outcome in major depressive disorder - A path analysis study SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE personality disorder; cognitive vulnerability; perceived stress; path analyses ID AXIS II SYMPTOMATOLOGY; DYSFUNCTIONAL ATTITUDES; SOCIAL SUPPORT; LIFE STRESS; TREATMENT RESPONSE; PERFECTIONISM; PREDICTORS; PATHOLOGY; THERAPY; RELAPSE AB Although personality disorder (PD) comorbidity has been associated with poor treatment outcome in major depressive disorder (MDD), little is known about mechanisms mediating this link. Converging evidence suggests that maladaptive cognitive patterns, particularly in interaction with stressors, might lead to poor treatment outcome in MDD subjects with PD pathology. The goal of this study was to test the role of PD comorbidity, cognitive vulnerability, and perceived stress in treatment outcome in MDD. Three hundred eighty-four MDD outpatients were enrolled in an 8-week open-label treatment of fluoxetine. Structural equation modeling and path analyses revealed that the effect of PD vulnerability on treatment outcome was fully mediated by increased pretreatment cognitive vulnerability and depression severity, which led to increased stress perception after treatment and poorer antidepressant response. Depressogenic cognitions might be continuously activated by chronic distress in MDD subjects reporting axis II pathology, leading to stress exacerbation and eventually poorer treatment outcome. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat, Depress Clin & Res Program, Boston, MA USA. Harvard Univ, Dept Psychol, Cambridge, MA USA. RP Candrian, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM mcandrian@partners.org FU NCCIH NIH HHS [R21 AT002974]; NIMH NIH HHS [R01 MH68376, R01 MH48483-05] NR 65 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 2007 VL 195 IS 9 BP 729 EP 737 DI 10.1097/NMD.0b013e318142cbd5 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 210NB UT WOS:000249461800003 PM 17984772 ER PT J AU Monje, ML Ramakrishna, NR Young, G Drappatz, J Doherty, LM Wen, PY Kesari, S AF Monje, Michelle L. Ramakrishna, Naren R. Young, Geoffrey Drappatz, Jan Doherty, Lisa M. Wen, Patrick Y. Kesari, Santosh TI Durable response of a radiation-induced, high-grade cerebellar glioma to temozolomide SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE chemotherapy; PET; radiation-induced glioma; temozolomide ID RECURRENT BRAIN-TUMOR; GLIOBLASTOMA-MULTIFORME; PET AB Background Radiation-induced high-grade gliomas are a rare but serious late complication of radiotherapy. We report a patient with radiation-induced cerebellar high-grade glioma who had a durable response to temozolomide. Patients and Methods Case report of a 77-year-old woman with a radiation-induced, high-grade cerebellar glioma that responded durably to temozolomide. Results Our patient developed a cerebellar high-grade glioma 9 years after treatment for a stage IV (T4N0M0) supraglottic laryngeal squamous cell carcinoma with cisplatinum and fluorouracil chemotherapy, and subsequently focal head and neck radiotherapy. Patient was treated with radiation and concurrent temozolomide (only partially due to toxicity) and was stable for 1 year without further adjuvant treatment. Subsequently the tumor recurred and the patient had a dramatic and durable response to standard 5 day dosing of adjuvant temozolomide. Conclusion High-grade gliomas are a late complication of radiation to the central nervous system and may respond to chemotherapy. C1 Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, Boston, MA 02115 USA. RP Kesari, S (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 44 Binney St,SW430, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 10 TC 2 Z9 2 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2007 VL 84 IS 2 BP 179 EP 183 DI 10.1007/s11060-007-9354-y PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 193VN UT WOS:000248303400008 PM 17332945 ER PT J AU Ying, WH AF Ying, Weihai TI NAD(+) and NADH in neuronal death SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Article DE NAD(+); NADH; neuronal death; brain injury; cerebral ischemia; neurodegenerative diseases ID POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; DELETERIOUS NETWORK HYPOTHESIS; NITRIC-OXIDE SYNTHASE; CELL-DEATH; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; AXON DEGENERATION; ASTROCYTE DEATH; BRAIN-INJURY AB Neuronal death is a key pathological event in multiple neurological diseases. Increasing evidence has suggested that NAD+ and NADH mediate not only energy metabolism and mitochondrial functions, but also calcium homeostasis, aging, and cell death. This article is written to provide an overview about the information suggesting significant roles of NAD+ and NADH in neuronal death in certain neurological diseases. Our latest studies have suggested that intranasal administration with NAD(+) can profoundly decrease ischemic brain damage. These observations suggest that NAD(+) administration may be a novel therapeutic strategy for some neurological diseases. C1 Univ Calif San Francisco, Dept Neurol 127, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Ying, WH (reprint author), Univ Calif San Francisco, Dept Neurol 127, 4150 Clement St, San Francisco, CA 94121 USA. EM Weihai.Ying@ucsf.edu NR 64 TC 13 Z9 13 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD SEP PY 2007 VL 2 IS 3 BP 270 EP 275 DI 10.1007/s11481-007-9063-5 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 209MC UT WOS:000249391600007 PM 18040861 ER PT J AU Calabrese, M Atzori, M Bernardi, V Morra, A Romualdi, C Rinaldi, L McAuliffe, MJM Barachino, L Perini, P Fischl, B Battistin, L Gallo, P AF Calabrese, Massimiliano Atzori, Matteo Bernardi, Valentina Morra, Aldo Romualdi, Chiara Rinaldi, Luciano McAuliffe, Matthew J. M. Barachino, Luigi Perini, Paola Fischl, Bruce Battistin, Leontino Gallo, Paolo TI Cortical atrophy is relevant in multiple sclerosis at clinical onset SO JOURNAL OF NEUROLOGY LA English DT Article DE multiple sclerosis; cortical thickness; cortical atrophy; neuronal degeneration ID APPEARING WHITE-MATTER; RELAPSING-REMITTING MS; WHOLE-BRAIN ATROPHY; STATUS SCALE EDSS; DIAGNOSTIC-CRITERIA; CEREBRAL-CORTEX; GREY-MATTER; VOLUME CHANGES; DISABILITY; MRI AB Introduction Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated. Methods 115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI. Global and regional Cortical Thickness (CTh) measurements, brain parenchyma fraction and T2 lesion load were analyzed. Results We found a significant global cortical thinning in p-MS (2.22 +/- 0.09 mm), RR-MS (2.16 +/- 0.10 mm) and SP-MS (1.98 +/- 0.11 mm) compared to CIS (2.51 +/- 0.11 mm) and HV (2.48 +/- 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = -0.393, p = 0.03) and absent in p-MS (r = -0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas. Discussion Cortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology. C1 Univ Hosp, Multiple Sclerosis Ctr Veneto Reg, Ist Clin Neurol, Dept Neurosci, I-35128 Padua, Italy. Neuroradiol Unit, Euganea Med, Padua, Italy. Univ Padua, Ctr Biotechnol, Dept Biol, CRIBI, Padua, Italy. NIH, Biomed Imaging Res Serv Sect, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Harvard Med Sch, Charlestown, MA USA. RP Calabrese, M (reprint author), Univ Hosp, Multiple Sclerosis Ctr Veneto Reg, Ist Clin Neurol, Dept Neurosci, Via Giustiniani 5, I-35128 Padua, Italy. EM calabresem@hotmail.it RI Romualdi, Chiara/K-1132-2016 OI Romualdi, Chiara/0000-0003-4792-9047 NR 38 TC 120 Z9 124 U1 1 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD SEP PY 2007 VL 254 IS 9 BP 1212 EP 1220 DI 10.1007/s00415-006-0503-6 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 216QD UT WOS:000249893200008 PM 17361339 ER PT J AU Yoshida, M McKeown, NM Rogers, G Meigs, JB Saltzman, E D'Agostino, R Jacques, PF AF Yoshida, Makiko McKeown, Nicola M. Rogers, Gail Meigs, James B. Saltzman, Edward D'Agostino, Ralph Jacques, Paul F. TI Surrogate markers of insulin resistance are associated with consumption of sugar-sweetened drinks and fruit juice in middle and older-aged adults SO JOURNAL OF NUTRITION LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; FRUCTOSE CORN SYRUP; BETA-CELL FUNCTION; GLYCEMIC INDEX; DIETARY FIBER; BODY-WEIGHT; BEVERAGE CONSUMPTION; SECRETORY DYSFUNCTION; METABOLIC SYNDROME; GLUCOSE-TOLERANCE AB In this study, we examined the association between sugar-sweetened drink, diet soda, and fruit juice consumption and surrogate measures of insulin resistance. Sugar-sweetened drink, diet soda, and fruit juice consumption was estimated using a semiquantitative FFQ in 2500 subjects at the fifth examination (1991-1995) of the Framingham Offspring Study. Surrogate markers of insulin resistance measured in this study included fasting insulin, fasting glucose, homeostatic model assessment of insulin resistance, and the insulin sensitivity index (ISI0,120). Sugar-sweetened drink consumption was positively associated with fasting insulin (none vs. >= 2 servings/d, 188 vs. 206 pmol/L, P-trend <0.001) after adjusting for potential confounders, Sugar-sweetened drink consumption was not associated with fasting glucose or ISI0,120. Fruit juice consumption was inversely associated with fasting glucose (none vs. >= 2 servings/d, 5.28 vs. 5.18 mmol/L, P-trend = 0.006), but not with fasting insulin (none vs. >= 2 servings/d, 200 vs. 188 pmol/L, P-trend = 0.37) or ISI0,120 (none vs. >= 2 servings/d, 26.0 vs. 27.0, P-trend = 0.19) in multivariate models. Diet soda consumption was not associated with any surrogate measures of insulin resistance after adjustment for potential confounders (insulin: none vs. >= 2 servings/d, 195 vs. 193 pmol/L, P-trend = 0.59; glucose: 5.26 vs. 5.24 mmol/L, P-trend = 0.84; and ISI0,120: 26.2 vs. 26.7, P-trend = 0.37). In these healthy adults, sugar-sweetened drink consumption appears to be unfavorably associated with surrogate measures reflecting hepatic more than peripheral insulin sensitivity. Studies of long-term beverage consumption using more direct measures of insulin sensitivity are clearly warranted. C1 Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Energy Metab Lab, Boston, MA 02111 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP McKeown, NM (reprint author), Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA. EM nicola.mckeown@tufts.edu FU NHLBI NIH HHS [N01-HC-25195] NR 47 TC 41 Z9 43 U1 1 U2 2 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2007 VL 137 IS 9 BP 2121 EP 2127 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 205JU UT WOS:000249110600021 PM 17709452 ER PT J AU Wright, ND Wylie-Rosett, J Lukoscheck, P Moadel, AB Soroudi, N AF Wright, Natania D. Wylie-Rosett, Judith Lukoscheck, Petra Moadel, Alyson B. Soroudi, Nafisseh TI The school yard kilds: A puppet show to promote a healthful lifestyle SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Editorial Material C1 Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Wright, ND (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer 1306, Bronx, NY 10461 USA. EM Nwright@aecom.yu.edu FU NHLBI NIH HHS [K07 HL003953, K07 HL003953-05]; NIDDK NIH HHS [P60 DK020541-29] NR 5 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 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD SEP-OCT PY 2007 VL 39 IS 5 BP 290 EP 291 DI 10.1016/j.jneb.2007.06.001 PG 2 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 214PE UT WOS:000249749800011 PM 17826351 ER PT J AU Chuang, SK Perrott, DH Susarla, SM Dodson, TB AF Chuang, Sung-Kiang Perrott, David H. Susarla, Srinivas M. Dodson, Thomas B. TI Age as a risk factor for third molar surgery complications SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ASYMPTOMATIC 3RD-MOLARS; EXTRACTION DIFFICULTY; HEALTH AB Purpose: The purpose of this study was to estimate the frequency of complications after third molar (M3) surgery, with age as the primary risk factor. Patients and Methods: This was a prospective cohort study of a sample of subjects having at least 1 M3 extracted as part of the American Association of Oral and Maxillofacial Surgeons' Age-Related Third Molar Study. The predictor variables were categorized as demographic, health status, anatomic, and pathological. The outcome variable was overall complications, including both intraoperative and postoperative complications. Appropriate univariate and bivariate statistics were computed. A multiple logistic regression model was used to evaluate the simultaneous effects of multiple covariates. Results: The study sample was comprised of 4,004 subjects having a total of 8,748 M3s removed. The mean age was 39.8 +/- 13.6 years, with 245 subjects (6.1%) age 25 and younger. Approximately half of the subjects were female. The overall complication rate was 19%. In bivariate analyses, age above 25 years, gender, American Society of Anesthesiologists classification, number of preoperatively identified risk factors for complication, impaction level of M3, evidence of periodontal disease, preoperative infection, and evidence of any pathology associated with M3 were associated with complications (P <= .15). In the multiple regression model, age above 25 years was associated with an increased risk of complications (odds ratio = 1.5; P = .05). Conclusions: The results of these analyses suggest that increased age (>25 years) appears to be associated with a higher complication rate for M3 extractions. (C) 2007 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02114 USA. Salinas Valley Mem Healthcare Syst, Salinas, CA USA. RP Chuang, SK (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM schuang@hsph.harvard.edu OI Susarla, Srinivas/0000-0003-0155-8260 NR 17 TC 41 Z9 46 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2007 VL 65 IS 9 BP 1685 EP 1692 DI 10.1016/j.joms.2007.04.019 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 206HJ UT WOS:000249174200004 PM 17719384 ER PT J AU Papadaki, M Kaban, L Kwolek, C Keith, D Troulis, M AF Papadaki, Maria Kaban, Leonard Kwolek, Christopher Keith, David Troulis, Maria TI Arterial stents for access and protection of the parotid and submandibular ducts during sialoendoscopy SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 21-24, 2005 CL Boston, MA SP Amer Assoc Oral & Maxillofacial Surg ID INTERVENTIONAL SIALENDOSCOPY; LASER LITHOTRIPSY; SALIVARY-GLANDS; DIAGNOSIS; SIALOLITHIASIS; ENDOSCOPY; DISEASES; EXPERIENCE C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Papadaki, M (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA. EM mtroulis@partners.org NR 19 TC 1 Z9 1 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2007 VL 65 IS 9 BP 1865 EP 1868 DI 10.1016/j.joms.2006.04.041 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 206HJ UT WOS:000249174200036 PM 17719416 ER PT J AU Hanson, GR Park, SE Suggs, JF Moynihan, AL Nha, KW Freiberg, AA Li, G AF Hanson, George R. Park, Sang E. Suggs, Jeremy F. Moynihan, Angela L. Nha, Kyung W. Freiberg, Andrew A. Li, Guoan TI In vivo kneeling biomechanics after posterior stabilized total knee arthroplasty SO JOURNAL OF ORTHOPAEDIC SCIENCE LA English DT Article ID POLYETHYLENE TIBIAL POST; DEEP FLEXION; FLUOROSCOPIC ANALYSIS; FIXED-BEARING; KINEMATICS; REPLACEMENT; FRACTURE; ABILITY; MOTION; RANGE AB Background. Kneeling is one of the activities sought by patients after total knee arthroplasty (TKA). This study investigated the six degrees of freedom (DOF) kinematics and three-dimensional (3D) contact during weight-bearing kneeling. Methods. A total of 16 South Korean female patients (22 knees) after posteriorly stabilized (PS) TKA (LPS-Flex) were randomly recruited and had the same surgeon. The patients were imaged using a dual fluoroscopic technique while they kneeled from initial to maximum flexion. The acquired images and 3D models were then used to recreate the in vivo pose of the components. Contact was determined by locating the surface intersections in the tibiofemoral and cam/post (between the femoral cam and tibial post) articular compartments. Results. Patients flexed, on average, from 107.3 degrees to 128.0 degrees during the kneeling activity. Changes in kinematics included 1.0mm of proximal, 0.9mm of medial, and 7.6mm of posterior translation and 1.7 degrees of varus rotation (P < 0.04). A difference in internal tibial rotation was not detected. Articular contact moved posteriorly by 5.9mm and 6.4mm in the medial and lateral compartments, respectively. Contact also moved medially by 3.2mm and 5.8mm in the medial and lateral compartments. A decrease in articular contact was observed in both condyles, and lateral condylar lift-off increased with flexion (P = 0.0001). More than 80% of the patients demonstrated cam/post engagement, which always occurred in the distal portion of the post. Conclusions. In this patient cohort, the knee joint was constrained during the weight-bearing activity such that femoral subluxation and dislocation were not observed. Furthermore, posterior cam/post engagement occurred only in the distal portion of the tibial post, which may improve the longevity of the post. The tibiofemoral and cam/post articular contact data presented in this study further suggest that kneeling may be performed by patients after clinically successful PS TKA who feel comfortable with the activity and are free of pain. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Dongguk Univ, Int Hosp, Dept Orthopaed Surg, Ilsan, South Korea. MIT, Dept Engn Mech, Cambridge, MA 02139 USA. Inje Univ, Dept Orthopaed Surg, Ilsan, South Korea. Ilsanpaik Hosp, Ilsan, South Korea. RP Li, G (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. NR 30 TC 16 Z9 17 U1 0 U2 7 PU SPRINGER TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0949-2658 J9 J ORTHOP SCI JI J. Orthop. Sci. PD SEP PY 2007 VL 12 IS 5 BP 476 EP 483 DI 10.1007/s00776-007-1165-7 PG 8 WC Orthopedics SC Orthopedics GA 216ZY UT WOS:000249919100010 PM 17909934 ER PT J AU Davis, A Barnes, C AF Davis, Amanda Barnes, Chris TI Thrombotic thrombocytopenic purpura in childhood: An uncommon but life-threatening cause of thrombocytopenia SO JOURNAL OF PAEDIATRICS AND CHILD HEALTH LA English DT Article DE ADAMTS-13; hemolytic anemia; thrombotic thrombocyto-penic purpura ID VON-WILLEBRAND-FACTOR; HEMOLYTIC-UREMIC SYNDROME; FACTOR-CLEAVING PROTEASE; ADAMTS-13; CHILDREN; PLASMA; DIAGNOSIS; TTP AB Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder characterised by microangiopathic haemolytic anaemia, thrombocytopenia and signs of ischaemic organ dysfunction such as neurological or renal impairment and fever. The diagnosis of TTP should be considered in any child presenting with thrombocytopenia, in particular those children with microangiopathic haemolysis, atypical immune thrombocytopenia purpura or Evan's syndrome. Distinguishing TTP from haemolytic uraemic syndrome is difficult, but where there is doubt about the diagnosis, a presumptive diagnosis of TTP should be made to allow potentially life-saving therapy with therapeutic plasma exchange. Recent advances in the molecular basis of the disease have resulted in assays for ADAMTS-13 activity, inhibitor levels and ADAMTS-13 mutation analysis. These assays help to distinguish TTP from haemolytic uraemic syndrome. However, the performance characteristics of these assays in the diagnosis and management of TTP are yet to be defined. C1 Royal Childrens & Womens Hosp, Dept Haematol, Melbourne, Vic, Australia. RP Davis, A (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55th Fruit Str, Boston, MA 02114 USA. EM akdavis@partners.org NR 14 TC 1 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1034-4810 J9 J PAEDIATR CHILD H JI J. Paediatr. Child Health PD SEP PY 2007 VL 43 IS 9 BP 640 EP 642 DI 10.1111/j.1440-1754.2007.01178.x PG 3 WC Pediatrics SC Pediatrics GA 206KI UT WOS:000249181900014 PM 17688649 ER PT J AU Sano, Y Gomez, FE Kang, W Lan, J Maeshima, Y Hermsen, JL Ueno, C Kudsk, KA AF Sano, Yoshifumi Gomez, F. Enrique Kang, Woodae Lan, Jinggang Maeshima, Yoshinori Hermsen, Joshua L. Ueno, Chikara Kudsk, Kenneth A. TI Intestinal polymeric immunoglobulin receptor is affected by type and route of nutrition SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID TOTAL PARENTERAL-NUTRITION; MAJOR ABDOMINAL-TRAUMA; MUCOSAL IMMUNITY; SEPTIC MORBIDITY; EPITHELIAL-CELLS; LYMPHOID-TISSUE; SECRETORY IGA; FED MICE; EXPRESSION; GUT AB Background: Secretory immunoglobulin A (SIgA) prevents adherence of pathogens at mucosal surfaces to prevent invasive infection. Polymeric immunoglobulin receptor (pIgR) is located on the basolateral surface of epithelial cells and binds dimeric immunoglobulin A (IgA) produced by plasma cells in the lamina propria. This IgA-pIgR complex is transported apically, where IgA is exocytosed as SIgA to the mucosal surface. Our prior work shows that mice fed intragastric (IG, an elemental diet model) and IV parenteral nutrition (PN) solution have reduced intestinal T and B cells, SIgA, and interleukin-4 (IL-4) compared with mice fed chow or a complex enteral diet (CED). Prior work also demonstrates a reduction in IgA transport to mucosal surfaces in IV PN-fed mice. Because IL-4 up-regulates pIgR production, this work studies the effects of these diets on intestinal pIgR. Methods: Male Institute of Cancer Research (ICR) mice were randomized to chow (n = 11) with IV catheter, CED (n = 10) or IG PN (n = 11) via gastrostomy and IV PN (n = 12) for 5 days. CED and PN were isocaloric and isonitrogenous. Small intestine was harvested for pIgR and IL-4 assays after mucosal washing for IgA. IgA and IL-4 levels were analyzed by enzyme-linked immunosorbent assay and pIgR by Western blot. Results: Small intestinal pIgR expression, IgA levels, and IL-4 levels decreased significantly in IV PN and IG PN groups. Conclusions: Lack of enteral stimulation affects multiple mechanisms responsible for decreased intestinal SIgA levels, including reduced T and B cells in the lamina propria, reduced Th-2 IgA-stimulating cytokines, and impaired expression of the IgA transport protein, pIgR. C1 William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu RI Lan, Jinggang/F-1776-2011 FU NIGMS NIH HHS [R01 GM53439] NR 37 TC 18 Z9 21 U1 0 U2 3 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD SEP-OCT PY 2007 VL 31 IS 5 BP 351 EP 356 DI 10.1177/0148607107031005351 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 206ID UT WOS:000249176200004 PM 17712142 ER PT J AU Kang, W Kudsk, KA Sano, Y Lan, J Yang-Xin, F Gomez, FE Maeshima, Y AF Kang, Woodae Kudsk, Kenneth A. Sano, Yoshifumi Lan, Jinggang Yang-Xin, Fu Gomez, F. Enrique Maeshima, Yoshinori TI Effects of lymphotoxin beta receptor blockade on intestinal mucosal immunity SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID TOTAL PARENTERAL-NUTRITION; UPPER RESPIRATORY-TRACT; CELL-ADHESION MOLECULE-1; LYMPHOID-TISSUE; IMMUNOGLOBULIN-A; BACTERIAL PNEUMONIA; PEYERS-PATCHES; FED MICE; GUT; SYSTEM AB Background: Mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) directs lymphocyte migration into gut-associated lymphoid tissue (GALT) through Peyer's patches (PPs). Parenteral nutrition (PN) impairs mucosal immunity by reducing PPs MAdCAM-1 expression, T and B cells in GALT, and intestinal and respiratory immunoglobulin (Ig) A levels. We previously showed that PN reduces lymphotoxin P receptor blockade (LT beta R) in PPs and intestine, and that stimulation with LT beta R agonist antibodies reverses these defects. To confirm that LT beta R regulates transcription of MAdCAM-1 message and more fully understand the effects of LT beta R on MAdCAM-1 function within the mucosal immune system, we studied the effect of LT beta R blockade with a chimeric LT beta R Ig-fusion protein on MAdCAM-1 mRNA levels, PP lymphocyte mass and IgA levels in the intestinal and respiratory tracts. Methods: Mice were cannulated and killed 3 days after receiving chow + control Ig, chow + LT beta R-Ig fusion protein (100 mu g IV), or PN + control Ig. The PPs of half of the animals were processed for lymphocyte count, and the other half were processed for complementary DNA and subsequent polymerase chain reaction (PCR). mRNA levels of MAdCAM-1 were determined by real-time PCR; intestinal and respiratory IgA levels were rneasured by ELISA. Results: PN significantly reduced PP lymphocyte mass, MAdCAM-1 mRNA, and intestinal IgA. As anticipated, LT beta R blockade significantly decreased PP cells and MAdCAM-1. mRNA, but not intestinal IgA because chow feeding was maintained. Both LT beta R blockade and PN decreased nasal IgA, but not significantly. Conclusions: LT beta R blockade in chow animals significantly reduces transcription of MAdCAM-1 gene and PPs lymphocyte mass. These data implicate inadequate LT beta R signaling as a major mechanism for decreased GALT cells with lack of enteral stimulation, and further establish the role of LT beta R in the mucosal immune system. C1 William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. Univ Wisconsin, Coll Med & Publ Hlth, Madison, WI USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wise.edu FU NIGMS NIH HHS [R01 GM53439] NR 40 TC 6 Z9 7 U1 0 U2 2 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD SEP-OCT PY 2007 VL 31 IS 5 BP 358 EP 364 DI 10.1177/0148607107031005358 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 206ID UT WOS:000249176200007 PM 17712143 ER PT J AU Bogren, A Teles, RP Torresyap, G Haffajee, AD Socransky, SS Wennstrom, JL AF Bogren, Anna Teles, Ricardo P. Torresyap, Gay Haffajee, Anne D. Socransky, Sigmund S. Wennstroem, Jan L. TI Clinical and microbiologic changes associated with the combined use of a powered toothbrush and a triclosan/copolymer dentifrice : A 3-year prospective study SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE gingivitis; microbiology; primary prevention; randomized controlled trial; toothbrushing; triclosan ID TRICLOSAN-CONTAINING DENTIFRICE; OSCILLATING/ROTATING ELECTRIC TOOTHBRUSH; DNA-DNA HYBRIDIZATION; AGED 3-80 YEARS; PLAQUE CONTROL; ORAL-HEALTH; MANUAL TOOTHBRUSHES; PERIODONTAL-DISEASE; ADULT-POPULATION; GINGIVITIS AB Background: Different means are available for self-performed oral hygiene. The aim of this study was to evaluate the clinical and microbiologic effects of a preventive homecare program including the combined use of a powered toothbrush and a triclosan/copolymer-containing dentifrice. Methods: A total of 160 adult subjects without signs of destructive periodontal disease were recruited for this 3-year randomized controlled trial. The subjects were assigned to a homecare program using an oscillating/rotating powered toothbrush and a triclosan/copolymer/fluoride-containing dentifrice (test) or a manual toothbrush and a standard fluoride-containing dentifrice (control). Supragingival polishing and reinforcement of homecare procedures were provided every 6 months. Plaque, bleeding on probing (BOP), and probing depth (PD) were scored at baseline and after 1, 2, and 3 years. Subgingival plaque samples were taken from the mesial aspect of each tooth at baseline and after 1, 2, and 3 years and were analyzed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. All data analyses were based on "intention-to-treat" with the subject as the statistical unit. Results: Compared to baseline, no significant changes in clinical parameters were observed during the 3 years, except for a reduction in the mean PD at the 2- and 3-year follow-up examinations (P < 0.05). No significant differences were found between the two groups with regard to plaque, BOP, or PD or in the mean counts of the 40 species at any time point. Conclusion: The study failed to prove additional benefits of the combined use of a powered toothbrush and a triclosan/ copolymer-containing dentifrice in adult subjects without signs of destructive periodontal disease. C1 Gothenburg Univ, Sahlgrenska Acad, Dept Periodontol, Inst Odontol, Gothenburg, Sweden. Forsyth Inst, Boston, MA USA. RP Bogren, A (reprint author), Gothenburg Univ, Sahlgrenska Acad, Dept Periodontol, Inst Odontol, Gothenburg, Sweden. EM anna.bogren@odontologi.gu.se FU NIDCR NIH HHS [DE-12861] NR 35 TC 8 Z9 9 U1 0 U2 3 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD SEP PY 2007 VL 78 IS 9 BP 1708 EP 1717 DI 10.1902/jop.2007.070028 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 215XV UT WOS:000249843200010 PM 17760540 ER PT J AU Grossi, SG Goodson, JM Gunsolley, JC Otomo-Corgel, J Bland, PS Doherty, F Comiskey, J AF Grossi, Sara G. Goodson, J. Max Gunsolley, John C. Otomo-Corgel, Joan Bland, Paul S. Doherty, Frances Comiskey, Judy TI Mechanical therapy with adjunctive minocycline microspheres reduces red-complex bacteria in smokers SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE arestin; drug delivery systems; microspheres; minocycline; periodontitis; smoking ID LOCALLY DELIVERED DOXYCYCLINE; PERIODONTAL THERAPY; CIGARETTE-SMOKING; SUBGINGIVAL MICROFLORA; RISK INDICATORS; DISEASE AB Background: Smoking increases the risk for periodontal disease and reduces the healing response. We examined the antimicrobial and clinical effects of scaling and root planing (SRP) with and without minocycline HCl 1 mg microspheres (MM) relative to smoking status in subjects with periodontitis. Methods: A total of 127 subjects (46 never smokers, 44 former smokers, and 37 current smokers) with moderate to advanced periodontitis were randomized to receive MM + SRP (N = 62) or SRP alone (N = 65). Subgingival plaque samples collected at baseline and day 30 were examined for the presence of 40 periodontal bacteria by DNA probe analysis. Results: MM + SRP reduced red-complex bacteria (RCB) numbers and proportions to a greater extent than SRP alone, irrespective of smoking status. RCB numbers were not reduced by SRP in current smokers. The difference in the reduction in numbers of RCB by SRP relative to MM + SRP in current smokers was statistically significant (P < 0.05). Numbers and proportions of orange complex bacteria (OCB) were reduced in all groups treated with MM + SRP. Proportions of OCB increased in current smokers treated with SRP alone. In current smokers, MM + SRP significantly reduced probing depth (PD), increased clinical attachment level (CAL), and reduced bleeding on probing (BOP) to a greater extent than SRP alone (P < 0.05). Conclusions: SRP alone was ineffective at reducing numbers or proportions of RCB or OCB in current smokers, whereas MM + SRP significantly reduced both. MM + SRP also improved PD, BOP, and CAL to a greater extent than SRP alone independent of smoking status. C1 E Carolina Univ, Brody Sch Med, Dept Pediat, Greenville, NC 27858 USA. Forsyth Inst, Dept Clin Res, Boston, MA USA. Virginia Commonwealth Univ, Dept Periodont, Richmond, VA USA. Univ Calif Los Angeles, Sch Dent, Dept Periodontol, Greater Los Angeles Vet Affairs Healthcare Syst,D, Los Angeles, CA 90024 USA. Univ Tennessee, Ctr Hlth Sci, Coll Dent, Dept Periodontol, Memphis, TN 38163 USA. Oral Hlth Consultants, Amherst, NY USA. OraPharma Inc, Warminster, PA USA. RP Grossi, SG (reprint author), E Carolina Univ, Brody Sch Med, Dept Pediat, Greenville, NC 27858 USA. EM grossis@ecu.edu NR 34 TC 20 Z9 22 U1 2 U2 10 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD SEP PY 2007 VL 78 IS 9 BP 1741 EP 1750 DI 10.1902/jop.2007.070118 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 215XV UT WOS:000249843200014 PM 17760544 ER PT J AU Kahkonen, S Yamashita, H Rytsala, H Suominen, K Ahveninen, J Isometsa, E AF Kaehkoenen, Seppo Yamashita, Hidehisa Rytsaelae, Heikki Suominen, Kirsi Ahveninen, Jyrki Isometsae, Erkki TI Dysfunction in early auditory processing in major depressive disorder revealed by combined MEG and EEG SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID EVENT-RELATED POTENTIALS; MISMATCH NEGATIVITY; SELECTIVE ATTENTION; COGNITIVE DEFICITS; HUMAN BRAIN; P300; MAGNETOENCEPHALOGRAPHY; MODULATION; NEUROPSYCHOLOGY; SCHIZOPHRENIA AB Background: Patients with major depressive disorder (MDD) show impairments in cognitive functions. However, neural mechanisms underlying these disturbances are poorly understood. We investigated whether MDD affects neural mechanisms of involuntary attention studied by auditory evoked potentials (AEPs) and auditory evoked magnetic fields (AEFs). Methods: AEPs and AEFs were studied in a passive odd-ball paradigm in 13 drug-free patients with unipolar MDD during an acute episode and 12 age-and sex-matched healthy subjects. Auditory responses to monaurally presented frequent " standard" tones, infrequent " deviant" tones (10% and 20% frequency change) and occasional " novel" sounds (complex sounds) were simultaneously recorded with whole-head magnetoencephalography (MEG) and electroencephalography (EEG). Results: P1 and P1 m latencies were decreased in patients with MDD, compared with those in healthy subjects. Further, the mismatch negativity amplitude to the 10% frequency deviance in the EEG, but not in the MEG, was increased in MDD. We observed no differences in N1/N1 m and P3a responses in the MEG and EEG. The magnitude of decrease in P1/P1 m latency correlated negatively with the severity of depression in the patients. Conclusions: Early auditory processing is impaired in patients with MDD during an acute episode, probably reflecting dysfunctional frontotemporal neural circuits. These dysfunctions may contribute to the cognitive disturbances observed in people with MDD. C1 Univ Helsinki, Cent Hosp, BioMag Lab, FIN-00029 HUS, Finland. Univ Helsinki, Congnit Brain Res Unit, FIN-00014 Helsinki, Finland. Hiroshima Univ, Dept Psychiat, Hiroshima, Japan. Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland. Univ Helsinki, Cent Hosp, Jorvi Hosp, Dept Psychiat, Espoo, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT, Cambridge, MA 02138 USA. Ctr Biomed Imaging, Charlestown, MA USA. RP Kahkonen, S (reprint author), Univ Helsinki, Cent Hosp, BioMag Lab, POB 340, FIN-00029 HUS, Finland. EM Seppo.Kahkonen@helsinki.fi NR 45 TC 26 Z9 28 U1 1 U2 6 PU CMA MEDIA INC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD SEP PY 2007 VL 32 IS 5 BP 316 EP 322 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 206AU UT WOS:000249157100002 PM 17823647 ER PT J AU Brown, VB Najavits, LM Cadiz, S Finkelstein, N Heckman, JP Rechberger, E AF Brown, Vivian B. Najavits, Lisa M. Cadiz, Sharon Finkelstein, Norma Heckman, Jennifer P. Rechberger, Elke TI Implementing an evidence-based practice: Seeking Safety group SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE adoption of innovation; group interventions; mental health; substance use/abuse; trauma ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL TREATMENT; SUBSTANCE USE DISORDERS; WOMEN; ABUSE; OUTCOMES AB This article presents findings from a multisite study on adopting and implementing an evidence-based practice, Seeking Safety, for women with co-occurring disorders and experiences of physical and sexual abuse. It focuses on what implementation decisions different sites made to optimize the compatibility of Seeking Safety with the site's needs and experiences and on issues posed by Rogers (1995) as relevant to successful diffusion of an innovative practice. A total of 157 clients and 32 clinicians reported on satisfaction with various aspects of the model. Cross-site differences are also examined. Results show that Seeking Safety appears to be an intervention that clinicians perceive as highly relevant to their practice, and one that adds value. Clients perceive the treatment as uniquely touching on their needs in a way that previous treatments had not. C1 PROTOTYPES, Ctr Innovat Hlth Mental Hlth & Social Serv, Los Angeles, CA USA. VA Boston, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Inst Hlth & Recovery, Cambridge, MA USA. ETR Associates, Stockton, CA USA. PROTOTYPES Syst Change Ctr, Los Angeles, CA USA. RP Brown, VB (reprint author), PROTOTYPES Syst Change Ctr, 5601 W Slauson Ave,Suite 200, Culver City, CA 90230 USA. EM protoceo@aol.com NR 24 TC 9 Z9 10 U1 2 U2 7 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD SEP PY 2007 VL 39 IS 3 BP 231 EP 240 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 235EY UT WOS:000251217500004 PM 18159776 ER PT J AU Kelly, JF Myers, MG AF Kelly, John F. Myers, Mark G. TI Adolescents' participation in Alcoholics Anonymous and Narcotics Anonymous: Review, implications and future directions SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE 12-step; Alcoholics Anonymous; Narcotics Anonymous; groups; adolescent; self-help ID SELF-HELP GROUPS; SUBSTANCE-ABUSE TREATMENT; MULTIVARIATE PROCESS MODEL; USE DISORDERS; INPATIENT TREATMENT; 12-STEP ATTENDANCE; MINNESOTA MODEL; DRUG-ABUSERS; INTERVENTION; INDIVIDUALS AB Youth treatment programs frequently employ 12-Step concepts and encourage participation in Alcoholics Anonymous (AA) and Narcotics Anonymous (NA). Since AA/NA groups are easily accessible at no charge and provide flexible support at times of high relapse risk they hold promise as a treatment adjunct in an increasingly cost-constricting economic climate. Yet, due to concerns related to adolescents' developmental status, skepticism exists regarding the utility of AA/NA for youth. This review evaluates the empirical evidence in this regard, identifies and discusses knowledge gaps, and recommends areas for future research. Searches were conducted in PsychINFO, Medline, relevant literature and by personal correspondence. Findings suggest youth may benefit from AA/NA participation following treatment, but conclusions are limited by four important factors: (1) a small number of studies; (2) no studies with outpatients; (3) existing evidence is solely observational; and ( 4) only partial measurement of the 12-Step construct. While surveys of adolescent SUD treatment programs indicate widespread clinical interest and application of adult-derived 12-Step approaches this level of enthusiasm has not been reflected in the research community. Qualitative research is needed to improve our understanding of youth-specific AA/NA barriers, and efficacy, comparative effectiveness, and process studies are still needed to inform clinical practice guidelines for youth providers. C1 Massachusetts Gen Hosp, Dept Psychiat, MGH Harvard Addict Res Program, Boston, MA 02114 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, MGH Harvard Addict Res Program, 60 Staniford St,132, Boston, MA 02114 USA. EM jkelly11@partners.org OI Myers, Mark/0000-0003-4044-2914 FU NIDA NIH HHS [5T32DA016184-02] NR 73 TC 40 Z9 40 U1 3 U2 8 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD SEP PY 2007 VL 39 IS 3 BP 259 EP 269 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 235EY UT WOS:000251217500007 PM 18159779 ER PT J AU Dobalian, A Tsao, JCI Putzer, GJ Menendez, SM AF Dobalian, Aram Tsao, Jennie C. I. Putzer, Gavin J. Menendez, Silvia M. TI Improving rural community preparedness for the chronic health consequences of bioterrorism and other public health emergencies SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Editorial Material ID PRIMARY-CARE; TERRORISM; ATTACKS; DISASTER; AMERICA; WORLD C1 VA Greater Los Angeles, Sepulveda Ambulatory Care Ctr & Nursing Home, Health Care Ctr Excellence Study Healthcare Provi, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Pediat Pain Program, Los Angeles, CA 90024 USA. Univ Florida, Dept Hlth Serv Res Management & Policy, Gainesville, FL USA. RP Dobalian, A (reprint author), VA Greater Los Angeles, Sepulveda Ambulatory Care Ctr & Nursing Home, Health Care Ctr Excellence Study Healthcare Provi, 16111 Plummer St 152,Bldg 25,Rm B110, Sepulveda, CA 91343 USA. EM adobalia@ucia.edu FU AHRQ HHS [U01 HS14355]; PHS HHS [R04RH01310] NR 30 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD SEP-OCT PY 2007 VL 13 IS 5 BP 476 EP 480 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 203RU UT WOS:000248992500008 PM 17762692 ER PT J AU Johansen, KL Chertow, GM AF Johansen, Kirsten L. Chertow, Glenn M. TI Chronic kidney disease mineral bone disorder and health-related quality of life among incident end-stage renal-disease patients SO JOURNAL OF RENAL NUTRITION LA English DT Article ID HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; MEDICAL OUTCOMES; MORTALITY; ASSOCIATION; MORBIDITY; ANEMIA; HEMO AB Objective: Our objective was to determine the extent to which chronic kidney disease mineral bone disorder (CKD-MBD) is associated with health-related quality of life among incident dialysis patients. Design: This study's design was a cross-sectional analysis. Setting: This was part of the United States Renal Data System Dialysis Morbidity and Mortality Study (DMMS), Wave 2. Patients: The patients comprised 2590 adult participants in DMMS Wave 2, for whom quality of life and laboratory data were available. Methods: We stratified patients according to their serum concentrations of phosphorus, calcium, and parathyroid hormone (PTH), and compared health-related quality of life as a function of these indicators in analyses adjusted for demographic, clinical, and other laboratory variables. Main Outcome Measures: Main outcome measures included Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and the Symptom score of the Kidney Disease Quality of Life. Results: Both high and low serum phosphorus concentrations were associated with lower PCS scores (-1.25 to -1.48 points compared with the reference category), as was low PTH (-1.49 points). Low serum phosphorus was associated with more severe symptoms of kidney disease (-3.88 points), but there were no associations between high phosphorus or either extreme of PTH and the Symptom score. Serum calcium concentration and the calcium x phosphorus product were unassociated with PCS or Symptom scores. There were no associations among phosphorus, calcium, or PTH and MCS. Analyses simultaneously controlling for serum phosphorus, calcium, and PTH showed similar results. Conclusion: High and low serum phosphorus and low PTH are associated with slightly poorer self-reported physical functioning. Clinical trials will be necessary to determine whether and to what extent improvement in health status may occur with the correction of selected disorders of mineral metabolism. (C) 2007 by the National Kidney Foundation, Inc. C1 San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johartsen@ucsf.edu FU NIDDK NIH HHS [N01 DK022498-002, K24 DK085446, N01 DK022498, N01-DK-1-2450] NR 27 TC 12 Z9 14 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 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD SEP PY 2007 VL 17 IS 5 BP 305 EP 313 DI 10.1053/j.jrn.2007.06.005 PG 9 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 213SW UT WOS:000249688400003 PM 17720099 ER PT J AU Mourikis, A Mankin, HJ Hornicek, FJ Raskin, KA AF Mourikis, Anastasios Mankin, Henry J. Hornicek, Francis J. Raskin, Kevin A. TI Treatment of proximal humeral chondrosarcoma with resection and allograft SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID FOLLOW-UP; BONE ALLOGRAFTS; LIMB SALVAGE; MANAGEMENT; TUMORS; RECONSTRUCTION; REPLACEMENT; TRANSPLANTATION; INFECTION; NEOPLASMS AB Chondrosarcoma of the proximal humerus is an uncommon malignant bone tumor, and limited information is available about treatment. We retrospectively reviewed 31 patients treated by resection and replacement with allograft implants during the past 24 years. The patients were followed up for an average of more than 16 years. Despite some allograft complications, the overall success rate for the grafts was 77%, and patient survival was 96%. Only 1 patient died. Two patients required amputation for local recurrences, and the remainder did reasonably well despite some functional problems. On the basis of this study and by comparison data, we believe that proximal humeral chondrosarcomas are less malignant than chondrosarcomas in other sites. In comparing them against 26 metallic implants, we believe that resection and allograft implantation remains a generally successful treatment, although the improvement of the metallic devices over the years has made this technique more available and acceptable. C1 Massachusetts Gen Hosp, Harvard Med School, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, 11224 Jackson Bldg, Boston, MA 02114 USA. EM hmankin@partners.org NR 36 TC 7 Z9 10 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP-OCT PY 2007 VL 16 IS 5 BP 519 EP 524 DI 10.1016/j.jse.2006.10.010 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 220IX UT WOS:000250151500004 PM 17521925 ER PT J AU Doornberg, J Elsner, A Kloen, P Marti, RK van Dijk, CN Ring, D AF Doornberg, Job Elsner, Andreas Kloen, Peter Marti, Rene K. van Dijk, C. Niek Ring, David TI Apparently isolated partial articular fractures of the radial head: Prevalence and reliability of radiographically diagnosed displacement SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID MASON TYPE-II; INTRAOBSERVER REPRODUCIBILITY; INTEROBSERVER RELIABILITY; CLASSIFICATION; ELBOW AB The purpose of this study was to measure the prevalence and reliability of the radiographic diagnosis of displacement of apparently isolated partial articular radial head fractures and use these factors to assess treatment considerations. Among 119 radiographically visible partial fractures of the radial head not associated with other wrist, forearm, or elbow injury, 101 were classified as Mason type 1 (85%), 1 1 as borderline between Mason type 1 and Mason type 2 fractures (9%), and 7 as Mason type 2 fractures (6%) according to Broberg and Morrey's modification of the Mason classification. The intraobserver reliability of the classification of Mason type 1 and type 2 fractures was excellent (mean K, 0.85), but the interobserver reliability was only moderate (multirater K, 0.45). Because apparently isolated, stable partial fractures of the radial head are infrequently displaced and observers have moderate disagreement regarding the diagnosis of displacement, it is likely that displacement is overdiagnosed. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Hand & Upper Extremity Serv, Boston, MA 02114 USA. Harvard Med Sch, Dept Orthoped Surg, Boston, MA USA. Univ Amsterdam, Orthoped Res Ctr, Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. Univ Amsterdam, Orthotrauma Res Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02116 USA. EM dring@partners.org NR 23 TC 17 Z9 17 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP-OCT PY 2007 VL 16 IS 5 BP 603 EP 608 DI 10.1016/j.jse.2006.10.015 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 220IX UT WOS:000250151500018 PM 17448692 ER PT J AU Lindenhovius, ALC Linzel, DS Doornberg, JN Ring, DC Jupiter, JB AF Lindenhovius, Anneluuk L. C. Linzel, Durk S. Doornberg, Job N. Ring, David C. Jupiter, Jesse B. TI Comparison of elbow contracture release in elbows with and without heterotopic ossification restricting motion SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID OPERATIVE RELEASE; RADIATION-THERAPY; STIFF ELBOW; EXCISION; BONE; HEAD; PREVENTION; FRACTURE AB We compared 16 patients with post-traumatic heterotopic ossification (HO) restricting elbow motion (but not complete bony ankylosis) after elbow trauma with 21 patients with capsular contracture alone to test the hypothesis that HO is associated with diminished motion after release. Patients with burns or head injury were excluded. The preoperative flexion arc averaged 59 degrees in the HO cohort and 52 degrees in the capsular contracture cohort. The mean flexion arc after the index surgery improved by 54 degrees to a mean arc of 113 degrees in the HO cohort and by 35 degrees to a mean of 87 degrees in the capsular contracture cohort (P =.02). After all subsequent procedures (including procedures to address residual stiffness in 1 patient in the HO cohort and 4 patients in the capsular contracture cohort), the flexion arc averaged 116 degrees in the HO cohort and 98 degrees in the capsular contracture cohort (P =. 19). Open release of post-traumatic elbow stiffness is more effective when HO hindering motion is removed than when there is capsular contracture alone. C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, DC (reprint author), Yawkey Ctr, Orthopaed Hand & Upper Extrim Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 30 TC 29 Z9 32 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP-OCT PY 2007 VL 16 IS 5 BP 621 EP 625 DI 10.1016/j.jse.2007.01.005 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 220IX UT WOS:000250151500021 PM 17644008 ER PT J AU Henket, M van Duijn, PJ Doornberg, JN Ring, D Jupiter, JB AF Henket, Marjolijn van Duijn, Pleun J. Doornberg, Job N. Ring, David Jupiter, Jesse B. TI A comparison of proximal radioulnar synostosis excision after trauma and distal biceps reattachment SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID LOW-DOSE RADIATION; HETEROTOPIC OSSIFICATION; 2-INCISION TECHNIQUE; ULNAR SYNOSTOSIS; CROSS-UNION; REPAIR; BRACHII; TENDON; PREVENTION; FRACTURES AB We tested the hypothesis that the results of operative resection of a proximal radioulnar synostosis are better when the synostosis is due to a distal biceps reattachment (1 1 patients) than when it occurs after trauma (13 patients). Two patients in the trauma cohort had recurrence of the synostosis, and I had repeat resection. Two patients in the trauma cohort and I in the biceps cohort had substantial loss of forearm rotation due to regrowth of heterotopic ossification without synostosis, and 2 patients were addressed with subsequent surgeries. The arc of forearm rotation after the index surgery averaged 94 in the trauma cohort and 131 in the biceps cohort. This study confirms that operative resection of a proximal radioulnar synostosis can restore substantial motion in most patients. The results for excision of a synostosis after a distal biceps reattachment were better than those of excision of a synostosis after trauma. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Orthopaed Hand & Upper Extrim Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrim Serv, Suite 2100,55 St, Boston, MA 02114 USA. EM dring@partners.org NR 30 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP-OCT PY 2007 VL 16 IS 5 BP 626 EP 630 DI 10.1016/j.jse.2007.01.003 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 220IX UT WOS:000250151500022 PM 17629506 ER PT J AU Doornberg, JN de Jong, IM Lindenhovius, ALC Ring, D AF Doornberg, Job N. de Jong, Inge M. Lindenhovius, Anneluuk L. C. Ring, David TI The anteromedial facet of the coronoid process of the ulna SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID ELBOW; FRACTURES; DISLOCATION; STABILITY AB Fracture of the anteromedial facet of the coronoid process has been recognized as an important type of coronoid fracture. We performed a quantitative analysis of 21 3-dimensional computed tomography scans to evaluate the degree to which the anteromedial facet protrudes as a distinct process separate from the proximal ulnar metaphysis. The distance between the center axis of the trochlear notch and the most medial edge of the anteromedial facet averaged 12.5 mm (range, 8.7-20.1 mm). The part of the maximum anteromedial facet width that was supported by the proximal ulnar metaphysis and diaphysis averaged 5.4 mm (range, 1.7-11.5 mm). On average, 58% of the anteromedial facet (range, 26%-82%) was unsupported by the proximal ulnar metaphysis and diaphysis. It is not surprising that this relatively vulnerable protrusion from the anteromedial facet of the coronoid is frequently a separate fracture fragment in complex traumatic elbow instability. C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Harvard Med Sch, Boston, MA 02114 USA. Univ Amsterdam, Orthotrauma Res Ctr, NL-1012 WX Amsterdam, Netherlands. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Harvard Med Sch, Yawkey Ctr Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM Bring@partners.org NR 11 TC 19 Z9 22 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP-OCT PY 2007 VL 16 IS 5 BP 667 EP 670 DI 10.1016/j.jse.2007.03.013 PG 4 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 220IX UT WOS:000250151500028 PM 17512221 ER PT J AU Gollogly, LK Ryeom, SW Yoon, SS AF Gollogly, Lila K. Ryeom, Sandra W. Yoon, Sam S. TI Down syndrome candidate region 1-like 1 (DSCR1-L1) mimics the inhibitory effects of DSCR1 on calcineurin signaling in endothelial cells and inhibits angiogenesis SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE angiogenesis; calcineurin; Down-syndrome candidate region 1 (DSCR1); Down syndrome candidate region 1-like 1 (DSCR1-L1) ID ACTIVATED T-CELLS; GROWTH-FACTOR; GENE-EXPRESSION; CYCLOSPORINE-A; NUCLEAR FACTOR; NF-AT; PROTEIN; TARGET; PROLIFERATION; MECHANISM AB In endothelial cells, binding of vascular endothelial growth factor (VEGF) to VEGF receptor 2 leads to the activation of the serine/threonine phosphatase calcineurin, dephosphorylation of the nuclear factor of activated T-cells (NF-AT) transcription factors, translocation of NF-AT to the nucleus, and expression of angiogenesis-related genes such as Cox-2. Down syndrome candidate region I (DSCR1) is transactivated by NF-AT nuclear translocation, and subsequently inhibits calcineurin activity, forming a negative feedback loop. While DSCR1 has a clearly defined role as an endogenous inhibitor of VEGF-calcineurinmediated angiogenesis in endothelial cells, the function of the DSCR1 family member, DSCRl-like 1 (DSCR1-L1), has not yet been investigated in endothelial cells. Here we show that a panel of pro-angiogenic factors, including VEGF, basic fibroblast growth factor (bFGF), angiopoietin 1, hepatocyte growth factor, as well as triiodo-L-thyronine (T,), does not induce DSCR1-L1 up-regulation in endothelial cells, while VEGF potently up-regulates DSCR1. To investigate the effects of DSCR1-L1 on endothelial cell function, we cloned the gene into a lentiviral vector and over-expressed DSCR1-L1 in human umbilical vein endothelial cells. Constitutive DSCR1-L1 overexpression prevented the nuclear translocation of NF-ATcl in response to VEGF, underscoring its role as a calcineurin inhibitor. Additionally, DSCR1-L1-transduced cells inhibited VEGF-induced endothelial cell migration, proliferation, and tube formation by 36, 77, and 39%, respectively, compared to cells infected with control virus. Overexpression of DSCR1-L1 in the transformed endothelial cell line Sven I ras also resulted in decreased proliferation. Our findings demonstrate that DSCR1-L1 is constitutively expressed in endothelial cells and acts similar to DSCR1 in inhibiting calcineurin activity and restraining VEGF-mediated angiogenesis. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Vasc Biol Program, Childrens Hosp, Boston, MA 02115 USA. RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 7B-7926,55 Fruit St, Boston, MA 02115 USA. EM syoon@partners.org FU NCI NIH HHS [5 K12 CA 87723-03, K12 CA087723, R21 CA117128, R21 CA117128-02] NR 23 TC 9 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2007 VL 142 IS 1 BP 129 EP 136 DI 10.1016/j.jss.2006.10.011 PG 8 WC Surgery SC Surgery GA 203PZ UT WOS:000248987800019 PM 17610901 ER PT J AU Geller, D Donnelly, C Lopez, F Rubin, R Newcorn, J Sutton, V Bakken, R Paczkowski, M Kelsey, D Sumner, C AF Geller, Daniel Donnelly, Craig Lopez, Frank Rubin, Richard Newcorn, Jeffrey Sutton, Virginia Bakken, Rosalie Paczkowski, Martin Kelsey, Douglas Sumner, Calvin TI Atomoxetine treatment for pediatric patients with attention-deficit/hyperactivity disorder with comorbid anxiety disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE anxiety; atomoxetine; attention-deficit/hyperactivity disorder; comorbid ID DEFICIT HYPERACTIVITY DISORDER; COMMUNITY SAMPLE; PSYCHIATRIC COMORBIDITY; STIMULANT MEDICATION; PANIC DISORDER; ADHD CHILDREN; METHYLPHENIDATE; ADOLESCENTS; SYMPTOMS; PHARMACOTHERAPY AB Objective: Research suggests 25% to 35% of children with attention-deficit/hyperactivity disorder (ADHD) have comorbid anxiety disorders. This double-blind study compared atomoxetine with placebo for treating pediatric ADHD with comorbid anxiety, as measured by the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Pediatric Anxiety Rating Scale (PARS). Method: Patients (ages 8-17 years) meeting DSM-IV criteria for ADHD and generalized anxiety disorder, separation anxiety disorder, and/or social phobia were randomized to 12 weeks of atomoxetine (n = 87) or placebo (n = 89). ADHDRS-IV-PI and PARS total scores were analyzed using analysis of covariance last observation carried forward and repeated-measures analyses. Results: Sixty-six patients in each group completed the study. Mean ADHDRS-IV-PI total score improved significantly for atomoxetine (n = 55; -10.5, SD 10.6) relative to placebo (n = 58; -1.4, SD 8.3; p<.001). Mean PARS total score also improved significantly for atomoxetine (n = 55; -5.5, SD 4.8) relative to placebo (n = 58; -3.2, SD 5.0; p=.011). Conclusions: Atomoxetine was efficacious in reducing ADHD symptoms in patients who have ADHD with comorbid anxiety and was well tolerated. There was also a significant reduction in independently assessed anxiety symptoms using both clinician-rated and self-rated measures, which merits further investigation. Results support consideration of atomoxetine for the treatment of ADHD in youths who have ADHD with comorbid anxiety disorder. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Grp, Cambridge, MA 02138 USA. Hitchcock Med Ctr, Dept Psychiat, Lebanon, NH USA. Child Dev Ctr, Maitland, FL USA. Univ Vermont, Coll Med, Burlington, VT 05405 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Lilly Res Labs, Indianapolis, IN USA. RP Geller, D (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Grp, Suite 2000,185 Alewife Brook Pkway, Cambridge, MA 02138 USA. EM dageller@Partners.org OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 49 TC 87 Z9 92 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2007 VL 46 IS 9 BP 1119 EP 1127 DI 10.1097/chi.0b013e3180ca8385 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 203PO UT WOS:000248986700004 PM 17712235 ER PT J AU Naik, AD Issac, TT Street, RL Kunik, ME AF Naik, Aanand D. Issac, Tim T. Street, Richard L., Jr. Kunik, Mark E. TI Understanding the quality chasm for hypertension control in diabetes: A structured review of "Co-maneuvers" used in clinical trials SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Review ID BLOOD-PRESSURE CONTROL; LIPID-LOWERING TREATMENT; CORONARY-ARTERY-DISEASE; SHARED DECISION-MAKING; RANDOMIZED-TRIAL; PRIMARY-CARE; MICROVASCULAR COMPLICATIONS; ANTIHYPERTENSIVE TREATMENT; UNCONTROLLED HYPERTENSION; CARDIOVASCULAR MORBIDITY AB Background: Observational studies routinely describe a significant gap between rates of blood pressure control in routine diabetes care compared with those achieved in randomized controlled trials (RCTs). Methods: We performed a systematic review of the literature to identify co-maneuvers used in RCTs, defined as ancillary activities or agents administered before, during, or immediately after the main agent under investigation (ie, principal maneuver), but not effectively translated to routine diabetes care. We searched multiple databases for RCTs evaluating the efficacy of treatments for hypertension control in adults with type 2 diabetes mellitus. We considered only phase III human studies of interventions that achieved blood pressure control and scrutinized all elements related to the implementation of the principal maneuver in each candidate study. These elements were then sorted into a taxonomy of co-maneuvers. Results: Nearly all eligible RCTs used highly consistent groups of co-maneuvers. These typically began with ( 1) the use of consensual and clearly stated blood pressure goals; ( 2) frequent visits in which blood pressure levels were measured and compared with predefined goals; and, if the goal was not attained, ( 3) modifications to the treatment based on a detailed action plan that included communication of adverse events. Patient education, feedback to clinicians, and interventions for medication adherence were not commonly used among eligible trials. Conclusions: Clinicians should translate key behavioral co-maneuvers along with clinically proven treatments for hypertension control in diabetes. These co-maneuvers are conceptually similar to collaborative goal setting and action planning interventions used in innovative chronic care programs. C1 Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr 152, S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Sect Geriatr, Houston, TX 77030 USA. Baylor Coll Med, Sect Diabetes & Endocrinol, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Texas A&M Univ, Dept Commun, College Stn, TX USA. RP Naik, AD (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.tmc.edu FU NIA NIH HHS [K23 AG027144, 5K23AG027144-02, K23 AG027144-03] NR 61 TC 10 Z9 10 U1 1 U2 3 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD SEP-OCT PY 2007 VL 20 IS 5 BP 469 EP 478 DI 10.3122/jabfm.2007.05.070026 PG 10 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 207YC UT WOS:000249286000006 PM 17823464 ER PT J AU Gibbs, JO Giobbie-Hurder, A Edelman, P McCarthy, M Fitzgibbons, RJ AF Gibbs, James O. Giobbie-Hurder, Anita Edelman, Perry McCarthy, Martin, Jr. Fitzgibbons, Robert J., Jr. TI Does delay of hernia repair in minimally symptomatic men burden the patient's family? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID INGUINAL-HERNIA; CLINICAL-TRIAL; HERNIORRHAPHY; PAIN AB BACKGROUND: Although inguinal hernia repair is a common and safe procedure, a significant portion of patients who undergo surgical repair experience postoperative chronic pain. We conducted a clinical trial to determine if delay of repair is a safe and acceptable alternative for men with minimally symptomatic inguinal hernias. Here we report on the effects of delay on the patient's family. STUDY DESIGN: Data are from a randomized trial in which men with asymptomatic or minimally symptomatic inguinal hernia were randomly assigned to either open tension-free repair (TFR) or watchful waiting (WW). Patients indicated a person who could assist them if necessary because of their hernia or hernia operation, and these persons (mostly spouses) answered a questionnaire at baseline and followup addressing concern about the patient's ability to perform home, social, and recreational activities and time spent assisting the patient with chores because of his hernia condition. RESULTS: In both intention-to-treat and as-treated analyses, at 2 years after enrollment, family members of patients assigned to WW were more likely to report concern about the patient's ability to perform the four types of activities. But a majority of respondents in both the WW and TFR groups indicated no concern about performance of any of the activities. In the as-treated analysis, family members of patients assigned to TFR who did not receive repair reported more time assisting the patient than those of TFR patients who received the assigned treatment. CONCLUSIONS: The results favor repair, but the low level of concern about the patient's functioning reported for both TFR and WW patients suggests that this is not a major issue in delaying repair of inguinal hernias in minimally symptomatic men. C1 Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Edward Hines Jr VA Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Mather Life Ways Inst Aging, Evanston, IL USA. Creighton Univ, Dept Surg, Omaha, NE 68178 USA. RP Gibbs, JO (reprint author), 1819 Dobson St, Evanston, IL 60202 USA. EM jgibbs@northwestern.edu FU AHRQ HHS [R01 HS09860] NR 9 TC 4 Z9 4 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2007 VL 205 IS 3 BP 409 EP 412 DI 10.1016/j.jamcollsurg.2007.04.020 PG 4 WC Surgery SC Surgery GA 208GQ UT WOS:000249308200003 PM 17765156 ER PT J AU Ferguson, CM AF Ferguson, Charles M. TI Ira A Ferguson Sr, MD, FACS and the other Tuskegee experiment SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Ferguson, CM (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Suite 460, Boston, MA 02114 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2007 VL 205 IS 3 BP 501 EP 509 DI 10.1016/j.jamcollsurg.2007.05.001 PG 9 WC Surgery SC Surgery GA 208GQ UT WOS:000249308200014 PM 17765167 ER PT J AU Agopian, VG Wulkersdorfer, B Chen, DC Lee, J Stelzner, M AF Agopian, Vatche G. Wulkersdorfer, Beatrix Chen, David C. Lee, Jane Stelzner, Matthias TI Growth factors enhance neomucosal development in tissue-engineered intestine SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 93rd Annual Clinical Congress of the American-College-of-Surgeons CY OCT 07-11, 2007 CL New Orleans, LA SP Amer Coll Surg C1 Univ Calif Los Angeles, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2007 VL 205 IS 3 SU S BP S14 EP S14 DI 10.1016/j.jamcollsurg.2007.06.027 PG 1 WC Surgery SC Surgery GA 209OG UT WOS:000249397300013 ER PT J AU Meltzer, AJ Houser, S Weiss, M Ng, C Sayre, J Cochrane, M Allan, J Madsen, J Rosengard, B Sachs, D AF Meltzer, Andrew J. Houser, Stuart Weiss, Matthew Ng, Choo Sayre, Jessica Cochrane, Meghan Allan, James Madsen, Joren Rosengard, Bruce Sachs, David TI Identification of isl-1+cardiac progenitor cells in miniature swine SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 93rd Annual Clinical Congress of the American-College-of-Surgeons CY OCT 07-11, 2007 CL New Orleans, LA SP Amer Coll Surg C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2007 VL 205 IS 3 SU S BP S63 EP S63 DI 10.1016/j.jamcollsurg.2007.06.154 PG 1 WC Surgery SC Surgery GA 209OG UT WOS:000249397300131 ER PT J AU Regenbogen, SE Lancaster, RT Lipsitz, SR Greenberg, CC Hutter, MM Gawande, AA AF Regenbogen, Scott E. Lancaster, R. Todd Lipsitz, Stuart R. Greenberg, Caprice C. Hutter, Matthew M. Gawande, Atul A. TI Does performance matter? Role of intraoperative factors versus preoperative risk in surgical outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 93rd Annual Clinical Congress of the American-College-of-Surgeons CY OCT 07-11, 2007 CL New Orleans, LA SP Amer Coll Surg C1 Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2007 VL 205 IS 3 SU S BP S73 EP S74 DI 10.1016/j.jamcollsurg.2007.06.183 PG 2 WC Surgery SC Surgery GA 209OG UT WOS:000249397300158 ER PT J AU Shults, C Sailhamer, E Li, YQ Liu, BL Spaniolas, K Tabbara, M Koustova, E Butt, M Velmahos, G de Moya, M Alam, HB AF Shults, Christian Sailhamer, Elizabeth Li, Yongqing Liu, Baoling Spaniolas, Konstantinos Tabbara, Malek Koustova, Elena Butt, Muhammad Velmahos, George de Moya, Marc Alam, Hasan B. TI Surviving blood loss without fluid resuscitation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 93rd Annual Clinical Congress of the American-College-of-Surgeons CY OCT 07-11, 2007 CL New Orleans, LA SP Amer Coll Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2007 VL 205 IS 3 SU S BP S34 EP S34 DI 10.1016/j.jamcollsurg.2007.06.078 PG 1 WC Surgery SC Surgery GA 209OG UT WOS:000249397300060 ER PT J AU Shults, C Chen, Z Sailhamer, E Rhee, P Spaniolas, K Velmahos, G de Moya, M Alam, HB AF Shults, Christian Chen, Zheng Sailhamer, Elizabeth Rhee, Peter Spaniolas, Konsiantinos Velmahos, George de Moya, Marc Alam, Hasan B. TI Is irreversible shock truly irreversible? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 93rd Annual Clinical Congress of the American-College-of-Surgeons CY OCT 07-11, 2007 CL New Orleans, LA SP Amer Coll Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2007 VL 205 IS 3 SU S BP S33 EP S33 DI 10.1016/j.jamcollsurg.2007.06.076 PG 1 WC Surgery SC Surgery GA 209OG UT WOS:000249397300058 ER PT J AU Bellinger, DC Trachtenberg, F Daniel, D Zhang, A Tavares, MA McKinlay, S AF Bellinger, David C. Trachtenberg, Felicia Daniel, David Zhang, Annie Tavares, Mary A. McKinlay, Sonja TI A dose-effect analysis of children's exposure to dental amalgam and neuropsychological function - The new England children's amalgam trial SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE dental amalgam; children; mercury; neuropsychology ID RANDOMIZED CLINICAL-TRIAL; MERCURY CONCENTRATIONS; URINE; RESTORATIONS; POLYMORPHISM AB Background. The New England Children's Amalgam Trial (NECAT) was a five-year randomized trial of 564 6- to 10-year-old children that compared the neuropsychological outcomes of those whose caries were restored using dental amalgam with the outcomes of those those whose caries were restored using mercury-free resin-based composite. The primary intention-to-treat analyses did not reveal significant differences between the treatment groups on the primary or secondary outcomes of the administered psychological tests: Full-Scale IQ score on the Wechsler Intelligence Scale for Children-Third Edition General Memory Index of the Wide Range Assessment of Memory and Learning and Visual-Motor Composite of the Wide Range Assessment of Visual Motor Abilities. Methods. To determine whether treatment group assignment, a dichotomous measure of exposure, was sufficiently sensitive to detect associations between mercury exposure and these outcomes, the authors conducted analyses to evaluate the associations between the primary and secondary outcomes and two continuously distributed indexes of potential exposure, surface-years of amalgam and urinary mercury excretion. Results. Neither index of mercury exposure was significantly associated with any of the outcomes. Conclusions. The authors found no evidence that exposure to mercury from dental amalgam was associated with any adverse neuropsychological effects over the five-year period after placement of amalgam restorations. Clinical Implications. Analyses of the outcomes of the NECAT study indicate that use of dental amalgam was not associated with an increase in children's risk of experiencing neuropsychological dysfunction. C1 New England Res Inst, Watertown, MA 02472 USA. Childrens Hosp, Boston, MA 02115 USA. Univ No Colorado, Sch Psychol Sci, Greeley, CO 80639 USA. Forsyth Inst, Boston, MA USA. RP McKinlay, S (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM smckinlay@neriscience.com FU NIDCR NIH HHS [U01 DE 11886] NR 18 TC 17 Z9 17 U1 0 U2 3 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2007 VL 138 IS 9 BP 1210 EP 1216 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 210LU UT WOS:000249458500010 PM 17785386 ER PT J AU Razani, J Kakos, B Orieta-Barbalace, C Wong, JT Casas, R Lu, P Alessi, C Josephson, K AF Razani, Jill Kakos, Bernadette Orieta-Barbalace, Carla Wong, Jennifer T. Casas, Rachel Lu, Po Alessi, Cathy Josephson, Karen TI Predicting caregiver burden from daily functional abilities of patients with mild dementia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE activities of daily living; observation-based ADLs; informant-based ADLs; functional assessment; caregiver burden; caregiver psychological distress; functional ability; dementia; cognitive impairment ID ALZHEIMERS-DISEASE; FAMILY CAREGIVERS; HEALTH; CARE; INVENTORY; SYMPTOMS; DISTRESS; PEOPLE; ADULTS; IMPACT AB OBJECTIVES: To assess the relationship between performance- and informant-based measures of activities of daily living (ADLs) in patients with early dementia and burden or psychological distress experienced by the patients' caregivers. DESIGN: Descriptive study. SETTING: Ambulatory center. PARTICIPANTS: Thirty-four patient-caregiver dyads in which the patient had mild dementia (Mini-Mental State Examination score > 17). MEASUREMENTS: A performance-based ADL measure (the Direct Assessment of Functional Status (DAFS)) was administered to patients with mild dementia. Caregivers completed an informant-based measure of patient functional status (instrumental activities of daily living). Caregivers also completed the Caregiver Burden Inventory (CBI) and the Brief Symptom Inventory (BSI). RESULTS: Significant correlations were found between the informant-based ADL measure and caregiver burden (CBI) and psychological distress (BSI) (correlation coefficient (r)=-0.34 to -0.71, all P <.05). Alternatively, fewer and weaker relationships were observed between the DAFS (performance-based) ADL measure and caregiver burden or distress ratings (r=-0.32 to -0.43, all P <.05). Of the seven tasks assessed using the DAFS, impairments in orientation, communication, financial, and transportation skills in patients were associated with greater time and developmental burden and greater hostility in caregivers. Impairment in financial skills in patients was the strongest predictor of time-dependence burden and hostility in caregivers, whereas impairment in patient transportation skills was the best predictor of developmental burden. CONCLUSION: The ADL abilities of cognitively impaired patients can predict caregiver burden and psychological distress, with informant-based measures having the greatest association with patient impairment. C1 Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. Univ Detroit Mercy, Dept Psychol, Detroit, MI 48221 USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Geriatr Res Educ & Clin Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, North Hills, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Razani, J (reprint author), Calif State Univ Northridge, Dept Psychol, 18111 Nordhoff St, Northridge, CA 91330 USA. EM jill.razani@csun.edu FU NIGMS NIH HHS [GM63787, GM048680, GM08395, R25 GM063787, S06 GM048680, S06 GM048680-12A10013, T34 GM008395] NR 26 TC 69 Z9 72 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2007 VL 55 IS 9 BP 1415 EP 1420 DI 10.1111/j.1532-5415.2007.01307.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 206IZ UT WOS:000249178400014 PM 17767684 ER PT J AU Shay, K AF Shay, Kenneth TI Who is responsible for a nursing home resident's daily oral care? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID RISK-FACTORS; PNEUMONIA C1 US Dept Vet Affairs, Off Geriatr & Extended Care, Washington, DC USA. Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. RP Shay, K (reprint author), US Dept Vet Affairs, Off Geriatr & Extended Care, Washington, DC USA. NR 15 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2007 VL 55 IS 9 BP 1470 EP 1471 DI 10.1111/j.1532-5415.2007.01280.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 206IZ UT WOS:000249178400023 PM 17767691 ER PT J AU Rentz, DM Huh, TJ Sardinha, LM Moran, EK Becker, JA Daffner, KR Sperling, RA Johnson, KA AF Rentz, Dorene M. Huh, Terri J. Sardinha, Lisa M. Moran, Erin K. Becker, John A. Daffner, Kirk R. Sperling, Reisa A. Johnson, Keith A. TI Intelligence quotient-adjusted memory impairment is associated with abnormal single photon emission computed tomography perfusion SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the International-Neuropsychological-Society CY FEB 01-04, 2006 CL Boston, MA SP Int Neuropsychol Soc DE aging; dementia risk; cognitive decline; Alzheimer's disease; imaging; mild cognitive impairment ID MILD COGNITIVE IMPAIRMENT; ADULT READING TEST; PRECLINICAL ALZHEIMERS-DISEASE; SELECTIVE REMINDING TEST; PREMORBID INTELLIGENCE; RESERVE HYPOTHESIS; CEREBRAL PERFUSION; APOLIPOPROTEIN-E; BRAIN ACTIVITY; WAIS-R AB Cognitive reserve among highly intelligent older individuals makes detection of early Alzheimer's disease (AD) difficult. We tested the hypothesis that mild memory impairment determined by IQ-adjusted norms is associated with single photon emission Computed tomography (SPECT) perfusion abnormality at baseline and predictive of future decline. Twenty-three subjects with a Clinical Dementia Rating (CDR) score of 0, were reclassified after scores were adjusted for IQ into two groups, 10 as having mild memory impairments for ability (IQ-MI) and 13 as memory-normal (IQ-MN). Subjects underwent cognitive and functional assessments at baseline and annual follow-up for 3 ,cars. Perfusion SPECT was acquired at baseline. At follow-up, the IQ-MI Subjects demonstrated decline in memory. visuospatial processing, and phonemic fluency, and 6 of 10 had progressed to a CDR of 0.5, while the Subjects did not show decline. The IQ-MI group had significantly lower perfusion than the IQ-MN group in parietal/precuneus, temporal, and opercular frontal regions. In contrast, higher perfusion was observed in IQ-MI compared with IQ-MN in the left medial frontal and rostral anterior cingulate regions. IQ-adjusted memory impairment in individuals with high cognitive reserve is associated with baseline SPECT abnormality in a pattern consistent with prodromal AD and predicts subsequent cognitive and functional decline. C1 Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Rentz, DM (reprint author), Brigham & Womens Hosp, Div Cognit & Behav Neurol, 221 Longwood Ave, Boston, MA 02115 USA. EM drentz@partners.org FU NIA NIH HHS [1R01 AG017935] NR 81 TC 7 Z9 7 U1 1 U2 3 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 SEP PY 2007 VL 13 IS 5 BP 821 EP 831 DI 10.1017/S1355617707071056 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 205UQ UT WOS:000249140500009 PM 17697413 ER PT J AU Merritt, R Zeitels, SM Austen, WG Lauwers, GY Gaissert, HA AF Merritt, Robert Zeitels, Steven M. Austen, William G., Jr. Lauwers, Gregory Y. Gaissert, Henning A. TI Staged closure of tracheogastrocutaneous fistula after esophagectomy for infiltrative granular cell tumor SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID ESOPHAGUS; MYOBLASTOMA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Gaissert, HA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Blake 1570,Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org NR 5 TC 1 Z9 1 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 SEP PY 2007 VL 134 IS 3 BP 805 EP 807 DI 10.1016/j.jtcvs.2007.05.029 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 203ZT UT WOS:000249013300049 PM 17723843 ER PT J AU Patel, MR Jacobson, BA De, A Frizelle, SP Janne, P Thumma, SC Whitson, BA Farassati, F Kratzke, RA AF Patel, Manish R. Jacobson, Blake A. De, Arpita Frizelle, Sandra P. Janne, Pasi Thumma, Saritha C. Whitson, Brian A. Farassati, Faris Kratzke, Robert A. TI Ras pathway activation in malignant mesothelioma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Ras; mesothelioma; translation; cap dependent; eukaryotic initiation factor 4E; eukaryotic initiation factor 4E ID PLEURAL MESOTHELIOMA; GENE-EXPRESSION; LUNG-CANCER; CELL-LINES; P53; TRANSLATION; MUTATIONS; MET; OVEREXPRESSION; PHENOTYPE AB Introduction: Mutations in Ras family genes are rare in malignant mesothelioma. The role of activation Of the Ras signaling pathway in the pathogenesis of mesothelioma is not clear. Methods: We studied the activation status of the Ras pathway and the status of other Ras-associated kinases in a panel of human mesotheliorna cell lines. In addition, we tested the effect of inhibition of several kinase pathways on mesotheliorna cell proliferation. The potential role of kinase signaling on the regulation of cap-dependent translation was also studied. Results: In general, Ras-guanosine triphosphate (GTP) was higher in mesotheliorna cell lines when compared with a nontransformed mesothelial cell line (LP9). Furthermore, known Ras effectors such as extracellular-regulated kinase 1/2, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase were found to be active in most of the mesotheliorna cell lines tested. Exposure to specific inhibitors of extracellular-regulated kinase 1/2 (U0126) and c-Jun N-terminal kinase (SP600125) significantly decreased the proliferation of H2596 and H2373 cells compared with mock-treated cells. SP600125-mediated c-Jun N-terminal kinase inhibition, but not extracellular-regulated kinase 1/2 inhibition, resulted in a decrease in phosphorylation of 4E-BP1, consequently decreasing cap-dependent activation. Conclusions: These experiments provide a rationale for targeting Ras and associated signaling pathways in mesothelioma and also suggest cap-dependent translation as one mechanism by which Ras induces proliferation in this disease. C1 Univ Minnesota, Sch Med, Div Hematol Oncol Transplant, Dept Med, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Surg, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Vet Affairs Med Ctr, Res Serv, Minneapolis, MN 55417 USA. RP Kratzke, RA (reprint author), Univ Minnesota, Sch Med, Div Hematol Oncol Transplant, Dept Med, MMC 480,420 Delaware St SE, Minneapolis, MN 55455 USA. EM kratz003@umn.edu RI Whitson, Bryan/B-5725-2009 NR 28 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2007 VL 2 IS 9 BP 789 EP 795 DI 10.1097/JTO.0b013e31811f3aab PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 210QN UT WOS:000249470800003 PM 17805054 ER PT J AU Uchihara, T Okubo, C Tanaka, R Minami, Y Inadome, Y Iijima, T Morishita, Y Fujita, J Noguchi, M AF Uchihara, Teruhito Okubo, Chigusa Tanaka, Ryota Minami, Yuko Inadome, Yukinori Iijima, Tatsuo Morishita, Yukio Fujita, Jiro Noguchi, Masayuki TI Neuronatin expression and its clinicopathological significance in pulmonary non-small cell carcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE neuronatin; non-small cell lung carcinoma; adenocarcinoma; prognosis; tumor marker ID GENE-EXPRESSION; MESSENGER-RNA; IDENTIFICATION; CLONING; BRAIN; PROTEIN; CANCER; TUMOR; LUNG AB Introduction: Neuronatin is a protein that is specifically expressed in the nervous system in the course of embryonal brain development, and its expression is limited to the pituitary gland in normal human adults. Neuronatin expression has been reported in some types of tumor. The purpose of this study was to clarify the significance of neuronatin expression in pulmonary non-small cell carcinoma. Methods: We determined the frequency of neuronatin expression in surgically resected samples from non-small cell lung carcinoma (51 adenocarcinoma and 41 squamous cell carcinoma) by immunohistochemical staining, and investigated the correlations between expression level and various clinicopathological features. Results: Expression of neuronatin was observed more frequently in squamous cell carcinoma (63%) than in adenocarcinoma (25%). In most cases, nontumorous lung tissue did not react with the antibody against neuronatin. In both adenocarcinorna and squamous cell carcinoma, less differentiated tumors expressed neuronatin more frequently than did differentiated tumors. In adenocarcinoma, but not squamous cell carcinoma, the prognosis of neuronatin-positive cases was significantly worse than that of neuronatin-negative cases. Conclusion: Neuronatin expression is specific for tumor tissue and was detected in both pulmonary adenocarcinoma and squamous cell carcinoma at high frequency, particularly in less differentiated tumors. Neuronatin expression is associated with poor prognosis in patients with adenocarcinoma, and may be useful as a prognostic marker for lung adenocarcinoma. C1 Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Pathol, Inst Basic Med Sci, Tsukuba, Ibaraki 3058575, Japan. Univ Ryukyus, Fac Med, Dept Internal Med 1, Dept Med & Therapeut Control & Prevent Infect Dis, Nishihara, Okinawa 90301, Japan. Gunma Prefectural Canc Ctr, Dept Thorac Surg, Ota, Japan. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Noguchi, M (reprint author), Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Pathol, Inst Basic Med Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. EM nmasayuk@md.tsukuba.ac.jp NR 19 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2007 VL 2 IS 9 BP 796 EP 801 DI 10.1097/JTO.0b013e318145af5e PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 210QN UT WOS:000249470800004 PM 17805055 ER PT J AU Turpie, AGG Bauer, KA Caprini, JA Comp, PC Gent, M Muntz, JE AF Turpie, A. G. G. Bauer, K. A. Caprini, J. A. Comp, P. C. Gent, M. Muntz, J. E. CA The Apollo Investigators TI Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE abdominal surgery; clinical trial; fondaparinux; intermittent pneumatic compression; prevention; venous; thromboembolism ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; MAJOR ORTHOPEDIC-SURGERY; PULMONARY-EMBOLISM; SUBCUTANEOUS HEPARIN; GENERAL-SURGERY; CLINICAL-TRIALS; METAANALYSIS; PROPHYLAXIS; THROMBOPROPHYLAXIS AB Background: The benefit of combined mechanical and pharmacologic methods for venous thromboembolism prevention after abdominal surgery has not been clearly established. Objectives: To compare the efficacy and safety of fondaparinux in conjunction with intermittent pneumatic compression vs. intermittent pneumatic compression alone in this context. Patients and Methods: This was a randomized, double-blind, placebo-controlled superiority trial. Patients aged at least 40 years undergoing abdominal surgery were randomized to receive either fondaparinux 2.5 mg or placebo s.c. for 5-9 days, starting 6-8 It postoperatively. All patients received intermittent pneumatic compression. The primary efficacy outcome was venous thromboembolism up to day 10. The main safety outcomes were major bleeding and all-cause mortality. Follow-up lasted 32 days. Results: Of the 1309 patients randomized, 842 (64.3%) were evaluable for efficacy. The venous thromboembolism. rate was 1.7% (7/424) in the fondaparinux-treated patients and 5.3% (22/418) in the placebo-treated patients (odds ratio reduction 69.8%; 95% confidence interval 27.9-87.3; P = 0.004). Fondaparinux significantly reduced the proximal deep vein thrombosis rate from 1.7% (7/417) to 0.2% (1/424; P = 0.037). Major bleeds occurred in 1.6% (10/635) and 0.2% (1/650) of fondaparinux-treated and placebo-treated patients, respectively (P = 0.006), none being fatal or involving a critical organ. By day 32, eight patients (1.3%) receiving fondaparinux and five (0.8%) receiving placebo had died. Conclusions: In patients undergoing abdominal surgery and receiving intermittent pneumatic compression, fondaparinux 2.5 mg reduced the venous thromboembolism rate by 69.8% as compared to pneumatic compression alone, with a low bleeding risk as compared to placebo. C1 Hamilton Hlth Sci Corp, Dept Med, Gen Div, Dept Med, Hamilton, ON L8L 2X2, Canada. McMaster Univ, Dept Med Hamilton Hlth Sci, Hamilton, ON, Canada. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NW Univ Feinberg, Sch Med, Chicago, IL USA. Univ Oklahoma, Coll Med, Oklahoma City, OK 73190 USA. McMaster Univ, Henderson Res Ctr, Hamilton, ON, Canada. Baylor Coll Med, Houston, TX 77030 USA. RP Turpie, AGG (reprint author), Hamilton Hlth Sci Corp, Dept Med, Gen Div, Dept Med, 237 Barton St E, Hamilton, ON L8L 2X2, Canada. EM turpiea@mcmaster.ca NR 35 TC 63 Z9 69 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD SEP PY 2007 VL 5 IS 9 BP 1854 EP 1861 DI 10.1111/j.1538-7836.2007.02657.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 207KR UT WOS:000249250500012 PM 17723125 ER PT J AU Govers-Riemslag, JWP Smid, M Cooper, JA Bauer, KA Rosenberg, RD Hack, CE Hamulyak, K Spronk, HMH Miller, GJ Ten Cate, H AF Govers-Riemslag, J. W. P. Smid, M. Cooper, J. A. Bauer, K. A. Rosenberg, R. D. Hack, C. E. Hamulyak, K. Spronk, H. M. H. Miller, G. J. Ten Cate, H. TI The plasma kallikrein-kinin system and risk of cardiovascular disease in men SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE coagulation; coronary heart disease; factor XII; plasma kalhkrein-kinin system; risk factors ID COAGULATION-FACTOR-XII; CORONARY-HEART-DISEASE; ACTIVATED FACTOR-XII; ACUTE MYOCARDIAL-INFARCTION; CLOTTING FACTOR-XI; MONOCLONAL-ANTIBODY; CONTACT SYSTEM; HAGEMAN-FACTOR; HEREDITARY ANGIOEDEMA; INHIBITOR COMPLEXES AB Background: The plasma kallikrein-kinin system (PKKS) has been implicated in cardiovascular disease, but activation of the PKKS has not been directly probed in individuals at risk of coronary heart disease (CHD) or stroke. Objective: To determine the involvement of the PKKS, including factor XI, in cardiovascular disease occurring in a nested case-control study from the Second Northwick Park Heart Study (NPHS-II). Methods and results: After a median follow-up of 10.7 years, 287 cases of CHD and stroke had been recorded and 542 age-matched controls were selected. When FXIIa-C1 esterase inhibitor (C1-inhibitor) concentrations were divided into tertiles (lowest tertile as reference), the odds ratios (ORs) at 95% CIs for CHD were 0.52 (0.34-0.80) in the middle tertile and 0.73 (0.49-1.09) in the highest tertile (P = 0.01 for the overall difference; P = 0.01 for CHD and stroke combined). For kallikrein-C1-inhibitor complexes, the ORs for stroke were 0.29 (0.12-0.72) and 0.67 (0.30-1.52) in the middle and high tertiles, respectively (P = 0.02). FXIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes were negatively related to smoking and fibrinogen (P < 0.005). FXIa-inhibitor complexes correlated strongly with FXIIa-inhibitor complexes. Conclusions: Lower levels of inhibitory complexes of the PKKS enzymes and particularly of FXIIa contribute to the risk of CHD and stroke in middle-aged men. This observation supports the involvement of the PKKS in atherothrombosis. C1 Univ Maastricht, Lab Clin Thrombosis & Haemostasis, NL-6200 MD Maastricht, Netherlands. Maastricht Univ, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands. Maastricht Univ, Dept Internal Med, Maastricht, Netherlands. Wolfson Inst Prevent Med, Med Res Council Cardiovasc Res Grp, London, England. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02115 USA. Sanquin, Amsterdam, Netherlands. Univ Hosp Maastricht, Dept Internal Med, Maastricht, Netherlands. RP Ten Cate, H (reprint author), Univ Maastricht, Lab Clin Thrombosis & Haemostasis, POB 616,UNS 50 Box 8, NL-6200 MD Maastricht, Netherlands. EM h.tencate@bioch.unimaas.nl FU NHLBI NIH HHS [HL54502, HL33014] NR 34 TC 54 Z9 55 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD SEP PY 2007 VL 5 IS 9 BP 1896 EP 1903 DI 10.1111/j.1538-7836.2007.02687.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 207KR UT WOS:000249250500018 PM 17723129 ER PT J AU Stelfox, HT Velmahos, GC Gettings, E Bigatello, LM Schmidt, U AF Stelfox, Henry Thomas Velmahos, George C. Gettings, Elise Bigatello, Luca M. Schmidt, Ulrich TI Computed tomography for early and safe discontinuation of cervical spine immobilization in obtunded multiply injured patients SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med DE blunt trauma; computed tomography; spinal injury; spinal immobilization; cervical collar ID MECHANICALLY VENTILATED PATIENTS; BLUNT TRAUMA PATIENTS; VENOUS THROMBOEMBOLISM; LIGAMENTOUS INJURIES; DYNAMIC FLUOROSCOPY; MAJOR TRAUMA; PLAIN FILMS; CARE; CLEARANCE; SCAN AB Background: Evaluation of the cervical spine (c-spine) in obtunded severely injured trauma patients is controversial, and spine immobilization is frequently prolonged. We examined the effect of two different c-spine evaluation protocols on c-spine immobilization and clinical outcomes. Methods: We prospectively evaluated consecutive intubated and mechanically ventilated patients admitted to the surgical intensive care unit (ICU) of a Level I academic trauma center with a diagnosis of multiple blunt injuries who had normal findings on high-resolution helical computed tomogram of Cl to T1 with reconstructions (HCTrecon). From July 1, 2003 to June 30, 2005 (n = 140), the findings of HCTrecon and either clinical examination or magnetic resonance imaging (MRI) were required to be normal to discontinue c-spine immobilization (clinical/MRI protocol). From July 1, 2005 to June 30, 2006 (n = 75), the policy was changed to require normal finding only on HCTrecon to discontinue c-spine immobilization (HCTrecon protocol). Results: Patients evaluated by the clinical/MRI and HCTrecon protocols had similar baseline characteristics. Compared with clinical/MRI patients, HCTrecon patients had their c-spines immobilized for fewer days (median, 6 days vs. 2 days; p < 0.001), were less likely to experience a complication of c-spine immobilization (64% vs. 37%, p = 0.010), required shorter periods of mechanical ventilation (median, 4 days vs. 3 days; p = 0.011), and had shorter stays in the ICU (median, 6 days vs. 4 days; p = 0.028) and hospital (median, 16 days vs. 14 days; p = 0.043). There was no difference in hospital mortality (13% vs. 16%, p = 0.920) and no missed c-spine injuries in either group. Conclusion: Discontinuation of c-spine precautions based on the normal findings of HCTrecon decreases the duration of c-spine immobilization in obtunded severely injured patients and is associated with fewer complications, fewer days of mechanical ventilation, and shorter stays in the ICU and hospital. C1 Univ Calgary, Dept Crit Care Med, Foothills Med Ctr, Calgary, AB T2N 2T9, Canada. Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Stelfox, HT (reprint author), Univ Calgary, Dept Crit Care Med, Foothills Med Ctr, EG23A,1403-29 St NW, Calgary, AB T2N 2T9, Canada. EM tom.stelfox@calgaryhealthregion.ca NR 44 TC 54 Z9 54 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD SEP PY 2007 VL 63 IS 3 BP 630 EP 636 DI 10.1097/TA.0b013e318076b537 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 211DA UT WOS:000249503300027 PM 18073612 ER PT J AU Latini, DM Hart, SL Knight, SJ Cowan, JE Ross, PL DuChane, J Carroll, PR AF Latini, David M. Hart, Stacey L. Knight, Sara J. Cowan, Janet E. Ross, Phillip L. DuChane, Janeen Carroll, Peter R. CA CaPSURETM Investigators TI The relationship between anxiety and time to treatment for patients with prostate cancer on surveillance SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; anxiety; prostate-specific antigen ID CONSERVATIVE MANAGEMENT; RADICAL PROSTATECTOMY; CAPSURE; MEN; PREDICTORS; RECURRENCE; RADIATION; OUTCOMES; THERAPY; ANTIGEN AB Purpose: Little is known about psychosocial factors affecting the decision to move from surveillance to active treatment in men with localized prostate cancer. We examined the impact of cancer anxiety on the decision to move from surveillance to treatment. Materials and Methods: We analyzed data from CaPSURE, a national observational prostate cancer registry. A total of 105 participants had localized disease, selected surveillance vs treatment and had at least 3 prostate specific antigen values available after baseline. Cancer anxiety was measured with a 3-item scale (alpha = 0.78). We calculated the rate of change in prostate specific antigen with time (prostate specific antigen velocity) and used the same formula to calculate the rate of change in cancer anxiety. We fit a Cox regression model to determine predictors of receiving treatment in the 3-year observation period, controlling for prostate specific antigen velocity, demographics and baseline clinical characteristics. Results: Prostate specific antigen velocity and the cancer anxiety change rate were significant independent predictors of treatment receipt (HR 1.02, 95% CI 1.004, 1.035, each p <0.01). Men with higher prostate specific antigen velocity (1.51 ng/ml per year or greater) were significantly more likely to receive treatment than men with lower prostate specific antigen velocity (HR 3.18, 95% CI 1.122, 9.016). The 2 velocity measures correlated only modestly (r = 0.29, p <0.001). Conclusions: Rather than being based only on clinical presentation and disease progression, decisions about treatment receipt for some men are influenced by cancer related anxiety. Men should be provided with more psychosocial support to perhaps delay treatment and the ensuing decrements in health related quality of life. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dan L Duncan Canc Ctr, Scott Dept Urol, Houston, TX USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Urol, Programs Urol Oncol & Genitourinary Canc E, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Latini, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care Utilizat Studies, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM latini@bcm.tmc.edu RI Hart, Stacey/E-4819-2011; OI Latini, David/0000-0002-6161-4861 FU NCI NIH HHS [P50 CA89520, PC040796] NR 20 TC 101 Z9 106 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2007 VL 178 IS 3 BP 826 EP 831 DI 10.1016/j.juro.2007.05.039 PN 1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 198PZ UT WOS:000248641300023 PM 17632144 ER PT J AU Lin, WC Uppot, RN Li, CS Hahn, PF Sahani, DV AF Lin, Wen-Chiung Uppot, Raul N. Li, Chao-Shiang Hahn, Peter F. Sahani, Dushyant V. TI Value of automated coronal reformations from 64-section multidetector row computerized tomography in the diagnosis of urinary stone disease SO JOURNAL OF UROLOGY LA English DT Article DE tomography; emission computed; kidney; ureter; calculi; diagnosis ID ACUTE FLANK PAIN; INTRAVENOUS UROGRAPHY; CT UROGRAPHY; HELICAL CT; TRACT; IMPACT AB Purpose: We determined the value of automated coronal reformation using 64-detector computerized tomography for the detection of urinary stones. Materials and Methods: A total of 72 patients underwent unenhanced 64-detector computerized tomography to diagnose urinary stones. Two radiologists independently reviewed coronal reformations and axial images at separate reading sessions. The stone detection rate, reader confidence and interpretation time per radiologist were recorded. Two radiologists reviewed coronal and axial images in consensus and served as the reference standard. Results: A total of 175 stones were diagnosed by consensus. Using coronal reformations 162 stones (92.6%) were detected by reader 1 and 157 (89.7%) were detected by reader 2. Using axial images 157 stones (90.3%) were detected by reader 1 and 155 (88.6%) were detected by reader 2. The reading time of coronal reformations was significantly shorter than that of axial images for each reader (p <0.01). Using coronal imaging to complement axial imaging 12 additional stones were detected and 23 were diagnosed with increased confidence by reader 1, while an additional 15 were detected and 8 were diagnosed with increased confidence by reader 2. The mean size of stones detected with coronal reformations alone was significantly smaller than that of the total stones. Excellent interobserver agreement was noted for coronal reformations and axial images (kappa coefficient: 0.91 and 0.904, respectively). Conclusions: Review of automated coronal reformations allows equally accurate and more rapid detection of urinary stones compared with axial images alone. In addition, coronal reformation of 64-detector computerized tomography adds value when used in conjunction with axial data sets. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdomina Imaging & Interventional Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Taipei City Hosp, Tri Serv Gen Hosp, Natl Def Med Ctr, Renai Branch, Taipei, Taiwan. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdomina Imaging & Interventional Radiol, 55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 19 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2007 VL 178 IS 3 BP 907 EP 911 DI 10.1016/j.juro.2007.05.042 PN 1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 198PZ UT WOS:000248641300047 PM 17651761 ER PT J AU Sajadi, KP Terris, MK Hamilton, RJ Cullen, J Amling, CL Kane, CJ Presti, JC Aronson, WJ Freedland, SJ AF Sajadi, Kamran P. Terris, Martha K. Hamilton, Robert J. Cullen, Jennifer Amling, Christopher L. Kane, Christopher J. Presti, Joseph C., Jr. Aronson, William J. Freedland, Stephen J. TI Body mass index, prostate weight and transrectal ultrasound prostate volume accuracy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; ultrasonography; obesity; prostatic hyperplasia ID RADICAL PROSTATECTOMY; SIZE; OBESITY; CANCER; HYPERPLASIA; OVERWEIGHT; DATABASE; RISK AB Purpose: Transrectal ultrasound can be used to calculate prostate volume, which has implications for benign and malignant prostate disease. We hypothesized that obesity may represent a technical challenge when performing transrectal ultrasound that decreases the accuracy of estimating prostate volume. Materials and Methods: We examined the records of men with previously untreated prostate cancer who underwent radical prostatectomy between 1995 and 2006 and who were in the Shared-Equal Access Regional Cancer Hospital database. Transrectal ultrasound volume calculations were correlated with radical prostatectomy specimen weight using the Spearman coefficient. We calculated the percent and absolute error, and evaluated the relationship between them and transrectal ultrasound volume, body mass index, age, prostate specific antigen and race using multivariate linear regression. Results: A total of 497 patients with preoperative transrectal ultrasound volume, specimen weight and body mass index data were identified in the Shared-Equal Access Regional Cancer Hospital database. Transrectal ultrasound volume correlated modestly with specimen weights (r = 0.692, p < 0.001). The median +/- SD absolute error was 9.6 +/- 11.4 gm and the median +/- SD percent error was 22.9% +/- 20.6%. Body mass index was not significantly related to absolute or percent error (p = 0.91 and 0.71, respectively). In addition, patient age, prostate specific antigen and race were not significantly related to absolute or percent error (p > 0.05). However, percent error but not absolute error was significantly predicted by transrectal ultrasound volume (p < 0.001 and 0.34, respectively). Smaller prostate size was associated with greater percent error, especially when transrectal ultrasound volume was less than 20 cc. Conclusions: Transrectal ultrasound volume correlates with specimen weight but it is an imperfect substitute with significant variation in error. The accuracy of transrectal ultrasound depends on measured volume but neither body mass index nor other patient specific variables had a significant impact. C1 Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. Augusta Vet Affairs Med Ctr, Augusta, GA USA. Durham Vet Affairs Med Ctr, Durham, NC USA. Duke Univ, Durham, NC USA. Ctr Prostate Dis Res, Rockville, MD USA. Univ Alabama, Birmingham, AL USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Stanford Univ, Stanford, CA 94305 USA. Palo Alto Vet Affairs Med Ctr, Palo Alto, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Sajadi, KP (reprint author), Med Coll Georgia, Urol Sect, 1120 15th St,BA 8414, Augusta, GA 30912 USA. EM ksajadi@mcg.edu OI Hamilton, Robert/0000-0002-6715-5934; Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [CA92131-01A1, R01CA100938] NR 19 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 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2007 VL 178 IS 3 BP 990 EP 995 DI 10.1016/j.juro.2007.05.049 PN 1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 198PZ UT WOS:000248641300074 PM 17632170 ER PT J AU Bradley, DA Hussain, M DiPaola, RS Kantoff, P AF Bradley, Deborah A. Hussain, Maha DiPaola, Robert S. Kantoff, Philip TI Bone directed therapies for prostate cancer SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 6th Cambridge Conference on Innovations and Challenges in Prostate Cancer CY OCT 30-31, 2006 CL Cambridge, MA DE prostate; prostatic neoplasms; bone and bones; neoplasm metastasis ID FUNCTIONAL DIFFUSION MAP; PLACEBO-CONTROLLED TRIAL; PHASE-II TRIAL; ZOLEDRONIC ACID; SKELETAL COMPLICATIONS; NATURAL-HISTORY; MINERAL DENSITY; METASTASES; PROGRESSION; MEN AB Purpose: Bone is the most common site of metastatic disease in prostate cancer and the lead cause of significant morbidity. Preclinical and clinical studies have provided insight into the pathophysiology of bone metastases and the changes that occur in the bone microenvironment that result in a favorable site of growth for prostate cancer. We provide an overview of recent advances in understanding bone biology, and bone targeted therapy research and development. Materials and Methods: We reviewed recent research findings related to the biology of bone metastases, approaches to targeting osteoclast function, approaches to targeting osteoblasts and advances in assessing the treatment response to bone targeted therapies in the context of prostate cancer management. Results: To date targeting some of the key players in the bone microenvironment has not been associated with a significant antitumor effect or with meaningful clinical benefit in phase III randomized trials. A significant limitation in the development of bone targeted therapy has been the inability to objectively assess treatment response. Investigation of improved imaging techniques are ongoing to provide better treatment assessment and, therefore, allow more rapid drug screening and development. Conclusions: It is our recommendation that future therapy development should be combination based, focusing on simultaneous targeting of multiple relevant pathways. Most important of all is the direct targeting of prostate cancer cells. C1 Univ Michigan, Med Ctr, Div Hematol & Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Hussain, M (reprint author), Univ Michigan, Med Ctr, Div Hematol & Oncol, Dept Internal Med, 7314 CCGC,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM mahahuss@umich.edu FU NCI NIH HHS [T32CA009357] NR 71 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2007 VL 178 IS 3 BP S42 EP S48 DI 10.1016/j.juro.2007.04.035 PN 2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 200VH UT WOS:000248790400008 PM 17644119 ER PT J AU Cooperberg, MR Broering, JM Kantoff, PW Carroll, PR AF Cooperberg, Matthew R. Broering, Jeannette M. Kantoff, Philip W. Carroll, Peter R. TI Contemporary trends in low risk prostate cancer: Risk assessment and treatment SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 6th Cambridge Conference on Innovations and Challenges in Prostate Cancer CY OCT 30-31, 2006 CL Cambridge, MA DE prostate; prostatic neoplasms; risk factors; prognosis; questionnaires ID RESEARCH ENDEAVOR CAPSURE; RADICAL PROSTATECTOMY; PREOPERATIVE NOMOGRAM; DISEASE RECURRENCE; UNITED-STATES; MANAGEMENT; INTERVENTION; VALIDATION AB Purpose: We updated national risk trends in prostate cancer with a focus on low risk tumors, reexamined trends in primary treatment for low risk tumors and substratified patients at low risk based on pretreatment clinical data. Materials and Methods: Data were abstracted from the CaPSURE (TM) registry. A total of 10,385 men were diagnosed between 1990 and 2006 with localized disease. Low risk was defined as prostate specific antigen 10 ng/ml or less, Gleason score 6 or less and clinical T stage 2a or less. Temporal trends were assessed for patient distribution among risk groups and in the low risk group for individual risk factors, Kattan nomogram prediction, Cancer of the Prostate Risk Assessment score and primary treatment. The ability of the Cancer of the Prostate Risk Assessment score to substratify low risk prostatectomy cases was evaluated with survival analysis. Results: The proportion of low risk tumors in CaPSURE almost doubled from 27.5% in 1990 to 1994, to 46.4% in 2000 to 2001 but it has been relatively constant since then. A growing proportion of low risk tumors are cT1c and virtually all are Gleason score 6. Prostate specific antigen and the percent of positive biopsies decreased throughout the study period, as did the mean Cancer of the Prostate Risk Assessment score. The use of active surveillance increased from a nadir of 6.2% in 2000 to 2001, to 10.2% in 2004 to 2006. The use of prostatectomy also increased, whereas the use of androgen deprivation and radiation decreased. The likelihood of recurrence increased significantly with increasing Cancer of the Prostate Risk Assessment scores. Conclusions: Patients at low risk can be further substratified to identify those at very low risk based on clinical variables. The use of surveillance is increasing but overtreatment remains a concern in these patients. C1 Univ Calif San Francisco, Mt Zion Med Ctr, Dept Urol,Program Urol Oncol, Urol Outcome Res Grp,Comprehens Canc Ctr, San Francisco, CA 94115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Cooperberg, MR (reprint author), Univ Calif San Francisco, Mt Zion Med Ctr, Dept Urol,Program Urol Oncol, Urol Outcome Res Grp,Comprehens Canc Ctr, 1600 Divisadero St,3rd Floor, San Francisco, CA 94115 USA. EM pcarroll@urol.ucsf.edu RI Cooperberg, Matthew/B-3867-2008 FU NCI NIH HHS [P50 CA089520, P50 CA089520-05] NR 19 TC 255 Z9 258 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2007 VL 178 IS 3 BP S14 EP S19 DI 10.1016/j.juro.2007.03.135 PN 2 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 200VH UT WOS:000248790400003 PM 17644125 ER PT J AU Kantoff, PW Beer, TM D'Amico, AV DiPaola, RS Eisenberger, MA Hussain, MHA Kelly, WK Mathew, P Morris, MJ Ryan, CJ Sandler, HM Thompson, IM Carroll, PR AF Kantoff, Philip W. Beer, Tomasz M. D'Amico, Anthony V. DiPaola, Robert S. Eisenberger, Mario. A. Hussain, Maha H. A. Kelly, William Kevin Mathew, Paul Morris, Michael J. Ryan, Charles J. Sandler, Howard M. Thompson, Ian M. Carroll, Peter R. TI Innovations and challenges in prostate cancer: Summary statement for the 6th Cambridge conference SO JOURNAL OF UROLOGY LA English DT Editorial Material DE prostate; prostatic neoplasms; clinical conference [publication type] ID PHASE-II; CARCINOMA; FINASTERIDE; TRIAL C1 Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Johns Hopkins Univ, Dep Oncol & Urol, Baltimore, MD USA. Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Radiat Oncol & Urol, Ann Arbor, MI 48109 USA. Yale Univ, Dept Med Oncol, New Haven, CT USA. Anderson Canc Ctr, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Dept Urol, San Antonio, TX USA. Cornell Univ, Joan & Sanford E Weill Coll Med, Genitourinary Oncol Serv, Dept Med, New York, NY USA. Cornell Univ, Joan & Sanford E Weill Coll Med, Sidney Kimmel Ctr Prostate & Urol Canc, Mem Sloan Kettering Canc Ctr, New York, NY USA. Cornell Univ, Joan & Sanford E Weill Coll Med, Dept Med, New York, NY USA. Univ Calif San Francisco, Dept Med, Program Urol Oncol, Urol Outcomes Res Grp,Comprehens Canc Ctr, San Francisco, CA USA. Univ Calif San Francisco, Dept Urol, Program Urol Oncol, Urol Outcomes Res Grp,Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Kantoff, PW (reprint author), Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. OI Morris, Michael J./0000-0002-9454-0096 NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2007 VL 178 IS 3 BP S5 EP S8 DI 10.1016/j.juro.2007.03.137 PN 2 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 200VH UT WOS:000248790400001 PM 17644118 ER PT J AU Daniel, JC Huynh, TT Zhou, W Kougias, P El Sayed, HF Huh, J Coselli, JS Lin, PH AF Daniel, Jonathan C. Huynh, Tam T. Zhou, Wei Kougias, Panagiotis El Sayed, Hosam F. Huh, Joseph Coselli, Joseph S. Lin, Peter H. TI Acute aortic dissection associated with use of cocaine SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CRACK COCAINE; CARDIOVASCULAR COMPLICATIONS; ABUSE; ANEURYSMS; DISEASE AB Purpose: Cocaine use can result in a variety of cardiovascular complications, including myocardial infarction, arterial thrombosis, coronary dissection, and cardiomyopathy. Cocaine-induced aortic dissection is uncommon and has been described largely in case reports. The purpose of this study was to review our experience with aortic dissection associated with cocaine abuse. Methods. A retrospective chart review was performed of all hospital records during a 15-year period in patients diagnosed with aortic dissection. Among the 164 cases of acute aortic dissection, 16 patients (9.8%) had used cocaine or its derivative, crack cocaine, within 24 hours prior to the onset of symptoms. The remaining 148 patients (90.2%) had no history of cocaine usage. Clinical features, management, and outcome in these two groups were compared. Results. In the cocaine group, powder cocaine was inhaled intranasally in I I patients (69%) and crack cocaine was smoked in five cases (31%). The mean duration between cocaine use and the onset of aortic dissection was 12.8 hours (range, 4 to 24 hours). Patients in the cocaine group were younger in age and more likely to have a history of polysubstance abuse than the non-cocaine cohort. In the cocaine group, the incidence of DeBakey dissection type 1, 11, IIIa, and IIIb was 19%, 25%, 38%, and 19%, respectively. In the group without cocaine use, the incidence of DeBakey dissection type 1, 11, IIIa, and IIIb was 18%, 23%, 39%, and 20%, respectively. Surgical intervention for aortic dissection was performed in 50% of the cocaine group and 45% of the non-cocaine group. In patients who underwent surgical repair, greater pulmonary complications occurred in the cocaine group than the non-cocaine group (n = 0.02). No difference was noted in the hospital length of stay or 30-day operative mortality among the two groups. Conclusions. Cocaine-associated aortic dissection occurs in predominantly male patients with illicit drug abuse who were younger than patients with aortic dissection without cocaine use. Greater pulmonary complications can occur in patients with cocaine-related aortic dissection following surgical interventions. C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Houston VAMC, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX 77030 USA. RP Lin, PH (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Houston VAMC, Div Vasc Surg & Endovasc Therapy, 2002 Holcomb Blvd, Houston, TX 77030 USA. EM plin@bcm.tmc.edu NR 27 TC 34 Z9 37 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2007 VL 46 IS 3 BP 427 EP 433 DI 10.1016/j.jvs.2007.05.040 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 208JL UT WOS:000249315500005 PM 17826227 ER PT J AU Kougias, P Lau, D El Sayed, HF Zhou, W Huynh, TT Lin, PH AF Kougias, Panagiotis Lau, Donald El Sayed, Hosarn F. Zhou, Wei Huynh, Tam T. Lin, Peter H. TI Determinants of mortality and treatment outcome following surgical interventions for acute mesenteric ischemia SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Southern-Association-for-Vascular-Surgery CY JAN 18-21, 2006 CL Phoenix, AZ SP SO Assoc Vasc Surg ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; INTESTINAL ISCHEMIA; REPERFUSION INJURY; CT ANGIOGRAPHY; NITRIC-OXIDE; ARTERY; REVASCULARIZATION; MANAGEMENT; INFILTRATION; EXPERIENCE AB Background: Acute mesenteric ischemia (AMI) is associated with high morbidity and mortality due in part to its diagnostic difficulty and operative challenges. The purpose of this study was to review our experience of surgical management in patients with this condition and to identify variables associated with adverse outcomes following surgical interventions. Methods. Hospital records and clinical data of all patients undergoing surgical interventions for AMI were reviewed during a recent 12-year period. Clinical outcomes as well as factors influencing mortality were analyzed. Results. A total of 72 patients (41 females, overall mean age 65 years, range 34 to 83 years) were included in the study. Thrombosis and embolism were the cause of AMI in 48 patients (67%) and 24 patients (33%), respectively. Abdominal pain was the most common presenting symptom (96%), followed by nausea (56%). Preoperative angiogram was performed in 61 patients (85%). All patients underwent operative interventions, which included thromboembolectomy (n = 22, 3 1 %), mesenteric bypass grafting (n = 33, 46%), patch angioplasty (n = 9, 12%), reimplantation (n = 5, 7%), and endarterectomy (n = 3, 4%). Bowel resection was necessary in 22 patients (31%) during the initial operation, and second-look operation was performed in 38 patients (53%). Perioperative morbidity and 30-day mortality rates were 39% and 31%, respectively. Univariate analysis showed renal insufficiency (P <.02), age > 70 (P <.001), metabolic acidosis (P <.02), and symptom duration (P <.005), and bowel resection in second-look operations (P <.01) were associated with mortality. Logistic regression analysis showed age > 70 (P =.03) and prolonged symptom duration (P =.02) were independent predictors of mortality. Conclusions. Elderly patients and those with a prolonged duration of symptoms had worse outcomes following surgical intervention for AML A high index of suspicion with prompt diagnostic evaluation may reduce time delay prior to surgical intervention, which may lead to improved patient survival. Aggressive surgical intervention should be performed as promptly as possible in patients once the diagnosis of AMI is made. C1 Houston VAMC, Baylor Coll Med, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. Michael E DeBakey VA Med Ctr, Houston, TX USA. RP Lin, PH (reprint author), Houston VAMC, Baylor Coll Med, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, 112,2002 Holcomb Blvd, Houston, TX 77030 USA. EM plin@bcm.tmc.edu NR 34 TC 75 Z9 85 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2007 VL 46 IS 3 BP 467 EP 474 DI 10.1016/j.jvs.2007.04.045 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 208JL UT WOS:000249315500014 PM 17681712 ER PT J AU Verity, EE Zotos, D Wilson, K Chatfield, C Lawson, VA Dwyer, DE Cunningham, A Learmont, J Dyer, W Sullivan, J Churchill, M Wesselingh, SL Gabuzda, D Gorry, PR McPhee, DA AF Verity, Erin E. Zotos, Dimitra Wilson, Kim Chatfield, Catherine Lawson, Victoria A. Dwyer, Dominic E. Cunningham, Anthony Learmont, Jennifer Dyer, Wayne Sullivan, John Churchill, Melissa Wesselingh, Steven L. Gabuzda, Dana Gorry, Paul R. McPhee, Dale A. TI Viral phenotypes and antibody responses in long-term survivors infected with attenuated human immunodeficiency virus type 1 containing deletions in the nef and long terminal repeat regions SO JOURNAL OF VIROLOGY LA English DT Article ID BLOOD-BANK COHORT; ACTIVE ANTIRETROVIRAL THERAPY; NEUTRALIZING ANTIBODY; HIV-1 INFECTION; MONOCLONAL-ANTIBODIES; LONGITUDINAL ANALYSIS; DISEASE PROGRESSION; MACROPHAGE TROPISM; LIVE; AIDS AB The Sydney Blood Bank Cohort (SBBC) consists of eight blood transfusion recipients infected with nef-attenuated human immunodeficiency virus type 1 (HIV-1) acquired from a single donor. Here, we show that viral phenotypes and antibody responses differ considerably between individual cohort members, despite the single source of infection. Replication of isolated virus varied from barely detectable to similar to that of the wild-type virus, and virus isolated from five SBBC members showed coreceptor usage signatures unique to each individual. Higher viral loads and stronger neutralizing antibody responses were associated with better-replicating viral strains, and detectable viral replication was essential for the development of strong and sustained humoral immune responses. Despite the presence of strong neutralizing antibodies in a number of SBBC members, disease progression was not prevented, and each cohort member studied displayed a unique outcome of infection with nef-attenuated HIV-1. C1 St Vincents Inst Med Res, Natl Serol Reference Lab, Fitzroy, Vic 3065, Australia. Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia. Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. Deakin Univ, Sch Biol & Chem Sci, Burwood, Vic, Australia. Westmead Millenium Inst, Ctr Virus Res, Westmead, NSW, Australia. Australian Red Cross Blood Serv, Sydney, NSW, Australia. Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP McPhee, DA (reprint author), St Vincents Inst Med Res, Natl Serol Reference Lab, 4th Floor,Healy Bldg,41 Victoria Parade, Fitzroy, Vic 3065, Australia. EM dale@nrl.gov.au OI Lawson, Victoria/0000-0002-7362-7176; Cunningham, Anthony/0000-0002-6744-5667 FU NIAID NIH HHS [AI054207, R21 AI054207]; NINDS NIH HHS [NS37277, R01 NS037277] NR 58 TC 19 Z9 19 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 SEP PY 2007 VL 81 IS 17 BP 9268 EP 9278 DI 10.1128/JVI.00650-07 PG 11 WC Virology SC Virology GA 202SL UT WOS:000248923700039 PM 17567690 ER PT J AU Mitchell, KA Rawl, SM Schmidt, CM Grant, M Ko, CY Baldwin, CM Wendel, C Krouse, RS AF Mitchell, Kimberly A. Rawl, Susan M. Schmidt, C. Max Grant, Marcia Ko, Clifford Y. Baldwin, Carol M. Wendel, Christopher Krouse, Robert S. TI Demographic, clinical, and quality of life variables related to embarrassment in veterans living with an intestinal stoma SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Article ID RECTAL-CANCER PATIENTS; SURGERY; ILEOSTOMY; COLOSTOMY; BODY AB OBJECTIVE: The study aims were to identify demographic, clinical, and quality of life variables related to embarrassment for people living with ostomies and to determine the experiences and/or feelings of veterans who were embarrassed by their ostomy. DESIGN: This was a cross-sectional, correlational study. SETTING AND SUBJECTS: A convenience sample of veterans (n = 239) living with ostomies from 3 VA medical centers was studied. The veterans were primarily Caucasian (84%), male (92%), and older (M = 69). INSTRUMENTS: The modified City of Hope Quality of Life-Ostomy questionnaire was used. Additionally, an open-ended question related to living with an ostomy was asked. METHODS: The questionnaire packets were mailed to participants and self-administered. RESULTS: Approximately half of the participants (48%) rated their embarrassment as low, but 26% reported high embarrassment. Participants with high embarrassment were compared to those with low embarrassment on demographic, clinical, and quality of life variables. High embarrassment was associated with poorer total quality of life (P < .001) and poorer quality of life on the physical (P < .001), psychological (P < .001), social (P < .001), and spiritual (P < .001) subscales. Younger (P < .001) and unpartnered veterans (P < .001) were more likely to be highly embarrassed. Veterans with high embarrassment had higher anxiety (P < .001) and depression (P < .001), more difficulty with intimacy (P < .001), and felt more isolated (P < .001). Spiritual domain variables like hopefulness were associated with low embarrassment (P < .001). Sources of embarrassment included leakage, odor, and noise. CONCLUSIONS: Embarrassment may negatively impact a person's quality of life; therefore, the variables associated with high embarrassment should be recognized and addressed. C1 Purdue Univ, Indiana Univ, Sch Nursing, Indianapolis, IN USA. St Francis Med Ctr, Coll Nursing, Peoria, IL USA. Ctr Nursing Res, Indianapolis, IN USA. Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA. City Hope Natl Med Ctr, Dept Nursing Res & Educ, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Arizona State Univ, SW Borderlands, Coll Nursing, Phoenix, AZ USA. So Arizona VA Hlth Care Syst, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. RP Krouse, RS (reprint author), 511 NE Greenleaf, Peoria, IL 61603 USA. EM kamitch@insightbb.com OI Baldwin, Carol/0000-0002-0732-2307; Rawl, Susan/0000-0003-2052-2853 NR 26 TC 29 Z9 30 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD SEP-OCT PY 2007 VL 34 IS 5 BP 524 EP 532 PG 9 WC Nursing SC Nursing GA 215YE UT WOS:000249844100014 PM 17876215 ER PT J AU Ran, Q Liang, HY Ikeno, Y Qi, WB Prolla, TA Roberts, LJ Wolf, N VanRemmen, H Richardson, A AF Ran, Qitao Liang, Hanyu Ikeno, Yuji Qi, Wenbo Prolla, Tomas A. Roberts, L. Jackson, II Wolf, Norman VanRemmen, Holly Richardson, Arlan TI Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID INNER MITOCHONDRIAL-MEMBRANE; 10-N-NONYL ACRIDINE-ORANGE; RAT-LIVER MITOCHONDRIA; CYTOCHROME-C; CALORIC RESTRICTION; OXIDATIVE STRESS; EXTENDED LONGEVITY; LIPID-PEROXIDATION; DNA-DAMAGE; CELL-LINE AB Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme that plays an important role in detoxification of oxidative damage to membrane lipids. Because oxidative stress is proposed to play a causal role in aging, we compared the life spans of Gpx4 heterozygous knockout mice (Gpx4(+/-) mice) and wild-type mice (WT mice). To our surprise, the median life span of Gpx4(+/-) mice (1029 days) was significantly longer than that of WT mice (963 days) even though the expression of Gpx4 was reduced approximately 50% in all tissues of Gpx4(+/-) mice. Pathological analysis revealed that Gpx4(+/-) mice showed a delayed occurrence of fatal tumor lymphoma and a reduced severity of glomerulonephritis. Compared to WT mice, Gpx4(+/-) mice showed significantly increased sensitivity to oxidative stress-induced apoptosis. Our data indicate that lifelong reduction in Gpx4 increased life span and reduced/retarded age-related pathology most likely through alterations in sensitivity of tissues to apoptosis. C1 [Ran, Qitao; Liang, Hanyu; Ikeno, Yuji; Qi, Wenbo; VanRemmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Ran, Qitao; Liang, Hanyu; Ikeno, Yuji; Qi, Wenbo; VanRemmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Ran, Qitao; Ikeno, Yuji; VanRemmen, Holly; Richardson, Arlan] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. [Prolla, Tomas A.] Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. [Prolla, Tomas A.] Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA. [Roberts, L. Jackson, II] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. [Roberts, L. Jackson, II] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Wolf, Norman] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Richardson, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM richardsona@uthscsa.edu RI Liang, Hanyu/A-1066-2010 FU NIA NIH HHS [P01 AG19316, P01AG020591, P30-AG13319]; NIGMS NIH HHS [R37GM42056] NR 64 TC 86 Z9 86 U1 1 U2 6 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2007 VL 62 IS 9 BP 932 EP 942 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AE UT WOS:000253829000002 PM 17895430 ER PT J AU Rosano, C Aizenstein, HJ Studenski, S Newman, AB AF Rosano, Caterina Aizenstein, Howard J. Studenski, Stephanie Newman, Anne B. TI A regions-of-interest volumetric analysis of mobility limitations in community-dwelling older adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LOWER-EXTREMITY FUNCTION; WHITE-MATTER LESIONS; CARDIOVASCULAR HEALTH; MRI FINDINGS; GAIT SPEED; SUBSEQUENT DISABILITY; COGNITIVE FUNCTION; IMPAIRED MOBILITY; MOTOR FUNCTION; BRAIN AB Background. In community-dwelling older adults, greater mobility impairment is associated with greater burden of diffuse brain Structural abnormalities, such as higher white matter hyperintensities. This study examined the association between gray matter volumes of regions related to motor control, gait, and balance and whether this association is independent of burden of white matter hyperintensities. Methods. A random sample of 327 participants of the Cardiovascular Health Study (78.3 +/- 4.1 years old, 57% women) contributed brain magnetic resonance imaging (MRI) and mobility data. A brain imaging automated method measured gray matter volume in cerebellum, basal ganglia, and prefrontal and parietal cortex in both hemispheres. Gait speed was measured while walking 15 feet at usual pace. Standing balance was assessed by timing tandem stance. Associations between each region's volume and gait speed or balance were measured before and after adjustment for demographics, head size, cardiovascular risk factors, and 0-9 grading scores of white matter hyperintensities. Results. Smaller left cerebellum and left prefrontal regions were associated with slower gait, independently of covariates and of white matter hyperintensities. Smaller right putamen, right posterior superior parietal cortex, and both left and right cerebellum were associated with balance difficulty, independently of covariates and white matter hyperintensities. Conclusions. Smaller gray matter volumes in regions crucial for motor control are associated with slower gait and poorer balance, and the association appears to be independent of other diffuse brain abnormalities such as white matter hyperintensities. C1 [Rosano, Caterina; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Aizenstein, Howard J.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. [Studenski, Stephanie; Newman, Anne B.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Sch Med, Pittsburgh, PA 15260 USA. [Studenski, Stephanie] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. RP Rosano, C (reprint author), 130 N Bellefield,Room 519, Pittsburgh, PA 15213 USA. EM rosanoc@edc.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU NHLBI NIH HHS [N01-HC-15103, N01-HC-35129, N01-HC-45133, N01-HC-55222, N01-HC-75150, N01-HC-85079, N01-HC-85086, U01 HL080295]; NIA NIH HHS [1 P30 AG024827, P30 AG024827] NR 46 TC 69 Z9 69 U1 1 U2 2 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2007 VL 62 IS 9 BP 1048 EP 1055 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AE UT WOS:000253829000018 PM 17895446 ER PT J AU Baggish, AL Nadiminti, H AF Baggish, Aaron L. Nadiminti, Hari TI Intracranial abscess from embolic Serratia marcescens endocarditis SO LANCET INFECTIOUS DISEASES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Cardiol, Cambridge, MA 02140 USA. Massachusetts Gen Hosp, Dept Med, Cambridge, MA 02140 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Cambridge, MA 02140 USA. EM abaggish@partners.org NR 0 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2007 VL 7 IS 9 BP 630 EP 630 DI 10.1016/S1473-3099(07)70213-X PG 1 WC Infectious Diseases SC Infectious Diseases GA 205CV UT WOS:000249091700021 PM 17714676 ER PT J AU Kavirajan, H Schneider, LS AF Kavirajan, Harish Schneider, Lon S. TI Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials SO LANCET NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; CEREBROVASCULAR-DISEASE; CLINICAL-TRIALS; DONEPEZIL; GALANTAMINE; MULTICENTER; CRITERIA AB Background Cholinesterase inhibitors and memantine do not have regulatory approval in most of the world for treatment of vascular dementia. A systematic review and meta-analysis was undertaken to assess the evidence for efficacy and safety of cholinesterase inhibitors and memantine in vascidar dementia. Methods PubMed, BIOSIS, International Pharmaceutical Abstracts, and Cochrane registries were searched for randomised, placebo-controlled trials on cholinesterase inhibitors and memantine in patients with vascular dementia. Trial methods, clinical characteristics, outcomes, and adverse events were extracted and checked. Meta-analytic methods using fixed-effects models were used to give summaries of each drug's effects. Findings Three donepezil, two galantamine, one rivastigmine, and two memantine trials, comprising 3093 patients on the study drugs and. 2090 patients on placebo, met the selection criteria. Trials were of 6-month duration with similar vascular dementia criteria and outcome measures. Cognitive effects on the Alzheimer's Disease Assessment scale were significant for all drugs, ranging from a -1.10 point mean difference (95% CI -2.15 to -0.05) for rivastigmine to -2.17 for 10 mg daily donepezil (95% CI -2.98 to -1.35). Only 5 mg daily donepezil had an effect on the Clinicians' Global Impression of Change scale (odds ratio 1.51 [95% CI 1.11-2.07]). No behavioural or functional benefits were observed, except for a -0.95 point difference (95% CI -1.74 to -0.16) with 10 mg daily donepezil on the Alzheimer's Disease Functional Assessment and Change Scale. Compared with placebo, more dropouts and adverse events (anorexia, nausea, vomiting, diarrhoea, and insomnia) occurred with the cholinesterase inhibitors, but not with memantine. Interpretation Cholinesterase inhibitors and memantine produce small benefits in cognition of uncertain clinical significance in patients with mild to moderate vascular dementia. Data are insufficient to support widespread use of these drugs in vascular dementia. Individual patient analyses are needed to identify subgroups of patients with vascular dementia who might benefit. C1 Univ Calif Los Angeles, Geffen Sch Med, Dept Gen Internal Med, Div Hlth Serv Res,Vet Affairs Greater Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA USA. RP Kavirajan, H (reprint author), 950 S Coast Dr,Suite 202, Mesa, CA 92626 USA. EM hkaviraj@yahoo.com FU NIA NIH HHS [AG 05142] NR 38 TC 139 Z9 168 U1 5 U2 24 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD SEP PY 2007 VL 6 IS 9 BP 782 EP 792 DI 10.1016/S1474-4422(07)70195-3 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 204SV UT WOS:000249065200017 PM 17689146 ER PT J AU Guss, J Cohen, MA Mirza, N AF Guss, Joel Cohen, Marc A. Mirza, Natasha TI Hard palate necrosis after bilateral internal maxillary artery embolization for epistaxis SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Combined Sections of the Triological-Society CY FEB 14-18, 2007 CL Marco Isl, FL SP Triol Soc DE epistaxis; embolization; necrosis; hard palate; nasal packing ID ANGIOGRAPHIC EMBOLIZATION; INTRACTABLE EPISTAXIS; POSTERIOR EPISTAXIS; MANAGEMENT AB Superselective embolization is an effective method of treating epistaxis that is refractory to conservative treatment. Soft tissue necrosis is a rare complication owing to the extensive collateral blood supply of the head and neck. We describe the case of a patient who developed unilateral necrosis of the mucosa overlying the hard palate after undergoing bilateral internal maxillary artery embolization. The presence of a nasopharyngeal balloon I and bilateral nasal packs for 2 days after embolization I may have compressed collateral vessels in the soft palate I and nose and contributed to this complication. Packing should be removed as soon as possible after embolization. C1 Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Guss, J (reprint author), 5 Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM joel.guss@uphs.upenn.edu NR 8 TC 13 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2007 VL 117 IS 9 BP 1683 EP 1684 DI 10.1097/MLG.0b013e318093ee8d PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 207QH UT WOS:000249265400027 PM 17667134 ER PT J AU Abramson, JS AF Abramson, Jeremy S. TI T-cell/histiocyte-rich B-cell lymphoma and the paradox of the host immune response SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID MALIGNANT-LYMPHOMA; SUBTYPES; CLASSIFICATION; BIOLOGY; CANCER C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. EM jabramson@partners.org NR 12 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP PY 2007 VL 48 IS 9 BP 1670 EP 1671 DI 10.1080/10428190701599021 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 214UR UT WOS:000249764200003 PM 17786700 ER PT J AU Torriani, M Thomas, BJ Bredella, MA Ouellette, H AF Torriani, Martin Thomas, Bijoy J. Bredella, Miriam A. Ouellette, Hugue TI Intramyocellular lipid quantification: comparison between 3.0-and 1.5-T H-1-MRS SO MAGNETIC RESONANCE IMAGING LA English DT Article DE proton magnetic resonance spectroscopy; muscle; lipids; 3.0 T ID MAGNETIC-RESONANCE-SPECTROSCOPY; H-1 MR SPECTROSCOPY; SKELETAL-MUSCLE; INSULIN SENSITIVITY; RELAXATION-TIMES; IMAGE-CONTRAST; 3 T; FAT; BRAIN; RESISTANCE AB Objective: This study aimed to prospectively compare measurement precision of calf intramyocellular lipid (IMCL) quantification at 3.0 and 1.5 T using H-1 magnetic resonance spectroscopy (H-1-MRS). Materials and Methods: We examined the soleus and tibialis anterior (TA) muscles of 15 male adults [21-48 years of age, body mass index (BMI)=21.9-38.0 kg/m(2)]. Each subject underwent 3.0- and 1.5-Tsingle-voxel, short-echo-time, point-resolved H-1-MRS both at baseline and at 31-day follow-up. The IMCL methylene peak (1.3 ppm) was scaled to unsuppressed water peak (4.7 ppm) using the LCModel routine. Full width at half maximum (FWHM) and signal-to-noise ratios (SNRs) of unsuppressed water peak were measured using jMRUI software. Measurement precision was tested by comparing interexamination coefficients of variation (CV) between different field strengths using Wilcoxon matched pairs signed rank test in all subjects. Overweight subjects (BMI>25 kg/m(2)) Were analyzed separately to examine the benefits of 3.0-T acquisitions in subjects with increased adiposity. Results: No significant difference between 3.0 and 1.5 T was noted in CVs for IMCL of soleus (P=.5). CVs of TA were significantly higher at 3.0 T (P=.02). SNR was significantly increased at 3.0 T for soleus (64%, P<.001) and TA (62%, P<.001) but was lower than the expected improvement of 100%. FWHM at 3.0 T was significantly increased for soleus (19%, P<.001) and TA (7%, P<.01). Separate analysis of overweight subjects showed no significant difference between 3.0- and 1.5-T CVs for IMCL of soleus (P=.8) and TA (P=.4). Conclusion: Using current technology, H-1-MRS for IMCL at 3.0 T did not improve measurement precision, as compared with 1.5 T. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Torriani, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. EM mtorriani@partners.org FU NCRR NIH HHS [RR01066, M01 RR001066-280422, M01 RR001066-298616, M01 RR001066] NR 25 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD SEP PY 2007 VL 25 IS 7 BP 1105 EP 1111 DI 10.1016/j.mri.2006.12.003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 204PJ UT WOS:000249056200011 PM 17707173 ER PT J AU Duncan, J Spengler, E Wolfe, J AF Duncan, Janet Spengler, Emily Wolfe, Joanne TI Providing pediatric palliative care: PACT in action SO MCN-THE AMERICAN JOURNAL OF MATERNAL-CHILD NURSING LA English DT Article DE end of life; interdisciplinary team; pediatric; polliative care ID PARENTAL PERSPECTIVES; HOSPITAL STAFF; LIFE; CHILDREN; END; QUALITY; CANCER; DEATH AB High-quality pediatric palliative care should be an expected standard in the United States, especially since the publication of the numerous position statements such as "Precepts of Palliative Care for Children and Adolescents and Their Families," a joint statement created by the Association of Pediatric Oncology Nurses, the National Association of Neonatal Nurses, and the Society of Pediatric Nurses. Although many barriers still exist, dedicated individuals and teams strive to promote models of excellence and improve care for children with life-threatening conditions and their families. The Pediatric Advanced Care Team, a joint project of Dana-Farber Cancer Institute and Children's Hospital, Boston, is one such interdisciplinary pediatric palliative care consultation service. Founded in 1997, we have grown and learned from formal study and our extensive clinical work with families, children, and our colleagues. This article describes our journey as an interdisciplinary, team forging a new service within two renowned medical institutions in which historically the primary emphasis of care has been on cure and innovation. Although these values remain, our work has resulted in an increased acceptance of balancing treatment of the underlying disease or condition along with treatment of the physical psychosocial, and spiritual needs of the child and family through life or death. One of our goals is to help promote a balance of hope for cure with hope for comfort, dignity, and integrity for every child and family. C1 DFCI, Pediat Adv Care Team, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Weill Cornell Med Sch, New York, NY USA. Childrens Hosp, Dana Farber Canc Inst, Pediat Adv Care Team, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Duncan, J (reprint author), DFCI, Pediat Adv Care Team, Boston, MA USA. EM janet.duizcan@childrens.harvard.edu NR 21 TC 19 Z9 19 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-929X J9 MCN-AM J MATERN-CHIL JI MCN-Am. J. Matern.-Child Nurs. PD SEP-OCT PY 2007 VL 32 IS 5 BP 279 EP 287 DI 10.1097/01.NMC.0000287997.97931.5f PG 9 WC Nursing SC Nursing GA 208KQ UT WOS:000249318600005 PM 17728588 ER PT J AU Prall, WC Czibere, A Jager, M Spentzos, D Libermann, TA Gattermann, N Haas, R Aivado, M AF Prall, Wolf C. Czibere, Akos Jaeger, Marcus Spentzos, Dimitrios Libermann, Towia A. Gattermann, Norbert Haas, Rainer Aivado, Manuel TI Age-related transcription levels of KU70, MGST1 and BIK in CD34+hematopoietic stem and progenitor cells SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE cDNA macroarray; gene expression; aging; HSC; hematopoietic stem cells; oncogenesis ID MICROSOMAL GLUTATHIONE TRANSFERASE; CD34(+) HEMATOPOIETIC STEM; DNA-REPAIR PROTEIN; OXIDATIVE STRESS; GENE; EXPRESSION; CAPACITY; PROTECTION; CANCER; CLASSIFICATION AB Despite the known longevity of human hematopoietic stem and progenitor cells (HSC), numerous functional impairments of these cells can be observed in an age-dependent manner. However, the molecular alterations associated with aging of HSC are largely unknown. Therefore, we scrutinized gene expression patterns of HSC from newborn, young and old healthy donors. CD34+ HSC were isolated via immuno-magnetic separation and evaluated by FACS analysis. We performed cDNA macroarray analyses on a first set of CD34+ samples (n = 13). We found the genes encoding KU-antigen 70 kD (KU70), microsomal glutathione S-transferase 1 (MGSTI) and BCL2-interacting killer (BIK) to possess agerelated mRNA expression levels. KU70 is a DNA repair gene and part of the DNA-dependent protein kinase (DNA-PK) complex. Its expression was negatively correlated with donor age showing highest expression levels in newborn, 2.6-fold lower levels in young and 6.3-fold lower levels in old donors. The transcription levels of MGSTI, a gene protecting against oxidative stress, progressively increased with age. Expression was lowest in newborn, 2.6-fold higher in young and 4.3-fold higher in old donors. BIK is a proapoptotic gene and its expression was positively correlated with donor age: lowest in newborn, 1.8-fold higher in young and 4. 1 -fold higher in old donors. These findings were confirmed with an independent, second set of CD34+ samples (n = 16) by means of quantitative real-time RT-PCR. Elucidation of age-dependent molecular alterations in healthy HSC facilitate a better understanding of functional impairments in hematopoiesis and may become valuable for anti-aging drug development and the emerging field of regenerative medicine. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, D-40225 Dusseldorf, Germany. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, BIDMC Genom Ctr, Boston, MA 02115 USA. Univ Dusseldorf, Dept Orthopaed, Lab Biomat & Regenerat Med, D-40225 Dusseldorf, Germany. Univ Munich, Downtown Hosp, Dept Surg, D-80336 Munich, Germany. RP Prall, WC (reprint author), Univ Muenchen, Chirurg Klin & Poliklin Innenstadt klinikum, Nussbaumstr 20, D-80336 Munich, Germany. EM wprall@BIDMC.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179 NR 52 TC 13 Z9 13 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD SEP PY 2007 VL 128 IS 9 BP 503 EP 510 DI 10.1016/j.mad.2007.06.008 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 218LL UT WOS:000250016900004 PM 17714764 ER PT J AU O'Connor, AM Bennett, C Stacey, D Barry, MJ Col, NE Eden, KB Entwistle, V Fiset, V Holmes-Rovner, M Khangura, S Llewellyn-Thomas, H Rovner, DR AF O'Connor, Annette M. Bennett, Carol Stacey, Dawn Barry, Michael J. Col, Nananda E. Eden, Karen B. Entwistle, Vikki Fiset, Valerie Holmes-Rovner, Margaret Khangura, Sara Llewellyn-Thomas, Hillary Rovner, David R. TI Do patient decision aids meet effectiveness Criteria of the international patient decision aid standards collaboration? A systematic review and meta-analysis SO MEDICAL DECISION MAKING LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HORMONE REPLACEMENT THERAPY; DIAGNOSED HYPERTENSIVE PATIENTS; BREAST-CANCER SUSCEPTIBILITY; INTERACTIVE VIDEO PROGRAM; PROSTATE-CANCER; MAKING INTERVENTION; ATRIAL-FIBRILLATION; PRENATAL-DIAGNOSIS; COMPUTER-PROGRAM AB Objective. To describe the extent to which patient decision aids (PtDAs) meet effectiveness standards of the International Patient Decision Aids Collaboration (IPDAS). Data sources. Five electronic databases (to July 2006) and personal contacts (to December 2006). Results. Among 55 randomized controlled trials, 38 (69%) used at least 1 measure that mapped onto an IPDAS effectiveness criterion. Measures of decision quality were knowledge scores (27 trials), accurate risk perceptions (12 trials), and value congruence with the chosen option (3 trials). PtDAs improved knowledge scores relative to usual care (weighted mean difference [WMD] = 15.2%, 95% confidence interval [CI] = 11.7 to 18.7); detailed PtDAs were somewhat more effective than simpler PtDAs (WMD = 4.6%, 95% CI= 3.0 to 6.2). PtDAs with probabilities improved accurate risk perceptions relative to those without probabilities (relative risk = 1.6, 95% CI = 1.4 to 1.9). Relative to simpler PtDAs, detailed PtDAs improved value congruence with the chosen option. Only 2 of 6 IPDAS decision process criteria were measured: feeling informed (15 trials) and feeling clear about values (13 trials). PtDAs improved these process measures relative to usual care (feeling uninformed WMD = -8.4, 95 % GI = -11.9 to -4.8; unclear values WMD = -6.3, 95 % CI = -10.0 to -2.7). There was no difference in process measures when detailed and simple PtDAs were compared. Conclusions. PtDAs improve decision quality and the decision process's measures of feeling informed and clear about values; however, the size of the effect varies across studies. Several IPDAS decision process measures have not been used. Future trials need to use a minimum data set of IPDAS evaluation measures, The degree of detail PtDAs require for positive effects on IPDAS criteria should be explored. C1 Univ Ottawa, Ottawa Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Maine Med Ctr, Portland, ME 04102 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Social Dimens Hlth Inst, Dundee, Scotland. Algonquin Coll, Ottawa, ON, Canada. Michigan State Univ, E Lansing, MI 48824 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. RP O'Connor, AM (reprint author), Univ Ottawa, Ottawa Hlth Res Inst, 1053 Carling Ave,ASB, Ottawa, ON K1Y 4E9, Canada. EM ohdec@ohri.ca OI Entwistle, Vikki/0000-0002-0856-4025 NR 82 TC 142 Z9 144 U1 0 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 SEP-OCT PY 2007 VL 27 IS 5 BP 554 EP 574 DI 10.1177/0272989x07307319 PG 21 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 223BS UT WOS:000250345200007 PM 17873255 ER PT J AU Barnato, AE Llewellyn-Thomas, HA Peters, EM Siminoff, L Collins, ED Barry, MI AF Barnato, Amber E. Llewellyn-Thomas, Hilary A. Peters, Ellen M. Siminoff, Laura Collins, E. Dale Barry, Michael J. TI Comunication and decision making in cancer care: Setting research priorities for decision Support/Patients' decision aids SO MEDICAL DECISION MAKING LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 21-24, 2005 CL San Francisco, CA SP Soc Med Decis Making ID QUALITY-OF-LIFE; HEALTH-CARE; ATRIAL-FIBRILLATION; HORMONE-THERAPY; BREAST-CANCER; PATIENT; COMMUNICATION; PREFERENCES; DISPARITIES; NUMERACY AB The following is a summary report from a special symposium titled, "Translating Research into Practice: Setting a Research Agenda for Clinical Decision Tools in Cancer Prevention, Early Detection, and Treatment," that was held on 23 October 2005 in San Francisco at the Annual Meeting of the Society for Medical Decision Making (SMDM). The symposium was designed to answer the question: "What are the top 2 research priorities in the field of patients' cancer-related decision aids?" After introductory remarks by Dr. Barry, each of four panelists Drs. Hilary Llewellyn - Thomas, Ellen Peters, Laura Siminoff, and Dale Collins-addressed the question and provided their rationale during prepared remarks. The moderator, Dr. Michael Barry, then facilitated a discussion between the panelists, with input from the audience, to further explore and add to the various proposed research questions. Finally, Dr. Amber Barnato conducted a simple vote count (see Table 1) to prioritize the panelists' and the audience's recommendations. C1 Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Ctr Evaluat Clin Sci, Hanover, NH 03756 USA. Decis Res, Eugene, OR USA. Virginia Commonwealth Univ, Richmond, VA USA. Dartmouth Hitchcock Med Ctr, Comprehens Breast Program, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, Hlth Serv Res Program, Boston, MA 02114 USA. RP Barnato, AE (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM barnatoae@upmc.edu RI Siminoff, Laura /H-6277-2012 FU NCI NIH HHS [1R13CA117811, R13 CA117811] NR 60 TC 18 Z9 18 U1 1 U2 10 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 SEP-OCT PY 2007 VL 27 IS 5 BP 626 EP 634 DI 10.1177/0272989x07306788 PG 9 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 223BS UT WOS:000250345200013 PM 17873249 ER PT J AU Song, JS Court, LE Cormack, RA AF Song, Jun S. Court, Laurence E. Cormack, Robert A. TI Monte Carlo calculation of rectal dose when using an intrarectal balloon during prostate radiation therapy SO MEDICAL DOSIMETRY LA English DT Article DE Monte Carlo; DVH; balloon; prostate cancer ID ESCALATION; CANCER AB Air-filled intrarectal balloons can be used to localize and immobilize the prostate for radiation therapy, allowing dose escalation to the prostate and reducing the probability of radiation proctitis, but also introducing potentially significant heterogeneity. We compare the Eclipse treatment planning system (TPS) with Monte Carlo (MC) simulations for 5 patients to assess how well a conventional TPS includes the effect of the balloon on doses near the rectum. The MC results show that, for a 27-Gy prescription to the 95% isodose line, Eclipse overestimates the volume of the rectum receiving more than 26 Gy (96%) by 2 similar to-10 cc and the volume of the rectum receiving between 12 similar to 15 Gy by 10 similar to 20 cc. Differential dose volume histograms are also computed and compared for individual fields in the anterior expansion of the rectum, and the TPS is again shown to predict higher mean dose in the region by 0.3 similar to 1.0 Gy. (C) 2007 American Association of Medical Dosimetrists. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Song, JS (reprint author), Dana Farber Canc Inst, Dept Biostat, Mail Stop LW225,44 Binney St, Boston, MA 02115 USA. EM jssong@jimmy.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 10 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0958-3947 J9 MED DOSIM JI Med. Dosim. PD FAL PY 2007 VL 32 IS 3 BP 151 EP 156 DI 10.1016/j.meddos.2006.11.002 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 206DB UT WOS:000249163000001 PM 17707193 ER PT J AU Schnyer, DM Dobbins, IG Nicholls, L Davis, S Verfaellie, M AF Schnyer, David M. Dobbins, Ian G. Nicholls, Lindsay Davis, Sarah Verfaellie, Mieke TI Item to decision mapping in rapid response learning SO MEMORY & COGNITION LA English DT Article ID WORD IDENTIFICATION; RECOGNITION MEMORY; FUSIFORM CORTEX; ABSTRACTIONIST; AUTOMATICITY; MECHANISMS; AUTOMATIZATION; SPECIFICITY; INVARIANCE; ATTENTION AB Repeated classification of a visually presented stimulus rapidly leads to a form of response learning that bypasses the original evaluation in favor of a more efficient response mechanism. In two experiments, we examined the level of input and output representations that make up this form of learning. In Experiment 1, alterations in the finger mapping of the output response had no effect on the expression of response learning, demonstrating that a classification decision, not motor output, is associated with repeated items. in Experiments 2A and 2B, we tested whether response learning would transfer across different visual exemplars of a studied item. There was no evidence of transfer to different visual exemplars, even when these exemplars were judged to be highly visually similar. Taken together, these results indicate that response learning consists of the formation of an association between a specific visual representation and a classification decision. C1 Univ Texas, Dept Psychol, Austin, TX 78712 USA. Boston VA Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Duke Univ, Durham, NC USA. Harvard Univ, Cambridge, MA 02138 USA. RP Schnyer, DM (reprint author), Univ Texas, Dept Psychol, A8000, Austin, TX 78712 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG08441, R37 AG008441-17, R37 AG008441, R01 AG008441]; NIMH NIH HHS [R01 MH057681-09, R01 MH057681, MH57681, K23MH64004, K23 MH064004-05, K23 MH064004]; NINDS NIH HHS [P50 NS026985, P50 NS26985, P50 NS026985-13] NR 33 TC 24 Z9 25 U1 1 U2 1 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0090-502X J9 MEM COGNITION JI Mem. Cogn. PD SEP PY 2007 VL 35 IS 6 BP 1472 EP 1482 DI 10.3758/BF03193617 PG 11 WC Psychology, Experimental SC Psychology GA 226AR UT WOS:000250560100026 PM 17948070 ER PT J AU Price, MD Herndon, JH AF Price, Mark D. Herndon, James H. TI Is running good for your knees? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID OSTEOARTHRITIS; RISK; WOMEN; SOCCER; MEN; HIP C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Price, MD (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. NR 18 TC 1 Z9 1 U1 0 U2 1 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 SEP-OCT PY 2007 VL 14 IS 5 BP 815 EP 816 DI 10.1097/gme.0b013e318095a4c4 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 209LB UT WOS:000249388900003 PM 17589377 ER PT J AU Styer, AK AF Styer, Aaron K. TI Adipocytokines and the postmenopausal metabolic syndrome: cause and effect, association, or neither? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID INSULIN-RESISTANCE; LEPTIN; WOMEN; DISEASE; ADIPONECTIN; THERAPY; GHRELIN; OBESITY; HEALTH C1 Massachusetts Gen Hosp, Fertil Ctr, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Styer, AK (reprint author), Massachusetts Gen Hosp, Fertil Ctr, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 17 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 SEP-OCT PY 2007 VL 14 IS 5 BP 817 EP 819 DI 10.1097/gme.0b013e31812F7b77 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 209LB UT WOS:000249388900004 PM 17693903 ER PT J AU Lee, SI AF Lee, Susanna I. TI An imaging algorithm for evaluation of abnormal uterine bleeding: does sonohysterography play a role? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID HYSTEROSCOPY C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lee, SI (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 7 TC 6 Z9 8 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 SEP-OCT PY 2007 VL 14 IS 5 BP 823 EP 825 DI 10.1097/gme.0b013c318136e1c6 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 209LB UT WOS:000249388900006 PM 17693897 ER PT J AU DeRubertis, FR Craven, PA Melhem, MF AF DeRubertis, Frederick R. Craven, Patricia A. Melhem, Mona F. TI Acceleration of diabetic renal injury in the superoxide dismutase knockout mouse: effects of tempol SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID NITRIC-OXIDE SYNTHESIS; OXIDATIVE STRESS; SIGNALING PATHWAYS; GLOMERULAR INJURY; NADPH OXIDASE; MICE; NEPHROPATHY; GENERATION; RATS; PEROXYNITRITE AB Indices of renal injury and oxidative stress were examined in mice with deficiency of cytosolic Cu2+/Zn2+ superoxide dismutase (SOD1-/-, KO) and their wild-type (WT) littermates with streptozotocin-induced diabetes. After 5 weeks of diabetes, KO diabetic (D) but not WT-D mice developed marked albuminuria, increases in glomerular content of transforming growth factor beta, collagen alpha 1(IV), and nitrotyrosine, and higher glomerular superoxide compared with corresponding values in nondiabetics. After 5 months of diabetes, increases in these parameters, mesangial matrix expansion, renal cortical malondialdehyde content, and severity of tubulointerstitial injury were all significantly greater, whereas cortical glutathione was lower, in KO-D than in WT-D. In contrast to WT-D, after 4 weeks of diabetes, KO-D mice did not develop the increase in inulin clearance (C-ln) characteristic of early diabetes. The nitric oxide synthase inhibitor N-omega-nitro-L-arginine methylester suppressed C-ln. in WT-D, but had no effect on C-ln in KO-D. Treatment of KO-D with the SOD mimetic tempol for 4 weeks suppressed albuminuria, increases in glomerular transforming growth factor beta, collagen alpha 1(IV), nitrotyrosine, and glomerular superoxide, and concurrently increased C-ln. The latter action of tempol in KO-D was blocked by the N-omega-nitro-L-arginine methylester. The findings provide support for a role for superoxide and its metabolism by SOD1 in the pathogenesis of renal injury in diabetes in vivo, and implicate increased interaction of superoxide with nitric oxide as a pathogenetic factor. Published by Elsevier Inc. C1 VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA 15240 USA. VA Pittsburgh Healthcare Syst, Dept Pathol, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15240 USA. RP DeRubertis, FR (reprint author), VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA 15240 USA. EM frederick.derubertis@med.va.gov NR 37 TC 53 Z9 56 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2007 VL 56 IS 9 BP 1256 EP 1264 DI 10.1016/j.metabol.2007.04.024 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 204NG UT WOS:000249050400015 PM 17697870 ER PT J AU Fukumura, D Jain, RK AF Fukumura, Dai Jain, Rakesh K. TI Tumor microvasculature and microenvironment: Targets for anti-angiogenesis and normalization SO MICROVASCULAR RESEARCH LA English DT Review DE angiogenesis; lymphangiogenesis; tumor; stromal cells; vascular endothelial growth factor; microenvironment; hypoxia; acidosis; interstitial fluid pressure; metastasis ID ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR-2 BLOCKADE; VASCULAR-PERMEABILITY FACTOR; HUMAN-MELANOMA CELLS; SOLID TUMORS; INTERSTITIAL HYPERTENSION; ANTIANGIOGENIC THERAPY; HOST MICROENVIRONMENT; LYMPHATIC METASTASIS; CANCER-THERAPY AB A solid tumor forms an organ-like entity comprised of neoplastic cells and non-transformed host stromal cells embedded in an extracellular matrix. Similar to normal tissues, blood vessels nourish cells residing in tumors. However, unlike normal blood vessels, tumor vasculature has abnormal organization, structure, and function. Tumor vessels are leaky and blood flow is heterogeneous and often compromised. Vascular hyperpermeability and the lack of functional lymphatic vessels inside tumors cause elevation of interstitial fluid pressure in solid tumors. Each of these abnormalities forms a physiological barrier to the delivery of therapeutic agents to tumors. Furthermore, elevated tumor interstitial fluid pressure increases fluid flow from the tumor margin into the peri-tumor area and may facilitate peri-tumor lymphatic hyperplasia and metastasis. Abnormal microcirculation in tumors also leads to a hostile microenvironment characterized by hypoxia and acidosis, which hinder the effectiveness of anti-tumor treatments such as radiation therapy and chemotherapy. In addition, host-tumor interactions regulate expression of pro- and anti-angiogenic factors and hence contribute to their imbalance and resulting pathophysiological characteristics of the tumor. Restoration of pro- and anti-angiogenic balance in tumors may "normalize" tumor vasculature and thus improve its function. Indeed, anti-angiogenic treatments directly targeting angiogenic signaling pathways as well as indirectly modulating angiogenesis show normalization of tumor vasculature and microenvironment at least transiently in both preclinical and clinical settings. Combination of cytotoxic therapy and anti-angiogenic treatment during the vascular normalization exhibits synergistic effect. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St Cox 7, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu FU NCI NIH HHS [P01 CA080124-039003, P01 CA080124, P01 CA080124-01A1, P01 CA080124-01A10001, P01 CA080124-01A19003, P01 CA080124-01A1S10001, P01 CA080124-01A1S19003, P01 CA080124-02, P01 CA080124-020001, P01 CA080124-029003, P01 CA080124-03, P01 CA080124-030001, P01 CA080124-04, P01 CA080124-040001, P01 CA080124-049003, P01 CA080124-05, P01 CA080124-050001, P01 CA080124-059003, P01 CA080124-05S10001, P01 CA080124-05S19003, P01 CA080124-06A2, P01 CA080124-06A25967, P01 CA080124-06A25972, P01 CA080124-07, P01-CA-80124, R01 CA085140, R01 CA085140-06, R01 CA085140-07, R01 CA085140-08, R01 CA096915, R01 CA096915-01, R01 CA096915-02, R01 CA096915-03, R01 CA096915-04, R01 CA096915-05, R01 CA115767, R01 CA115767-01A1, R01 CA115767-02, R01-CA11576-01, R01-CA85140, R01-CA96915, R24 CA085140, R24 CA085140-01, R24 CA085140-02, R24 CA085140-03, R24 CA085140-04, R24 CA085140-05, R35 CA056591, R35 CA056591-07, U01 CA084301, U01 CA084301-06, U01 CA084301-07, U01 CA084301-08, U01 CA084301-09, U01-CA084301] NR 96 TC 322 Z9 351 U1 14 U2 96 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP-NOV PY 2007 VL 74 IS 2-3 BP 72 EP 84 DI 10.1016/j.mvr.2007.05.003 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 238EL UT WOS:000251430000002 PM 17560615 ER PT J AU Guan, S Chen, M Woodley, D Li, W AF Guan, Shengxi Chen, Mei Woodley, David Li, Wei TI Nck beta adapter controls neuritogenesis by maintaining the cellular paxillin level SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOTORECEPTOR AXON GUIDANCE; GROWTH-FACTOR-BB; ACTIN POLYMERIZATION; SIGNAL-TRANSDUCTION; PROTEIN; SYSTEM; LOCALIZATION; FIBROBLASTS; ACTIVATION; DROSOPHILA AB The SH2/SH3 adapter Nck has an evolutionarily conserved role in neurons, linking the cell surface signals to actin cytoskelleton-mediated responses. The mechanism, however, remains poorly understood. We have investigated the role of Nck/Nck alpha/Nck1 versus Grb4/Nck beta/Nck2 side-by-side in the process of mammalian neuritogenesis. Here we show that permanent genetic silencing of Nck beta, but not Nck alpha, completely blocked nerve growth factor-induced neurite outgrowth in PC12 cells and dramatically disrupted the axon and dendrite tree in primary rat cortical neurons. By screening for changes among the components reportedly present in complex with Nck, we found that the steady-state level of paxillin was significantly reduced in Nck beta knockdown, but not Nck alpha knockdown, neurons. Interestingly, Nck beta knockdown did not affect the paxillin level in glial cells and several other cell types of various tissue origins. Genetic silencing of paxillin blocked neuritogenesis, just like Nck beta knockdown. Reintroducing a nondegradable Nck beta into Nck beta short interfering RNA-expressing PC12 cells rescued paxillin from down-regulation and allowed the resumption of neuritogenesis. Forced expression of paxillin in Nck beta knockdown PC12 also rescued its capacity for neuritogenesis. Finally, Nck beta, but not Nck alpha, binds strongly to paxillin and treatment of the neurons with proteosome inhibitors prevented paxillin down-regulation in Nck beta knockdown neurons. Thus, Nck beta maintains paxillin stability during neuritogenesis. C1 Univ So Calif, Keck Sch Med, Dept Dermatol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, USC Norris Canc Ctr, Los Angeles, CA 90033 USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. RP Li, W (reprint author), 1303 N Mission Rd, Los Angeles, CA 90033 USA. EM wli@usc.edu FU NIAMS NIH HHS [GM/AR67100-01] NR 27 TC 13 Z9 13 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 SEP PY 2007 VL 27 IS 17 BP 6001 EP 6011 DI 10.1128/MCB.01807-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 203MQ UT WOS:000248979100006 PM 17591694 ER PT J AU Matsumura, K Chang, BHJ Fujimiya, M Chen, W Kulkarni, RN Eguchi, Y Kimura, H Kojima, H Chan, L AF Matsumura, Kazuhiro Chang, Benny Hung-Junn Fujimiya, Mineko Chen, Weiqin Kulkarni, Rohit N. Eguchi, Yutaka Kimura, Hiroshi Kojima, Hideto Chan, Lawrence TI Aquaporin 7 is a beta-cell protein and regulator of intraislet glycerol content and glycerol kinase activity, beta-cell mass, and insulin production and secretion SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-MYC; WATER CHANNEL; GENOMIC STRUCTURE; COLLECTING DUCT; GENE-EXPRESSION; ADIPOSE-TISSUE; RAT ISLETS; MOUSE; CLONING; MICE AB To investigate if intracellular glycerol content plays a role in the regulation of insulin secretion in pancreatic P cells, we studied the expression of the glycerol channels, or aquaglyceroporins, encoded by the aquaporin 3 (Aqp3), Aqp7, and Aqp9 genes in mouse islets. We found expression of Aqp7 only, not that of Aqp3 or Aqp9, in the endocrine pancreas at both the mRNA (by reverse transcription-PCR) and protein (by immunohistochemistry) levels. Immunohistochemistry revealed a complete overlap between insulin and Aqp7 immunostaining in the pancreatic islet. Inactivation of Aqp7 by gene targeting produced viable and healthy mice. Aqp7(-/-) mice harbored an increased intraislet glycerol concentration with a concomitant increase of the glycerol kinase transcript level and enzyme activity. The islet triglyceride content in the Aqp7(-/-) mice was also increased compared to that in the Aqp7(+/+) mice. Interestingly, Aqp7(-/-) mice displayed reduced beta-cell mass and insulin content but increased insulin-1 and insulin-2 mRNAs. The reduction of P-cell mass in Aqp7(-/-) mice can be explained at least in part by a reduction in cell proliferation through protein kinase C and the c-myc cascade, with a reduction in the transcript levels of these two genes. Concomitantly, there was a decreased rate of apoptosis, as reflected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and caspase 3 and Bax expression in Aqp7(-/-) mice. Compared with Aqp7(+/+) islets, islets isolated from Aqp7(-/-) mice secreted insulin at a higher rate under basal low-glucose conditions and on exposure to a high (450 mg/dl) glucose concentration. Aqp7(-/-) mice exhibited normal fasting blood glucose levels but elevated blood insulin levels. Their plasma glucose response to an intraperitoneal (i.p.) glucose tolerance test was normal, but their plasma insulin concentrations were higher than those of wild-type mice during the 2-h test. An i.p. insulin tolerance test showed similar plasma glucose lowering in Aqp7(-/-) and Aqp7(+/+) mice, with no evidence of insulin resistance. In conclusion, we found that pancreatic P cells express AQP7, which appears to be a key regulator of intraislet glycerol content as well as insulin production and secretion. C1 Baylor Coll Med, Dept Med, Div Endocrinol Diabet & Metab, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Div Endocrinol Diabet & Metab, Houston, TX 77030 USA. Shiga Univ Med Sci, Dept Mol Genet Med, Otsu, Shiga 52021, Japan. Shiga Univ Med Sci, Dept Anat, Otsu, Shiga 52021, Japan. Shiga Univ Med Sci, Dept Crit & Intens Care Med, Otsu, Shiga 52021, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Chang, BHJ (reprint author), Baylor Coll Med, Dept Med, Div Endocrinol Diabet & Metab, 1 Baylor Pl, Houston, TX 77030 USA. EM bchang@bcm.edu; Ichan@bcm.edu RI Chen, Weiqin/B-3220-2011; OI Chen, Weiqin/0000-0002-3894-5953 FU NHLBI NIH HHS [HL-51586, R01 HL051586]; NIDDK NIH HHS [R01-DK67536, DK-68037, P30-DK56338, R01 DK068037, P30 DK056338, R01 DK067536] NR 44 TC 36 Z9 40 U1 2 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 SEP PY 2007 VL 27 IS 17 BP 6026 EP 6037 DI 10.1128/MCB.00384-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 203MQ UT WOS:000248979100008 PM 17576812 ER PT J AU Xu, L Jain, RK AF Lei, Xu Jain, Rakesh K. TI Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma SO MOLECULAR CANCER RESEARCH LA English DT Article ID VEGF-INDUCED ANGIOGENESIS; RENAL-CELL CARCINOMA; HISTONE DEACETYLASE; TUMOR ANGIOGENESIS; PATHOLOGICAL CONDITIONS; MULTIPLE GENES; MESSENGER-RNAS; FACTOR PIGF; FACTOR-I; CANCER AB Two recent clinical trials have shown that the placenta growth factor (PIGF) is up-regulated after bevacizumab treatment in colorectal cancer and after SU1 1248 treatment in metastatic renal cell carcinoma. The regulation of expression for the vascular endothelial growth factor (VEGF) has been well documented in human tumors; however, the data for PlGF are lacking. We investigated the epigenetic regulation of PlGF and correlated the results with clinicopathologic features. We used plgf promoter analysis, cDNA microarray, immunohistochemistry, and Northern blot analysis to determine the expression level of PlGF in 22 human lung carcinoma and 11 colorectal tumors and in 12 cell lines. Sodium bisulfite modification of genomic DNA followed by methylation-specific PCR (MSP) and sequencing were used to determine the methylation status of the PlGF promoter. Treatments with 5-aza-2'-deoxycytidine and trichostatin A (TSA) were used to reactivate PlGF expression. Significance analysis showed that PIGF expression level was low in human lung and colorectal tumor tissues and in cell lines. PlGF gene promoter was hypermethylated. Treatment with the demethylating agent 5-Aza-dC restored PlGF transcript expression in the lung and colon carcinoma cell lines. By combining the results from cDNA microarray, immunohistochemistry, and MSP, we report, for the first time, that the PlGF gene promoter is methylated, and methylation may be one of the mechanisms that contributes to the low PlGF expression level in human lung and colorectal tumor tissues and cell lines. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. RP Xu, L (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, 100 Blossom St,Cox-7, Boston, MA 02114 USA. EM lei@steele.mgh.harvard.edu FU NCI NIH HHS [R01-CA85140, P01-CA80124, U01-CA84301] NR 34 TC 27 Z9 27 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2007 VL 5 IS 9 BP 873 EP 880 DI 10.1158/1541-7786.MCR-06-0141 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 211GJ UT WOS:000249512000001 PM 17704140 ER PT J AU Echchgadda, I Song, CS Oh, T Ahmed, M De La Cruz, IJ Chatterjee, B AF Echchgadda, Ibtissam Song, Chung S. Oh, Taesung Ahmed, Mohamed De La Cruz, Isidro John Chatterjee, Bandana TI The xenobiotic-sensing nuclear receptors pregnane x receptor, constitutive androstane receptor, and orphan nuclear receptor hepatocyte nuclear factor 4 alpha in the regulation of human Steroid- Bile acid-sulfotransferase SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID VITAMIN-D-RECEPTOR; HUMAN CYTOSOLIC SULFOTRANSFERASES; DEHYDROEPIANDROSTERONE-SULFOTRANSFERASE; GENE-EXPRESSION; TRANSCRIPTIONAL CONTROL; MOLECULAR-CLONING; AGONIST LIGAND; MOUSE-LIVER; CAR; METABOLISM AB The nuclear receptors pregnane X receptor ( PXR) and constitutive androstane receptor ( CAR) are the primary transcription factors coordinating induced expression of the enzymes and proteins directing oxidative, conjugative, and transport phases of endobiotic and xenobiotic metabolism, whereas hepatocyte nuclear factor 4 alpha ( HNF4 alpha), a regulator of hepatic lipid homeostasis, can modify the PXR/ CAR response. Steroid- and bile acid-sulfotransferase ( SULT2A1) promotes phase II metabolism through its sulfonating action on certain endobiotics,including steroids and bile acids, and on diverse xenobiotics, including therapeutic drugs. This study describes characterization of a PXR- and CAR-inducible composite element in the human SULT2A1 promoter and its synergistic interaction with HNF4 alpha. Inverted and direct repeats of AG( G/ T) TCA ( IR2 and DR4), both binding to PXR and CAR, define the composite element. Differential recognition of the composite element by PXR and CAR is evident because single-site mutation at either IR2 or DR4 in the natural gene abolished the PXR response, whereas mutations at both repeats were necessary to abrogate completely the CAR response. The composite element conferred xenobiotic response to a heterologous promoter, and the cognate ligands induced PXR and CAR recruitment to the chromatin-associated response region. An HNF4 alpha element adjacent to the - 30 position enhanced basal promoter activity. Although functioning as a synergizer, the HNF4 alpha element was not essential for the PXR/ CAR response. An emerging role of SULT2A1 in lipid and caloric homeostasis suggests that illumination on the regulatory interactions driving human SULT2A1 expression may reveal new avenues to control certain metabolic disorders. C1 Univ Texas, Hlth Sci Ctr, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Echchgadda, I (reprint author), Univ Texas, Hlth Sci Ctr, Inst Biotechnol, Dept Mol Med, 15355 Lambda Dr, San Antonio, TX 78245 USA. FU NIA NIH HHS [AG10486] NR 44 TC 41 Z9 44 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 2007 VL 21 IS 9 BP 2099 EP 2111 DI 10.1210/me.2007-0002 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 204CG UT WOS:000249020200005 PM 17595319 ER PT J AU Giraud, J Haas, M Feener, EP Copps, KD Dong, XC Dunn, SL White, MF AF Giraud, Jodel Haas, Michael Feener, Edward P. Copps, Kyle D. Dong, Xiaocheng Dunn, Sarah L. White, Morris F. TI Phosphorylation of irs1 at SER-522 inhibits insulin signaling SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; RECEPTOR SUBSTRATE-1 IRS-1; TYROSINE PHOSPHORYLATION; MEDIATED DEGRADATION; RESISTANCE; SER(307); OBESITY; MODULATION; ALPHA; MICE AB Multisite phosphorylation of Irs1 on serine and threonine residues regulates insulin signaling that can contribute to insulin resistance. We identified by mass spectrometry the phosphorylation of Ser522 in rat Irs1 ( S522(Irs1)). The functional effects of this phosphorylation site were investigated in cultured cells using a sequencespecific phosphoserine antibody. Insulin stimulated the phosphorylation of S522(Irs1) in L6 myoblasts and myotubes. S522(Irs1) phosphorylation was inhibited by wortmannin, whereas PD98059, rapamycin, or glucose-starvation had no effect. Reducing Akt expression with small interfering RNA inhibited insulin-stimulated phosphorylation of S522(Irs1), suggesting the involvement of the phosphatidylinositol 3-kinase3 -> Akt cascade. A S522(Irs1)-> A522(Irs1) substitution increased insulinstimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-> E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Together, these results suggest the phosphatidylinositol 3-kinase -> Akt cascade can inhibit insulin signaling through the phosphorylation of S522(Irs1). C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Div Endocrinol,Childrens Hosp Boston, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Giraud, J (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Div Endocrinol,Childrens Hosp Boston, Room 04210,300 Longwood Ave, Boston, MA 02115 USA. FU NIDDK NIH HHS [P30 DK036836, DK038712, DK067818] NR 30 TC 25 Z9 25 U1 2 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 2007 VL 21 IS 9 BP 2294 EP 2302 DI 10.1210/me.2007-0159 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 204CG UT WOS:000249020200020 PM 17579213 ER PT J AU Holers, VM Wood, A Takahashi, K Ezekowitz, AB Arend, WP Banda, NK AF Holers, V. Michael Wood, Allyson Takahashi, Kazue Ezekowitz, Alan B. Arend, William P. Banda, Nirmal K. TI The alternative pathway is both necessary and sufficient for the complement-dependent injury found in the effector phase of collagen antibody induced arthritis (CAIA) SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 11th European Meeting on Complement in Human Disease CY SEP 08-11, 2007 CL Cardiff, WALES C1 Univ Colorado, Dept Med, Div Rheumatol, Aurora, CO 80045 USA. Univ Colorado, Dept Immunol, Div Rheumatol, Aurora, CO 80045 USA. Denver & Hlth Sci Ctr, Aurora, CO 80045 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD SEP PY 2007 VL 44 IS 16 BP 3913 EP 3913 DI 10.1016/j.molimm.2007.06.016 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 211GK UT WOS:000249512100020 ER PT J AU Mihai, S Chiriac, MT Takahashi, K Thurman, JM Holers, VM Zillikens, D Botto, M Sitaru, C AF Mihai, Sidonia Chiriac, Mircea T. Takahashi, Kazue Thurman, Joshua M. Holers, V. Michael Zillikens, Detlef Botto, Marina Sitaru, Cassian TI The alternative pathway of complement activation is critical for blister induction in experimental autoimmune epidermolysis bullosa SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 11th European Meeting on Complement in Human Disease CY SEP 08-11, 2007 CL Cardiff, WALES C1 Univ Lubeck, Dept Dermatol, Lubeck, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80202 USA. Univ London Imperial Coll Sci Technol & Med, Sch Med, Rheumatol Sect, London SW7 2AY, England. RI Sitaru, Cassian/E-5830-2010 OI Sitaru, Cassian/0000-0002-0370-1270 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD SEP PY 2007 VL 44 IS 16 BP 3913 EP 3913 DI 10.1016/j.molimm.2007.06.017 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 211GK UT WOS:000249512100021 ER PT J AU Clatworthy, AE Pierson, E Hung, DT AF Clatworthy, Anne E. Pierson, Emily Hung, Deborah T. TI Targeting virulence: a new paradigm for antimicrobial therapy SO NATURE CHEMICAL BIOLOGY LA English DT Review ID SMALL-MOLECULE INHIBITORS; ANTHRAX LETHAL FACTOR; QUORUM-SENSING SIGNAL; PSEUDOMONAS-AERUGINOSA; III SECRETION; HALOGENATED FURANONES; ERWINIA-CAROTOVORA; ZEBRAFISH EMBRYOS; ESCHERICHIA-COLI; DRUG DISCOVERY AB Clinically significant antibiotic resistance has evolved against virtually every antibiotic deployed. Yet the development of new classes of antibiotics has lagged far behind our growing need for such drugs. Rather than focusing on therapeutics that target in vitro viability, much like conventional antibiotics, an alternative approach is to target functions essential for infection, such as virulence factors required to cause host damage and disease. This approach has several potential advantages including expanding the repertoire of bacterial targets, preserving the host endogenous microbiome, and exerting less selective pressure, which may result in decreased resistance. We review new approaches to targeting virulence, discuss their advantages and disadvantages, and propose that in addition to targeting virulence, new antimicrobial development strategies should be expanded to include targeting bacterial gene functions that are essential for in vivo viability. We highlight both new advances in identifying these functions and prospects for antimicrobial discovery targeting this unexploited area. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02142 USA. RP Hung, DT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM hung@molbio.mgh.harvard.edu NR 61 TC 487 Z9 501 U1 25 U2 176 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD SEP PY 2007 VL 3 IS 9 BP 541 EP 548 DI 10.1038/nchembio.2007.24 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 203IJ UT WOS:000248968000010 PM 17710100 ER PT J AU Jain, RK Finn, AV Kolodgie, FD Gold, HK Virmani, R AF Jain, Rakesh K. Finn, Aloke V. Kolodgie, Frank D. Gold, Herman K. Virmani, Renu TI Antiangiogenic therapy for normalization of atherosclerotic plaque vasculature: a potential strategy for plaque stabilization SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Review DE angiogenesis; atherosclerosis; cancer; hemorrhage; vascular normalization ID ENDOTHELIAL GROWTH-FACTOR; SUDDEN CORONARY DEATH; E-DEFICIENT MICE; INTRAPLAQUE HEMORRHAGE; TUMOR VASCULATURE; CELL-ADHESION; MAST-CELLS; MACULAR DEGENERATION; COMBINATION THERAPY; KNOCKOUT MOUSE AB Angiogenesis within human atherosclerotic plaques has an important role in plaque progression as immature blood vessels leak red blood cells and inflammatory mediators into the plaque center. Accumulation of free cholesterol from red blood cell membranes potentially increases the size of the necrotic core and triggers a chain of events that promote plaque destabilization. Antiangiogenic agents have been shown to prune some tumor vessels and 'normalize' the structure and function of the remaining vasculature, thereby improving the access of chemotherapeutic agents to tumors. We propose that antiangiogenic therapy can similarly stabilize vulnerable 'rupture-prone' plaques by pruning and normalizing immature intraplaque vessels, preventing further intraplaque hemorrhage. This normalization would limit necrotic core enlargement, further luminal narrowing and the degree of inflammation. Such normalization has been realized using vascular endothelial growth factor antagonists for the treatment of cancer and age-related macular degeneration. The development of this novel approach to prevent plaque progression might add to the armamentarium of preventive measures for acute myocardial infarction, stroke and sudden cardiac death. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol & Med, Director Edwin L Steele Lab Tumor Biol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Intervent Cardiol Cardiol Div, Boston, MA USA. CVPath Inst Inc, Gaithersburg, MD USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Cox 7 100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu; hgold@partners.org NR 77 TC 79 Z9 82 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD SEP PY 2007 VL 4 IS 9 BP 491 EP 502 DI 10.1038/ncpcardio0979 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 203AZ UT WOS:000248948800009 PM 17712362 ER PT J AU Schneider, SA Walker, RH Bhatia, KP AF Schneider, Susanne A. Walker, Ruth H. Bhatia, Kailash P. TI The Huntington's disease-like syndromes: what to consider in patients with a negative Huntington's disease gene test SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Review DE Huntington's disease; Huntington's disease-like syndromes; junctophilin 3; prion disease; spinocerebellar ataxia type 17 ID DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY; HALLERVORDEN-SPATZ-SYNDROME; TATA-BINDING PROTEIN; KINASE-ASSOCIATED NEURODEGENERATION; TRINUCLEOTIDE REPEAT EXPANSIONS; DOMINANT SPINOCEREBELLAR ATAXIA; CHOREA-ACANTHOCYTOSIS; CLINICAL-FEATURES; BASAL GANGLIA; DENTATORUBROPALLIDOLUYSIAN ATROPHY AB Huntington's disease (HD), which is caused by a triplet-repeat expansion in the IT15 gene (also known as huntingtin or HD), accounts for about 90% of cases of chorea of genetic etiology. In recent years, several other distinct genetic disorders have been identified that can present with a clinical picture indistinguishable from that of HD. These disorders are termed Huntington's disease-like (HDL) syndromes. So far, four such conditions have been recognized, namely disorders attributable to mutations in the prion protein gene (HDLI), the junctophilin 3 gene (HDL2), and the gene encoding the TATA box-binding protein (HDL4/SCAI 7), and a recessively inherited HD phenocopy in a single family (HDL3), the genetic basis of which is currently poorly understood. These disorders, however, account for only a small proportion of cases with the HD phenotype but a negative genetic test for HD, and the list of HDL genes and conditions is set to grow. In this article, we review the most important HD phenocopy disorders identified to date and discuss the clinical clues that guide further investigation. We will concentrate on the four so-called HDL syndromes mentioned above, as well as other genetic disorders such as dentatorubralpallidoluysian atrophy, neuroferritinopathy, pantothenate-kinase-associated neurodegeneration and chorea-acanthocytosis. C1 UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England. James J Peters Vet Affairs Med Ctr, Dept Neurol, Movement Disorders Clin, Bronx, NY USA. Mt Sinai Sch Med, Dept Neurol, New York, NY USA. RP Bhatia, KP (reprint author), UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England. EM kbhatia@ion.ucl.ac.uk NR 76 TC 44 Z9 45 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD SEP PY 2007 VL 3 IS 9 BP 517 EP 525 DI 10.1038/ncpneuro0606 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 205PI UT WOS:000249126700012 PM 17805246 ER PT J AU Manolio, TA Rodriguez, LL Brooks, L Abecasis, G Ballinger, D Daly, M Donnelly, P Faraone, SV Frazer, K Gabriel, S Gejman, P Guttmacher, A Harris, EL Insel, T Kelsoe, JR Lander, E McCowin, N Mailman, MD Nabel, E Ostell, J Pugh, E Sherry, S Sullivan, PF Thompson, JF Warram, J Study, G Wholley, D Milos, PM Collins, FS AF Manolio, Teri A. Rodriguez, Laura Lyman Brooks, Lisa Abecasis, Goncalo Ballinger, Dennis Daly, Mark Donnelly, Peter Faraone, Stephen V. Frazer, Kelly Gabriel, Stacey Gejman, Pablo Guttmacher, Alan Harris, Emily L. Insel, Thomas Kelsoe, John R. Lander, Eric McCowin, Norma Mailman, Matthew D. Nabel, Elizabeth Ostell, James Pugh, Elizabeth Sherry, Stephen Sullivan, Patrick F. Thompson, John F. Warram, James Study, GoKinD Wholley, David Milos, Patrice M. Collins, Francis S. CA Gain Collaborative Res Grp Collaborative Assoc Study Int Multi-Center ADHD Genetics Mol Genetics Schizophrenia Collab Bipolar Genome Study Major Depression Stage 1 Genomewid TI New models of collaboration in genome-wide association studies: the Genetic Association Information Network SO NATURE GENETICS LA English DT Editorial Material ID BREAST-CANCER; SUSCEPTIBILITY; LOCI; VARIANTS; MULTIPLE; LINKAGE; SAMPLE; RISK AB The Genetic Association Information Network ( GAIN) is a public- private partnership established to investigate the genetic basis of common diseases through a series of collaborative genome-wide association studies. GAIN has used new approaches for project selection, data deposition and distribution, collaborative analysis, publication and protection from premature intellectual property claims. These demonstrate a new commitment to shared scientific knowledge that should facilitate rapid advances in understanding the genetics of complex diseases. C1 US NIH, NHGRI, Bethesda, MD 20892 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Perlegen Sci, Mountain View, CA 94043 USA. Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. Univ Oxford, Oxford OX1 3TG, England. SUNY Upstate Med Univ, Syracuse, NY 13210 USA. Scripps Res Inst, La Jolla, CA 92037 USA. Evanston NW Healthcare, Evanston, IL 60201 USA. Northwestern Univ, Evanston, IL 60201 USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Vet Admin San Diego Healthcare Syst, La Jolla, CA 92093 USA. Fdn NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Natl Lib Med, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21224 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. Pfizer Inc, Pharmacogenom Pfizer Global Res & Dev, Groton, CT 06340 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Helicos BioSci Corp, Cambridge, MA 02139 USA. RP Manolio, TA (reprint author), US NIH, NHGRI, 31 Ctr Dr, Bethesda, MD 20892 USA. EM manolio@nih.gov; manolio@nih.gov RI Abecasis, Goncalo/B-7840-2010; OI Abecasis, Goncalo/0000-0003-1509-1825; Thompson, John/0000-0001-8568-3311; Faraone, Stephen/0000-0002-9217-3982 NR 25 TC 200 Z9 207 U1 1 U2 13 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 SEP PY 2007 VL 39 IS 9 BP 1045 EP 1051 DI 10.1038/ng2127 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 205OA UT WOS:000249122400003 ER PT J AU Harley, JB AF Harley, John B. TI IL-7R alpha and multiple sclerosis risk SO NATURE GENETICS LA English DT Editorial Material ID SINGLE NUCLEOTIDE POLYMORPHISMS; GENOMIC CONVERGENCE; CANDIDATE GENES; ASSOCIATIONS; DISEASE AB The discovery of genetic risk factors for multiple sclerosis has proven difficult. IL- 7R alpha, encoded by IL7R, is a pleiomorphic cytokine receptor now implicated in the pathogenesis of multiple sclerosis in independently replicated genetic association studies. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 73104 USA. RP Harley, JB (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM harley@omrf.org NR 14 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2007 VL 39 IS 9 BP 1053 EP 1054 DI 10.1038/ng0907-1053 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 205OA UT WOS:000249122400004 PM 17728770 ER PT J AU Lee-Kirsch, MA Gong, M Chowdhury, D Senenko, L Engel, K Lee, YA de Silva, U Bailey, SL Witte, T Vyse, TJ Kere, J Pfeiffer, C Harvey, S Wong, A Koskenmies, S Hummel, O Rohde, K Schmidt, RE Dominiczak, AF Gahr, M Hollis, T Perrino, FW Lieberman, J Hubner, N AF Lee-Kirsch, Min Ae Gong, Maolian Chowdhury, Dipanjan Senenko, Lydia Engel, Kerstin Lee, Young-Ae de Silva, Udesh Bailey, Suzanna L. Witte, Torsten Vyse, Timothy J. Kere, Juha Pfeiffer, Christiane Harvey, Scott Wong, Andrew Koskenmies, Sari Hummel, Oliver Rohde, Klaus Schmidt, Reinhold E. Dominiczak, Anna F. Gahr, Manfred Hollis, Thomas Perrino, Fred W. Lieberman, Judy Huebner, Norbert TI Mutations in the gene encoding the 3 '-5 ' DNA exonuclease TREX1 are associated with systemic lupus erythematosus SO NATURE GENETICS LA English DT Article ID AICARDI-GOUTIERES-SYNDROME; NUCLEAR-BODIES; MICE AB TREX1 acts in concert with the SET complex in granzyme A - mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutieres syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/ 417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P= 4.1x10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE. C1 Tech Univ Dresden, Klin Kinder & Jugendmed, D-01307 Dresden, Germany. Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. Harvard Univ, Sch Med, Dept Pediat, CBR Inst Biomed Res, Boston, MA 02125 USA. Charite Univ Med Berlin, D-13353 Berlin, Germany. Wake Forest Univ Hlth Sci, Dept Biochem, Ctr Struct Biol, Winston Salem, NC 27157 USA. Hannover Med Sch, Klin Immunol, D-30625 Hannover, Germany. Hammersmith Hosp, Imperial Coll, Fac Med, Sect Rheumatol & Mol Genet, London W12 0NN, England. Karolinska Inst, Dept Biosci & Nutr, S-14157 Huddinge, Sweden. Clin Res Ctr, S-14157 Huddinge, Sweden. Tech Univ Dresden, Dermatol Klin, D-01307 Dresden, Germany. Wake Forest Univ Hlth Sci, Dept Biochem, Winston Salem, NC 27157 USA. Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Dermatol, FIN-00014 Helsinki, Finland. Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland. RP Lee-Kirsch, MA (reprint author), Tech Univ Dresden, Klin Kinder & Jugendmed, D-01307 Dresden, Germany. EM minae.lee-kirsch@uniklinikum-dresden.de; nhuebner@mdc-berlin.de RI Kere, Juha/A-9179-2008; Dominiczak, Anna/D-2262-2009; Lieberman, Judy/A-2717-2015; Witte, Torsten/B-5783-2016; Wong, Andrew/M-8899-2016 OI Kere, Juha/0000-0003-1974-0271; Wong, Andrew/0000-0003-2079-4779 FU NIAID NIH HHS [AI45587]; NIGMS NIH HHS [GM069962] NR 15 TC 301 Z9 311 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2007 VL 39 IS 9 BP 1065 EP 1067 DI 10.1038/ng2091 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 205OA UT WOS:000249122400013 PM 17660818 ER PT J AU Norman, PJ Abi-Rached, L Gendzekhadze, K Korbel, D Gleimer, M Rowley, D Bruno, D Carrington, CVF Chandanayingyong, D Chang, YH Crespi, C Saruhan-Direskeneli, G Fraser, PA Hameed, K Kamkamidze, G Koram, KA Layrisse, Z Matamoros, N Mila, J Park, MH Pitchappan, RM Ramdath, DD Shiau, MY Stephens, HAF Struik, S Verity, DH Vaughan, RW Tyan, D Davis, RW Riley, EM Ronaghi, M Parham, P AF Norman, Paul J. Abi-Rached, Laurent Gendzekhadze, Ketevan Korbel, Daniel Gleimer, Michael Rowley, Don Bruno, Dan Carrington, Christine V. F. Chandanayingyong, Dasdayanee Chang, Yih-Hsin Crespi, Catalina Saruhan-Direskeneli, Gueher Fraser, Patricia A. Hameed, Kamran Kamkamidze, Giorgi Koram, Kwadwo A. Layrisse, Zulay Matamoros, Nuria Mila, Joan Park, Myoung Hee Pitchappan, Ramasamy M. Ramdath, D. Dan Shiau, Ming-Yuh Stephens, Henry A. F. Struik, Siske Verity, David H. Vaughan, Robert W. Tyan, Dolly Davis, Ronald W. Riley, Eleanor M. Ronaghi, Mostafa Parham, Peter TI Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans SO NATURE GENETICS LA English DT Article ID IMMUNOGLOBULIN-LIKE RECEPTOR; MHC CLASS-I; HLA-B; CRYSTAL-STRUCTURE; HUMAN GENOME; CUTTING EDGE; NK CELLS; COMPLEX; GENES; POLYMORPHISMS AB Interactions of killer cell immunoglobulin- like receptors ( KIRs) with major histocompatibility complex ( MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/ S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of HLA- A and HLA- B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA- B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/ S1 evolution in modern sub- Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression. C1 Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. Stanford Univ, Sch Med, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. Univ W Indies, Fac Med Sci, Dept Preclin Sci, St Augustine, Trinid & Tobago. Mahidol Univ, Fac Med, Dept Transfus Med, Bangkok 10700, Thailand. Mahidol Univ, Siriraj Hosp, Bangkok 10700, Thailand. Chung Shan Med Univ, Sch Med Lab & Biotechnol, Taichung 402, Taiwan. Hosp Univ Son Dureta, Serv Immunol, Palma de Mallorca 07014, Spain. Istanbul Univ, Dept Physiol, Fac Med, Istanbul, Turkey. CBR, Biomed Res Inst, Boston, MA 02115 USA. Aga Khan Univ Hosp, Dept Med, Karachi, Pakistan. REA Ctr, Dept Clin Immunol, GE-0160 Tbilisi, Rep of Georgia. Univ Ghana, Noguchi Mem Inst Med Res, Legon, Ghana. IVIC, Ctr Expt Med Miguel Layrisse, Caracas 21827, Venezuela. Seoul Natl Univ, Coll Med, Dept Lab Med, Seoul 110744, South Korea. Madurai Kamaraj Univ, Sch Biol Sci, Ctr Adv Studies Funct Genom, Madurai 625021, Tamil Nadu, India. Hungkuang Univ, Inst Technol, Taichung 433, Taiwan. Royal Free & Unic Coll Med Sch, Ctr Nephrol & Anthony Nolan Trust, London NW3 2QG, England. Moorfields Eye Hosp, London EC1V 2PD, England. Guys & St Thomas Fdn Trust, Clin Transplantat Lab, London SE1 9RT, England. Kings Coll London, London SE1 9RT, England. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. RP Norman, PJ (reprint author), Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. EM paul.norman@stanford.edu; peropa@stanford.edu RI Abi-Rached, Laurent/H-7236-2012; Park, Myoung Hee/J-5483-2012; Riley, Eleanor/C-8960-2013; Crespi, Catalina/A-5543-2013; OI Riley, Eleanor/0000-0003-3447-3570; Crespi, Catalina/0000-0003-0781-9708; Korbel, Daniel/0000-0002-4682-9928 FU NIAID NIH HHS [AI17892, AI24258, AI64520] NR 49 TC 132 Z9 136 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2007 VL 39 IS 9 BP 1092 EP 1099 DI 10.1038/ng2111 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 205OA UT WOS:000249122400018 PM 17694054 ER PT J AU Choi, W Fang-Yen, C Badizadegan, K Oh, S Lue, N Dasari, RR Feld, MS AF Choi, Wonshik Fang-Yen, Christopher Badizadegan, Kamran Oh, Seungeun Lue, Niyom Dasari, Ramachandra R. Feld, Michael S. TI Tomographic phase microscopy SO NATURE METHODS LA English DT Article ID DIGITAL HOLOGRAPHIC MICROSCOPY; REFRACTIVE-INDEX; RESOLUTION; CELLS AB We report a technique for quantitative three-dimensional (3D) mapping of refractive index in live cells and tissues using a phase-shifting laser interferometric microscope with variable illumination angle. We demonstrate tomographic imaging of cells and multicellular organisms, and time-dependent changes in cell structure. Our results will permit quantitative characterization of specimen-induced aberrations in high-resolution microscopy and have multiple applications in tissue light scattering. C1 MIT, GR Harrison Spectroscopy Lab, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Feld, MS (reprint author), MIT, GR Harrison Spectroscopy Lab, 77 Massachusetts Ave 6-014, Cambridge, MA 02139 USA. EM msfeld@mit.edu OI Fang-Yen, Christopher/0000-0002-4568-3218 FU NCRR NIH HHS [P41-RR02594-18] NR 15 TC 345 Z9 351 U1 11 U2 74 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD SEP PY 2007 VL 4 IS 9 BP 717 EP 719 DI 10.1038/NMETH1078 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 209MG UT WOS:000249392000018 PM 17694065 ER PT J AU Hillman, EMC Moore, A AF Hillman, Elizabeth M. C. Moore, Anna TI All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast SO NATURE PHOTONICS LA English DT Article ID IN-VIVO DETECTION; FLUORESCENCE; TOMOGRAPHY; PROBE; MICE; VISUALIZATION; TISSUE; TUMORS; TIME AB Optical molecular imaging in small animals harnesses the power of highly specific and biocompatible contrast agents for drug development and disease research(1-7). However, the widespread adoption of in vivo optical imaging has been inhibited by its inability to clearly resolve and identify targeted internal organs. Optical tomography(8-11) and combined X-ray and micro-computed tomography (micro-CT)(12) approaches developed to address this problem are generally expensive, complex or incapable of true anatomical co-registration. Here, we present a remarkably simple all-optical method that can generate co-registered anatomical maps of a mouse's internal organs, while also acquiring in vivo molecular imaging data. The technique uses a time series of images acquired after injection of an inert dye. Differences in the dye's in vivo biodistribution dynamics allow precise delineation and identification of major organs. Such co-registered anatomical maps permit longitudinal organ identification irrespective of repositioning or weight gain, thereby promising greatly improved accuracy and versatility for studies of orthotopic disease, diagnostics and therapies. C1 Columbia Univ, Dept Biomed Engn, Lab Funct Opt Imaging, New York, NY 10027 USA. Massachusetts Gen Hosp, HMS Athinoula A Martinos Ctr Biomed Imaging, MIT, MGH,Mol Imaging Lab, Charlestown, MA 02129 USA. RP Hillman, EMC (reprint author), Columbia Univ, Dept Biomed Engn, Lab Funct Opt Imaging, 1210 Amsterdam Ave, New York, NY 10027 USA. EM eh2245@columbia.edu RI Hillman, Elizabeth/B-9854-2009; OI Hillman, Elizabeth M. C./0000-0001-5511-1451 FU NCI NIH HHS [U54 CA126513]; NIDDK NIH HHS [R01 DK064850, R01 DK064850-01, R01 DK072137, R01 DK072137-01A1, R21 DK071225, R21 DK071225-01] NR 30 TC 109 Z9 109 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1749-4885 J9 NAT PHOTONICS JI Nat. Photonics PD SEP PY 2007 VL 1 IS 9 BP 526 EP 530 DI 10.1038/nphoton.2007.146 PG 5 WC Optics; Physics, Applied SC Optics; Physics GA 212PK UT WOS:000249609100018 PM 18974848 ER PT J AU Levine, RL Pardanani, A Tefferi, A Gilliland, DG AF Levine, Ross L. Pardanani, Animesh Tefferi, Ayalew Gilliland, D. Gary TI Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders SO NATURE REVIEWS CANCER LA English DT Review ID STEM-CELL TRANSPLANTATION; CHRONIC MYELOMONOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE MUTATION; CHRONIC MYELOID-LEUKEMIA; CAUSE NOONAN-SYNDROME; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; V617F MUTATION; BCR-ABL AB The myeloproliferative disorders polycythaemia vera (PV), essential thombocythaemia (ET), and primary myelofibrosis (PMF) are clonal disorders of multipotent haematopoietic progenitors. The genetic cause of these diseases was not known until 2005, when several independent groups demonstrated that most patients with PV, ET and PMF acquire a single point mutation in the cytoplasmic tyrosine kinase JAK2 ( JAK2V617F). These discoveries have changed the landscape for diagnosis and classification of PV, ET and PMF, and show the ability of genomic technologies to identify new molecular targets in human malignancies with pathogenetic, diagnostic and therapeutic significance. C1 Mayo Clin, Div Hematol, Rochester, MN 55905 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02155 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. Broad Inst Harvard, Boston, MA 02115 USA. MIT, Cambridge Ctr 7, Boston, MA 02115 USA. RP Tefferi, A (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayakew@Mayo.edu; ggilliland@rics.bwh.harvard.edu NR 112 TC 281 Z9 291 U1 2 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD SEP PY 2007 VL 7 IS 9 BP 673 EP 683 DI 10.1038/nrc2210 PG 11 WC Oncology SC Oncology GA 203ZN UT WOS:000249012700014 PM 17721432 ER PT J AU Faivre, S Demetri, G Sargent, W Raymond, E AF Faivre, Sandrine Demetri, George Sargent, William Raymond, Eric TI Molecular basis for sunitinib efficacy and future clinical development SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID TYROSINE KINASE INHIBITOR; GASTROINTESTINAL STROMAL TUMORS; RENAL-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; ENDOTHELIAL PROGENITOR CELLS; MALATE SU11248; PHASE-II; BREAST-CANCER; PATIENTS PTS; LUNG-CANCER AB Sunitinib malate (SU11248/ Sutent; Pfizer) is a multitargeted tyrosine kinase inhibitor that has potent anti-angiogenic and antitumour activities. Definitive efficacy has been demonstrated in advanced renal cell carcinoma and in gastrointestinal stromal tumours that are refractory or intolerant to imatinib (Gleevec; Novartis), which has provided the basis for the recent regulatory approvals for these indications. This article summarizes the discovery and development of sunitinib, and discusses key issues for the multitargeted approach in cancer treatment, such as markers of response and development of resistance, and their significance for the future development of sunitinib and other multikinase inhibitors. C1 Hop Beaujon, APHP, SIHC, Beaujon Bichat & RayLab, F-92118 Clichy, France. Denis Diderot Univ, F-92118 Clichy, France. Ludwig Ctr Dana Farber Harvard, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Pfizer Inc, New York, NY 10017 USA. RP Raymond, E (reprint author), Hop Beaujon, APHP, SIHC, Beaujon Bichat & RayLab, 100 Blvd Gen Leclerc, F-92118 Clichy, France. EM eric.raymond@bjn.aphp.fr NR 63 TC 379 Z9 393 U1 3 U2 53 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2007 VL 6 IS 9 BP 734 EP 745 DI 10.1038/nrd2380 PG 12 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 207FG UT WOS:000249236400018 PM 17690708 ER PT J AU Russell, SJ Kahn, CR AF Russell, Steven J. Kahn, C. Ronald TI Endocrine regulation of ageing SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID ELEGANS LIFE-SPAN; TRANSCRIPTION FACTOR FOXO1; RANDOMIZED CONTROLLED-TRIAL; PANCREATIC BETA-CELLS; CAENORHABDITIS-ELEGANS; C-ELEGANS; INSULIN-RECEPTOR; OXIDATIVE STRESS; ADIPOSE-TISSUE; DROSOPHILA-MELANOGASTER AB Over the past 15 years it has become clear that mutations in genes that regulate endocrine signalling pathways can prolong lifespan. Lifespan can be increased by altered endocrine signalling in a group of cells or a single tissue, which indicates that crosstalk between tissues functions to coordinate ageing of the organism. These endocrine pathways might serve as targets for the manipulation of the ageing process and prevention of age-related diseases. RP Russell, SJ (reprint author), Harvard Univ, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. EM steven.russell@joslin.harvard.edu; c.ronald.kahn@joslin.harvard.edu NR 131 TC 198 Z9 208 U1 6 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD SEP PY 2007 VL 8 IS 9 BP 681 EP 691 DI 10.1038/nrm2234 PG 11 WC Cell Biology SC Cell Biology GA 203ZP UT WOS:000249012900008 PM 17684529 ER PT J AU Sharpless, NE Depinho, RA AF Sharpless, Norman E. Depinho, Ronald A. TI How stem cells age and why this makes us grow old SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID MURINE HEMATOPOIETIC STEM; GENOME-WIDE ASSOCIATION; BONE-MARROW-TRANSPLANTATION; TELOMERE DYSFUNCTION; LIFE-SPAN; PROGENITOR CELLS; SELF-RENEWAL; HUMAN FIBROBLASTS; MULTIPLE-MYELOMA; OXIDATIVE STRESS AB Recent data suggest that we age, in part, because our self-renewing stem cells grow old as a result of heritable intrinsic events, such as DNA damage, as well as extrinsic forces, such as changes in their supporting niches. Mechanisms that suppress the development of cancer, such as senescence and apoptosis, which rely on telomere shortening and the activities of p53 and p16(INK4a), may also induce an unwanted consequence: a decline in the replicative function of certain stem-cell types with advancing age. This decreased regenerative capacity appears to contribute to some aspects of mammalian ageing, with new findings pointing to a 'stem-cell hypothesis' for human age-associated conditions such as frailty, atherosclerosis and type 2 diabetes. C1 Univ N Carolina, Dept Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci, Ctr Appl Canc Sci, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Sharpless, NE (reprint author), Univ N Carolina, Dept Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM ron_depinho@dfci.harvard.edu; nes@med.unc.edu NR 126 TC 441 Z9 459 U1 14 U2 77 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD SEP PY 2007 VL 8 IS 9 BP 703 EP 713 DI 10.1038/nrm2241 PG 11 WC Cell Biology SC Cell Biology GA 203ZP UT WOS:000249012900010 PM 17717515 ER PT J AU Schacter, DL Addis, DR Buckner, RL AF Schacter, Daniel L. Addis, Donna Rose Buckner, Randy L. TI Remembering the past to imagine the future: the prospective brain SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID WESTERN SCRUB-JAYS; MENTAL TIME-TRAVEL; AUTOBIOGRAPHICAL MEMORY; TEMPORAL ORGANIZATION; THINKING; MIND; RETRIEVAL; NETWORK; MODEL AB A rapidly growing number of recent studies show that imagining the future depends on much of the same neural machinery that is needed for remembering the past. These findings have led to the concept of the prospective brain; an idea that a crucial function of the brain is to use stored information to imagine, simulate and predict possible future events. We suggest that processes such as memory can be productively re- conceptualized in light of this idea. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Schacter, DL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM dls@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061; Addis, Donna Rose/0000-0002-6231-1491 NR 45 TC 708 Z9 718 U1 15 U2 127 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD SEP PY 2007 VL 8 IS 9 BP 657 EP 661 DI 10.1038/nrn2213 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 201PX UT WOS:000248846200012 PM 17700624 ER PT J AU Nummenmaa, A Auranen, T Hamalainen, MS Jaaskelainen, IP Sams, M Vehtari, A Lampmen, J AF Nummenmaa, Aapo Auranen, Toni Haemaelaeinen, Matti S. Jaeaeskelaeinen, Iiro P. Sams, Mikko Vehtari, Aki Lampmen, Jouko TI Automatic relevance determination based hierarchical Bayesian MEG inversion in practice SO NEUROIMAGE LA English DT Article DE MEG; inverse problem; hierarchical modeling; Variational Bayes; automatic relevance determination ID CORTICAL ACTIVITY; MODEL AB In recent simulation studies, a hierarchical Variational Bayesian (VB) method, which can be seen as a generalisation of the traditional minimum-norm estimate (MNE), was introduced for reconstructing distributed MEG sources. Here, we studied how nonlinearities in the estimation process and hyperparameter selection affect the inverse solutions, the feasibility of a full Bayesian treatment of the hyperparameters, and multimodality of the true posterior, in an empirical dataset wherein a male subject was presented with pure tone and checkerboard reversal stimuli, alone and in combination. An MRI-based cortical surface model was employed. Our results show, with a comparison to the basic MINE, that the hierarchical VB approach yields robust and physiologically plausible estimates of distributed sources underlying MEG measurements, in a rather automated fashion. (c) 2007 Elsevier Inc. All rights reserved. C1 Helsinki Univ Technol, Lab Computat Engn, FIN-02150 Espoo, Finland. Helsinki Univ Technol, Adv Magnet Imaging Ctr, FIN-02150 Espoo, Finland. Helsinki Univ Technol, Low Temp Lab, Brain Res Unit, FIN-02150 Espoo, Finland. MIT, Harvard Mit Div Hlth Sci & Technol, Massachusetts Gen Hosp, Sch Med,Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02139 USA. RP Nummenmaa, A (reprint author), Helsinki Univ Technol, Lab Computat Engn, FIN-02150 Espoo, Finland. EM Aapo.Nummenmaa@hut.fi RI Auranen, Toni/J-7137-2012; Jaaskelainen, Iiro/C-7392-2012; Sams, Mikko/G-7060-2012; Vehtari, Aki/A-7584-2008; Hamalainen, Matti/C-8507-2013; Lampinen, Jouko/D-3927-2014 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Vehtari, Aki/0000-0003-2164-9469; FU NCRR NIH HHS [P41 RR014075, P41 RR014075-075760, P41RR14075]; NICHD NIH HHS [5R01HD040712-04, R01 HD040712, R01 HD040712-04]; NINDS NIH HHS [5R01NS044319-04, R01 NS044319, R01 NS044319-04] NR 25 TC 19 Z9 19 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP 1 PY 2007 VL 37 IS 3 BP 876 EP 889 DI 10.1016/j.neuroimage.2007.04.021 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 206BZ UT WOS:000249160200017 PM 17627847 ER PT J AU Seidman, LJ Thermenos, HW Koch, JK Ward, M Breiter, H Goldstein, JM Goodman, JM Faraone, SV Tsuang, MT AF Seidman, Larry J. Thermenos, Heidi W. Koch, Jennifer K. Ward, Michael Breiter, Hans Goldstein, Jill M. Goodman, Julie M. Faraone, Stephen V. Tsuang, Ming T. TI Auditory verbal working memory load and thalamic activation in nonpsychotic relatives of persons with schizophrenia: An fMRI replication SO NEUROPSYCHOLOGY LA English DT Review DE schizophrenia; genetics; functional MRI; working memory; thalamus ID ANTERIOR CINGULATE CORTEX; DORSOLATERAL PREFRONTAL CORTEX; CONTINUOUS PERFORMANCE-TEST; STROOP TASK-PERFORMANCE; NEUROPSYCHOLOGICAL FUNCTION; VULNERABILITY INDICATOR; BIOLOGICAL RELATIVES; 1ST-DEGREE RELATIVES; SUSTAINED ATTENTION; PREPULSE INHIBITION AB First-degree relatives of persons with schizophrenia are at genetic risk for the illness and show deficits on high-load information-processing tasks. In a prior study of auditory working memory (WM) using functional MR1 (fMRI), the authors demonstrated that adult relatives had significantly increased activation in the dorsomedial (DM) thalamus, anterior cingulate, and prefrontal cortex (H, W. Thermenos et al., 2004). In this study, the authors extended this work using a parametric WM task designed for fMRI in an independent, unmedicated sample. Twelve norpsychotic relatives of persons with schizophrenia and 13 healthy controls were administered multiple versions of an auditory continuous performance test during fMRI. Data were analyzed using Statistical Parametric Mapping software. Compared with controls, relatives showed significantly greater task-elicited activation in the DM thalamus. When fMRI C1 Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Div Publ Psychiat,Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02215 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Connors Ctr Womens Hlth & Gender Biol, Dept Med, Div Womens Hlth, Boston, MA USA. SUNY Upstate Med Univ, Med Genet Res Ctr, New York, NY USA. SUNY Upstate Med Univ, Dept Psychiat, New York, NY USA. Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. RP Seidman, LJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Div Publ Psychiat,Massachusetts Mental Hlth Ctr, 401 Pk Dr, Boston, MA 02215 USA. EM lseidman@bidmc.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [MH 63951, MH 43518, MH-46318, MH65562, R25 MH 60485] NR 103 TC 15 Z9 15 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD SEP PY 2007 VL 21 IS 5 BP 599 EP 610 DI 10.1037/08944105.21.5.599 PG 12 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 205HO UT WOS:000249104800009 PM 17784808 ER PT J AU Oscar-Berman, M Marinkovic, K AF Oscar-Berman, Marlene Marinkovic, Ksenija TI Alcohol: Effects on neurobehavioral functions and the brain SO NEUROPSYCHOLOGY REVIEW LA English DT Review DE alcoholism; frontal lobes; limbic system; cerebellum; right hemisphere ID ANTISOCIAL PERSONALITY-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE SPECTROSCOPY; EMOTIONAL FACIAL EXPRESSION; TERM ABSTINENT ALCOHOLICS; EVENT-RELATED POTENTIALS; SIMULATED GAMBLING TASK; SUBSTANCE USE DISORDERS; CORPUS-CALLOSUM AB Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction. C1 Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Anthinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Oscar-Berman, M (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, L-815,715 Albany St, Boston, MA 02118 USA. EM oscar@bu.edu FU NIAAA NIH HHS [K01 AA013402, K01-AA13402, K05 AA000219, K05-AA00219, R01 AA007112, R01-AA07112] NR 244 TC 194 Z9 201 U1 13 U2 67 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 EI 1573-6660 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD SEP PY 2007 VL 17 IS 3 BP 239 EP 257 DI 10.1007/s11065-007-9038-6 PG 19 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 220FH UT WOS:000250142100005 PM 17874302 ER PT J AU Caplan, JP Epstein, LA Quinn, DK Stevens, JR Stern, TA AF Caplan, Jason P. Epstein, Lucy A. Quinn, Davin K. Stevens, Jonathan R. Stern, Theodore A. TI Neuropsychiatric effects of prescription drug abuse SO NEUROPSYCHOLOGY REVIEW LA English DT Review DE prescription drugs; abuse; sedative-hypnotics; stimulants; anticholinergics; steroids ID ANDROGENIC STEROID USE; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; TERM BENZODIAZEPINE USE; DEFICIT HYPERACTIVITY DISORDER; TRIHEXYPHENIDYL ARTANE ABUSE; UNITED-STATES; ANTICHOLINERGIC DRUGS; NORMAL MEN; SUBSTANCE DEPENDENCE; ANABOLIC-STEROIDS AB Prescription drugs have become a major category of abused substances, and there is evidence that the prevalence of prescription drug abuse may soon overtake that of illicit drugs. Study of prescription drugs has been hampered by vague terminology, since prescription drugs are only separated from other drugs of abuse by social and legal constructs. Reviewed herein is published literature on the abuse of four major categories of abused prescription drugs: sedative-hypnotics, stimulants, anabolic steroids, and anticholinergics. The review emphasizes evidence regarding the effects of these drugs on neural systems. Other abused prescription drugs that fall outside of the major categories are also briefly addressed. C1 UPH Hosp, Behav Hlth Serv, Tucson, AZ USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Arizona, Dept Psychiat, Tucson, AZ USA. RP Caplan, JP (reprint author), UPH Hosp, Behav Hlth Serv, 5th Floor,2800 E Ajo Way, Tucson, AZ USA. EM jcaplan@email.arizona.edu NR 157 TC 28 Z9 31 U1 2 U2 12 PU CONSULTANTS BUREAU/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD SEP PY 2007 VL 17 IS 3 BP 363 EP 380 DI 10.1007/s11065-007-9037-7 PG 18 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 220FH UT WOS:000250142100012 PM 17701457 ER PT J AU Zhang, XY Tan, YL Zhou, DF Haile, CN Wu, GY Cao, LY Kosten, TA Kosten, TR AF Zhang, Xiang Yang Tan, Yun Long Zhou, Dong Feng Haile, Colin N. Wu, Gui Ying Cao, Lian Yuan Kosten, Therese A. Kosten, Thomas R. TI Nicotine dependence, symptoms and oxidative stress in male patients with schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; nicotine; cigarette smoking; oxidative stress; antioxidant enzymes; symptom ID LIPID-PEROXIDATION; PARKINSONS-DISEASE; CIGARETTE-SMOKING; TOBACCO SMOKING; DIFFERENT FORMS; IN-VITRO; ENZYMES; ASSOCIATION; RELEVANCE; DOPAMINE AB The high rate of smoking in schizophrenia may reflect patients' attempts to reduce the side effects of antipsychotic medications, and one mechanism for this reduction may be a reduction in oxidative stress and free radical-mediated brain damage that may contribute to schizophrenic symptoms and to complications of its treatment. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS), side effects were assessed with the Simpson and Angus Rating Scale ( SAS), and malondialdehyde (MDA), superoxide dismutase ( SOD), glutathione peroxidase (GSH- Px) and catalase ( CAT) activities were measured in plasma. All of these measures were compared in 130 male inpatients with DSM-IV schizophrenia: 104 smokers and 26 non-smokers. The results showed that the positive PANSS symptoms were lower in smokers than non-smokers (14.5 vs 17.5), while the negative symptoms were lower in those who smoked more cigarettes (r = -0.23). The SAS showed no differences. The CAT activity was correlated with both GSH- Px and SOD activities. Of the three enzymes only the CAT activity was significantly higher in smokers than non-smokers ( 2.9 vs 1.6 U/ml), but greater SOD activity correlated more cigarettes smoked ( r = 0.24). Consistent with some protection against oxidative stress, MDA also was significantly lower in smokers than non-smokers (9.2 vs 14.4 nmol/ml). The fewer positive symptoms in smokers and fewer negative symptoms in those who smoked more cigarettes may be a selection bias, but appears to be associated with decreased oxidative stress and lipid peroxidation in schizophrenics who smoke tobacco. C1 Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China. Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing, 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. EM xyzhang@bcm.edu; zhoudf@bjmu.edu.cn OI Haile, Colin/0000-0001-8293-7291 FU NIDA NIH HHS [K05 DA 0454, P50 DA 18827] NR 39 TC 24 Z9 26 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2007 VL 32 IS 9 BP 2020 EP 2024 DI 10.1038/sj.npp.1301317 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 200US UT WOS:000248788900017 PM 17228336 ER PT J AU Zhang, J Kawashima, S Yokoyama, M Huang, P Hill, CE AF Zhang, J. Kawashima, S. Yokoyama, M. Huang, P. Hill, C. E. TI Protective effect of endothelial nitric oxide synthase against induction of chemically-induced diabetes in mice SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE eNOS overexpression; alloxan; streptozotocin; type I diabetes ID STIMULATES GLUCOSE-TRANSPORT; SKELETAL-MUSCLE; INHIBITOR SILDENAFIL; CONNEXIN EXPRESSION; INSULIN; ENOS; VASORELAXATION; STREPTOZOTOCIN; HYPERTENSION; LACKING AB Since activation of endothelial nitric oxide synthase has been shown to exert protective effects against the metabolic syndrome, while endothelial nitric oxide synthase knockout mice develop hyperinsulinemia and glucose intolerance, we hypothesised that endothelial nitric oxide might play a protective role against induction of diabetes. The role of endothelial nitric oxide in the development of chemically-induced diabetes has been determined using mice in which the bioavailability of endothelial nitric oxide was either increased, through upregulation of endothelial nitric oxide synthase, or absent, through deletion of endothelial nitric oxide synthase gene. Diabetes was induced intraperitoneally with either a single dose of alloxan, streptozotocin, or multiple low doses of streptozotocin and blood glucose monitored twice a week. The role of cyclic guanosine monophosphate was investigated in wildtype mice by treatment with the phosphodiesterase inhibitor, tadalafil, during diabetes induction. Results showed that the incidence of diabetes was markedly decreased in mice overexpressing endothelial nitric oxide synthase, compared to wildtype or endothelial nitric oxide synthase knockout mice, regardless of the method of diabetes induction. Under normal physiological conditions, or during diabetes induction with alloxan or multiple low doses of streptozotocin, blood glucose was significantly lower in mice overexpressing endothelial nitric oxide synthase compared to wildtype or knockout mice. Treatment with tadalafil had no effect on the incidence or severity of diabetes in wildtype mice. We conclude that upregulation of endothelial nitric oxide synthase exerts a protective action against diabetes induction through a direct effect of nitric oxide, independently of cyclic guanosine monophosphate. (c) 2007 Elsevier Inc. All rights reserved. C1 Australian Natl Univ, John Curtin Sch Med Res, Div Neurosci, Canberra, ACT 2602, Australia. Kobe Univ, Sch Med, Dept Internal Med, Kobe, Hyogo 650, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Hill, CE (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Div Neurosci, Canberra, ACT 2602, Australia. EM caryl.hill@anu.edu.au RI Hill, Caryl/D-8972-2011 NR 21 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD SEP PY 2007 VL 17 IS 2 BP 69 EP 74 DI 10.1016/j.niox.2007.06.001 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 206BB UT WOS:000249157800003 PM 17658282 ER PT J AU Aldredge, LM AF Aldredge, Lakshi M. TI The role of sentinel node biopsy in patients with cutaneous melanoma SO NURSING CLINICS OF NORTH AMERICA LA English DT Article AB The role of sentinel lymph node biopsy (SLNB) as a prognostic indicator in melanoma patients has been controversial in the fields of surgical oncology and dermatology for decades. This minimally invasive surgical technique was introduced in 1990 for diagnosing melanoma lymphatic metastases and has been deemed the standard of surgical care of cutaneous malignant melanoma by the World Health Organization and the Sunbelt Melanoma Clinical Trial. Its usefulness as a prognostic indicator of metastases led to expanded applications for breast, colon, gastric, esophageal, head and neck, thyroid, and lung cancers. This article first provides an overview of cutaneous melanoma and staging methods and treatment modalities. A brief study of the lymphatic system and the SLNB procedure are reviewed, followed by a discussion of its usefulness in patients who have melanoma, including risks and benefits. This article also discusses nursing considerations for patients undergoing the procedure, and patient education tips. Lastly, future indications for SLNB and new prognostic indicators for melanoma are discussed. C1 Portland VA Med Ctr, Serv Dermatol, Portland, OR 97207 USA. RP Aldredge, LM (reprint author), Portland VA Med Ctr, Serv Dermatol, POB 1034, Portland, OR 97207 USA. EM lakshi.aldredge@va.gov NR 14 TC 0 Z9 0 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 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD SEP PY 2007 VL 42 IS 3 BP 379 EP + DI 10.1016/j.cnur.2007.06.001 PG 16 WC Nursing SC Nursing GA 221MX UT WOS:000250233100003 PM 17825660 ER PT J AU Twomey, JG Gallo, AM Knafl, KA Angst, DB FeethaM, S Hadley, E AF Twomey, John G. Gallo, Agatha M. Knafl, Kathleen A. Angst, Denise B. FeethaM, Suzanne Hadley, Emily TI Health professionals' reports about information needs of families who have a child with a genetic condition SO NURSING & HEALTH SCIENCES LA English DT Meeting Abstract C1 [Gallo, Agatha M.; FeethaM, Suzanne; Hadley, Emily] Univ Illinois, Chicago, IL USA. [Twomey, John G.] Massachusetts Gen Hosp, Inst Hlth Prof, Boston, MA 02114 USA. [Angst, Denise B.] Advocate Hlth Care, Park Ridge, IL USA. [Knafl, Kathleen A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1441-0745 J9 NURS HEALTH SCI JI Nurs. Health Sci. PD SEP PY 2007 VL 9 IS 3 BP 238 EP 238 PG 1 WC Nursing SC Nursing GA 272GV UT WOS:000253848800027 ER PT J AU Misra, A Ganda, OP AF Misra, Anoop Ganda, Om P. TI Migration and its impact on adiposity and type 2 diabetes SO NUTRITION LA English DT Review DE migration; type 2 diabetes; obesity; physical activity; nutrition; ethnicity ID CORONARY-HEART-DISEASE; INSULIN-RESISTANCE-SYNDROME; IMPAIRED GLUCOSE-TOLERANCE; ASIAN INDIAN ADOLESCENTS; TOKELAU-ISLAND MIGRANT; BODY-FAT DISTRIBUTION; RISK-FACTORS; METABOLIC SYNDROME; UNITED-STATES; JAPANESE-AMERICANS AB In this review, we discuss the impact of migration on the incidence and prevalence of obesity and type 2 diabetes mellitus (T2DM) in different ethnic groups and populations. We also analyze the determinants of such phenomena in view of the global increase in the migration and escalating prevalence of obesity and T2DM. The risk escalation of the obesity and T2DM followed a gradient, as migrants (Blacks, Hispanics, Chinese, South Asians, etc.) became more affluent and urbanized, indicating an important role of environmental factors. A stepwise increase in the prevalence of obesity in Blacks along the path of migration (5% in Nigeria, 23% in Jamaica, and 39% in the United States) is a classic example. Furthermore, South Asian migrants, who are particularly predisposed to develop insulin resistance and T2DM, showed nearly four times prevalence rates of T2DM than rural sedentee populations. Similar observations were also reported in intracountry migrants and resettled indigenous populations. The determinants were found to include nutrition transition, physical inactivity, gene-environment interaction, stress, and other factors such as ethnic susceptibility. However, certain contradictory trends were also seen in some migrant communities and have been explained by various phenomena such as healthy migrant effect, "salmon bias", and adherence to traditional diets. A review of the evidence suggests a critical role of environmental factors in conferring an increased risk of obesity and T2DM. The important contributory factors to this phenomenon were urbanization, mechanization, and changes in nutrition and lifestyle behaviors, but the role of stress and asyet unknown factors remain to be determined. (c) 2007 Elsevier Inc. All rights reserved. C1 Fortis Hosp, Dept Diabet & Metab Dis, New Delhi, India. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Misra, A (reprint author), Fortis Hosp, Dept Diabet & Metab Dis, New Delhi, India. EM anoopmisra@metabolicresearchindia.com FU NHLBI NIH HHS [HL73168-02]; NIDDK NIH HHS [DK 60115-02] NR 119 TC 125 Z9 127 U1 5 U2 38 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD SEP PY 2007 VL 23 IS 9 BP 696 EP 708 DI 10.1016/j.nut.2007.06.008 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 198ZT UT WOS:000248666700010 PM 17679049 ER PT J AU Lieber, CS Leo, MA Cao, Q Mak, KM Ren, CL Ponomarenko, A Wang, XL DeCarli, LM AF Lieber, Charles S. Leo, Maria A. Cao, Qi Mak, Ki M. Ren, Chaoling Ponomarenko, Anatoly Wang, Xiaolei DeCarli, Leonore M. TI The combination of S-adenosylmethionine and dilinoleoylphosphatidylcholine attenuates nonalcoholic steatohepatitis produced by a high-fat diet in rats SO NUTRITION RESEARCH LA English DT Article DE nonalcoholic steatohepatitis; fat; S-adenosylmethionine; dilinoleoylphosphatidylcholine; rats ID ALCOHOLIC LIVER-DISEASE; ADENOSYL-L-METHIONINE; HEPATIC STELLATE CELLS; INJURY; DLPC; INTERVENTION; HEPATOCYTES; EXPRESSION; INDUCTION; THERAPY AB In the pathogenesis of nonalcoholic steatohepatitis (NASH), oxidative stress resulting from free radicals generated by cytochrome P4502E1 (CYP2E1) plays a major role suggesting the importance of antioxidants. The objective of this study was to assess in a high-fat (HF) diet rat model the effects of the combination of S-adenosylmethionine (SAMe) plus dilinoleoylphosphatidylcholine (DLPC) in the treatment of NASH. To test the hypothesis that these 2 antioxidants are beneficial in NASH, male Sprague-Dawley rats were fed 5 different diets for 6 weeks: control, HF diet and HF plus, SAMe, and DLPC or their combination. As expected, the HF diet significantly increased hepatic triacylglycerols and CYP2E1 levels. However, only the combination diet opposed this effect, consistent with different actions of the 2 antioxidants. Next, 24 additional rats divided in 2 groups were fed the HF or the HF + SAMe + DLPC diets for 3 weeks. Dietary intake was similar, but liver triacylglycerols dropped from 76.1 +/- 6.8 to 49.4 +/- 3.5 mg/g (P = .002), and hepatic CYP2E1 messenger RNA (mRNA) decreased after treatment (P = .01), with a trend for less CYP2E1 protein. This was accompanied by a 41% reduction of hepatic 4-hydroxynonenal (P = .008), reflecting control of oxidative stress. Furthermore, the hepatic inflammatory cytokine tumor necrosis factor alpha mRNA and tumor necrosis factor alpha protein decreased (P = .05 and P = .01, respectively) with attenuation of alpha 1(I) procollagen mRNA and type I collagen levels (P = .01 and P = .02, respectively). We concluded that the combination SAMe + DLPC might be beneficial in NASH by reducing oxidative stress and associated liver injury. (c) 2007 Elsevier Inc. All rights reserved. C1 Mt Sinai Sch Med, James J Peters VA Med Ctr, Ctr Alcohol Res & Treatment, Sect Liver Dis & Nutr, Bronx, NY 10468 USA. RP Lieber, CS (reprint author), Mt Sinai Sch Med, James J Peters VA Med Ctr, Ctr Alcohol Res & Treatment, Sect Liver Dis & Nutr, Bronx, NY 10468 USA. EM liebercs@aol.com FU NCCIH NIH HHS [R01 AT001583, R01 AT001583-04] NR 36 TC 15 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD SEP PY 2007 VL 27 IS 9 BP 565 EP 573 DI 10.1016/j.nutres.2007.07.005 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 210UB UT WOS:000249480000008 PM 18769506 ER PT J AU Gragnoli, C Cronsell, J AF Gragnoli, Claudia Cronsell, Jennifer TI PPAR gamma P12A variant in type 2 diabetes in Italians SO OBESITY AND METABOLISM-MILAN LA English DT Article DE association; Italian; PPAR gamma P12A; type 2 diabetes ID PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA-2; PPAR-GAMMA GENE; PRO12ALA POLYMORPHISM; ASSOCIATION; RISK; P12A C1 [Gragnoli, Claudia] Bios Multidiagnost Biotech & Res Fdn, I-00197 Rome, Italy. [Gragnoli, Claudia; Cronsell, Jennifer] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gragnoli, Claudia; Cronsell, Jennifer] Harvard Univ, Sch Med, Boston, MA USA. [Gragnoli, Claudia] Univ Roma Tor Vergata, Rome, Italy. RP Gragnoli, C (reprint author), Bios Multidiagnost Biotech & Res Fdn, Via Chelini 20, I-00197 Rome, Italy. EM Claudia.Gragnoli@gmail.com FU Bios Multi-Diagnostic Biotech; Research Foundation in Rome; Rotary Foundation International; NIH Training Program in Endocrinology and Diabetes [DK07028]; Massachusetts General Hospital, Boston, MA [DK30834] FX We thank the entire network of medical and nursing staff of private, public and academic clinical centers from center of Italy for their contribution to recruitment of T2D patients, families and control subjects. A special thank goes to the medical, nursing, molecular biology and administrative staff of Bios Multi-Diagnostic Biotech and Research Foundation in Rome for their precious help with the recruitment, blood withdrawal, DNA extraction and generous financial support. We thank Dr. Ethan Lange of the University of North Carolina, Chapel Hill, NC for statistical advice. CG expresses deep gratitude to the Rotary Foundation International for supporting genetic studies of T2D in Italians. CG has received support by NIH Training Program in Endocrinology and Diabetes DK07028 grant for the genetic studies of T2D in Italians. This study was supported in part by NIH grant DK30834 of Dr. Joel Habener at Massachusetts General Hospital, Boston, MA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1825-3865 J9 OBES METAB-MILAN JI Obes. Metab.-Milan PD SEP PY 2007 VL 3 IS 3 BP 99 EP 100 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 339HK UT WOS:000258568500001 ER PT J AU Lipton, A Cook, RJ Major, P Smith, MR Coleman, RE AF Lipton, Allan Cook, Richard J. Major, Pierre Smith, Matthew R. Coleman, Robert E. TI Zoledronic acid and survival in breast cancer patients with bone Metastases and elevated markers of osteoclast activity SO ONCOLOGIST LA English DT Article DE biologic markers; breast neoplasms; survival rate; zoledronic acid ID SKELETAL COMPLICATIONS; DOUBLE-BLIND; PAMIDRONATE DISODIUM; BIOCHEMICAL MARKERS; MULTIPLE-MYELOMA; PREDICTIVE-VALUE; SOLID TUMORS; DISEASE; TURNOVER; WOMEN AB Objective. Most breast cancer patients with bone metastases will receive bisphosphonate treatment. This post hoc analysis investigated whether early normalization of urinary N-telopeptide of type I collagen (NTX) levels during bisphosphonate therapy correlates with a long-term reduction in skeletal-related event (SRE) risk and mortality in patients with breast cancer. Methods. This was a retrospective subset analysis of a phase III randomized trial comparing i.v. zoledronic acid with pamidronate treatment in patients with bone metastases from breast cancer or multiple myeloma. Patients with breast cancer who had NTX assessments at baseline and at months I and 3 (n = 342) were classified as normal (NTX < 64 nmol/mmol creatinine) or elevated (NTX :64 nmol/mmol creatinine). The relative risk for an SRE or death was estimated with Cox regression models. Results. Among the 328 evaluable patients treated with zoledronic acid, 196 patients (59.7%) had elevated baseline NTX, with 149 of those patients (76.0%) having normalized NTX levels and 31 patients (15.8%) having persistently elevated NTX levels at 3 months. The normalized NTX group had significantly lower risks for a first SRE, a first fracture or surgery to bone, or death than the group that had persistently elevated NTX levels. Conclusions. These results suggest that early normalization of elevated baseline NTX while receiving zoledronic acid is associated with longer event-free and overall survival times compared with persistently elevated NTX. Further analyses in cancer patients with elevated marker levels are warranted to confirm the implications of these findings. C1 Milton S Hershey Med Ctr, Penn State Canc Inst, Hershey, PA 17033 USA. Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Univ Sheffield, Weston Pk Hosp, Canc Res Ctr, Sheffield, S Yorkshire, England. RP Lipton, A (reprint author), Milton S Hershey Med Ctr, Penn State Canc Inst, 500 Univ Dr, Hershey, PA 17033 USA. EM alipton@psu.edu NR 27 TC 74 Z9 79 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 SEP PY 2007 VL 12 IS 9 BP 1035 EP 1043 DI 10.1637/theoncologist.12-9-1035 PG 9 WC Oncology SC Oncology GA 217BZ UT WOS:000249924700001 PM 17914073 ER PT J AU Penson, RT Gu, F Harris, S Thiel, MM Lawton, N Fuller, AF Lynch, TJ AF Penson, Richard T. Gu, Fei Harris, Susan Thiel, Mary Martha Lawton, Nat Fuller, Arlan F., Jr. Lynch, Thomas J., Jr. TI Hope SO ONCOLOGIST LA English DT Article DE oncology; support; psychosocial; cancer ID METASTATIC BREAST-CANCER; DECISION-MAKING; GROUP-THERAPY; INFORMATION NEEDS; PATIENTS VIEWS; SURVIVAL; CARE; PROGNOSIS; STRESS; HEALTH AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. A patient with recurrent ovarian cancer, now in a 12-year remission after recurrence, and her surgeon, discussed their experiences and feelings around the hopes and fears of cancer and its treatment. Hope sustains many through dark times, and is at the core of the wonderful resilience of many who wrestle with cancer. Concerns about false hope, unrealistic expectations, assumptions, engaging in realistic hopefulness, and the joys and stresses embodied in hope and how they frame the caregiver-patient relationship are discussed. The literature and limited evidence base are reviewed. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Yawkey 9066,55 Fruit St, Boston, MA 02114 USA. EM rpenson@partners.org NR 42 TC 10 Z9 12 U1 2 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD SEP PY 2007 VL 12 IS 9 BP 1105 EP 1113 DI 10.1634/theoncologist.12-9-1105 PG 9 WC Oncology SC Oncology GA 217BZ UT WOS:000249924700008 PM 17914080 ER PT J AU Ozbaydar, M Chung, S Diller, D Warner, JJP AF Ozbaydar, M. Chung, S. Diller, D. Warner, J. J. P. TI Arthroscopic reconstruction of the rotator cuff SO ORTHOPADE LA English DT Article ID FULL-THICKNESS TEARS; 3-DIMENSIONAL REPAIR SITE; DOUBLE-ROW FIXATION; FOLLOW-UP; TENDON; SUPRASPINATUS; DEBRIDEMENT; MANAGEMENT; INTEGRITY; STRENGTH AB Arthroscopic rotator cuff repair has become the gold standard, and is now accepted throughout the world as the method of choice, for rotator cuff repair. As well as an experienced surgeon and meticulously correct arthroscopic technique, careful patient selection and adequate postoperative management are of decisive importance if a good postoperative outcome is to be achieved. With due consideration for all these factors the success rate is over 90%, as measured not only with reference to objective criteria, but also by patients' reports of their how satisfied they are with the result. This paper aims to report the indications, arthroscopic technique and postoperative protocol, and also the results of arthroscopic rotator cuff repair. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Shoulder Serv, Boston, MA 02114 USA. EM jwarner@partners.org RI Ozbaydar, Mehmet/D-7391-2016 NR 32 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0085-4530 J9 ORTHOPADE JI Orthopade PD SEP PY 2007 VL 36 IS 9 BP 825 EP + DI 10.1007/s00132-007-1134-z PG 7 WC Orthopedics SC Orthopedics GA 208HL UT WOS:000249310300006 PM 17701159 ER PT J AU Rubash, HE Parvataneni, HK AF Rubash, Harry E. Parvataneni, Hari K. TI The pants too short, the leg too long: Leg length inequality after THA SO ORTHOPEDICS LA English DT Article ID TOTAL HIP-ARTHROPLASTY; DISCREPANCY C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. RP Rubash, HE (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, 55 Fruit St,Ste 3700, Boston, MA 02114 USA. NR 8 TC 12 Z9 14 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD SEP PY 2007 VL 30 IS 9 BP 764 EP 765 PG 2 WC Orthopedics SC Orthopedics GA 210WM UT WOS:000249486300023 PM 17899929 ER PT J AU Chien, W Rosowski, JJ Merchant, SN AF Chien, Wade Rosowski, John J. Merchant, Saumil N. TI Investigation of the mechanics of type III stapes colurnella tyrnpanoplasty using laser-doppler vibrometry SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT 140th Annual Meeting of the American-Otological-Society CY APR 27-28, 2007 CL San Diego, CA SP Amer Otol Soc DE air-bone gap; laser-doppler vibrometry; middle ear; mechanics; tympanoplasty ID MIDDLE-EAR MECHANICS; TYMPANIC MEMBRANE; TYMPANOPLASTY; COLUMELLA AB Objectives: To investigate the middle ear mechanics of Type III stapes columella tympanoplasty using laser-Doppler vibrometry (LDV) and to determine whether LDV was useful in the identification of structural factors responsible for poor hearing outcomes. Background: The Type III stapes columella tympanoplasty procedure involves placing a tympanic membrane (TM) graft directly onto the stapes head. Postoperative hearing results vary widely, with air-bone gaps (ABGs) ranging from 10 to 60 dB. Methods: Laser-Doppler vibrometry measurements were performed in 22 patients (23 ears) who underwent Type III stapes columella tympanoplasty. The measurements were made at three locations on the TM graft: over the stapes head, over the round window, and on the anterior TM. The LDV results were correlated with the clinical and audiologic findings. Results: The 23 ears were divided into three groups: Nonaerated ears (n = 2). The ABGs were 30 to 60 dB. The TM velocities over all three locations were 20 to 40 dB lower than normal umbo velocity (in normally hearing subjects). Fixed stapes with aerated middle ear (n = 2). The ABGs were 40 to 60 dB, and TM velocities were equivalent to normal umbo velocity in one case and lower by 15 to 20 dB in another case. Mobile stapes and aerated middle ear (n = 19). There were two subgroups in this category: 1) small ABGs less than 25 dB (n = 7) and large gaps greater than or equal to 25 dB (n = 12). There were small differences in TM graft velocity at all three measurement locations between these two subgroups. However, these small differences did not explain the large difference in ABG between the two subgroups. Conclusion: Nonaeration of the middle ear and stapes fixation lead to large residual conductive hearing losses after Type III tympanoplasty. Laser-Doppler vibrometry can aid in the diagnosis of nonaeration of the middle ear but does not readily diagnose stapes fixation. Postoperative results can vary even in cases of a mobile stapes and an aerated middle ear. We hypothesize that these variations may be the result of differences in the coupling between the TM graft and the stapes head. Measurements of TM velocities by means of LDV did not show clear differences between cases with good hearing and cases with poor hearing in ears with a mobile stapes and an aerated ear. Except for diagnosis of nonaeration of the middle ear, LDV seems to have limited clinical usefulness to identify causes of failure after Type III tympanoplasty. RP Chien, W (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM wadechien@hotmail.com FU NIDCD NIH HHS [DC000020, T32 DC000020, R01 DC004798-07, DC04798, R01 DC004798] NR 14 TC 6 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD SEP PY 2007 VL 28 IS 6 BP 782 EP 787 DI 10.1097/MAO.0b013e31811f40fb PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 205BD UT WOS:000249087000011 PM 17948356 ER PT J AU Wang, S Lim, G Mao, J Sung, B Yang, L Mao, J AF Wang, Shuxing Lim, Grewo Mao, Ji Sung, Backil Yang, Lifing Mao, Jianren TI Central glucocorticoid receptors regulate the upregulation of spinal cannabinoid-1 receptors after peripheral nerve injury in rats SO PAIN LA English DT Article DE neuropathic pain; glucocorticoid receptor; cannabinoid receptor; allodynia; hyperalgesia ID NEUROPATHIC PAIN BEHAVIORS; MORPHINE-TOLERANCE; BASOLATERAL AMYGDALA; DIABETIC NEUROPATHY; IDIOPATHIC FORMS; HYPERALGESIA; MECHANISMS; EXPRESSION; EFFICACY; MODEL AB Previous studies have shown that peripheral nerve injury upregulated both glucocorticoid receptors (GR) and cannabinoid-1 receptors (CBIR) within the spinal cord dorsal horn in rats. However, the relationship between the expression of spinal GR and CB I R after nerve injury remains unclear. Here, we examined the hypothesis that the upregulation of spinal CB I R induced by chronic constriction nerve injury (CCI) in rats would be regulated by spinal GR. CCI induced the upregulation of spinal CB1R primarily within the ipsilateral spinal cord dorsal horn as revealed by Western blot and immunohistochemistry. The expression of CBIR in CCI rats was substantially attenuated by intrathecal treatment with either the GR antagonist RU38486 or a GR antisense oligonucleotide given twice daily for postoperative day 1-6, whereas the expression of spinal CBIR was enhanced following intrathecal administration of a GR sense oligonucleotide twice daily for postoperative day 1-6. Furthermore, the upregulation of spinal CBIR after nerve injury was prevented in adrenalectomized rats, which was at least partially restored with the intrathecal administration of an exogenous GR agonist dexamethasone, indicating that corticosteroids (endogenous GR agonists) were critical to spinal GR actions. Since the development of neuropathic pain behaviors in CCI rats was attenuated by either RU38486 or a GR antisense oligonucleotide, these results suggest that CBIR is a downstream target for spinal GR actions contributory to the mechanisms of neuropathic pain. (C) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,MGH Ctr Translat Pain, Boston, MA 02114 USA. RP Mao, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,MGH Ctr Translat Pain, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [DA08835]; NINDS NIH HHS [NS45681, R01 NS42661] NR 56 TC 22 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2007 VL 131 IS 1-2 BP 96 EP 105 DI 10.1016/j.pain.2006.12.019 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 207FD UT WOS:000249236100012 PM 17258396 ER PT J AU Sung, B Wang, S Zhou, B Lim, G Yang, L Zeng, Q Lim, JA Wang, JD Kang, JX Mao, J AF Sung, Backil Wang, Shuxing Zhou, Bei Lim, Grewo Yang, Liling Zeng, Qing Lim, Jeong-Ae Wang, Jing Dong Kang, Jing X. Mao, Jianren TI Altered spinal arachidonic acid turnover after peripheral nerve injury regulates regional glutamate concentration and neuropathic pain behaviors in rats SO PAIN LA English DT Article DE glutamate transporter; neuropathic pain; nerve injury; phospholipase A2; arachidonic acid; glutamate uptake; microdialysis; high pressure liquid chromatography; gas chromatography ID POLYUNSATURATED FATTY-ACIDS; AMINO-ACIDS; PHOSPHOLIPASE A(2); PROSTAGLANDIN E-2; TRANSPORTER SUBTYPES; THERMAL HYPERALGESIA; SCIATIC-NERVE; NITRIC-OXIDE; CELL-DEATH; MECHANISMS AB Spinal glutamate transporters (GT) have been implicated in the mechanisms of neuropathic pain; however, how spinal GT uptake activity is regulated remains unclear. Here we show that alteration of spinal arachidonic acid (AA) turnover after periplieral nerve injury regulated regional GT uptake activity and glutamate homeostasis. Chronic constriction nerve injury (CCI) in rats sianificantly reduced spinal GT uptake activity (H-3-glutamate uptake) with an associated increase in extracellular AA and glutamate concentration from spinal microdialysates on postoperative day 8. AACOCF3 (a cytosolic phospholipase A2 inhibitor, 30 mu g) given intrathecally twice a day for postoperative day 1-7 reversed this CCI-induced spinal AA production, prevented the reduced spinal GT uptake activity and increased extracellular glutamate concentration. Conversely, alteration of spinal AA metabolism by diclofenac (a cyclooxygenase 1/2 inhibitor, 200 mu g) further reduced spinal GT uptake activity and increased extracellular glutamate concentration in CCI rats. GT uptake activity was also attenuated when AA (10 or 100 nM) was directly added into spinal samples of naive rats in an in vitro 3 H-glutamate uptake assay, indicating a direct inhibitory effect of AA on GT uptake activity. Consistent with these findings, AACOCF3 reduced the development of both thermal hyperalgesia and mechanical allodynia, whereas diclofenac exacerbated thermal hyperalgesia, in CCI rats. Thus, spinal AA turnover may serve as a regulator in CCI-induced changes in regional GT uptake activity, glutamate homeostasis, and neuropathic pain behaviors. These data suggest that regulating spinal AA turnover may be a useful approach to improving the clinical management of neuropathic pain. (C) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Div Pain Med,Pain Res, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Mao, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Div Pain Med,Pain Res, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [R01 DA008835-10, R01 DA008835-09, R01 DA008835]; NINDS NIH HHS [R01 NS045681-03, R01 NS45681, R01 NS042661-04, R01 NS042661-03, R01 NS045681, R01 NS042661, R01 NS42661, R01 NS045681-04] NR 76 TC 25 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2007 VL 131 IS 1-2 BP 121 EP 131 DI 10.1016/j.pain.2006.12.020 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 207FD UT WOS:000249236100015 PM 17267128 ER PT J AU Gallagher, RM AF Gallagher, Rollin M. TI Selective, tailored, biopsychosocial pain treatment: Our past is our future SO PAIN MEDICINE LA English DT Editorial Material C1 Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD SEP PY 2007 VL 8 IS 6 BP 471 EP 474 DI 10.1111/j.1526-4637.2007.00361.x PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 206PV UT WOS:000249196300001 PM 17716318 ER PT J AU Ingelfinger, J AF Ingelfinger, J. TI Renal responses to developmental origins of health and disease [DOHaD] SO PEDIATRIC NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD SEP PY 2007 VL 22 IS 9 BP 1419 EP 1419 PG 1 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 189GL UT WOS:000247977300071 ER PT J AU Chattergoon, NN Louey, S O'Tierney, PF Girard, GD Thomburg, KL AF Chattergoon, N. N. Louey, S. O'Tierney, P. F. Girard, G. D. Thomburg, K. L. TI Thyroid hormone is a potent regulator of fetal sheep cardiomyocyte proliferation SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Aspen Perinatal Biology Conference 2007 CY AUG 25-28, 2007 CL Aspen, CO C1 Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR USA. Oregon Hlth & Sci Univ, Sch Med, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2007 VL 62 IS 3 BP 382 EP 382 PG 1 WC Pediatrics SC Pediatrics GA 203KJ UT WOS:000248973200042 ER PT J AU Jonker, S Giratid, M Giraud, G Chattergoon, N Louey, S Thornburg, K AF Jonker, S. Giratid, M. Giraud, G. Chattergoon, N. Louey, S. Thornburg, K. TI Myocyte proliferation contributes to anemia-induced fetal cardiac enlargement SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Aspen Perinatal Biology Conference 2007 CY AUG 25-28, 2007 CL Aspen, CO C1 Oregon Hlth & Sci Univ, Heart Res Ctr, Dept Physiol & Pharmacol, Cardiovasc Med, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Jonker, S (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr, Dept Physiol & Pharmacol, Cardiovasc Med, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2007 VL 62 IS 3 BP 382 EP 382 PG 1 WC Pediatrics SC Pediatrics GA 203KJ UT WOS:000248973200043 ER PT J AU O'Tierney, PF Anderson, DF Loucy, S Thornburg, KL Giraud, GD AF O'Tierney, P. F. Anderson, D. F. Loucy, S. Thornburg, K. L. Giraud, G. D. TI Reduced systolic pressure load, in vivo, decreases cell cycle activity in the fetal sheep heart SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Aspen Perinatal Biology Conference 2007 CY AUG 25-28, 2007 CL Aspen, CO C1 Oregon Hlth & Sci Univ, Hlth Res Ctr, Dept Physiol & Pharmacol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Hlth Res Ctr, Dept Med, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. RP O'Tierney, PF (reprint author), Oregon Hlth & Sci Univ, Hlth Res Ctr, Dept Physiol & Pharmacol, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2007 VL 62 IS 3 BP 382 EP 382 PG 1 WC Pediatrics SC Pediatrics GA 203KJ UT WOS:000248973200047 ER PT J AU Choate, M DuPriest, E Lin, B Xue, H Kupfer, P Roullet, JB Bagby, S AF Choate, M. DuPriest, E. Lin, B. Xue, H. Kupfer, P. Roullet, J. B. Bagby, S. TI Maternal protein restriction in swine: Increased aortic Nox 4 mRNA in both fetal and juvenile offspring parallels increased mesenteric NADPH oxidase-dependent ANGII reactivity in juveniles SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Aspen Perinatal Biology Conference 2007 CY AUG 25-28, 2007 CL Aspen, CO C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2007 VL 62 IS 3 BP 383 EP 383 PG 1 WC Pediatrics SC Pediatrics GA 203KJ UT WOS:000248973200052 ER PT J AU Christison-Lagay, ER Hall, JF Wales, PW Bailey, K Terluk, A Goldstein, AM Ein, SH Masiakos, PT AF Christison-Lagay, Emily R. Hall, Jason F. Wales, Paul W. Bailey, Karen Terluk, Andrew Goldstein, Allan M. Ein, Sigmund H. Masiakos, Peter T. TI Nonoperative management of perianal abscess in infants is associated with decreased risk for fistula formation SO PEDIATRICS LA English DT Article DE perianal abscess; fistula in ano ID IN-ANO; PERIRECTAL ABSCESS; CHILDREN; CHILDHOOD AB OBJECTIVE. We sought to determine the frequency of progression in infants of perianal abscess with and without surgical drainage to fistula in ano to optimize a treatment plan for these children. METHODS. A retrospective cohort study was conducted of all patients who were <= 1 year of age and presented with perianal abscess to 2 pediatric tertiary care institutions during a 10-year period ( January 1995 to February 2005, inclusive). Patients were divided into those who underwent surgical drainage and those who did not, and the rate of subsequent fistula formation was determined. RESULTS. Of 165 children initially identified, follow-up was available for 140. Ninetyfour percent of children were male. Mean age was 4.2 +/-3.1 months. Of the 140 patients, 83 abscesses were drained and 57 were not drained. Of patients who underwent surgical drainage, 50 developed a fistula, whereas of those who did not undergo drainage only 9 developed a fistula. Synchronous administration of antibiotics ( intravenous or oral) used in 57 of 58 patients from 1 institution was associated with an even greater decrease in fistula formation ( 12.5%) in the undrained population. CONCLUSIONS. Perianal abscess formation in infants who are younger than 12 months is a separate entity from abscess formation in older age groups. In this largest study to date, a combined center series of patients who presented to 2 academic pediatric hospitals with infantile perianal abscess, local hygiene and systemic antibiotics without surgical drainage minimized formation of fistula in ano. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Surg,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. Univ Toronto, Dept Surg, Toronto, ON, Canada. Hosp Sick Children, Dept Pediat Surg, Toronto, ON M5G 1X8, Canada. RP Masiakos, PT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Surg,Dept Surg, Warren 11,55 Fruit St, Boston, MA 02114 USA. EM pmasiakos@partners.org NR 14 TC 17 Z9 17 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2007 VL 120 IS 3 BP E548 EP E552 DI 10.1542/peds.2006-3092 PG 5 WC Pediatrics SC Pediatrics GA 207DO UT WOS:000249232000059 PM 17682038 ER PT J AU Lerner, EA Iuga, AO Reddy, VB AF Lerner, Ethan A. Iuga, Aurel O. Reddy, Vemuri B. TI Maxadilan, a PAC1 receptor agonist from sand flies SO PEPTIDES LA English DT Article DE maxadilan; PAC1; receptor; PACAP; leishmaniasis ID POTENT VASODILATORY PEPTIDE; FLY LUTZOMYIA-LONGIPALPIS; SALIVA; LEISHMANIASIS; INFECTION; BRAIN; CELLS AB In 1991, a potent 61 amino acid vasodilator peptide, named maxadilan, was isolated from the salivary glands of the sand fly. Subsequently, it was shown that this peptide specifically and potently activated the mammalian PAC1 receptor, one of the three receptors for PACAP. These studies and the link between maxadilan and leishmaniasis are discussed. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Lerner, EA (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA USA. EM ethan.lerner@cbrc2.mgh.harvard.edu FU NIAMS NIH HHS [R01 AR042005, R01 AR042005-08] NR 21 TC 27 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD SEP PY 2007 VL 28 IS 9 BP 1651 EP 1654 DI 10.1016/j.peptides.2007.06.021 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 218TQ UT WOS:000250038200007 PM 17681401 ER PT J AU Lelievre, V Favrais, G Abad, C Adle-Biassette, H Lu, Y Germano, PM Cheung-Lau, G Pisegna, JR Gressens, P Lawson, G Waschek, JA AF Lelievre, V. Favrais, G. Abad, C. Adle-Biassette, H. Lu, Y. Germano, P. M. Cheung-Lau, G. Pisegna, J. R. Gressens, P. Lawson, G. Waschek, J. A. TI Gastrointestinal dysfunction in mice with a targeted mutation in the gene encoding vasoactive intestinal polypeptide: A model for the study of. intestinal ileus and Hirschsprung's disease SO PEPTIDES LA English DT Article DE vasoactive intestinal peptide; knockout; peristalsis; gastrointestinal transit ID CYCLASE-ACTIVATING POLYPEPTIDE; ADENOCARCINOMA CELL-LINES; SMOOTH-MUSCLE; EPITHELIAL-CELLS; SONIC HEDGEHOG; TROPHIC FACTOR; VIP RECEPTORS; RAT JEJUNUM; PEPTIDE; PROLIFERATION AB In 1970, Drs. Said and Mutt isolated a novel peptide from porcine intestinal extracts with powerful vasoactive properties, and named it vasoactive intestinal peptide (VIP). Since then, the biological actions of VIP in the gut as well as its signal transduction pathways have been extensively studied. A variety of in vitro and in vivo studies have indicated that VIP, expressed in intrinsic non-adrenergic non-cholinergic (NANC) neurons, is a potent regulator of gastrointestinal (GI) motility, water absorption and ion flux, mucus secretion and immune homeostasis. These VIP actions are believed to be mediated mainly by interactions with highly expressed VPAC(1) receptors and the production of nitric oxide (NO). Furthermore, VIP has been implicated in numerous physiopathological conditions affecting the human gut, including pancreatic endocrine tumors secreting VIP (VIPomas), insulin-dependent diabetes, Hirschsprung's disease, and inflammatory bowel syndromes such as Crohn's disease and ulcerative colitis. To further understand the physiological roles of VIP on the GI tract, we have begun to analyze the anatomical and physiological phenotype of C57BL/6 mice lacking the VIP gene. Herein, we demonstrate that the overall intestinal morphology and light microscopic structure is significantly altered in VIP-/- mice. Macroscopically there is an overall increase in weight, and decrease in length of the bowel compared to wild type (WT) controls. Microscopically, the phenotype was characterized by thickening of smooth muscle layers, increased villi length, and higher abundance of goblet cells. Alcian blue staining indicated that the latter cells were deficient in mucus secretion in VIP-/- mice. The differences became more pronounced from the duodenum to the distal jejunum or ileum of the small bowel but, became much less apparent or absent in the colon with the exception of mucus secretion defects. Further examination of the small intestine revealed larger axonal trunks and unusual unstained patches in myenteric plexus. Physiologically, the VIP-/- mice showed an impairment in intestinal transit. Moreover, unlike WT C57BL/6 mice, a significant percentage of VIP-/- mice died in the first postnatal year with overt stenosis of the gut. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. INSERM, U676, Paris, France. Univ Paris 07, Fac Med Denis Diderot, IFR02, IFR25, Paris, France. Hop Claude Bernard, Serv Anat Pathol, Paris, France. VA Greater Los Angeles Hlthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Lab Anim Med, Los Angeles, CA USA. RP Waschek, JA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. EM jwaschek@mednet.ucla.edu OI Abad, Catalina/0000-0001-9144-9310; Favrais, Geraldine/0000-0002-0301-2053; Lelievre, Vincent/0000-0003-4150-8233 FU NICHD NIH HHS [R01 HD034475-09, R01 HD034475-07, R01 HD034475-05A1, R01 HD034475-03, R01 HD034475, P01 HD006576-27S10021, P01 HD006576-270021, P01 HD006576-250021, HD0657, R01 HD034475-06, HD34475, P01 HD006576, P01 HD006576-240021, P01 HD006576-260021, P01 HD006576-280021, P01 HD006576-290011, R01 HD034475-04, R01 HD034475-08] NR 41 TC 43 Z9 46 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD SEP PY 2007 VL 28 IS 9 BP 1688 EP 1699 DI 10.1016/j.peptides.2007.05.006 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 218TQ UT WOS:000250038200012 PM 17606312 ER PT J AU Dobbs, JL Sloan, DM Karpinski, A AF Dobbs, Jennifer L. Sloan, Denise M. Karpinski, Andrew TI A psychometric investigation of two self-report measures of emotional expressivity SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE emotional expression; emotion; confirmatory factor analysis; exploratory factor analysis ID MODEL; DISORDER; FACETS; OLDER AB Two commonly used self-report measures of emotional expressivity were evaluated in this study, the emotional expressivity scale (EES; Kring, Smith, & Neale, 1994) and the Berkeley expressivity questionnaire (BEQ; Gross & John, 1995). The EES is intended to capture emotion expressivity in general, reflecting a one-factor model. The BEQ is intended to capture the general domain of emotional expressivity by assessing internal emotional experience and the expression of positive and negative emotions, reflecting a hierarchical three-factor model. The proposed models of the EES and the BEQ were examined using exploratory and confirmatory factor analysis. Results support the hypothesized factor structure of the EES, but do not support the BEQ. (c) 2007 Elsevier Ltd. All rights reserved. C1 Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. RP Dobbs, JL (reprint author), Temple Univ, Dept Psychol, Weiss Hall, Philadelphia, PA 19122 USA. EM jdobbs@temple.edu NR 24 TC 7 Z9 8 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD SEP PY 2007 VL 43 IS 4 BP 693 EP 702 DI 10.1016/j.paid.2007.01.010 PG 10 WC Psychology, Social SC Psychology GA 193HA UT WOS:000248263900006 ER PT J AU Bent, S AF Bent, Stephen TI Editorial: assessing the safety of dietary supplements SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material ID MEDICINES C1 Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Bent, S (reprint author), Vet Adm Med Ctr, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. EM Stephen.Bent@ucsf.edu NR 11 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2007 VL 16 IS 9 BP 958 EP 960 DI 10.1002/pds.1450 PG 3 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 210TC UT WOS:000249477500002 PM 17705239 ER PT J AU Joshi, VA Kucherlapati, R AF Joshi, Victoria A. Kucherlapati, Raju TI Pharmacogenomics of lung cancer: with a view to address EGFR-targeted therapies SO PHARMACOGENOMICS LA English DT Review DE adenocarcinoma; EGFR; erlotinib; gefitinib; lung; pharmacogenetics; resistance ID GROWTH-FACTOR-RECEPTOR; CHEMOTHERAPY-NAIVE PATIENTS; TYROSINE KINASE INHIBITOR; ADVANCED SOLID TUMORS; GENE COPY NUMBER; ACQUIRED-RESISTANCE; PHASE-II; IRREVERSIBLE INHIBITOR; GEFITINIB SENSITIVITY; MOLECULAR PREDICTORS AB Epidermal growth factor receptor (EGFR)-targeted therapies have demonstrated variable success in treating individuals with non-small-cell lung cancer. Understanding the molecular mechanisms of response and resistance to this class of treatment has led to patient selection strategies that may improve outcomes. The second generation of EGFR-targeted therapies is now under clinical evaluation and may prove to be successful at circumventing a portion of primary or acquired resistance to first-generation tyrosine kinase inhibitors. These principles are generally applicable to the field of targeted therapy and predictive pharmacogenomics. C1 Harvard Univ, Massachusetts Gen Hosp, Partners Healthcare Ctr Genet & Genom, Dept Pathol,Sch Med, Cambridge, MA 02138 USA. RP Joshi, VA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Partners Healthcare Ctr Genet & Genom, Dept Pathol,Sch Med, Cambridge, MA 02138 USA. EM vjoshi@partners.org; rkucherlapati@rcs.bwh.harvard.edu NR 75 TC 2 Z9 2 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD SEP PY 2007 VL 8 IS 9 BP 1211 EP 1220 DI 10.2217/14622416.8.9.1211 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 225VQ UT WOS:000250546700017 PM 17924836 ER PT J AU Verma, S Watt, GM Mal, Z Hasan, T AF Verma, Sarika Watt, Gregory M. Mal, Zhiming Hasan, Tayyaba TI Strategies for enhanced photodynamic therapy effects SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; MOUSE-TUMOR MODEL; DENSITY-LIPOPROTEIN RECEPTORS; OVARIAN-CARCINOMA CELLS; PROSTATE-CANCER CELLS; IN-VIVO; FLUENCE RATE; CHOROIDAL NEOVASCULARIZATION; CELLULAR UPTAKE; SUBCELLULAR-LOCALIZATION AB Photodynamic therapy (PDT) is a treatment modality for the selective destruction of cancerous and nonneoplastic pathologies that involves the simultaneous presence of light, oxygen and a light-activatable chemical called a photosensitizer (PS) to achieve a cytotoxic effect. The photophysics and mechanisms of cell killing by PDT have been extensively studied in recent years, and PDT has received regulatory approval for the treatment of a number of diseases worldwide. As the application of this treatment modatity expands with regard to both anatomical sites and disease stages, it will be important to develop strategies for enhancing PDT outcomes. This article focuses on two broad approaches for PDT enhancement: (1) mechanism-based combination treatments in which PDT and a second modality can be designed to either increase the susceptibility of tumor cells to PDT or nullify the treatment outcome-mitigating molecular responses triggered by PDT of tumors, and (2) the more recent approaches of PS targeting, either by specific cellular function-sensitive linkages or via conjugation to macromolecules. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. EM thasan@partners.org FU NCI NIH HHS [P01 CA084203, R01 CA119388]; NIAMS NIH HHS [R01 AR040352] NR 111 TC 123 Z9 128 U1 5 U2 40 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2007 VL 83 IS 5 BP 996 EP 1005 DI 10.1111/j.1751-1097.2007.00166.x PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 216MF UT WOS:000249881400002 PM 17880492 ER PT J AU Popescu, G Park, Y Dasari, RR Badizadegan, K Feld, MS AF Popescu, Gabriel Park, YongKeun Dasari, Ramachandra R. Badizadegan, Kamran Feld, Michael S. TI Coherence properties of red blood cell membrane motions SO PHYSICAL REVIEW E LA English DT Article ID DIFFRACTION PHASE; MICROSCOPY; FLUCTUATIONS; ERYTHROCYTES; DYNAMICS; SKELETON; FIELDS; MODULI AB We use a highly sensitive, noncontact, optical interferometric technique to quantify the red blood cell membrane fluctuations at the nanometer and millisecond scales. The results reveal significant properties of both temporal and spatial coherence associated with the membrane dynamics. We show that these correlations can be accounted for by the viscoelastic properties of the cell membrane. From this measurement, we extract the loss and storage moduli associated with the membrane and find a crossover frequency at which the buffer viscosity seems to become dominant. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. RP Popescu, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. EM gpopescu@mit.edu RI Park, YongKeun/B-9017-2009 NR 31 TC 51 Z9 51 U1 0 U2 4 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD SEP PY 2007 VL 76 IS 3 AR 031902 DI 10.1103/PhysRevE.76.031902 PN 1 PG 5 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 215CL UT WOS:000249785800082 PM 17930266 ER PT J AU Braun, L Fausto-Sterling, A Fullwiley, D Hammonds, EM Nelson, A Quivers, W Reverby, SM Shields, AE AF Braun, Lundy Fausto-Sterling, Anne Fullwiley, Duana Hammonds, Evelynn M. Nelson, Alondra Quivers, William Reverby, Susan M. Shields, Alexandra E. TI Racial categories in medical practice: How useful are they? SO PLOS MEDICINE LA English DT Article ID HEALTH DISPARITIES; GENETIC-STRUCTURE; RACE; ETHNICITY; SCIENCE; PERSPECTIVE; CANCER; RACE/ETHNICITY; EPIDEMIOLOGY; ASSOCIATION C1 Brown Univ, Fac Committee Sci & Technol Studies, Dept Mol & Cellular Biol, Program Women Studies, Providence, RI 02912 USA. Brown Univ, Dept Pathol & Lab Med, African Studies, Providence, RI 02912 USA. Harvard Univ, Dept Anthropol, Africa & African Amer Studies, Cambridge, MA USA. Harvard Univ, Fac Dev & Diversity, Africa & African Amer Studies, Cambridge, MA USA. Yale Univ, Dept Sociol, African Amer Studies, New Haven, CT 06520 USA. Wellesley Coll, Dept Phys, Wellesley, MA USA. Wellesley Coll, Dept Women Studies, Wellesley, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Ctr Genom Vulnerab Populat & Hlth Disparities, Boston, MA USA. RP Fausto-Sterling, A (reprint author), Brown Univ, Fac Committee Sci & Technol Studies, Dept Mol & Cellular Biol, Program Women Studies, Providence, RI 02912 USA. EM Anne_Fausto-Sterling@brown.edu FU NHGRI NIH HHS [P20 HG003400] NR 82 TC 61 Z9 61 U1 1 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD SEP PY 2007 VL 4 IS 9 BP 1423 EP 1428 AR e271 DI 10.1371/journal.pmed.0040271 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 214WE UT WOS:000249768100002 PM 17896853 ER PT J AU Lesic, B Lepine, F Deziel, E Zhang, JW Zhang, QH Padfield, K Castonguay, MH Milot, S Stachel, S Tzika, AA Tompkins, RG Rahme, LG AF Lesic, Biliana Lepine, Francois Deziel, Eric Zhang, Jiangwen Zhang, Qunhao Padfield, Katie Castonguay, Marie-Helene Milot, Sylvain Stachel, Scott Tzika, A. Aria Tompkins, Ronald G. Rahme, Laurence G. TI Inhibitors of pathogen intercellular signals as selective anti-infective compounds SO PLOS PATHOGENS LA English DT Article ID PSEUDOMONAS-QUINOLONE SIGNAL; QUORUM-SENSING INHIBITORS; LUXR-LUXI FAMILY; TRANSCRIPTIONAL REGULATORS; AERUGINOSA VIRULENCE; WHOLE CELLS; INFECTIONS; GENES; IDENTIFICATION; MVFR AB Long-term antibiotic use generates pan-resistant super pathogens. Anti-infective compounds that selectively disrupt virulence pathways without affecting cell viability may be used to efficiently combat infections caused by these pathogens. A candidate target pathway is quorum sensing (QS), which many bacterial pathogens use to coordinately regulate virulence determinants. The Pseudomonas aeruginosa MvfR-dependent QS regulatory pathway controls the expression of key virulence genes; and is activated via the extracellular signals 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), whose syntheses depend on anthranilic acid ( AA), the primary precursor of 4-hydroxy-2-alkylquinolines (HAQs). Here, we identified halogenated AA analogs that specifically inhibited HAQ biosynthesis and disrupted MvfR-dependent gene expression. These compounds restricted P. aeruginosa systemic dissemination and mortality in mice, without perturbing bacterial viability, and inhibited osmoprotection, a widespread bacterial function. These compounds provide a starting point for the design and development of selective anti-infectives that restrict human P. aeruginosa pathogenesis, and possibly other clinically significant pathogens. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Surg Microbiol & Mol Genet, Boston, MA 02114 USA. Harvard Med Sch, Dept Microbiol & Mol Genet, Boston, MA USA. Shriners Burns Inst, Boston, MA USA. INRS, Inst Armand Frappier, Laval, PQ, Canada. Harvard Univ, Bauer Ctr Genom Res, Cambridge, MA 02138 USA. RP Rahme, LG (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Surg Microbiol & Mol Genet, Boston, MA 02114 USA. EM rahme@amber.mgh.harvard.edu RI Zhang, Jiangwen/A-7654-2013; Deziel, Eric/A-7678-2008 OI Deziel, Eric/0000-0002-4609-0115 FU NIAID NIH HHS [R01 AI063433, R01AI063433] NR 52 TC 97 Z9 98 U1 2 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD SEP PY 2007 VL 3 IS 9 BP 1229 EP 1239 AR e126 DI 10.1371/journal.ppat.0030126 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 214WG UT WOS:000249768300006 PM 17941706 ER PT J AU Lewinsohn, DA Winata, E Swarbrick, GM Tanner, KE Cook, MS Null, MD Cansler, ME Sette, A Sidney, J Lewinsohn, DM AF Lewinsohn, Deborah A. Winata, Ervina Swarbrick, Gwendolyn M. Tanner, Katie E. Cook, Matthew S. Null, Megan D. Cansler, Meghan E. Sette, Alessandro Sidney, John Lewinsohn, David M. TI Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B SO PLOS PATHOGENS LA English DT Article ID MYCOBACTERIUM-BOVIS BCG; T-CELL RESPONSES; 19-KDA LIPOPROTEIN; INFECTED-CELLS; MICE; IDENTIFICATION; COMPLEX; RESISTANCE; EXPRESSION; CLONING AB CD8(+) T cells are essential for host defense to intracellular bacterial pathogens such as Mycobacterium tuberculosis (Mtb), Salmonella species, and Listeria monocytogenes, yet the repertoire and dominance pattern of human CD8 antigens for these pathogens remains poorly characterized. Tuberculosis ( TB), the disease caused by Mtb infection, remains one of the leading causes of infectious morbidity and mortality worldwide and is the most frequent opportunistic infection in individuals with HIV/AIDS. Therefore, we undertook this study to define immunodominant CD8 Mtb antigens. First, using IFN-gamma ELISPOT and synthetic peptide arrays as a source of antigen, we measured ex vivo frequencies of CD8(+) T cells recognizing known immunodominant CD4(+) T cell antigens in persons with latent tuberculosis infection. In addition, limiting dilution was used to generate panels of Mtb-specific T cell clones. Using the peptide arrays, we identified the antigenic specificity of the majority of T cell clones, defining several new epitopes. In all cases, peptide representing the minimal epitope bound to the major histocompatibility complex (MHC)-restricting allele with high affinity, and in all but one case the restricting allele was an HLA-B allele. Furthermore, individuals from whom the T cell clone was isolated harbored high ex vivo frequency CD8(+) T cell responses specific for the epitope, and in individuals tested, the epitope represented the single immunodominant response within the CD8 antigen. We conclude that Mtb-specific CD8(+) T cells are found in high frequency in infected individuals and are restricted predominantly by HLA-B alleles, and that synthetic peptide arrays can be used to define epitope specificities without prior bias as to MHC binding affinity. These findings provide an improved understanding of immunodominance in humans and may contribute to a development of an effective TB vaccine and improved immunodiagnostics. C1 Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. La Jolla Inst Allergy & Immunol, San Diego, CA USA. RP Lewinsohn, DM (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. EM lewinsod@ohsu.edu RI Yehorov, Bohdan/Q-1365-2015; Lewinsohn, David/I-4936-2013 OI Yehorov, Bohdan/0000-0001-7526-0315; Lewinsohn, David/0000-0001-9906-9494 FU NIAID NIH HHS [R01 AI054474, R01 AI048090, R01AI054474, R01AI48090]; PHS HHS [N01-A1-400081] NR 62 TC 77 Z9 78 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD SEP PY 2007 VL 3 IS 9 BP 1240 EP 1249 AR e127 DI 10.1371/journal.ppat.0030127 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 214WG UT WOS:000249768300007 PM 17892322 ER PT J AU Li, H Bubley, GJ Balk, SP Gaziano, JM Pollak, M Stampfer, MJ Ma, J AF Li, Haojie Bubley, Glenn J. Balk, Stephen P. Gaziano, J. Michael Pollak, Michael Stampfer, Meir J. Ma, Jing TI Hypoxia-inducible factor-I alpha (HIF-I alpha) gene polymorphisms, circulating insulin-like growth factor binding protein (IGFBP)-3 levels and prostate cancer SO PROSTATE LA English DT Article DE insulin-like growth factor (IGF)-I; vascular endothelial growth factor (VEGF); prospective; nested case-control study ID RENAL-CELL CARCINOMA; FACTOR 1-ALPHA; FACTOR-1-ALPHA GENE; FACTOR IGF; EXPRESSION; HIF-1-ALPHA; ANGIOGENESIS; RISK; DEGRADATION; MODULATION AB BACKGROUND. The Hypoxia-inducible factor-1 (HIF-1) plays an important role in regulating angiogenesis in response to hypoxia. Two non-synonymous polymorphisms (P582S C -> T and A58ST G -> A) in the coding region of the subunit 1 alpha (HIF-1 alpha) gene have been associated with enhanced stability of the protein and androgen-independent prostate cancer (CaP). Insulin-like growth factor binding protein (IGFBP)-3 mRNA is more abundantly expressed in hypoxia-related inflammatory angiogenesis and recent in vivo data suggest that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis. METHODS. We examined the association of these polymorphisms with CaP among 1,072 incident cases and 1,271 controls, and further explored their joint associations with various prediagnostic plasma vascular endothelial growth factor (VEGF), IGF-I, and IGFBP-3 levels. RESULTS. Neither the P582S nor the A588T polymorphism was associated with risk of overall or metastatic/fatal CaP. However, we found that, among men with the homozygous CC wildtype (but not CT/TT) of the HIF-1 alpha P582S, higher IGFBP-3 levels (>= vs. = 3 prescriptions of >= 15 pills of simvastatin, pravastatin, lovastatin, or atorvastatin vs nonusers, based on pharmacy dispensing records. Results: After controlling for age at death, gender, cognitive function at study entry, brain weight, and presence of cerebral microvascular lesions, the odds ratio (OR) for each unit increase in Braak NFT stage in statin users vs nonusers was 0.44 (95% CI: 0.20 to 0.95). The OR for each unit increase in Consortium to Establish a Registry for Alzheimer's Disease (CERAD) staging of NPs did not deviate significantly from unity (OR 0.69; 95% CI: 0.32 to 1.52). However, the risk for typical AD pathology (Braak stage >= IV and CERAD rating >= moderate) was reduced in statin users (OR 0.20; 95% CI: 0.05 to 0.86). Conclusions: These findings demonstrate an association between antecedent statin use and neurofibrillary tangle burden at autopsy. Additional study is needed to examine whether statin use may be causally related to decreased development of Alzheimer disease-related neuropathologic changes. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, MIRECC, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, MIRECC, Seattle, WA 98195 USA. Univ Washington, Dept Med, MIRECC, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. RP Li, G (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way,Mail Code S-116 6 E, Seattle, WA 98108 USA. EM gli@u.washington.edu RI Sonnen, 37382016/H-3738-2016 OI Sonnen, 37382016/0000-0001-9267-8705 FU NIA NIH HHS [K08AG023670, K08 AG023670, K23AG020020, P50AG005136, R01 AG023801, R01AG023801, U01AG006781] NR 41 TC 145 Z9 149 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 28 PY 2007 VL 69 IS 9 BP 878 EP 885 DI 10.1212/01.wnl.0000277657.95487.1c PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 204EA UT WOS:000249025200010 PM 17724290 ER PT J AU Das, S Raj, L Zhao, B Kimura, Y Bernstein, A Aaronson, SA Lee, SW AF Das, Sanjeev Raj, Lakshmi Zhao, Bo Kimura, Yuki Bernstein, Alan Aaronson, Stuart A. Lee, Sam W. TI Hzf determines cell survival upon genotoxic stress by modulating p53 transactivation SO CELL LA English DT Article ID PROLYL ISOMERASE PIN1; ZINC-FINGER PROTEIN; DNA-DAMAGE; APOPTOTIC FUNCTION; ANTICANCER AGENTS; 2-HYBRID SYSTEM; FEEDBACK LOOP; CYCLE ARREST; BINDING; ACTIVATION AB A critical unresolved issue about the genotoxic stress response is how the resulting activation of the p53 tumor suppressor can lead either to cell-cycle arrest and DNA repair or to apoptosis. We show here that hematopoietic zinc finger ( Hzf), a zinc-finger-containing p53 target gene, modulates p53 transactivation functions in an autoregulatory feedback loop. Hzf is induced by p53 and binds to its DNA-binding domain, resulting in preferential transactivation of proarrest p53 target genes over its proapoptotic target genes. Thus, p53 activation results in cell-cycle arrest in Hzf wild-type MEFs, while in Hzf(-/-) MEFs, apoptosis is induced. Exposure of Hzf null mice to ionizing radiation resulted in enhanced apoptosis in several organs, as compared to in wild-type mice. These findings provide novel insights into the regulation of p53 transactivation function and suggest that Hzf functions as a key player in regulating cell fate decisions in response to genotoxic stress. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. CUNY Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM sam.lee@cbrc2.mgh.harvard.edu FU NCI NIH HHS [2R01 CA078356, 1R01 CA097216, 2R01 CA085214, 2R01 CA085681, P01 CA080058, P01 CA80058, R01 CA078356, R01 CA078356-10, R01 CA085214, R01 CA085681, R01 CA085681-08, R01 CA097216, R01 CA097216-06] NR 46 TC 98 Z9 105 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 24 PY 2007 VL 130 IS 4 BP 624 EP 637 DI 10.1016/j.cell.2007.06.013 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 208KY UT WOS:000249319400014 PM 17719541 ER PT J AU Storch, KF Paz, C Signorovitch, J Raviola, E Pawlyk, B Li, T Weitz, CJ AF Storch, Kai-Florian Paz, Carlos Signorovitch, James Raviola, Elio Pawlyk, Basil Li, Tiansen Weitz, Charles J. TI Intrinsic circadian clock of the mammalian retina: Importance for retinal processing of visual information SO CELL LA English DT Article ID MESSENGER-RNA EXPRESSION; GENE-EXPRESSION; SUPRACHIASMATIC NUCLEUS; MOUSE RETINA; RAT RETINA; MELATONIN; RHYTHMS; CELLS; MICE; DROSOPHILA AB Circadian clocks are widely distributed in mammalian tissues, but little is known about the physiological functions of clocks outside the suprachiasmatic nucleus of the brain. The retina has an intrinsic circadian clock, but its importance for vision is unknown. Here we show that mice lacking Bmal1, a gene required for clock function, had abnormal retinal transcriptional responses to light and defective inner retinal electrical responses to light, but normal photoreceptor responses to light and retinas that appeared structurally normal by light and electron microscopy. We generated mice with a retina-specific genetic deletion of Bmal1, and they had defects of retinal visual physiology essentially identical to those of mice lacking Bmal1 in all tissues and lacked a circadian rhythm of inner retinal electrical responses to light. Our findings indicate that the intrinsic circadian clock of the retina regulates retinal visual processing in vivo. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol,Berman Gund Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Weitz, CJ (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM cweitz@hms.harvard.edu FU NEI NIH HHS [EY10309, R01 EY001344, R01 EY010309, EY001344]; NINDS NIH HHS [NS055831, R01 NS055831, R01 NS055831-01] NR 54 TC 179 Z9 183 U1 4 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 24 PY 2007 VL 130 IS 4 BP 730 EP 741 DI 10.1016/j.cell.2007.06.045 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 208KY UT WOS:000249319400022 PM 17719549 ER PT J AU Rigamonti, D Bolognini, D Mutti, C Zuccato, C Tartari, M Sola, F Valenza, M Kazantsev, AG Cattaneo, E AF Rigamonti, Dorotea Bolognini, Daniele Mutti, Cesare Zuccato, Chiara Tartari, Marzia Sola, Francesco Valenza, Marta Kazantsev, Aleksey G. Cattaneo, Elena TI Loss of huntingtin function complemented by small molecules acting as repressor element 1/neuron restrictive silencer element silencer modulators SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUROTROPHIC FACTOR; TARGET GENES; NEURONAL GENES; RAT-BRAIN; DISEASE; EXPRESSION; TRANSCRIPTION; CELLS; BDNF; RECEPTORS AB Increased levels of the repressor element 1/neuron restrictive silencer element (RE1/NRSE) silencing activity promoter, and a consequent reduction in the transcription of many RE1/NRSE-bearing neuronal genes, including brain-derived neurotrophic factor (BDNF), have been demonstrated in Huntington disease (HD) and represent one possible effector of its selective neuronal vulnerability. Restoring the expression levels of neuronal genes in diseased neurons therefore seems to be an attractive therapeutic approach. To this end, we have developed a cell-based reporter assay for monitoring RE1/NRSE silencing activity and validated it by genetically inactivating the RE1/NRSE or pharmacologically stimulating global transcription. In a pilot compound screen, we identified three closely related structural analogues that up-regulate reporter expression at low nanomolar concentrations, and follow-up studies have shown that they efficaciously increase endogenous BDNF levels in HD cells. Moreover, one of the compounds increases the viability of HD cells. Our findings suggest a new avenue for the development of drugs for HD and other neurodegenerative disorders based on the pharmacological up-regulation of the production of the neuronal survival factor BDNF and of other RE1/NRSE-regulated neuronal genes. C1 Univ Milan, Ctr Stem Cell Res, I-20133 Milan, Italy. Univ Milan, Dept Pharmacol Sci, I-20133 Milan, Italy. Dialect Srl, I-20014 Nerviano Mi, Italy. Nerviano Med Sci Srl, Dept Biol, I-20014 Nerviano Mi, Italy. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Cattaneo, E (reprint author), Univ Milan, Ctr Stem Cell Res, Via Balzaretti 9, I-20133 Milan, Italy. EM elena.cattaneo@unimi.it OI ZUCCATO, CHIARA/0000-0003-1771-3392; VALENZA, MARTA/0000-0002-7048-9257; CATTANEO, ELENA/0000-0002-0755-4917 FU Telethon [GGP06250] NR 44 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 24 PY 2007 VL 282 IS 34 BP 24554 EP 24562 DI 10.1074/jbc.M609885200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202VU UT WOS:000248933000009 PM 17565993 ER PT J AU Zhou, Y Zhong, Y Wang, Y Zhang, X Batista, DL Gejman, R Ansell, PJ Zhao, J Weng, C Klibanski, A AF Zhou, Yunli Zhong, Ying Wang, Yingying Zhang, Xun Batista, Dalia L. Gejman, Roger Ansell, Peter J. Zhao, Jing Weng, Catherine Klibanski, Anne TI Activation of p53 by MEG3 non-coding RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA SUPERFAMILY; PTEN TUMOR-SUPPRESSOR; UP-REGULATION; DNA-DAMAGE; GENE NAG-1; MORPHOGENETIC PROTEIN; GROWTH ARREST; CHROMOSOME 12; CANCER-CELLS; EXPRESSION AB MEG3 is a maternally expressed imprinted gene suggested to function as a non-coding RNA. Our previous studies suggest that MEG3 has a function of tumor suppression. The tumor suppressor p53 plays a central role in tumor suppression and mediates the functions of many other tumor suppressors. Therefore, we hypothesized that MEG3 functions through activation of p53. We found that transfection of expression constructs for MEG3 and its isoforms results in a significant increase in p53 protein levels and dramatically stimulates p53-dependent transcription from a p53-responsive promoter. Using this as the functional assay, we demonstrated that the open reading frames encoded by MEG3 transcripts are not required for MEG3 function, and the folding of MEG3 RNA is critical to its function, supporting the concept that MEG3 functions as a non-coding RNA. We further found that MEG3 stimulates expression of the growth differentiation factor 15 (GDF15) by enhancing p53 binding to the GDF15 gene promoter. Interestingly, MEG3 does not stimulate p21(CIP1) expression, suggesting that MEG3 can regulate the specificity of p53 transcriptional activation. p53 degradation is mainly mediated by the mouse double minute 2 homolog (MDM2). We found that MDM2 levels were down-regulated in cells transfected with MEG3, suggesting that MDM2 suppression contributes at least in part to p53 accumulation induced by MEG3. Finally, we found that MEG3 is able to inhibit cell proliferation in the absence of p53. These data suggest that MEG3 non-coding RNA may function as a tumor suppressor, whose action is mediated by both p53-dependent and p53-independent pathways. C1 Massachusetts Gen Hosp, Neuendrocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuropathol Unit, Boston, MA 02114 USA. RP Zhou, Y (reprint author), Massachusetts Gen Hosp, Neuendrocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM yzhou2@partners.org FU NIA NIH HHS [R03AG026060]; NIDDK NIH HHS [R01DK40947] NR 60 TC 223 Z9 252 U1 1 U2 22 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 24 PY 2007 VL 282 IS 34 BP 24731 EP 24742 DI 10.1074/jbc.M702029200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202VU UT WOS:000248933000028 PM 17569660 ER PT J AU Grundt, P Prevatt, KM Cao, JJ Taylor, M Floresca, CZ Choi, JK Jenkins, BG Luedtke, RR Newman, AH AF Grundt, Peter Prevatt, Katherine M. Cao, Jianjing Taylor, Michelle Floresca, Christina Z. Choi, Ji-Kyung Jenkins, Bruce G. Luedtke, Robert R. Newman, Amy Hauck TI Heterocyclic analogues of N-(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)butyl)arylcarboxamides with functionalized linking chains as novel dopamine D3 receptor ligands: Potential substance abuse therapeutic agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID D-3 RECEPTOR; PARTIAL AGONISTS; DRUG-ABUSE; ANTAGONISTS; DISCOVERY; BINDING; DESIGN; PET; PERMEABILITY; RADIOTRACER AB Dopamine D3 receptor antagonists and partial agonists have been shown to modulate drug-seeking effects induced by cocaine and other abused substances. Compound 6 [PG01037, (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-trans-but-2-enyl)-4-pyridine-2-ylbenzamide)] and related analogues are currently being evaluated in animal models of drug addiction. In these studies, a discrepancy between in vitro binding affinity, in vivo occupancy, and behavioral potency has been observed. The purpose of this study was to examine (1) modifications of the 2-pyridylphenyl moiety of 6 and (2) hydroxyl, acetyl, and cyclopropyl substitutions on the butylamide linking chain systematically coupled with 2-fluorenylamide or 2-pyridylphenylamide and 2-methoxy- or 2,3-dichloro-substituted phenylpiperazines to measure the impact on binding affinity, D2/D3 selectivity, lipophilicity, and function. In general, these modifications were well tolerated at the human dopamine D3 (hD3) receptor (K-i = 1-5 nM) as measured in competition binding assays. Several analogues showed > 100-fold selectivity for dopamine D3 over D2 and D4 receptors. In addition, while all the derivatives with an olefinic linker were antagonists, in quinpirole-stimulated mitogenesis at hD3 receptors, several of the hydroxybutyl-linked analogues (16, 17, 21) showed partial agonist activity. Finally, several structural modifications reduced lipophilicities while retaining the desired binding profile. C1 Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program, Med Chem Sect, Baltimore, MD 21224 USA. Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Newman, AH (reprint author), Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program, Med Chem Sect, Baltimore, MD 21224 USA. EM anewman@intra.nida.ni.gov FU Intramural NIH HHS; NIDA NIH HHS [DA13584-01, DA13584-03S1, R01 DA016187] NR 45 TC 66 Z9 67 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 23 PY 2007 VL 50 IS 17 BP 4135 EP 4146 DI 10.1021/jm0704200 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 200JB UT WOS:000248758600018 PM 17672446 ER PT J AU Baena-Gonzalez, E Rolland, F Thevelein, JM Sheen, J AF Baena-Gonzalez, Elena Rolland, Filip Thevelein, Johan M. Sheen, Jen TI A central integrator of transcription networks in plant stress and energy signalling SO NATURE LA English DT Article ID ACTIVATED PROTEIN-KINASE; ARABIDOPSIS-THALIANA; GENE-EXPRESSION; NITRATE REDUCTASE; SUCROSE; TRANSDUCTION; IDENTIFICATION; PATHWAYS; LEAVES; METABOLISM AB Photosynthetic plants are the principal solar energy converter sustaining life on Earth. Despite its fundamental importance, little is known about how plants sense and adapt to darkness in the daily light-dark cycle, or how they adapt to unpredictable environmental stresses that compromise photosynthesis and respiration and deplete energy supplies. Current models emphasize diverse stress perception and signalling mechanisms(1,2). Using a combination of cellular and systems screens, we show here that the evolutionarily conserved Arabidopsis thaliana protein kinases, KIN10 and KIN11 (also known as AKIN10/At3g01090 and AKIN11/At3g29160, respectively), control convergent reprogramming of transcription in response to seemingly unrelated darkness, sugar and stress conditions. Sensing and signalling deprivation of sugar and energy, KIN10 targets a remarkably broad array of genes that orchestrate transcription networks, promote catabolism and suppress anabolism. Specific bZIP transcription factors partially mediate primary KIN10 signalling. Transgenic KIN10 overexpression confers enhanced starvation tolerance and lifespan extension, and alters architecture and developmental transitions. Significantly, double kin10 kin11 deficiency abrogates the transcriptional switch in darkness and stress signalling, and impairs starch mobilization at night and growth. These studies uncover surprisingly pivotal roles of KIN10/11 in linking stress, sugar and developmental signals to globally regulate plant metabolism, energy balance, growth and survival. In contrast to the prevailing view that sucrose activates plant SnRK1s (Snf1-related protein kinases)(3-6), our functional analyses of Arabidopsis KIN10/11 provide compelling evidence that SnRK1s are inactivated by sugars and share central roles with the orthologous yeast Snf1 and mammalian AMPK in energy signalling. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. VIB, Dept Mol Microbiol, B-3001 Louvain, Belgium. Katholieke Univ Leuven, Inst Bot & Microbiol, Mol Cell Biol Lab, B-3001 Louvain, Belgium. RP Rolland, F (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM baena@molbio.mgh.harvard.edu; filip.rolland@bio.kuleuven.be RI Thevelein, Johan/A-7897-2013; Baena-Gonzalez, Elena/G-5811-2013 OI Thevelein, Johan/0000-0002-2626-0180; Baena-Gonzalez, Elena/0000-0001-6598-3579 NR 45 TC 495 Z9 510 U1 19 U2 166 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 23 PY 2007 VL 448 IS 7156 BP 938 EP U10 DI 10.1038/nature06069 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 202OM UT WOS:000248912900049 PM 17671505 ER PT J AU Meyer, GS Hales, CA Amrein, PC Sharma, A Kradin, RL Swartz, MN AF Meyer, Gregg S. Hales, Charles A. Amrein, Philip C. Sharma, Amita Kradin, Richard L. Swartz, Morton N. TI A 61-year-old man with recurrent fevers - Intravascular large-B-cell lymphoma involving the lungs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; UNKNOWN ORIGIN; COMPUTED-TOMOGRAPHY; FDG-PET; CHEMOTHERAPY; PNEUMONIA; FEATURES C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pulm Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Meyer, GS (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 31 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 23 PY 2007 VL 357 IS 8 BP 807 EP 816 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 202MU UT WOS:000248906700011 PM 17715414 ER PT J AU Hansen, ML Gunn, PW Kaelber, DC AF Hansen, Matthew L. Gunn, Paul W. Kaelber, David C. TI Underdiagnosis of hypertension in children and adolescents SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; BLOOD-PRESSURE; UNITED-STATES; YOUNG-ADULTS; OVERWEIGHT; DISEASE; CHILDHOOD; ATHEROSCLEROSIS; POPULATION; PREVALENCE AB Context Pediatric hypertension is increasing in prevalence with the pediatric obesity epidemic. Diagnosis of hypertension in children is complicated because normal and abnormal blood pressure values vary with age, sex, and height and are therefore difficult to remember. Objectives To determine the frequency of undiagnosed hypertension and prehypertension and to identify patient factors associated with this underdiagnosis. Design, Setting, and Participants A cohort study of 14 187 children and adolescents aged 3 to 18 years who were observed at least 3 times for well-child care between June 1999 and September 2006 in the outpatient clinics in a large academic urban medical system in northeast Ohio. For children and adolescents who met criteria for hypertension or prehypertension at 3 or more well-child care visits, the proportion with a hypertension-related International Classification of Diseases, Ninth Revision code in the diagnoses list, problem list, or past medical history list of any visit was determined. Main Outcome Measures Proportion of children and adolescents with 3 or more elevated age-adjusted and height-adjusted blood pressure measurements at well-child care visits and with a diagnosis of hypertension or prehypertension documented in the electronic medical record. Multivariate logistic regression identified patient factors associated with a correct diagnosis. Results Of 507 children and adolescents (3.6%) who had hypertension, 131 (26%) had a diagnosis of hypertension or elevated blood pressure documented in the electronic medical record. Patient factors that increased the adjusted odds of a correct diagnosis were a 1-year increase in age over age 3 (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03-1.16), number of elevated blood pressure readings beyond 3 (OR, 1.77; 95% CI, 1.21-2.57), increase of 1% in height-for-age percentile (OR, 1.02; 95% CI, 1.01-1.03), having an obesity-related diagnosis (OR, 2.61; 95% CI, 1.49-4.55), and number of blood pressure readings in the stage 2 hypertension range (OR, 1.68; 95% CI, 1.29-2.19). Of 485 children and adolescents (3.4%) who had prehypertension, 55 (11%) had an appropriate diagnosis documented in the electronic medical record. Patient factors that increased the adjusted odds of being diagnosed with prehypertension included a 1-year increase in age over age 3 (OR, 1.21; 95% CI, 1.09-1.34) and number of elevated blood pressure readings beyond 3 (OR, 3.07; 95% CI, 2.20-4.28). Conclusions Hypertension and prehypertension were frequently undiagnosed in this pediatric population. Patient age, height, obesity-related diagnoses, and magnitude and frequency of abnormal blood pressure readings all increased the odds of diagnosis. C1 Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Oregon Hlth & Sci Univ, Sch Med, Dept Emergency Med, Portland, OR USA. Metrohlth Med Ctr, Dept Internal Med, Cleveland, OH USA. Metrohlth Med Ctr, Dept Pediat, Cleveland, OH USA. Partners Healthcare, Ctr Informat Technol Leadership, Boston, MA USA. Harvard Univ, Boston Childrens Hosp, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kaelber, DC (reprint author), 18 Upton St, Cambridge, MA 02139 USA. EM dkaelber@partners.org NR 24 TC 309 Z9 325 U1 0 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 22 PY 2007 VL 298 IS 8 BP 874 EP 879 DI 10.1001/jama.298.8.874 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 202CS UT WOS:000248880200021 PM 17712071 ER PT J AU Isselbacher, EM AF Isselbacher, Eric M. TI Dissection of the descending thoracic aorta - Looking into the future SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID STENT-GRAFT PLACEMENT C1 Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Thorac Aort Ctr, YAW 5800,55 Fruit St, Boston, MA 02114 USA. EM cisselbacher@partners.org NR 11 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 21 PY 2007 VL 50 IS 8 BP 805 EP 807 DI 10.1016/j.jacc.2007.04.072 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201DQ UT WOS:000248812100012 PM 17707187 ER PT J AU Liu, XS Huang, YM Pokreisz, P Vermeersch, P Marsboom, G Swinnen, M Verbeken, E Santos, J Pellens, M Giflijns, H Van de Werf, F Bloch, KD Janssens, S AF Liu, Xiaoshun Huang, Yariming Pokreisz, Peter Vermeersch, Pieter Marsboom, Glenn Swinnen, Marc Verbeken, Eric Santos, Jose Pellens, Marijke Giflijns, Hilde Van de Werf, Frans Bloch, Kenneth D. Janssens, Stefan TI Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID INHALED NO; IN-VIVO; PLATELET-AGGREGATION; ISOSORBIDE DINITRATE; VENTRICULAR-FUNCTION; PRIMARY ANGIOPLASTY; BLOOD-FLOW; INJURY; HEART; PERFUSION AB Objectives The purpose of this study was to test if nitric oxide (NO) could improve microvascular perfusion and decrease tissue injury in a porcine model of myocardial ischemia and reperfusion (I/R). Background Inhaled NO is a selective pulmonary vasodilator with biologic effects in remote vascular beds. Methods In 37 pigs, the midportion of the left anterior descending coronary artery was occluded for 50 min followed by 4 h of reperfusion. Pigs were treated with a saline infusion (control; n = 14), intravenous nitroglycerin (IV-NTG) at 2 mu g/kg/min (n = 11), or inhaled nitric oxide (iNO) at 80 parts per million (n = 12) beginning 10 min before balloon deflation and continuing throughout reperfusion. Results Total myocardial oxidized NO species in the infarct core was greater in the iNO pigs than in the control or IV-NTG pigs (0.60 +/- 0.05 nmol/mg tissue vs. 0.40 +/- 0.03 nmol/mg tissue and 0.40 +/- 0.02 nmol/mg tissue, respectively; p < 0.01 for both). Infarct size, expressed as percentage of left ventricle area at risk (AAR), was smaller in the iNO pigs than in the control or IV-NTG pigs (31 +/- 6% AAR vs. 58 +/- 7% AAR and 46 +/- 7% AAR, respectively; p < 0.05 for both) and was associated with less creatine phosphokinase-MB release. Inhaled NO improved endocardial and epicardial blood flow in the infarct zone, as measured using colored microspheres (p < 0.001 vs. control and IV-NTG). Moreover, NO inhalation reduced leukocyte infiltration, as reflected by decreased cardiac myeloperoxidase activity (0.8 +/- 0.2 U/mg tissue vs. 2.3 +/- 0.8 U/mg tissue in control and 1.4 +/- 0.4 U/mg tissue in IV-NTG; p < 0.05 for both) and decreased cardiomyocyte apoptosis in the infarct border zone. Conclusions Inhalation of NO just before and during coronary reperfusion significantly improves microvascular perfusion, reduces infarct size, and may offer an attractive and novel treatment of myocardial infarction. C1 Univ Leuven, Flanders Interuniv Inst Biotechnol, Dept Cardiol, Louvain, Belgium. Univ Leuven, Flanders Interuniv Inst Biotechnol, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium. Univ Leuven, Dept Pathol, Louvain, Belgium. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Janssens, S (reprint author), Univ Leuven, Flanders Interuniv Inst Biotechnol, Dept Cardiol, Louvain, Belgium. EM stefan-janssens@uz.kuleuven.ac.be RI Vermeersch, Pieter/M-8352-2016; OI Van de Werf, Frans/0000-0001-9479-7767 NR 55 TC 57 Z9 61 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 21 PY 2007 VL 50 IS 8 BP 808 EP 817 DI 10.1016/j.jacc.2007.04.069 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201DQ UT WOS:000248812100013 PM 17707188 ER PT J AU Colijn, C Cohen, T Murray, M AF Colijn, Caroline Cohen, Ted Murray, Megan TI Emergent heterogeneity in declining tuberculosis epidemics SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE epidemiology; networks; mathematical model; delay model; reinfection ID MYCOBACTERIUM-TUBERCULOSIS; REINFECTION; INFECTION; MODEL; TRANSMISSION; POPULATIONS; NETWORKS; CONTACT; DISEASE AB Tuberculosis is a disease of global importance: over 2 million deaths are attributed to this infectious disease each year. Even in areas where tuberculosis is in decline, there are sporadic outbreaks which are often attributed either to increased host susceptibility or increased strain transmissibility and virulence. Using two mathematical models, we explore the role of the contact structure of the population, and find that in declining epidemics, localized outbreaks may occur as a result of contact heterogeneity even in the absence of host or strain variability. We discuss the implications of this finding for tuberculosis control in low incidence settings. (c) 2007 Published by Elsevier Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Social Med & Hlth Inequal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Colijn, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. EM ccolijn@hsph.harvard.edu RI Cohen, Ted/G-8101-2011 FU NIAID NIH HHS [K08 AI055985, K08 AI055985-05] NR 33 TC 12 Z9 12 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD AUG 21 PY 2007 VL 247 IS 4 BP 765 EP 774 DI 10.1016/j.jtbi.2007.04.015 PG 10 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 203RC UT WOS:000248990700017 PM 17540410 ER PT J AU Wu, HM Sharp, GC Zhao, QY Shirato, H Jiang, SB AF Wu, Huanmei Sharp, Gregory C. Zhao, Qingya Shirato, Hiroki Jiang, Steve B. TI Statistical analysis and correlation discovery of tumor respiratory motion SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID REAL-TIME TUMOR; RADIATION-THERAPY; ORGAN MOTION; RADIOTHERAPY; TRACKING; FEASIBILITY; MODEL AB Tumors, especially in the thorax and abdomen, are subject to respiratory motion, and understanding the structure of respiratory motion is a key component to the management and control of disease in these sites. We have applied statistical analysis and correlation discovery methods to analyze and mine tumor respiratory motion based on a finite state model of tumor motion. Aggregates ( such as minimum, maximum, average and mean), histograms, percentages, linear regression and multi-round statistical analysis have been explored. The results have been represented in various formats, including tables, graphs and text description. Different graphs, for example scatter plots, clustered column figures, 100% stacked column figures and box-whisker plots, have been applied to highlight different aspects of the results. The internal tumor motion from 42 lung tumors, 30 of which have motion larger than 5 mm, has been analyzed. Results for both inter-patient and intra-patient motion characteristics, such as duration and travel distance patterns, are reported. New knowledge of patient-specific tumor motion characteristics have been discovered, such as expected correlations between properties. The discovered tumor motion characteristics will be utilized in different aspects of image-guided radiation treatment, including treatment planning, online tumor motion prediction and real-time radiation dose delivery. C1 IUPUI, Purdue Sch Engn & Technol, Comp & Informat Technol, Indianapolis, IN 46202 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 060, Japan. Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA. RP Wu, HM (reprint author), IUPUI, Purdue Sch Engn & Technol, Comp & Informat Technol, Indianapolis, IN 46202 USA. EM hw9@iupui.edu RI Shirato, Hiroki/A-7068-2010 FU NCI NIH HHS [1R21 CA 110177-01A1] NR 19 TC 27 Z9 32 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 21 PY 2007 VL 52 IS 16 BP 4761 EP 4774 DI 10.1088/0031-9155/52/16/004 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 205CC UT WOS:000249089700004 PM 17671334 ER EF