FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Samaha, FF Szapary, PO Iqbal, N Williams, MM Bloedon, LT Kochar, A Wolfe, ML Rader, DJ AF Samaha, FF Szapary, PO Iqbal, N Williams, MM Bloedon, LT Kochar, A Wolfe, ML Rader, DJ TI Effects of rosiglitazone on lipids, adipokines, and inflammatory markers in nondiabetic patients with low high-density lipoprotein cholesterol and metabolic syndrome SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE adipocytokines; lipids; inflammation; lipoprotein metabolism; arteriosclerosis ID TYPE-2 DIABETES-MELLITUS; RANDOMIZED CONTROLLED-TRIAL; IMPROVES GLYCEMIC CONTROL; ACTIVATED RECEPTOR-GAMMA; ARTERY-DISEASE PATIENTS; C-REACTIVE PROTEIN; ADIPOSE-TISSUE; PPAR-GAMMA; PIOGLITAZONE; METFORMIN AB Background - PPAR-gamma agonists improve insulin sensitivity and glycemic control in type 2 diabetes and may reduce atherosclerosis progression. Thus, PPAR-gamma agonists may be an effective therapy for metabolic syndrome. However, the full spectrum of potentially antiatherogenic mechanisms of PPAR-gamma agonists have not been fully tested in nondiabetic patients with metabolic syndrome. Methods and Results - We performed a prospective, double-blinded, placebo-controlled study of 60 nondiabetic subjects with low high-density lipoprotein cholesterol ( HDL-C) level and metabolic syndrome to rosiglitazone 8 mg daily or placebo for 12 weeks. We found no significant effect of rosiglitazone on HDL-C ( + 5.5% versus + 5.8%, P = 0.89), and an increase in total cholesterol ( + 8% versus + 1%; P = 0.03). Nevertheless, rosiglitazone significantly increased adiponectin ( + 168% versus + 25%; P = 0.001), and lowered resistin ( - 6% versus + 4%; P = 0.009), C- reactive protein ( - 32% versus + 36%, P = 0.002), interleukin ( IL)-6 ( - 22% versus + 4%, P < 0.001), and soluble tumor-necrosis factor-alpha receptor-2 ( - 5% versus + 7%, P < 0.001). Conclusions - These findings suggest that rosiglitazone, presumably through its PPAR-gamma agonist properties, has direct effects on inflammatory markers and adipokines in the absence of favorable lipid effects. These findings may help explain the mechanism underlying the possible antiatherosclerotic effects of rosiglitazone. C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Div Cardiovasc, Dept Med, Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Cardiovasc Inst, Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. RP Samaha, FF (reprint author), Philadelphia VA Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM rick.samaha@med.va.gov FU NCRR NIH HHS [M01-RR00040] NR 30 TC 88 Z9 101 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2006 VL 26 IS 3 BP 624 EP 630 DI 10.1161/01.ATV.0000200136.567196.30 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 012WW UT WOS:000235372600029 PM 16357312 ER PT J AU Cooper, RA AF Cooper, RA TI Adapting: Financial planning for a life with multiple sclerosis. SO ASSISTIVE TECHNOLOGY LA English DT Book Review C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM rcooper@pitt.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD SPR PY 2006 VL 18 IS 1 BP 122 EP 122 PG 1 WC Rehabilitation SC Rehabilitation GA 046UZ UT WOS:000237837900011 ER PT J AU Stack, EC Smith, KM Ryu, H Cormier, K Chen, MH Hagerty, SW Del Signore, SJ Cudkowicz, ME Friedlander, RM Ferrante, RJ AF Stack, EC Smith, KM Ryu, H Cormier, K Chen, MH Hagerty, SW Del Signore, SJ Cudkowicz, ME Friedlander, RM Ferrante, RJ TI Combination therapy using minocycline and coenzyme Q(10) in R6/2 transgenic Huntington's disease mice SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Huntington's disease; therapy; R6/2 mice; coenzyme Q(10); minocycline ID CYTOCHROME-C RELEASE; MOUSE MODELS; REMACEMIDE; SCLEROSIS; BRAIN AB Huntington's disease (HD) is a fatal neurodegenerative disorder of genetic origin with no known therapeutic intervention that can slow or halt disease progression. Transgenic murine models of HD have significantly improved the ability to assess potential therapeutic strategies. The R6/2 murine model of HD, which recapitulates many aspects of human HD, has been used extensively in pre-clinical HD therapeutic treatment trials. Of several potential therapeutic candidates, both minocycline and coenzyme Q(10)(CoQ(10)) have been demonstrated to provide significant improvement in the R6/2 mouse. Given the specific cellular targets of each compound, and the broad array of abnormalities thought to underlie HID, we sought to assess the effects of combined minocycline and CoQ(10) treatment in the R6/2 mouse. Combined minocycline and CoQ(10) therapy provided an enhanced beneficial effect, ameliorating behavioral and neuropathological alterations in the R6/2 mouse. Minocycline and CoQ(10) treatment significantly extended survival and improved rotarod performance to a greater degree than either minocycline or CoQ(10) alone. In addition, combined minocycline and CoQ(10) treatment attenuated gross brain atrophy, striatal neuron atrophy, and huntingtin aggregation in the R6/2 mice relative to individual treatment. These data suggest that combined minocycline and CoQ(10) treatment may offer therapeutic benefit to patients suffering from HD. (c) 2005 Elsevier B.V. All rights reserved. C1 Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. Bedford VA Med Ctr, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol & Psychiat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg,Neuropoptosis Lab, Boston, MA 02115 USA. RP Ferrante, RJ (reprint author), Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. EM rjferr@bu.edu RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 FU NINDS NIH HHS [NS039324, NS045242, NS045806] NR 37 TC 71 Z9 79 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD MAR PY 2006 VL 1762 IS 3 BP 373 EP 380 DI 10.1016/j.bbadis.2005.11.002 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 013VV UT WOS:000235439000014 PM 16364609 ER PT J AU Galande, AK Weissleder, R Tung, CH AF Galande, AK Weissleder, R Tung, CH TI Fluorescence probe with a pH-sensitive trigger SO BIOCONJUGATE CHEMISTRY LA English DT Article ID TUMOR; PEPTIDES; DESIGN; CANCER AB Acid-catalyzed hydrolysis was used as the mechanism to design a new type of environmentally sensitive fluorescence probe. A mild and selective periodate oxidation of the 2-amino alcohol of serine in the presence of a disulfide bond was developed to prepare dialdehyde peptides. Two identical fluorochrome hydrazide derivatives were then linked to the dialdehyde peptide forming an acid-labile hydrazone linkage. This self-quenched probe is weakly fluorescent at a physiological pH of 7.4 but shows more than 3-fold fluorescence enhancement at pH 4.5. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Rm 5410, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R21 CA114149, P50-CA86355, R01 CA99385] NR 25 TC 24 Z9 25 U1 4 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 2006 VL 17 IS 2 BP 255 EP 257 DI 10.1021/bc050330e PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 024WD UT WOS:000236226200001 PM 16536452 ER PT J AU Gould, GG Altamirano, AV Javors, MA Frazer, A AF Gould, GG Altamirano, AV Javors, MA Frazer, A TI A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters SO BIOLOGICAL PSYCHIATRY LA English DT Article DE serotonin transporter; norepinephrine transporter; dual uptake inhibitor; venlafaxine; amitriptyline; quantitative autoradiography ID REUPTAKE INHIBITOR VENLAFAXINE; SPECIES-SCANNING MUTAGENESIS; RAT-BRAIN; IN-VIVO; QUANTITATIVE AUTORADIOGRAPHY; CYTOCHROME-P450 ENZYMES; H-3 CYANOIMIPRAMINE; DRUG-INTERACTIONS; DORSAL RAPHE; UPTAKE SITES AB Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT. Serotonergic effects occur with lower doses, whereas both serotonergic and noradrenergic effects occur with higher doses of venlafaxine. Chronic treatment of rats with selective serotonin reuptake inhibitors decreases NET binding sites. We hypothesized venlafaxine would affect monoamine transporters dose-dependently, with low doses causing selective reduction of SERT binding sites and higher doses reducing both SERT and NET binding sites. Rats were treated for 21 days with a low (15 mg/kg/day) or high (70 mg/kg/day) dose of venlafaxine, vehicle, or other antidepressants. The SERT and NET density was determined by quantitative autoradiography. Neither dose of venlafaxine nor amitriptyline reduced binding to either the SERT or NET. In rats with noradrenergic terminals destroyed by 6-hydroxydopamine, venlafaxine still failed to reduce SERT binding. Alsom rats treated simultaneously with sertraline plus desipramine exhibited reductions in both SERT and NET binding. Chronic venlafaxine treatment affected SERT and NET binding differently from paroxetine or desipramine. The inability of venlafaxine to reduce SERT or NET binding sites is not due to its dual uptake inhibiting properties. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Gould, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM gouldg@uthscsa.edu OI Gould, Georgianna/0000-0002-5470-8763 FU NIMH NIH HHS [MH57001] NR 57 TC 37 Z9 37 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2006 VL 59 IS 5 BP 408 EP 414 DI 10.1016/j.biopsych.2005.07.011 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 019PY UT WOS:000235850400004 PM 16140280 ER PT J AU Green, MF Nuechterlein, KH Breitmeyer, B Mintz, J AF Green, MF Nuechterlein, KH Breitmeyer, B Mintz, J TI Forward and backward visual masking in unaffected siblings of schizophrenic patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE visual masking; schizophrenia; vulnerability; visual processing; backward masking; siblings ID INFORMATION-PROCESSING DEFICITS; NEGATIVE-SYMPTOM SCHIZOPHRENIA; VULNERABILITY; CHANNELS; PERFORMANCE; MECHANISM; TRANSIENT; DISORDER; SYSTEM; MANIA AB Visual masking tasks assess the earliest stages of visual processing. This study examined visual masking performance for forward and backward masking tasks in siblings of schizophrenic patients and healthy comparison subjects. A staircase method was used to ensure that unmasked target identification was equivalent across subjects to eliminate differences due to discrimination of simple perceptual inputs. Four computerized visual masking tasks were administered to 43 siblings of patients and 42 normal comparison subjects. The tasks included: 1) locating a target; 2) identifying a target with a high-energy mask; 3) identifying a target with a low-energy mask; and 4) a paracontrast/metacontrast procedure with nonoverlapping target and mask. Across masking conditions, there was a significant group by forward/backward interaction, meaning that siblings showed a larger difference from control subjects in backward versus forward masking. This group difference was more pronounced in the location condition. These results support the theory that visual masking procedures may be indicators of vulnerability to schizophrenia. The pattern of findings in this report (larger group differences on backward versus forward masking and on the location condition) suggests that the activity of transient visual channels may be particularly linked to vulnerability. C1 Univ Calif Los Angeles, NPI, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Houston, Dept Psychol, Houston, TX 77004 USA. RP Green, MF (reprint author), Univ Calif Los Angeles, NPI, Geffen Sch Med, Dept Psychiat & Biobehav Sci, 300 Med Plaza,Room 2263, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu FU NIMH NIH HHS [MH-43292, MH-30911, MH-37705] NR 44 TC 29 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2006 VL 59 IS 5 BP 446 EP 451 DI 10.1016/j.biopsych.2005.06.035 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 019PY UT WOS:000235850400010 PM 16139818 ER PT J AU Smoller, JW Biederman, J Arbeitman, L Doyle, AE Fagerness, J Perlis, RH Sklar, P Faraone, SV AF Smoller, JW Biederman, J Arbeitman, L Doyle, AE Fagerness, J Perlis, RH Sklar, P Faraone, SV TI Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; association; 5HT1B; genetic; inattentive subtype ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; STRIATAL DOPAMINE RELEASE; SEROTONIN RECEPTOR; KNOCKOUT MICE; 5-HT1B RECEPTORS; GENOMEWIDE SCAN; MESSENGER-RNA; LINKAGE; FAMILY AB Preclinical and genetic studies have implicated the 5HT1B receptor gene (HTR1B) in attention-deficit/hyperactivity disorder (ADHD). Association with a single nucleotide polymorphism (SNP; G861C) has been observed, but more extensive linkage disequilibrium analyses have not been reported. To examine haplotype structure, we genotyped 21 SNPs in and around the gene in 12 multigenerational CEPH pedigrees. We identified a haplotype block encompassing HTR1B and performed haplotype and single-marker association analyses for the eight SNPs within or flanking this block in 229 families of ADHD probands. In light of previous studies suggesting distinct genetic influences on ADHD subtypes, we also examined association with the inattentive and combined subtypes. We observed nonsignificant overtransmission of the G861 allele to ADHD offspring (one-tailed p = .07). Single-marker and haplotype tests of a haplotype block encompassing HTR1B revealed no other associations with ADHD. However, this haplotype block was associated with the inattentive subtype (global p < .01). Additionally, three SNPs in this block were nominally (p <.05) associated with the inattentive subtype, although these did not remain significant after correction for multiple testing. As reported in previous studies, we found paternal overtransmission of the G861 allele to offspring with ADHD; this appeared to be largely attributable to inattentive cases. These analyses suggest that variation in the HTR1B gene may primarily affect the inattentive subtype of ADHD. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Pediat Psychopharmacol Unit, Boston, MA 02115 USA. SUNY Upstate Med Univ, Med Genet Res Program, Syracuse, NY USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37694, R01HD37999]; NIMH NIH HHS [K-08 MH01770, R01MH66877] NR 48 TC 60 Z9 64 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2006 VL 59 IS 5 BP 460 EP 467 DI 10.1016/j.biopsych.2005.07.017 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 019PY UT WOS:000235850400012 PM 16197923 ER PT J AU Sitnikova, T West, WC Kuperberg, GR Holcomb, PJ AF Sitnikova, T West, WC Kuperberg, GR Holcomb, PJ TI The neural organization of semantic memory: Electrophysiological activity suggests feature-based segregation SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE semantics; human; brain mapping; cerebral cortex; anatomy; anatomy; physiology; visual perception; evoked potentials; electroencephalography ID EVENT-RELATED POTENTIALS; POSITRON EMISSION TOMOGRAPHY; DUAL-CODING THEORY; BRAIN POTENTIALS; CORTICAL REGIONS; MANIPULATABLE OBJECTS; CATEGORY-SPECIFICITY; MODALITY SPECIFICITY; SCALP DISTRIBUTIONS; LEXICAL RETRIEVAL AB Despite decades of research, it remains controversial whether semantic knowledge is anatomically segregated in the human brain. To address this question, we recorded event-related potentials (ERPs) while participants viewed pictures of animals and tools. Within the 200-600-ms epoch after stimulus presentation, animals (relative to tools) elicited an increased anterior negativity that, based on previous ERP studies, we interpret as associated with semantic processing of visual object attributes. In contrast, tools (relative to animals) evoked an enhanced posterior left-lateralized negativity that, according to prior research, might reflect accessing knowledge of characteristic motion and/or more general functional properties of objects. These results support the hypothesis of the neuroanatomical knowledge organization at the level of object features: the observed neurophysiological activity was modulated by the features that were most salient for object recognition. The high temporal resolution of ERPs allowed us to demonstrate that differences in processing animals and tools occurred specifically within the time-window encompassing semantic analysis. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Sitnikova, T (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM tatiana@nmr.mgh.harvard.edu FU NICHD NIH HHS [R01 HD025889, HD25889, R01 HD025889-16, R01 HD043251, R01 HD043251-04, R37 HD025889] NR 99 TC 35 Z9 36 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD MAR PY 2006 VL 71 IS 3 BP 326 EP 340 DI 10.1016/j.biopsycho.2005.07.003 PG 15 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 018JO UT WOS:000235760700014 PM 16129544 ER PT J AU Pavletic, SZ Martin, P Lee, SJ Mitchell, S Jacobsohn, D Cowen, EW Turner, ML Akpek, G Gilman, A McDonald, G Schubert, M Berger, A Bross, P Chien, JW Couriel, D Dunn, JP Fall-Dickson, J Farrell, A Flowers, MED Greinix, H Hirschfeld, S Gerber, L Kim, S Knobler, RT Lachenbruch, PA Miller, FW Mittleman, B Papadopoulos, E Parsons, SK Przepiorka, D Robinson, M Ward, M Reeve, B Rider, LG Shulman, H Schultz, KR Weisdorf, D Vogelsang, GB AF Pavletic, SZ Martin, P Lee, SJ Mitchell, S Jacobsohn, D Cowen, EW Turner, ML Akpek, G Gilman, A McDonald, G Schubert, M Berger, A Bross, P Chien, JW Couriel, D Dunn, JP Fall-Dickson, J Farrell, A Flowers, MED Greinix, H Hirschfeld, S Gerber, L Kim, S Knobler, RT Lachenbruch, PA Miller, FW Mittleman, B Papadopoulos, E Parsons, SK Przepiorka, D Robinson, M Ward, M Reeve, B Rider, LG Shulman, H Schultz, KR Weisdorf, D Vogelsang, GB TI Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. Response Criteria Working Group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogencic cell transplantation; response criteria; consensus ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; SLEEP QUALITY INDEX; CANCER-PATIENTS; PINCH STRENGTH; PSYCHOMETRIC EVALUATION; RHEUMATOID-ARTHRITIS; SYMPTOM-INVENTORY; RANDOMIZED-TRIAL; ACTIVITIES SCALE AB The lack of standardized criteria for quantitative measurement of therapeutic response in clinical trials poses a major obstacle for the development of new agents in chronic g-raft-versus-host disease (GVHD). This consensus document was developed to address several objectives for response criteria to be used in chronic GVHD-related clinical trials. The proposed measures should be practical for use both by transplantation and nontransplantation medical providers, adaptable for use in adults and in children, and focused on the most important chronic GVHD manifestations. The measures should also give preference to quantitative, rather than semiquantitative, measures; capture information regarding signs, symptoms, and function separately from each other; and use validated scales whenever possible to demonstrate improved patient outcomes and meet requirements for regulatory approval of novel agents. Based on these criteria, we propose a set of measures to be considered for use in clinical trials, and forms for data collection are provided (http://www.asbmt.org/ GvHDForms). Measures should be made at 3-month intervals and whenever major changes are made in treatment. Provisional definitions of complete response, partial response, and progression are proposed for each organ and for overall outcomes. The proposed response criteria are based on current expert consensus opinion and are intended to improve consistency in the conduct and reporting of chronic GVHD trials, but their use remains to be demonstrated in practice. (C) 2006 American Society for Blood and Marrow Transplantation. C1 NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Chicago, IL 60614 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Natl Inst Nursing Res, NIH, Bethesda, MD USA. Med Univ Vienna, Vienna, Austria. NIEHS, NIH, Bethesda, MD USA. NIAMSD, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Tufts New England Med Ctr, Boston, MA USA. Univ Tennessee, Memphis, TN USA. NEI, NIH, Bethesda, MD 20892 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. Univ Minnesota, Minneapolis, MN USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov RI Hirschfeld, Steven/E-2987-2016; OI Hirschfeld, Steven/0000-0003-0627-7249; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS; NCI NIH HHS [R01 CA118953] NR 66 TC 233 Z9 245 U1 2 U2 5 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2006 VL 12 IS 3 BP 252 EP 266 DI 10.1016/j.bbmt.2006.01.008 PG 15 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 024JF UT WOS:000236190600002 PM 16503494 ER PT J AU Koporc, Z Bigenzahn, S Blaha, P Fariborz, E Selzer, E Sykes, M Muehlbacher, F Wekerle, T AF Koporc, Z Bigenzahn, S Blaha, P Fariborz, E Selzer, E Sykes, M Muehlbacher, F Wekerle, T TI Induction of mixed chimerism through transplantation of CD45-congenic mobilized peripheral blood stem cells after nonmyeloablative irradiation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE mixed chimerism; mouse; congenic; peripheral blood stem cells (PBSC); bone marrow transplantation (BMT) ID COLONY-STIMULATING FACTOR; BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC PROGENITOR CELLS; DONOR-SPECIFIC TOLERANCE; ALLOGENEIC TRANSPLANTATION; COSTIMULATION BLOCKADE; FLT3 LIGAND; ENGRAFTMENT; MICE; DISEASE AB Clinical translation of the mixed-chimerism approach for inducing transplantation tolerance would be facilitated if mobilized peripheral blood stem cells (mPBSCs) could be used instead of bone marrow cells (BMCs). Because the use of mPBSCs for this purpose has not been investigated in nonmyeloablative murine protocols, we explored the engraftment potential of mPBSCs in a CD45-congenic model as a first step. After 2, 1.5, or 1 Gy of total body irradiation, CD45.1 B6 hosts received unseparated granulocyte colony-stimulating factor-mobilized CD45.2 B6 PBSCs or unseparated CD45.2 B6 BMCs. The same total cell numbers, or aliquots of mPBSCs and BMCs containing similar numbers of c-kit(+) cells, were transplanted both with and without a short course of rapamycin-based immunosuppression (IS). Transplantation of mPBSCs induced long-term multilineage macrochimerism, but chimerism levels were significantly lower than among recipients of the same number of BMCs. Transplanting aliquots containing similar numbers of c-kit(+) cells reduced the difference between mPBSCs and BMCs, but lower levels of chimerism were nonetheless observed in mPBSC recipients. Chimerism levels correlated more closely with the number of transplanted progenitor cells as determined by colony-forming unit assays. IS did not affect chimerism levels, indicating that the donor CD45 isoform, or other minor disparities do not pose a major barrier to engraftment. Our findings indicate that under nonmyeloablative conditions, progenitor cells contained in mPBSCs have an engraftment capacity similar to progenitor cells from BMCs, allowing induction of lasting mixed chimerism with moderate cell numbers. On a cell-per-cell basis, unseparated BMCs have some advantages that may be minimized if tire number of progenitor cells is equalized. These results are expected to facilitate the development of mPBSC-based allogencic tolerance protocols. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Med Univ Vienna, Vienna Gen Hosp, Dept Surg, Div Transplantat, A-1090 Vienna, Austria. Med Univ Vienna, Vienna Gen Hosp, Dept Internal Med 1, Div Hematol, A-1090 Vienna, Austria. Med Univ Vienna, Vienna Gen Hosp, Dept Radiotherapy & Radiobiol, A-1090 Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Wekerle, T (reprint author), Med Univ Vienna, Vienna Gen Hosp, Dept Surg, Div Transplantat, Waehringer Guertel 18, A-1090 Vienna, Austria. EM Thomas.Wekerle@meduniwien.ac.at RI Selzer, Edgar/K-7547-2015; OI Wekerle, Thomas/0000-0001-5159-2796 NR 41 TC 9 Z9 9 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2006 VL 12 IS 3 BP 284 EP 292 DI 10.1016/j.bbmt.2005.11.011 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 024JF UT WOS:000236190600005 PM 16503497 ER PT J AU Hahn, T Wall, D Camitta, B Davies, S Dillon, H Gaynon, P Larson, RA Parsons, S Seidenfeld, J Weisdorf, D McCarthy, PL AF Hahn, T Wall, D Camitta, B Davies, S Dillon, H Gaynon, P Larson, RA Parsons, S Seidenfeld, J Weisdorf, D McCarthy, PL TI The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of acute lymphoblastic leukemia in adults SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Texas Transplant Inst, San Antonio, TX USA. Med Coll Wisconsin, Midwest Childrens Ctr, Milwaukee, WI 53226 USA. Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. Cincinnati Childrens Hosp & Med Ctr, Cincinnati, OH USA. Leukemia & Lymphoma Soc, White Plains, NY USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Chicago, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Boston, MA 02111 USA. Blue Cross & Blue Shield Assoc Technol Evaluat Ct, Chicago, IL USA. Univ Minnesota, Minneapolis, MN USA. RP Hahn, T (reprint author), Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2006 VL 12 IS 3 BP 368 EP 369 DI 10.1016/j.bbmt.2006.02.002 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 024JF UT WOS:000236190600015 ER PT J AU Hahn, T Wall, D Camitta, B Davies, S Dillon, H Gaynon, P Larson, RA Parsons, S Seidenfeld, J Weisdorf, D McCarthy, PL AF Hahn, T Wall, D Camitta, B Davies, S Dillon, H Gaynon, P Larson, RA Parsons, S Seidenfeld, J Weisdorf, D McCarthy, PL TI The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of acute lymphoblastic leukemia in children SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Texas Transplant Inst, San Antonio, TX USA. Med Coll Wisconsin, Midwest Childrens Hosp, Milwaukee, WI 53226 USA. Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. Cincinnati Childrens Hosp & Med Ctr, Cincinnati, OH USA. Leukemia & Lymphoma Soc, White Plains, NY USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Chicago, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Boston, MA 02111 USA. Blue Cross & Blue Shield Assoc Technol Evaluat Ct, Chicago, IL USA. Univ Minnesota, Minneapolis, MN USA. RP Hahn, T (reprint author), Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2006 VL 12 IS 3 BP 370 EP 371 DI 10.1016/j.bbmt.2006.02.001 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 024JF UT WOS:000236190600016 ER PT J AU Skazinik-Wikiel, ME Kaneko-Tarui, T Kashiwagi, A Pru, JK AF Skazinik-Wikiel, ME Kaneko-Tarui, T Kashiwagi, A Pru, JK TI Sphingosine-1-phosphate receptor expression and signaling correlate with uterine prostaglandin-endoperoxide synthase 2 expression and angiogenesis during early pregnancy SO BIOLOGY OF REPRODUCTION LA English DT Article DE angiogenesis; cyclooxygenase-2; decidua; developmental biology; G-protein-coupled receptor; implantation; pregnancy; signal transduction; sphingosine-1-phosphate; uterus ID CYCLOOXYGENASE GENE-EXPRESSION; ENDOMETRIAL STROMAL CELLS; PROTEIN-COUPLED RECEPTOR; HUMAN ENDOTHELIAL-CELLS; SPHINGOSINE 1-PHOSPHATE; LYSOPHOSPHATIDIC ACID; EMBRYO IMPLANTATION; MOUSE UTERUS; GROWTH-FACTORS; UP-REGULATION AB Signaling mechanisms coordinating uterine angiogenesis and tissue remodeling during decidualization are not completely understood. Prostanoid signaling is thought to play a functionally important role in each of these events. In the present study, we demonstrate that the subfamily of G-protein-coupled receptors that binds and becomes activated by the terminal signaling lipid in the sphingolipid pathway, sphingosine-1-phosphate (SIP), were expressed during uterine decidualization. Three of the five known S1P receptors, termed endothelial differentiation genes (Edg; Edg1, Edg3, and Edg5) were upregulated in the uterine deciduum from Day of Pregnancy (DOP) 4.5 to 7.5, while Edg6 and Edg8 expression remained unchanged. Consistent with angiogenesis in general during decidualization, we believe EDG1 and EDG5 to be regulated by the embryo because no microvascular expression for these receptors was observed in oil-induced deciduomas. Observed expression of EDG1 and EDG5 showed a similar expression pattern to that previously reported for prostaglandin-endoperoxide synthase 2 (PTGS2), transitioning from the sublumenal stromal compartment in the antimesometrial pole (DOP 5) to the microvasculature of the mesometrial pole (DOP 7). Furthermore, these two receptors colocalized with PTGS2 at three additional sites at the maternal:fetal interface throughout pregnancy. Treatment of cultured predecidualized stromal cells with SIP resulted in upregulation of Ptgs2 mRNA and PTGS2 protein, but not the downstream enzyme prostacyclin synthase. These combined results suggest the existence of a link between the sphingolipid and prostanoid signaling pathways in uterine physiology, and that, based on their expression pattern, S1P receptors function to coordinate uterine mesometrial angiogenesis during the implantation phase of early gestation. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Pru, JK (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Room 6613B,Bldg 149,149 13th St, Charlestown, MA 02129 USA. EM jpru@partners.org RI Kaneko-Tarui, Tomoko/E-3319-2010 FU NIEHS NIH HHS [R01-ES012070] NR 55 TC 22 Z9 22 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 2006 VL 74 IS 3 BP 569 EP 576 DI 10.1095/biolreprod.105.046714 PG 8 WC Reproductive Biology SC Reproductive Biology GA 014AV UT WOS:000235452000016 PM 16319286 ER PT J AU Pavoor, PV Gearing, BP Muratoglu, O Cohen, RE Bellare, A AF Pavoor, PV Gearing, BP Muratoglu, O Cohen, RE Bellare, A TI Wear reduction of orthopaedic bearing surfaces using polyelectrolyte multilayer nanocoatings SO BIOMATERIALS LA English DT Article DE wear mechanisms; polyethylene; joint replacements; total hip replacement prosthesis ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL JOINT REPLACEMENT; LAYER POLYMER-FILMS; DIAMOND-LIKE CARBON; CROSS-LINKING; DLC COATINGS; THIN-FILMS; ULTRATHIN; PROSTHESES; ELECTROCHROMISM AB This work explores the use of conformal polyelectrolyte multilayer (PEM) coatings for wear reduction of orthopedic bearing surfaces. These films, with easily tunable architectures, provide excellent adhesion to a wide variety of metallic, plastic, and ceramic Substrates. For this study, PEM films, only a few hundred nanometers thick, were assembled by sequential adsorption of poly(acrylic acid) and poly(allylamine hydrochloride). It was observed that the pH of the polylectrolyte solutions used for film assembly needs careful consideration to avoid any adverse effects on film structure when exposed to physiological conditions of pH and ionic strength. The wear reducing capacity of these coatings in the presence of bovine calf serum-lubricant solution was established for metal/metal systems at the meso/microscale over 30 cycles of reciprocating motion, as well as for the commonly used metal/ultra-high molecular weight polyethylene (UHMWPE) system over 500,000 cycles of bi-directional motion in a macroscale pin-on-disk test. In the latter case, the use of the films reduced UHMWPE wear by LIP to 33% when compared with the uncoated control. This is the first clinically relevant laboratory demonstration of the wear-reducing ability of these films. Further optimization will be needed before this novel class of materials can be used by the orthopedic community. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Orthopaed Nanotechnol Lab, Boston, MA 02115 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Bellare, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Orthopaed Nanotechnol Lab, 75 Francis St,MRB 106, Boston, MA 02115 USA. EM anuj@alum.mit.edu NR 39 TC 22 Z9 22 U1 4 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAR PY 2006 VL 27 IS 8 BP 1527 EP 1533 DI 10.1016/j.biomaterials.2005.08.022 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 004DJ UT WOS:000234731900038 PM 16174529 ER PT J AU Wannomae, KK Christensen, SD Freiberg, AA Bhattacharyya, S Harris, WH Muratoglu, OK AF Wannomae, KK Christensen, SD Freiberg, AA Bhattacharyya, S Harris, WH Muratoglu, OK TI The effect of real-time aging on the oxidation and wear of highly cross-linked UHMWPE acetabular liners SO BIOMATERIALS LA English DT Article DE highly cross-linked polyethylene; wear; oxidation; free radical; acetabular component ID MOLECULAR-WEIGHT POLYETHYLENE; GAMMA-STERILIZATION; HIP; RESISTANCE; WALKING; CUPS AB Irradiation decreases the wear of ultra-high molecular weight polyethylene (UHMWPE) but generates residual free radicals, precursors to long-term oxidation. Melting or annealing is used in quenching free radicals. We hypothesized that irradiated and once-annealed UHMWPE would oxidize while irradiated and melted UHMWPE would not, and that the oxidation in the former would increase wear. Acetabular liners were real-time aged by immersion in an aqueous environment that closely mimicked the temperature and oxygen concentration of synovial fluid. After 95 weeks of real-time aging, once-annealed components were oxidized; the melted components were not. The wear rate of the real-time aged irradiated and once-annealed components was higher than the literature reported values of other contemporary highly cross-linked UHMWPEs. Single annealing after irradiation used with terminal gamma sterilization may adversely affect the long-term oxidative stability of UHMWPE components. (C) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ-1206, Boston, MA 02114 USA. EM omuratoglu@partners.org NR 23 TC 37 Z9 39 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAR PY 2006 VL 27 IS 9 BP 1980 EP 1987 DI 10.1016/j.biomaterials.2005.10.002 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 007IO UT WOS:000234962500037 PM 16271756 ER PT J AU Burns, CG MacRae, CA AF Burns, CG MacRae, CA TI Purification of hearts from zebrafish embryos SO BIOTECHNIQUES LA English DT Article ID ACID-BINDING PROTEIN; EXPRESSION; MORPHOGENESIS; REVEALS; GENES C1 Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Burns, CG (reprint author), Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM gburns@cvrc.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL075431]; NIA NIH HHS [K01 AG023562, 1K01AG023562] NR 14 TC 23 Z9 24 U1 0 U2 3 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 2006 VL 40 IS 3 BP 274 EP + DI 10.2141/000112135 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 024QF UT WOS:000236210400004 PM 16568816 ER PT J AU Didenko, VV Baskin, DS AF Didenko, VV Baskin, DS TI Horseradish peroxidase-driven fluorescent labeling of nanotubes with quantum dots SO BIOTECHNIQUES LA English DT Article ID WALLED CARBON NANOTUBES; VISUALIZATION AB We describe the first enzyme-driven technique for fluorescent labeling of single-wallet! carbon nanotubes (SWNTs). The labeling was performed via enzymatic biotinylation of nanotubes in the tyramide-horseradish peroxidase (HRP) reaction. Both direct and indirect-fluorescent labeling of SWNTS was achieved using either biotinvl tyramide or fuorescently tagged tyramides. Biotinylated SWNTs later reacted with streptavidin-conjugated fluorophores. Linking semiconductor nanocrystals, quantum clots (Q-clots), to the surface of nanotubes resulted in their fluorescent visualization, whereas conventional fluorophores bound to SWNTs directly or through biotin-streptavidin linkage, were completely quenched. Enzymatic biotinylation permits fluorescent visualization of carbon nanotubes, which could be useful flora number of biomedical applications. In addition, other organic molecules such as proteins, antibodies, or DNA can be conjugated to biotinylated SWNTs using this approach. C1 Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Methodist Neurol Inst, Houston, TX USA. RP Didenko, VV (reprint author), 2002 Holcombe Blvd,Bldg 109,Room 204, Houston, TX 77030 USA. EM vdidenko@bcm.tmc.edu FU NIA NIH HHS [R03 AG022664, R03 AG022664-01] NR 13 TC 10 Z9 10 U1 1 U2 7 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 2006 VL 40 IS 3 BP 295 EP + DI 10.2144/000112110 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 024QF UT WOS:000236210400007 PM 16568818 ER PT J AU MacDonald, BA Sund, M Grant, MA Pfaff, KL Holthaus, K Zon, LI Kalluri, R AF MacDonald, BA Sund, M Grant, MA Pfaff, KL Holthaus, K Zon, LI Kalluri, R TI Zebrafish to humans: evolution of the alpha 3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome SO BLOOD LA English DT Article ID T-CELL EPITOPE; BASEMENT-MEMBRANE COLLAGEN; NC1 DOMAIN; ALPHA-3(IV) COLLAGEN; DIFFERENTIAL EXPRESSION; MOLECULAR-BASIS; GLOMERULONEPHRITIS; DISEASE; GENES; AUTOANTIGEN AB Goodpasture syndrome is an autoimmune vascular disease associated with kidney and lung failure, with pathogenic circulating autoantibodies targeted to a set of discontinuous epitope sequences within the noncollagenous domain-1 (NC1) of the alpha 3 chain of type IV collagen (alpha 3(IV)NC1), the Goodpasture autoantigen. We demonstrate that basement membrane extracted NC1 domain preparations from Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio do not bind Goodpasture autoantibodies, while Xenopus laevis, chicken, mouse and human alpha 3(IV)NC1 domains bind autoantibodies. The a3(IV) chain is not present in C elegans and Drosophila melanogaster, but is first detected in the Danio rerio. Interestingly, native Danio rerio a3(IV)NC1 does not bind Goodpasture autoantibodies. Next, we cloned, sequenced, and generated recombinant Danio rerio alpha 3(IV)NC1 domain. In contrast to recombinant human alpha 3(IV)NC1 domain, there was complete absence of autoantibody binding to recombinant Danio rerio alpha 3(IV)NC1. Three-dimensional molecular modeling from existing x-ray coordinates of human NC1 domain suggest that evolutionary alteration of electrostatic charge and polarity due to the emergence of critical serine, aspartic acid, and lysine residues, accompanied by the loss of asparagine and glutamine, contributes to the emergence of the 2 major Goodpasture epitopes on the human alpha 3(IV)NC1 domain, as it evolved from the Danio rerio over 450 million years. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Matrix Biol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Mol & Vasc Med, Boston, MA 02215 USA. Childrens Hosp, Dana Farber Canc Inst, Howard Hughes Med Inst, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Howard Hughes Med Inst, Div Hematol & Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. RP Kalluri, R (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Matrix Biol, DANA 514,330 Brookline Ave, Boston, MA 02215 USA. EM rkalluri@bidmc.harvard.edu RI Kalluri, Raghu/E-2677-2015; OI Kalluri, Raghu/0000-0002-2190-547X; Sund, Malin/0000-0002-7516-9543 FU NIDDK NIH HHS [DK62987, DK55001] NR 43 TC 14 Z9 18 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2006 VL 107 IS 5 BP 1908 EP 1915 DI 10.1182/blood-2005-05-1814 PG 8 WC Hematology SC Hematology GA 016PQ UT WOS:000235632700032 PM 16254142 ER PT J AU Kavanagh, DG Kaufmann, DE Sunderji, S Frahm, N Le Gall, S Boczkowski, D Rosenberg, ES Stone, DR Johnston, MN Wagner, BS Zaman, MT Brander, C Gilboa, E Walker, BD Bhardwaj, N AF Kavanagh, DG Kaufmann, DE Sunderji, S Frahm, N Le Gall, S Boczkowski, D Rosenberg, ES Stone, DR Johnston, MN Wagner, BS Zaman, MT Brander, C Gilboa, E Walker, BD Bhardwaj, N TI Expansion of HIV-specific CD4(+) and CD8(+) T cells by dendritic cells transfected with mRNA encoding cytoplasm- or lysosome-targeted Nef SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLASS-I; RESTRICTED PRESENTATION; LYMPHOCYTE EPITOPES; IMMUNE-RESPONSES; ANTIGEN; INFECTION; VACCINE; PROTEIN; IMMUNOTHERAPY AB Transfection with synthetic mRNA is a safe and efficient method of delivering antigens to dendritic cells for immunotherapy. Targeting antigens to the lysosome can sometimes enhance the CD4(+) T-cell response. We transfected antigen-presenting cells (All with mRNA encoding Gag-p24 and cytoplasmic, lysosomal, and secreted forms of Nef. Antigen-specific cytotoxic T cells were able to lyse the majority of transfected targets, indicating that transfection was efficient. Transfection of APCs with a Nef construct bearing lysosomal targeting signals produced rapid and prolonged antigen presentation to CD4(+) and CD8(+) T cells. Polyclonal CD4(+) and CD8(+) T-cell lines recognizing multiple distinct epitopes were expanded by coculture of transfected dendritic cells with peripheral blood mononuclear cells from viremic and aviremic HIV-infected subjects. Importantly, lysosome-targeted antigen drove a significantly greater expansion of Nef-specific CD4(+) T cells than cytoplasmic antigen. The frequency of recognition of CD8 but not CD4 epitopes by mRNA-expanded T cells was inversely proportional to sequence entropy and was similar to ex vivo responses from a large chronic cohort. Thus human dendritic cells transfected with mRNA-encoding lysosome-targeted HIV antigen can expand a broad, polyclonal repertoire of antiviral T cells, offering a promising approach to HIV immunotherapy. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Med Ctr, Ctr Genet & Cellular Therapies, Dept Surg, Durham, NC USA. Lemuel Shattuck Hosp, Boston, MA USA. NYU, Sch Med, New York, NY USA. RP Kavanagh, DG (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM dkavanagh@partners.org OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [1 F32 AI058457-01, F32 AI058457, N01-AI-15422] NR 35 TC 45 Z9 45 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2006 VL 107 IS 5 BP 1963 EP 1969 DI 10.1182/blood-2005-04-1513 PG 7 WC Hematology SC Hematology GA 016PQ UT WOS:000235632700039 PM 16249391 ER PT J AU Arango, JI Restrepo, A Schneider, DL Callander, NS Ochoa-Bayona, JL Restrepo, MI Bradshaw, P Patterson, J Freytes, CO AF Arango, JI Restrepo, A Schneider, DL Callander, NS Ochoa-Bayona, JL Restrepo, MI Bradshaw, P Patterson, J Freytes, CO TI Incidence of Clostridium difficile-associated diarrhea before and after autologous peripheral blood stem cell transplantation for lymphoma and multiple myeloma SO BONE MARROW TRANSPLANTATION LA English DT Article DE C. difficile-associated diarrhea; hematologic malignancies; autologous peripheral blood stem cell transplantation; high-dose chemotherapy ID ANTIBIOTIC-ASSOCIATED DIARRHEA; INFECTION; TOXIN; RECIPIENTS; ANTIBODY; COLITIS AB Diarrhea is a major cause of morbidity and discomfort for patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT). There are multiple causes of diarrhea in patients undergoing transplantation including antineoplastic chemotherapy, antimicrobials and infection, including Clostridium difficile as the most common pathogen involved. The purpose of this study was to determine the incidence of C. difficile-associated diarrhea (CDAD) 1 week before and 30 days after APBSCT, and to identify risk factors for the development of CDAD including diagnosis. Two hundred and forty-two patients underwent APBSCT for multiple myeloma and lymphoma between October 1996 and October 2001 in two teaching hospitals. Diarrhea was reported in 157 (64.9%) subjects. One hundred and thirty-five out of the 157 subjects were tested for the presence of C. difficile toxin A. These subjects constitute the study group. The incidence of CDAD was 15%. Two thirds of the patients who developed CDAD had multiple myeloma and one third had lymphoma; this difference did not attain statistical significance. The use of cephalosporins ( P = 0.03) and the use of intravenous vancomycin ( P = 0.02) were the only identified risk factors associated with the development of CDAD. Patients treated with paclitaxel as part of the mobilization regimen had a lower incidence of CDAD than patients who received hematopoietic growth factor only ( P = 0.01). C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Arango, JI (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, Mail Code 7880, San Antonio, TX 78229 USA. EM arangoj@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 NR 19 TC 32 Z9 33 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2006 VL 37 IS 5 BP 517 EP 521 DI 10.1038/sj.bmt.1705269 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 014RX UT WOS:000235498700012 PM 16435018 ER PT J AU Ruutu, T Barosi, G Benjamin, RJ Clark, RE George, JN Gratwohl, A Holler, E Iacobelli, M Kentouche, K Lammle, B Moake, JL Richardon, P Socie, G Zeigler, Z Niederwieser, D Barbui, T AF Ruutu, T Barosi, G Benjamin, RJ Clark, RE George, JN Gratwohl, A Holler, E Iacobelli, M Kentouche, K Lammle, B Moake, JL Richardon, P Socie, G Zeigler, Z Niederwieser, D Barbui, T TI Transplantation-associated microangiopathy: diagnostic criteria based on a consensus process by an International Working Group SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the European-Group-for-Blood-and-Morrow-Transplantation/22nd Meeting of the EBMT-Nures-Group/5th Meeting of the EMBT-Data-Management-Group CY MAR 19-22, 2006 CL Hamburg, GERMANY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 Univ Helsinki, Cent Hosp, Helsinki, Finland. IRCCS, Policlin San Matteo, Pavia, Italy. Amer Red Cross, New England Reg, Dedham, MA USA. Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Basel Hosp, CH-4031 Basel, Switzerland. Univ Regensburg Klinikum, Regensburg, Germany. Gentium, Villa Guardia, Como, Italy. Univ Jena, D-6900 Jena, Germany. Univ Hosp Bern, CH-3010 Bern, Switzerland. Baylor Coll Med, Houston, TX 77030 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hop St Louis, Paris, France. Inst Transfus Med, Pittsburgh, PA USA. Univ Leipzig, D-7010 Leipzig, Germany. Osped Riuniti Bergamo, I-24100 Bergamo, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2006 VL 37 SU 1 BP S2 EP S2 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 028WT UT WOS:000236520200005 ER PT J AU Guenther, FH Ghosh, SS Tourville, JA AF Guenther, FH Ghosh, SS Tourville, JA TI Neural modeling and imaging of the cortical interactions underlying syllable production SO BRAIN AND LANGUAGE LA English DT Review DE speech production; model; fMRI; Broca's area; premotor cortex; motor cortex; speech acquisition; sensorimotor learning; neural transmission delays ID POSITRON-EMISSION-TOMOGRAPHY; VENTRAL PREMOTOR CORTEX; LATERAL TEMPORAL-LOBE; HUMAN AUDITORY-CORTEX; SPEECH MOTOR CONTROL; BASAL GANGLIA; NETWORK MODEL; FUNCTIONAL-ORGANIZATION; SENSORIMOTOR CORTEX; PARKINSONS-DISEASE AB This paper describes a neural model of speech acquisition and production that accounts for a wide range of acoustic, kinematic, and neuroimaging data concerning the control of speech movements. The model is a neural network whose components correspond to regions of the cerebral cortex and cerebellum, including premotor, motor, auditory, and somatosensory cortical areas. Computer simulations of the model verify its ability to account for compensation to lip and jaw perturbations during speech. Specific anatomical locations of the model's components are estimated, and these estimates are used to simulate fMRI experiments of simple syllable production. (c) 2005 Elsevier Inc. All rights reserved. C1 Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. Harvard Univ, MIT, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Guenther, FH (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. EM guenther@cns.bu.edu OI Ghosh, Satrajit/0000-0002-5312-6729 FU NIDCD NIH HHS [R01 DC01925, R01 DC001925, R01 DC002852, R01 DC02852, R29 DC002852] NR 120 TC 365 Z9 375 U1 3 U2 27 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAR PY 2006 VL 96 IS 3 BP 280 EP 301 DI 10.1016/j.bandl.2005.06.001 PG 22 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 027SB UT WOS:000236434600004 PM 16040108 ER PT J AU Ozanne, EM Klemp, JR Esserman, LJ AF Ozanne, EM Klemp, JR Esserman, LJ TI Breast cancer risk assessment and prevention: A framework for shared decision-making consultations SO BREAST JOURNAL LA English DT Article DE breast cancer; biomarkers; decision making; prevention; risk stratification ID PROPHYLACTIC BILATERAL MASTECTOMY; HEALTHY POSTMENOPAUSAL WOMEN; SURGICAL ADJUVANT BREAST; ESTROGEN PLUS PROGESTIN; BOWEL PROJECT P-1; FAMILY-HISTORY; MAMMOGRAPHIC DENSITIES; OVARIAN-CANCER; MUTATION CARRIERS; CLINICAL-PRACTICE AB Options for breast cancer prevention, used in combination with screening and surveillance, include lifestyle modifications, chemoprevention with tamoxifen, and prophylactic surgery. Preventive health decisions are often preference driven: patients typically must choose whether to initiate effective treatments that hold the possibility of side effects that can negatively impact quality of life. This situation demands that patients be well informed and have a full understanding of the risks associated with each option. Investigators have developed a comprehensive decision-making framework designed to support breast cancer prevention consultations within a shared decision-making setting. The framework integrates predictive information from current risk models within the context of a woman's general health to appropriately frame breast cancer risk management consultations and outlines the application of available treatments and emerging biomarker information to individual patient decisions. Using an evidence-based approach, specialized risk-benefit projections can be provided in the clinical setting. A more comprehensive individualized risk profile allows for tailored medical management plans and can better prepare patients to make informed decisions. The framework is intended to encourage a shared decision-making approach to prevention consultations, a method for researchers to increase accrual to trials, and to more quickly incorporate new findings into the routine of practice. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. UCSF Med Ctr, Carol Franc Buck Breast Canc Ctr, Dept Surg & Radiol, San Francisco, CA USA. RP Ozanne, EM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM elissa@mgh-ita.org NR 79 TC 19 Z9 19 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1075-122X J9 BREAST J JI Breast J. PD MAR-APR PY 2006 VL 12 IS 2 BP 103 EP 113 DI 10.1111/j.1075-122X.2006.00217.x PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 019FM UT WOS:000235821000003 PM 16509834 ER PT J AU Kumar, S Raje, N Hideshima, T Ishitsuka, K Podar, K Le Gouille, S Chauhan, D Richardson, P Munshi, NC Anderson, K AF Kumar, S Raje, N Hideshima, T Ishitsuka, K Podar, K Le Gouille, S Chauhan, D Richardson, P Munshi, NC Anderson, K TI FQPD, a novel immunomodulatory drug, has significant in vitro activity in multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; novel therapeutics; apoptosis; drug resistance ID THALIDOMIDE ANALOGS; THERAPY; RESISTANCE; ANGIOGENESIS; CELLS AB Multiple myeloma (MM) is a plasma cell malignancy that claims thousands of lives each year and has considerable morbidity. The disease remains incurable despite recent advances in the understanding of the disease biology and the introduction of more effective drugs is needed. This study evaluated the anti-MM activity of 3-(7-fluoro-4H-quinazolin-3-yl)-piperidine-2,6-dione, hydrochloride (FQPD), a novel immunomodulatory drug. FQPD inhibited the proliferation of multiple MM cell lines, including those resistant to conventional treatments, such as dexamethasone. It induced apoptosis in MM cell lines, as well as freshly isolated patient MM cells, without cytotoxicity on normal human lymphocytes. Moreover, it induced apoptosis in MM cells adherent to bone marrow (BM) stromal cells or in the presence of cytokines, such as interleukin-6 and vascular endothelial growth factor, confirming its ability to overcome the protective effects of the BM milieu. Apoptosis in the MM cells was mediated via poly-ADP ribose polymerase cleavage as well as cleavage of caspase 8 and caspase 9. Our studies therefore demonstrated in vitro anti-MM activity of FQPD and provide the rationale for its in vivo evaluation in animal models and derived clinical trials. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA. RP Anderson, K (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 FU NCI NIH HHS [IP50 CA10070-01, R0-1 CA 50947]; PHS HHS [P0-1 78378] NR 18 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2006 VL 132 IS 6 BP 698 EP 704 DI 10.1111/j.1365-2141.2005.05946.x PG 7 WC Hematology SC Hematology GA 012HX UT WOS:000235330300003 PM 16487170 ER PT J AU Lazarus, HM Perez, WS Klein, JP Kollman, C Bate-Boyle, B Bredeson, CN Gale, RP Geller, RB Keating, A Litzow, MR Marks, DI Miller, CB Rizzo, JD Spitzer, TR Weisdorf, DJ Zhang, MJ Horowitz, MM AF Lazarus, HM Perez, WS Klein, JP Kollman, C Bate-Boyle, B Bredeson, CN Gale, RP Geller, RB Keating, A Litzow, MR Marks, DI Miller, CB Rizzo, JD Spitzer, TR Weisdorf, DJ Zhang, MJ Horowitz, MM TI Autotransplantation versus HLA-matched unrelated donor transplantation for acute myeloid leukaemia: a retrospective analysis from the Center for International Blood and Marrow Transplant Research SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE autograft; unrelated allograft; acute myeloid leukaemia; bone marrow transplantation; haematopoietic stem cell transplant ID ACUTE MYELOGENOUS LEUKEMIA; TOTAL-BODY IRRADIATION; HIGH-DOSE CYTARABINE; STEM-CELL TRANSPLANTATION; ACUTE MYELOBLASTIC-LEUKEMIA; ACUTE MYELOCYTIC-LEUKEMIA; DISEASE-FREE SURVIVAL; BONE-MARROW; 1ST REMISSION; INTENSIVE CHEMOTHERAPY AB Most acute myeloid leukaemia (AML) patients lack human leucocyte antigen-identical sibling donors for transplantation. Autotransplants and unrelated donor (URD) transplants are therapeutic options. To compare autologous versus URD transplantation for AML in first (CR1) or second complete remission (CR2), we studied the outcomes of 668 autotransplants were compared with 476 URD transplants reported to the Center for International Blood and Marrow Transplant Research. Proportional hazards regression adjusted for differences in prognostic variables. In multivariate analyses transplant-related mortality (TRM) was significantly higher and relapse lower with URD transplantation. Adjusted 3-year survival probabilities were: in CR1 57 (53-61)% with autotransplants and 44 (37-51)% URD (P = 0.002), in CR2 46 (39-53)% and 33 (28-38)% respectively (P = 0.006). Adjusted 3-year leukaemia-free survival (LFS) probabilities were: CR1 53 (48-57)% with autotransplants and 43 (36-50)% with URD (P = 0.021), CR2 39 (32-46)% and 33 (27-38)% respectively (P = 0.169). Both autologous and URD transplantation produced prolonged LFS. High TRM offsets the superior antileukaemia effect of URD transplantation. This retrospective, observational database study showed that autotransplantation, in general, offered higher 3-year survival for AML patients in CR1 and CR2. Cytogenetics, however, were known in only two-thirds of patients and treatment bias cannot be eliminated. C1 Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Hlth Policy Inst, Milwaukee, WI 53226 USA. Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. Jaeb Ctr Hlth Res, Tampa, FL USA. Univ Minnesota, Div Haematol Oncol & Transplantat, Minneapolis, MN USA. Univ Manitoba, CancerCare Manitoba, Winnipeg, MB, Canada. Ctr Adv Studies Leukemia, Los Angeles, CA USA. Arizona Canc Ctr, Scottsdale, AZ USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Bristol Childrens Hosp, Bristol, Avon, England. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Horowitz, MM (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Hlth Policy Inst, 8701 Watertown Plank Rd,POB 26509, Milwaukee, WI 53226 USA. EM marymh@hpi.mcw.edu FU NCI NIH HHS [U24-CA76518] NR 59 TC 35 Z9 38 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2006 VL 132 IS 6 BP 755 EP 769 DI 10.1111/j.1365-2141.2005.05947.x PG 15 WC Hematology SC Hematology GA 012HX UT WOS:000235330300010 PM 16487177 ER PT J AU Tsai, PS Evans, JE Green, KM Sullivan, RM Schaumberg, DA Richards, SM Dana, MR Sullivan, DA AF Tsai, PS Evans, JE Green, KM Sullivan, RM Schaumberg, DA Richards, SM Dana, MR Sullivan, DA TI Proteomic analysis of human meibomian gland secretions SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID AMINO-ACID-SEQUENCES; OCULAR SURFACE; BLEPHARITIS PATIENTS; MASS-SPECTROMETRY; PROTEIN DATABASE; LACRIMAL GLAND; EXPRESSION; IMMUNOREACTIVITY; LAMININ-5; PEPTIDES AB Background/aim: Human tears contain hundreds of proteins that may exert a significant influence on tear film stability, ocular surface integrity, and visual function. The authors hypothesise that many of these proteins originate from the meibomian gland. This study's aim was to begin to develop the proteomic methodology to permit the testing of their hypothesis. Methods: Meibomian gland secretions were collected from the lower eyelids of adult volunteers and placed in a chloroform-methanol mixture. Samples were partitioned in a biphasic system and non-lipid phase materials were reduced, alkylated, and trypsin digested to obtain peptides for protein identification. This peptide mixture was separated by m-capillary reverse phase chromatography and the effluent examined by nano-electrospray MS and data dependent MS/MS. SEQUEST software was used to identify proteins from the MS/MS spectra. Results: The methodological approach to date has permitted the identification of more than 90 proteins in human meibomian gland secretions. Proteins include the alpha 2-macroglobulin receptor, IgA alpha chain, farnesoid X activated receptor, interferon regulatory factor 3, lacritin precursor, lactotransferrin, lipocalin 1, lysozyme C precursor, potential phospholipid transporting ATPase IK, seven transmembrane helix receptor (also termed somatostatin receptor type 4), testes development related NYD-SP21 (also termed high affinity IgE receptor beta subunit), and TrkC tyrosine kinase. Conclusions: These findings indicate that the meibomian gland secretes a number of proteins into the tear film. It is quite possible that these proteins contribute to the dynamics of the tear film in both health and disease. C1 Schepens Eye Res Inst, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. RP Sullivan, DA (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM sullivan@vision.eri.harvard.edu FU NEI NIH HHS [EY05612, R01 EY005612] NR 33 TC 64 Z9 66 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAR PY 2006 VL 90 IS 3 BP 372 EP 377 DI 10.1136/bjo.2005.080846 PG 6 WC Ophthalmology SC Ophthalmology GA 013QS UT WOS:000235424800033 PM 16488965 ER PT J AU Kaphingst, KA Zanfini, CJ Emmons, KM AF Kaphingst, KA Zanfini, CJ Emmons, KM TI Accessibility of web sites containing colorectal cancer information to adults with limited literacy (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE literacy; internet; cancer ID WORLD-WIDE-WEB; HEALTH INTERVIEW SURVEY; SCREENING-TESTS; READABILITY; INTERNET; QUALITY; EDUCATION; KNOWLEDGE; CONSUMERS; RISK AB The Internet could be a key channel for disseminating information about colorectal cancer (CRC) screening. Little research, however, has systematically examined factors other than writing style related to the reading difficulty of cancer information on the Internet. In the present study we assessed the reading difficulty of 19 CRC Web sites. We assessed pages within selected sites containing information on CRC screening or prevention using the SMOG readability formula and Suitability Assessment of Materials instrument. The average SMOG reading grade level was 12.8. The SAM results indicated common problems with the sites, including (1) lack of review of key ideas; (2) insufficient use of illustrations for key messages; (3) crowded layout and long line lengths; (4) small type size and lack of cues to highlight key content; and (5) lack of interactive features. Many Web sites providing CRC information may be too difficult for the average American adult and much too difficult for adults with limited literacy. The unique features of the Internet that could support learning are not being utilized. The Internet could be a powerful tool for educating individuals about CRC, but the barrier of difficult content must be addressed along with access barriers. C1 NHGRI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Ctr Community Baseds Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Amer Heart Assoc, Williston, VT 05495 USA. RP Kaphingst, KA (reprint author), NHGRI, Bldg 31,Room B2B37,31 Ctr Dr,MSC 2030, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov FU NCI NIH HHS [5R01CA098864] NR 36 TC 34 Z9 35 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2006 VL 17 IS 2 BP 147 EP 151 DI 10.1007/s10552-005-5116-3 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 004LO UT WOS:000234754500003 PM 16425092 ER PT J AU Polyak, K AF Polyak, K TI Pregnancy and breast cancer: The other side of the coin SO CANCER CELL LA English DT Editorial Material ID REPRODUCTIVE FACTORS; RECEPTOR C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu NR 9 TC 43 Z9 45 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2006 VL 9 IS 3 BP 151 EP 153 DI 10.1016/j.ccr.2006.02.026 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 026YD UT WOS:000236378500003 PM 16530699 ER PT J AU Varghese, S Rabkin, SD Liu, R Nielsen, PG Ipe, T Martuza, RL AF Varghese, S Rabkin, SD Liu, R Nielsen, PG Ipe, T Martuza, RL TI Enhanced therapeutic efficacy of IL-12, but not GM-CSF, expressing oncolytic herpes simplex virus for transgenic mouse derived prostate cancers SO CANCER GENE THERAPY LA English DT Article DE oncolytic virus; herpes simplex virus; prostate cancer; MHC class I; IL-12 ID COLONY-STIMULATING FACTOR; MHC CLASS-I; AUTOLOGOUS TUMOR VACCINES; CD8(+) T-LYMPHOCYTES; PHASE-I; REPLICATION-COMPETENT; ANTITUMOR IMMUNITY; INTERFERON-GAMMA; ANTIGEN PRESENTATION; METASTATIC MELANOMA AB Replication competent oncolytic herpes simplex viruses (HSV) with broad-spectrum activity against various cancers, including prostate cancer, exert a dual effect by their direct cytocidal action and by eliciting tumor-specific immunity. These viruses can deliver immunoregulatory molecules to tumors so as to enhance the cumulative antitumor response. This is particularly desirable for prostate cancers, which are usually poorly immunogenic. Initial studies described herein comparing the efficacy of three different oncolytic HSVs (G207, G47 Delta, and NV1023) to inhibit the growth of the poorly immunogenic TRAMP-C2 mouse prostate tumors demonstrated that NV1023 was most effective in treating established tumors. The expression of IL-12 on an NV1023 background (NV1042), but not the expression of GM-CSF (NV1034), further enhanced the efficacy of NV1023 in two murine prostate cancer models with highly variable MHC class I levels, Pr14-2 with 91% and TRAMP-C2 with 2% of cells staining. NV1042 also inhibited the growth of distant noninoculated tumors in both prostate cancer models. NV1042 treated tumors exhibited increased immune cell infiltration and decreased levels of angiogenesis. Thus, an IL-12 expressing oncolytic herpes virus, which is capable of direct cytotoxicity and can modulate the otherwise suboptimal immune response through concomitant expression of the cytokine at the site of tumor destruction, could serve as a valuable clinical agent to seek out both overt and occult prostate cancers. C1 Harvard Univ, Dept Neurosurg, Mol Neurosurg Lab, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rabkin, SD (reprint author), Harvard Univ, Dept Neurosurg, Mol Neurosurg Lab, Massachusetts Gen Hosp,Sch Med, CNY-149,Box 17, Charlestown, MA 02129 USA. EM rabkin@helix.mgh.harvard.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NCI NIH HHS [1R01CA102139-01A1] NR 61 TC 56 Z9 60 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAR PY 2006 VL 13 IS 3 BP 253 EP 265 DI 10.1038/sj.cgt.7700900 PG 13 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 012SY UT WOS:000235361200004 PM 16179929 ER PT J AU MacDonald, SM DeLaney, TF Loeffler, JS AF MacDonald, SM DeLaney, TF Loeffler, JS TI Proton beam radiation therapy SO CANCER INVESTIGATION LA English DT Article DE cancer treatment; protons; radiotherapy ID RELATIVE BIOLOGICAL EFFECTIVENESS; HIGH-DOSE IRRADIATION; HEPATOCELLULAR-CARCINOMA; PROSTATE-CANCER; UVEAL MELANOMA; SKULL BASE; X-RAY; PHOTON RADIOTHERAPY; POTENTIAL ROLE; TUMOR-CONTROL C1 Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02115 USA. NYU, Med Ctr, Ctr Canc, New York, NY 10016 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02115 USA. NR 53 TC 18 Z9 18 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PD MAR PY 2006 VL 24 IS 2 BP 199 EP 208 DI 10.1080/07357900500524751 PG 10 WC Oncology SC Oncology GA 020ZB UT WOS:000235950900013 PM 16537190 ER PT J AU Houldin, A Curtiss, CP Haylock, PJ AF Houldin, Arlene Curtiss, Carol P. Haylock, Pamela J. TI Executive summary SO CANCER NURSING LA English DT Editorial Material ID CANCER SURVIVORSHIP; TRENDS; NATION C1 Univ Penn, Sch Nursing, Adult Oncol Nurse Practitioner Program, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Palliat Care Serv, Philadelphia, PA USA. Univ Texas, Med Branch, Sch Nursing, Galveston, TX 77550 USA. RP Houldin, A (reprint author), Univ Penn, Sch Nursing, Adult Oncol Nurse Practitioner Program, Philadelphia, PA 19104 USA. EM bouldin@nursing.upenn.edu; carol.curtiss@verizon.net; pjhaylock@indian-creek.net NR 13 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD MAR-APR PY 2006 VL 29 IS 2 SU S BP 6 EP 11 DI 10.1097/00002820-200603002-00003 PG 6 WC Oncology; Nursing SC Oncology; Nursing GA 097AY UT WOS:000241419800003 PM 16779948 ER PT J AU Garraway, LA Sellers, WR AF Garraway, LA Sellers, WR TI From integrated genomics to tumor lineage dependency SO CANCER RESEARCH LA English DT Review ID ANTICANCER DRUG SCREEN; TRANSCRIPTION FACTOR; CELL LINES; MOLECULAR-BIOLOGY; MITF; MELANOMA; SURVIVAL; CANCER; GENE; DIFFERENTIATION AB In principle, genomic information derived from tumors should illuminate critical cellular dependencies that are tractable to therapeutic targeting; however, realizing this ideal remains difficult. Using an integrated analysis of high-resolution single nucleotide polymorphism maps and gene expression databases associated with the NCI60 collection cancer cell lines, we identified the transcription factor MITF as an amplified oncogene in melanoma that is critical for anchoring lineage dependence and malignant character. Similar combined genomic approaches may be useful in other cancer types to learn how critical regulators of tumor lineage are linked to genomic alterations in cancer cells. C1 Dana Farber Canc Inst, Melanoma Program Med Oncol, Cambridge, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D1542,44 Binney St, Boston, MA 02115 USA. EM Levi_Garraway@dfci.harvard.edu NR 25 TC 18 Z9 19 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2006 VL 66 IS 5 BP 2506 EP 2508 DI 10.1158/0008-5472.CAN-05-4604 PG 3 WC Oncology SC Oncology GA 019HO UT WOS:000235826400003 PM 16510564 ER PT J AU McKee, TD Grandi, P Mok, W Alexandrakis, G Insin, N Zimmer, JP Bawendi, MG Boucher, Y Breakefield, XO Jain, RK AF McKee, TD Grandi, P Mok, W Alexandrakis, G Insin, N Zimmer, JP Bawendi, MG Boucher, Y Breakefield, XO Jain, RK TI Degradation of fibrillar collagen in a human melanoma xenograft improves the efficacy of an oncolytic herpes simplex virus vector SO CANCER RESEARCH LA English DT Article ID GENE-THERAPY; ADENOVIRUS; CANCER; TUMORS; EXPRESSION; INCREASES; TRANSPORT; CELLS AB Oncolytic viral therapy provides a promising approach to treat certain human malignancies. These vectors improve oil replication-deficient vectors by increasing the viral load within tumors through preferential viral replication within tumor cells. However, the inability to efficiently propagate throughout the entire tumor and infect cells distant from the injection site has limited the capacity of oncolytic viruses to achieve consistent therapeutic responses. Here we show that the spread of the oncolytic herpes simplex virus (HSV) vector MGH2 within the human melanoma Mu89 is limited by the fibrillar collagen in the extracellular matrix. This limitation seems to be size specific as nanoparticles of equivalent size to the virus distribute within tumors to the same extent whereas smaller particles distribute more widely. Due to limited viral penetration, tumor cells in inaccessible regions continue to grow, remaining out of the range of viral infection, and tumor eradication cannot be achieved. Matrix modification with bacterial collagenase coinjection results in a significant improvement in the initial range of viral distribution within the tumor. This results in an extended range of infected tumor cells and improved virus propagation, ultimately leading to enhanced therapeutic outcome. Thus, fibrillar collagen can be a formidable barrier to viral distribution and matrix-modifying treatments can significantly enhance the therapeutic response. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Neurosci Program, Charlestown, MA USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI McKee, Trevor/0000-0002-2195-6146 FU NCI NIH HHS [F32 CA097818, P01CA80124] NR 20 TC 197 Z9 200 U1 2 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2006 VL 66 IS 5 BP 2509 EP 2513 DI 10.1158/0008-5472.CAN-05-2242 PG 5 WC Oncology SC Oncology GA 019HO UT WOS:000235826400004 PM 16510565 ER PT J AU Stanbrough, M Bubley, GJ Ross, K Golub, TR Rubin, MA Penning, TM Febbo, PG Balk, SP AF Stanbrough, M Bubley, GJ Ross, K Golub, TR Rubin, MA Penning, TM Febbo, PG Balk, SP TI Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer SO CANCER RESEARCH LA English DT Article ID KETO REDUCTASE SUPERFAMILY; 5 17-BETA-HYDROXYSTEROID-DEHYDROGENASE; 3-BETA-HYDROXYSTEROID DEHYDROGENASE; DIHYDROTESTOSTERONE LEVELS; DIFFERENTIAL EXPRESSION; MEDICAL ADRENALECTOMY; SYNDECAN-1 EXPRESSION; DEPRIVATION THERAPY; RECEPTOR MUTATIONS; MOLECULAR-BIOLOGY AB Androgen receptor (AR) plays a central role in prostate cancer, and most patients respond to androgen deprivation therapies, but they invariably relapse with a more aggressive prostate cancer that has been termed hormone refractory or androgen independent. To identify proteins that mediate this tumor progression, gene expression in 33 androgen-independent prostate cancer bone marrow metastases versus 22 laser capture-microdissected primary prostate cancers was compared using Affymetrix oligonucleotide microarrays. Multiple genes associated with aggressive behavior were increased in the androgen-independent metastatic tumors (MMP9, CKS2, LRRC15, WNT5A, EZH2, E2F3, SDC1, SKP2, and BIRC5), whereas a candidate tumor suppressor gene (KLF6) was decreased. Consistent with castrate androgen levels, androgen-regulated genes were reduced 2- to 3-fold in the androgen-independent tumors. Nonetheless, they were still major transcripts in these tumors, indicating that there was partial reactivation of AR transcriptional activity. This was associated with increased expression of AR (5.8-fold) and multiple genes mediating androgen metabolism (HSD3B2, AKR1C3, SRD5A1, AKR1C2, AKR1C1, and UGT2B15). The increase in aldo-keto reductase family 1, member C3 (AKRIC3), the prostatic enzyme that reduces adrenal androstenedione to testosterone, was confirmed by real-time reverse transcription-PCR and immunohistochemistry. These results indicate that enhanced intracellular conversion of adrenal androgens to testosterone and dihydrotestosterone is a mechanism by which prostate cancer cells adapt to androgen deprivation and suggest new therapeutic targets. C1 Beth Israel Deaconess Med Ctr, Dept Med, Canc Biol Program, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. RP Balk, SP (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Canc Biol Program, 330 Brookline Ave, Boston, MA 02215 USA. EM sbalk@bidmc.harvard.edu OI Rubin, Mark/0000-0002-8321-9950; Penning, Trevor/0000-0002-3937-1066 FU NCI NIH HHS [R01 CA90744-02] NR 67 TC 589 Z9 610 U1 6 U2 45 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2006 VL 66 IS 5 BP 2815 EP 2825 DI 10.1158/0008-5472.CAN-05-4000 PG 11 WC Oncology SC Oncology GA 019HO UT WOS:000235826400043 PM 16510604 ER PT J AU Colilla, S Kantoff, PW Neuhausen, SL Godwin, AK Daly, MB Narod, SA Garber, JE Lynch, HT Brown, M Weber, BL Rebbeck, TR AF Colilla, S Kantoff, PW Neuhausen, SL Godwin, AK Daly, MB Narod, SA Garber, JE Lynch, HT Brown, M Weber, BL Rebbeck, TR TI The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers SO CARCINOGENESIS LA English DT Article ID ESTROGEN-RECEPTOR STATUS; POLYGLUTAMINE REPEAT LENGTH; ASHKENAZI JEWISH WOMEN; CIGARETTE-SMOKING; OVARIAN-CANCER; CUMULATIVE RISK; GENE-MUTATIONS; TOBACCO-SMOKE; PENETRANCE; FAMILIES AB Women with BRCA1 mutations are at an elevated risk for breast cancer. AIB1 (NCOA3/SRC3) genotype and smoking may alter this risk. We examined the differences in breast cancer risk by AIB1 polyglutamine repeat polymorphism and pre-diagnosis smoking habits for BRCA1 mutation carriers to determine if there was an interaction between smoking and AIB1 genotype. Multivariate Cox proportional hazards regression was used with 316 female BRCA1 mutation carriers to model breast cancer risk. Ever having smoked was associated with a decreased breast cancer risk [Hazard Ratio (HR) = 0.63, 95% CI, 0.47-0.87]. A dose-response relationship between number of pack-years smoked and breast cancer risk was also found for women who smoked < 20 pack years of cigarettes (HR = 0.72, 95% CI, 0.52-1.00) and for women who smoked >= 20 pack years (HR = 0.41, 95% CI, 0.23-0.71; P for trend = 0.0007). Women with a 28 repeat allele for AIB1 had a significantly reduced risk of breast cancer (HR = 0.72, 95% CI, 0.51-1.00). Women who smoked >= 20 pack-years with a 28 repeat allele had an even greater reduced risk of breast cancer (HR = 0.19, 95% CI, 0.07-0.54) compared to women who were never smokers with no 28 allele. Since AIB1 appears to modulate the effect of endogenous hormones via the estrogen receptor, and smoking affects circulating hormone levels, these results support evidence that steroid hormones play an important role in breast carcinogenesis in BRCA1 mutation carriers, and suggest mechanisms for developing novel cancer prevention strategies for BRCA1 mutation carriers. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Canc, Boston, MA 02215 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Womens Coll Hosp, Toronto, ON M5S 1N8, Canada. Creighton Univ, Dept Prevent Med, Omaha, NE 68178 USA. RP Colilla, S (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Room 916,423 Guardian Dr, Philadelphia, PA 19104 USA. EM scolilla@cceb.med.upenn.edu RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [R01-CA57601, R01-CA102776, R01-CA74415, R01-CA83855, T32-CA009679]; NIEHS NIH HHS [R21-ES-011658] NR 64 TC 22 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2006 VL 27 IS 3 BP 599 EP 605 DI 10.1093/carcin/bgi246 PG 7 WC Oncology SC Oncology GA 018NN UT WOS:000235771300028 PM 16244359 ER PT J AU Devi, S Kennedy, RH Joseph, L Shekhawat, NS Melchert, RB Joseph, J AF Devi, S Kennedy, RH Joseph, L Shekhawat, NS Melchert, RB Joseph, J TI Effect of long-term hyperhomocysteinemia on myocardial structure and function in hypertensive rats SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE homocysteine; hypertension; oxidation; cardiac remodeling; fibrosis; heart failure ID REDUCTION-OXIDATION REDOX; SMOOTH-MUSCLE-CELLS; EXTRACELLULAR-MATRIX; HEART-FAILURE; ENDOTHELIAL DYSFUNCTION; GLUTATHIONE-PEROXIDASE; GENE-EXPRESSION; VENTRICULAR HYPERTROPHY; PLASMA HOMOCYSTEINE; MURINE MODEL AB Background: Postulated mechanisms of hyperhomocysteinemia (Hhe) overlap with proposed mechanisms of adverse cardiac remodeling such as altered collagen metabolism and oxidant stress. Hence we examined the hypothesis that Hhe would promote myocardial fibrosis and systolic dysfunction. Methods: Three-month-old spontaneously hypertensive rats (SHRs) were divided into three groups: (1) control, given amino-acid defined diet for 20 weeks; (2) Hhe group, given Hhe-inducing diet for 20 weeks; and (3) combined diet group, which were given Hhe-inducing diet for 10 weeks (which leads to myocardial fibrosis and diastolic dysfunction as shown in our prior studies) and subsequently returned to amino acid-defined diet for 10 more weeks. At the end of the treatment period, plasma homocysteine (Hcy) levels and blood pressure were measured, and hearts were isolated for histomorphometric and biochemical assessment of cardiac remodeling and myocardial oxidative stress, and for in vitro cardiac function studies. Results: The Hhe animals demonstrated a significant increase in the ratio of collagenous to noncollagenous protein due to reactive interstitial fibrosis, and increased myocardial oxidant stress, compared to the control group. Systolic function was significantly depressed in the Hhe animals compared to the control group. These changes were partially prevented by return to control diet at 10 weeks. Conclusions: Our results demonstrate that clinically relevant levels of Hhe accelerate progression of hypertensive heart disease to systolic dysfunction and that increased myocardial oxidant stress may play a role in this process. Considering the high prevalence of hypertension and Hhe in the general population, our findings may have great clinical significance. (C) 2006 Elsevier Inc. All rights reserved. C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Loyola Univ, Chicago Stritch Sch Med, Dept Physiol, Maywood, IL 60153 USA. RP Joseph, J (reprint author), VA Boston Healthcare Syst, Cardiol Sect 111, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM jacob.joseph@med.va.gov OI Melchert, Russell/0000-0003-4813-6911 NR 39 TC 36 Z9 40 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD MAR-APR PY 2006 VL 15 IS 2 BP 75 EP 82 DI 10.1016/j.carpath.2005.11.001 PG 8 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 030WA UT WOS:000236664600002 PM 16533695 ER PT J AU Golks, A Brenner, D Schmitz, I Watzl, C Krueger, A Krammer, PH Lavrik, IN AF Golks, A Brenner, D Schmitz, I Watzl, C Krueger, A Krammer, PH Lavrik, IN TI The role of CAP3 in CD95 signaling: new insights into the mechanism of procaspase-8 activation SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE CAP3; CD95; apoptosis ID GEL-ELECTROPHORESIS; MOLECULAR-CLONING; MOUSE CASPASE-8; COMPLEX DISC; APOPTOSIS; PROTEINS; RECEPTOR; FLICE; OLIGOMERIZATION; INDUCTION AB Formation of the CD95 (APO-1/Fas) death inducing signaling complex (DISC) plays a central role in CD95 signaling. Previously, CD95 DISC composition was analyzed by two-dimensional gel electrophoresis and four major cytotoxicity-associated proteins (CAP1-4) were found. CAP1 and CAP2 were defined to be unmodified and phosphorylated FADD, respectively. CAP4 was identified as procaspase-8a. CAP3, however, has remained elusive. In this study, we demonstrate that CAP3 is an intermediate of procaspase-8 processing. CAP3 is generated within seconds of DISC formation and subsequently processed to the prodomain of procaspase-8a that is known as p26 (CAP5). These findings lead to new insights into the mechanism of procaspase-8 processing and apoptosis initiation. C1 German Canc Res Ctr, Div Immunogenet, Tumorimmunol Program, D-69120 Heidelberg, Germany. Univ Dusseldorf, Inst Mol Med, D-40225 Dusseldorf, Germany. Univ Heidelberg, Inst Immunol, D-69120 Heidelberg, Germany. Dana Farber Canc Inst, Lab Lymphocyte Biol, Boston, MA 02140 USA. RP Krammer, PH (reprint author), German Canc Res Ctr, Div Immunogenet, Tumorimmunol Program, INF 280, D-69120 Heidelberg, Germany. EM p.krammer@dkfz.de RI Lavrik, Inna/C-1700-2009; Krueger, Andreas/B-9427-2009; Watzl, Carsten/B-4911-2013; Schmitz, Ingo/G-2093-2013 OI Krueger, Andreas/0000-0001-7873-7334; Watzl, Carsten/0000-0001-5195-0995; Schmitz, Ingo/0000-0002-5360-0419 NR 29 TC 21 Z9 21 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAR PY 2006 VL 13 IS 3 BP 489 EP 498 DI 10.1038/sj.cdd.4401766 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 012SV UT WOS:000235360800015 PM 16179941 ER PT J AU Ozdener, H Yee, KK Cao, J Brand, JG Teeter, JH Rawson, NE AF Ozdener, H Yee, KK Cao, J Brand, JG Teeter, JH Rawson, NE TI Characterization and long-term maintenance of rat taste cells in culture SO CHEMICAL SENSES LA English DT Article DE culture; gustducin; imaging; proliferation; taste receptor ID CIRCUMVALLATE PAPILLAE; ADHESION MOLECULE; BUD CELLS; FUNGIFORM PAPILLAE; RECEPTOR-CELLS; FINE STRUCTURE; TRANSDUCTION; EXPRESSION; INNERVATION; DENERVATION AB Taste cells have a limited life span and are replaced from a basal cell population, although the specific factors involved in this process are not well known. Short- and long-term cultures of other sensory cells have facilitated efforts to understand the signals involved in proliferation, differentiation, and senescence, yet few studies have reported successful primary culture protocols for taste cells. Furthermore, no studies have demonstrated both proliferation and differentiation in vitro. In this study, we have developed an in vitro culture system to maintain and utilize rat primary taste cells for more than 2 months without losing key molecular and biochemical features. Gustducin, phospholipase C-beta(2) (PLC-beta(2)), T1R3, and T2R5 mRNA were detected in the cultured cells by reverse transcriptase-polymerase chain reaction. Western blot analysis demonstrated gustducin and PLC-beta(2) expression in the same samples, which was confirmed by immunocytochemistry. Labeling with bromo-2-deoxyuridine (BrdU) demonstrated proliferation, and a subset of BrdU-labeled cells were also immunoreactive for either gustducin or PLC-beta(2), indicating differentiation of newly generated cells in vitro. Cultured cells also exhibited increases in intracellular calcium in response to several taste stimuli. These results indicate that taste cells from adult rats can be generated and maintained under the described conditions for at least 2 months. This system will enable further studies of the processes involved in proliferation, differentiation, and function of mammalian taste receptor cells in an in vitro preparation. C1 Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Dent Med, Dept Biochem, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Ozdener, H (reprint author), Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA. EM hozdener@monell.org NR 44 TC 23 Z9 26 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD MAR PY 2006 VL 31 IS 3 BP 279 EP 290 DI 10.1093/chemse/bjj030 PG 12 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 025GI UT WOS:000236252900011 PM 16452455 ER PT J AU Pieretti-Vanmarcke, R Donahoe, PK Szotek, P Manganaro, T Lorenzen, MK Lorenzen, J Connolly, DC Halpern, EF MacLaughlin, DT AF Pieretti-Vanmarcke, R Donahoe, PK Szotek, P Manganaro, T Lorenzen, MK Lorenzen, J Connolly, DC Halpern, EF MacLaughlin, DT TI Recombinant human Mullerian inhibiting substance inhibits long-term growth of MIS type II receptor-directed transgenic mouse ovarian cancers in vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL-GROWTH; DEVELOPMENTAL EXPRESSION; DUCT REGRESSION; COLONY GROWTH; HORMONE; IMMUNOASSAY; CARCINOMA; FAMILY; ASSAY; GENE AB Purpose: Mullerian inhibiting substance (MIS) is a glycoprotein hormone that causes Mullerian duct regression in male embryos. In short-term experiments, recombinant human MIS (rhMIS) inhibits xenotransplanted human ovarian cancer cell lines that are thought to be of Mullerian origin. Because this highly lethal cancer has a high recurrence rate after conventional chemotherapy, new treatments are warranted. We examined whether rh MIS as a novel, nontoxic, naturally occurring growth inhibitor can be an effective anticancer drug in long-term studies in vivo against allograft tumors that recapitulate human ovarian carcinoma. Experimental Design: Mouse ovarian carcinoma (MOVCAR) cell lines expressing the early region of the SV40 virus, including the large and small T-antigen genes under transcriptional control of a portion of the murine MIS receptor type II (MISRII) gene promoter, were derived from TgMISIIR-TAg transgenic mice. rh MIS was tested against MOVCAR cells in growth inhibition assays in vitro, and in vivo in 6-week-old female nude mice. Tumor growth in animals was measured at weekly intervals for up to 20 weeks. Results: MOVCAR cells and tumors express MISRII by Western blot, immunohistochemical, and Northern blot analyses. rh MIS significantly inhibited MOVCAR cell growth in vitro and in vivo in three separate long-term allotransplantation experiments. Conclusions: Because rh MIS is an effective anticancer agent in in vitro and in long-term in vivo preclinical experiments against MISRII-positive tumors, we predict that rh MIS can be used safely and effectively to treat human ovarian malignancies. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol & Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Pieretti-Vanmarcke, R (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Dept Surg, 185 Cambridge St,CPZN 6200, Boston, MA 02114 USA. EM rpierettivanmarcke@partners.org FU NCI NIH HHS [CA 17393]; NICHD NIH HHS [HD 32212] NR 48 TC 25 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2006 VL 12 IS 5 BP 1593 EP 1598 DI 10.1158/1078-0432.CCR-05-2108 PG 6 WC Oncology SC Oncology GA 021MT UT WOS:000235988000027 PM 16533786 ER PT J AU Dominitz, JA Dire, CA Billingsley, KG Todd-Stenberg, JA AF Dominitz, JA Dire, CA Billingsley, KG Todd-Stenberg, JA TI Complications and antireflux medication use after antireflux surgery SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID LAPAROSCOPIC NISSEN FUNDOPLICATION; GASTROESOPHAGEAL-REFLUX DISEASE; QUALITY-OF-LIFE; VETERANS-AFFAIRS; SURGICAL THERAPY; FOLLOW-UP; TERM; POPULATION; PREVALENCE; EXPERIENCE AB Background & Aims: Although antireflux surgery is increasingly common, few studies have assessed the associated complications and health care use after surgery. The aim of this study was to estimate postoperative complications and continued use of antireflux medications and to identify predictors of complications. Methods: Through a review of the Department of Veterans Affairs administrative databases, all patients undergoing antireflux surgery from October 1, 1990, through January 29, 2001, were identified. Of 3367 patients identified, 22:2 were excluded as a result of a diagnosis of esophageal cancer, achalasia, or because there was no diagnosis related to gaistroesophageal reflux disease. Medication use was determined for 2406 patients who had a minimum of 1 year of follow-up, including :1 or more outpatient visits at least 6 months after surgery and during the time when national pharmacy records were available. Results: Dysphagia was recorded in:19.4%, dilation was performed in 6.4%, and a repeat antireflux surgery was performed in 2.3%. The surgical mortality rate was .8%. Prescriptions were dispensed repeatedly for H-2 receptor antagonists in 23.8%, proton pump inhibitors in 34.3%, and promotility agents in 9.2% of patients. Overall, 49.8% of patients received. at least 3 prescriptions for one of these medications. Conclusions: A moderate proportion of patients undergoing antireflux surgeries experienced complications and approximately 50% of patients received multiple prescriptions for antireflux medications at a median of 5 years of follow-up evaluation. Therefore, before surgery is performed, patients considering surgery should be counseled fully about the risk for complications and the likelihood of continued antireflux medication use. C1 VA Puget Sound Hlth Care Syst, Seattle Div S 111 Gastro, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div S 111 Gastro, NW Hlth Serv Res & Dev Ctr Excellence, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jason.dominitz@va.gov OI Dominitz, Jason/0000-0002-8070-7086 NR 38 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2006 VL 4 IS 3 BP 299 EP 305 DI 10.1016/j.cgh.2005.12.019 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 023AF UT WOS:000236096700010 PM 16527692 ER PT J AU El-Serag, HB Hampel, H Javadi, F AF El-Serag, HB Hampel, H Javadi, F TI The association between diabetes and hepatocellular carcinoma: A systematic review of epidemiologic evidence SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Review ID NONALCOHOLIC FATTY LIVER; POPULATION-BASED COHORT; CHRONIC HEPATITIS-C; RISK-FACTORS; UNITED-STATES; NATURAL-HISTORY; CANCER-MORTALITY; VIRAL-HEPATITIS; VIRUS-INFECTION; US ADULTS AB Background & Aims: We conducted a systematic review and a meta-analysis to estimate the magnitude and determinants of association between diabetes and hepatocellular carcinoma (HCC). Methods: MEDLINE searches were conducted for published full studies (between January 1.966 and February 2005) that provided risk estimates and met criteria concerning the definition of exposure and outcomes. Two investigators independently performed standardized search and data abstraction. Unadjusted and adjusted odds ratios for individual outcomes Were obtained or calculated for each study and were synthesized using a random-effects model. Results: A total of 26 studies met our inclusion and exclusion criteria. Among 13 case-control studies, diabetes was associated significantly with HCC in 9 studies (pooled odds ratio, 2.5; 95% confidence interval, 1.8-3.5). Among 13 cohort studies, diabetes was associated significantly with HCC in 7 studies (pooled risk ratio, 2.5; 95% confidence interval, 1.9-.2). The results were relatively consistent in different populations, different geographic locations, and a variety of control groups. The signifiicant association between HCC and diabetes was independent of alcohol use or viral hepatitis in the :10 studies that examined these factors. Few studies adjusted for diet and obesity. Conclusions: Diabetes is associated with an increased risk for HIM However, more research is required to examine issues related to the duration and treatment of diabetes, and confounding by diet and obesity. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Gastroenterol, Houston, TX USA. RP El-Serag, HB (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 41 TC 381 Z9 399 U1 2 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2006 VL 4 IS 3 BP 369 EP 380 DI 10.1016/j.cgh.2005.12.007 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 023AF UT WOS:000236096700020 PM 16527702 ER PT J AU Mankin, HJ Trahan, CA Barnett, NA Laughead, J Bove, CM Pastores, GM AF Mankin, HJ Trahan, CA Barnett, NA Laughead, J Bove, CM Pastores, GM TI A questionnaire study for 128 patients with Gaucher disease SO CLINICAL GENETICS LA English DT Article DE cardiac issues; Gaucher disease; musculoskeletal; neuropsychologic; visceral ID ENZYME REPLACEMENT THERAPY; MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; LYSOSOMAL STORAGE DISORDERS; QUALITY-OF-LIFE; DEFICIENCY; REGISTRY; ADULTS; CELLS AB Gaucher disease is an uncommon autosomal recessive disorder characterized by lysosomal storage of glucosyl ceramide, a material released during cell degradation. Patients with Gaucher disease often have significant hematologic, bone structural, and visceral problems which sometimes greatly affect their health and life style. Based on some extraordinary scientific discoveries over the past 45 years, a treatment system has evolved which consists of administration of an enzyme, which destroys the lysosome-stored material and to some extent restores the patients to good health. There are still some problems for these patients; however, and the purpose of the study is to define some of the clinical, sociologic, and psychologic problems with a specially designed questionnaire. Questionnaire data was collected for 128 patients from two institutions with complete anonymity, and the information compared against data from a National Health Inteview Survey. The results show that many of the patients still have fairly extensive problems, which could possibly be helped by some alterations in treatment protocols. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NYU Hosp, New York, NY USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Gray 6 Orthopaed, Boston, MA 02114 USA. EM hmankin@partners.org NR 33 TC 10 Z9 12 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAR PY 2006 VL 69 IS 3 BP 209 EP 217 DI 10.1111/j.1399-0004.2006.00573.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 019MI UT WOS:000235840300005 PM 16542385 ER PT J AU Sartor, O AF Sartor, Oliver TI The continuing challenge of hormone-refractory prostate cancer SO CLINICAL GENITOURINARY CANCER LA English DT Editorial Material ID PROGNOSTIC-SIGNIFICANCE; LEUKEMIA GROUP-B-9480; SURVIVAL; ANTIGEN; MEN C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sartor, O (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD MAR PY 2006 VL 4 IS 4 BP 238 EP 239 DI 10.3816/CGC.2006.n.001 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 112LG UT WOS:000242526800001 PM 16729904 ER PT J AU Saad, F Higano, CS Sartor, O Colombel, M Murray, R Mason, MD Tubaro, A Schulman, C AF Saad, Fred Higano, Celestia S. Sartor, Oliver Colombel, Marc Murray, Robin Mason, Malcolm D. Tubaro, Andrea Schulman, Claude TI The role of bisphosphonates in the treatment of prostate cancer: Recommendations from an expert panel SO CLINICAL GENITOURINARY CANCER LA English DT Review DE androgen ablation; androgen-independent prostate cancer; bone metastases; hormone-sensitive prostate cancer; osteoporosis ID ANDROGEN-DEPRIVATION THERAPY; LONG-TERM EFFICACY; PREVENT BONE LOSS; ZOLEDRONIC ACID; DOUBLE-BLIND; SKELETAL COMPLICATIONS; CONTROLLED-TRIAL; PAMIDRONATE DISODIUM; BREAST-CARCINOMA; MULTIPLE-MYELOMA AB In this study, we provide consensus guidelines for the use of bisphosphonates in men with prostate cancer. To this end, an expert panel composed of urologists, medical oncologists, radiation oncologists, and endocrinologists met to review current clinical evidence for the use of bisphosphonates in patients with different stages of prostate cancer to derive consensus recommendations. Physicians should be proactive in monitoring bone loss in patients receiving long-term androgen-deprivation therapy for prostate cancer. Further study is needed before recommending the routine use of bisphosphonates in men with nonmetastatic prostate cancer. However, if a patient has clinically significant bone loss, use of a bisphosphonate to prevent further compromise of bone integrity should be strongly considered, regardless of hormonal and metastatic status. Bone scans are the preferred method for the identification of bone metastases. In patients with hormonerefractory prostate cancer and bone metastases, zoledronic acid is the only bisphosphonate indicated for the prevention of skeletal complications. In conclusion, patients with prostate cancer are at high risk for skeletal morbidity. Bisphosphonates have been shown to prevent cancer treatment-induced bone loss in men receiving androgen-deprivation therapy as well as skeletal complications in men with bone metastases. However, further study of the use of bisphosphonates across the clinical spectrum of prostate cancer is needed. C1 Univ Montreal, Ctr Hosp, Hop Notre Dame, Montreal, PQ H2L 4M1, Canada. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Univ Lyon 1, F-69365 Lyon, France. Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. Univ Cardiff Wales, Velindre Hosp, Sch Med, Cardiff, Wales. Univ Roma La Sapienza, Rome, Italy. Univ Clin Brussels, Brussels, Belgium. RP Saad, F (reprint author), Univ Montreal, Ctr Hosp, Hop Notre Dame, 1560 Rue Sherbrooke E, Montreal, PQ H2L 4M1, Canada. EM fred.saad@ssss.gouv.qc.ca NR 28 TC 24 Z9 24 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD MAR PY 2006 VL 4 IS 4 BP 257 EP 262 DI 10.3816/CGC.2006.n.004 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 112LG UT WOS:000242526800004 PM 16729908 ER PT J AU Humphrey, PA Halabi, S Picus, J Sanford, B Vogelzang, NJ Small, EJ Kantoff, PW AF Humphrey, Peter A. Halabi, Susan Picus, Joel Sanford, Ben Vogelzang, Nicholas J. Small, Eric J. Kantoff, Philip W. CA Canc Leukemia Grp B Eastern Cooperative Oncology Grp SW Oncology Grp TI Prognostic significance of plasma scatter factor/hepatocyte growth factor levels in patients with metastatic hormone-refractory prostate cancer: Results from cancer and leukemia group B 150005/9480 SO CLINICAL GENITOURINARY CANCER LA English DT Article DE c-Met; NK4; prognosis; suramin ID C-MET; FACTOR/SCATTER FACTOR; STROMAL CELLS; ANTITUMOR-ACTIVITY; EPITHELIAL-CELLS; TYROSINE KINASE; TUMOR-GROWTH; IN-VITRO; HEPATOCYTE; RECEPTOR AB Background: Scatter factor, also known as hepatocyte growth factor (SF/HGF), is a polypeptide growth factor thought to be important in the growth and spread of prostatic carcinoma. Patients and Methods: Scatter factor/HGF levels in pretreatment plasma samples from 171 men with metastatic hormone-refractory prostate cancer enrolled in CALGB 9480 were quantified by solid-phase, enzyme-linked immunosorbent assay. Results: The Cox proportional hazards model was used to assess the prognostic importance of SF/HGF with adjustment for established prognostic factors. Median SF/HGF was 991 pg/mL (range, 212-2733 pg/mL). In a univariate analysis, although plasma SF/HGF levels above versus below the median value did not reach statistical significance (P = 0.0862), the cutoff point of > 935 pg/mL was associated with a significant reduction in overall survival (P = 0.0334). Patients with SF/HGF levels > 935 pg/mL experienced a median survival of 15 months compared with 19 months for men with SF/HGF levels :5 935 pg/mL. In a multivariate analysis, adjusting for SF/HGF, prostatespecific antigen, lactate dehydrogenase, and performance status, only plasma alkaline phosphatase was significantly associated with overall survival (hazard ratio, 1.7; 95% confidence interval, 1.2-2.5; P = 0.0017). Conclusion: Higher plasma levels of SF/HGF in men with hormonerefractory prostate cancer are associated with a decreased patient survival. Currently, SF/HGF levels do not appear to be of value as a contributor to multivariate models for prediction of outcome, but the association with decreased survival suggests that SF/HGF might be a potential target for therapy. C1 Washington Univ, Med Ctr, Dept Pathol & Immunol, St Louis, MO 63110 USA. Duke Univ, Med Ctr, B Stat Ctr, Canc & Leukemia Grp, Durham, NC 27706 USA. Univ Chicago, Canc Res Ctr, Dept Med, Sect Hematol & Oncol, Chicago, IL 60637 USA. Univ Calif San Francisco, Mt Zion Canc Ctr, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Humphrey, PA (reprint author), Washington Univ, Med Ctr, Dept Pathol & Immunol, 660 S Euclid Ave,Campus Box 8118, St Louis, MO 63110 USA. EM humphrey@path.wustl.edu FU NCI NIH HHS [CA47559, CA47555, CA26806, CA77406, CA60138, CA47577, CA11789, CA41287, CA31983, CA16450, CA04457, CA74811, CA02599, CA03927, CA04326, CA12046, CA21060, CA31946, CA32291, CA33601, CA47642, CA77298, CA77658] NR 53 TC 29 Z9 30 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD MAR PY 2006 VL 4 IS 4 BP 269 EP 274 DI 10.3816/CGC.2006.n.006 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 112LG UT WOS:000242526800006 PM 16729910 ER PT J AU Williams, ME AF Williams, Mark E. TI Coronary revascularization in diabetic chronic kidney disease/end-stage renal disease: A nephrologist's perspective SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID DRUG-ELUTING STENTS; RANDOMIZED CONTROLLED-TRIAL; ACUTE MYOCARDIAL-INFARCTION; INSTITUTE DYNAMIC REGISTRY; ARTERY-BYPASS GRAFT; CARDIOVASCULAR-DISEASE; DIALYSIS PATIENTS; NATIONAL HEART; RISK-FACTORS; REPLACEMENT THERAPY C1 Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 113 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2006 VL 1 IS 2 BP 209 EP 220 DI 10.2215/CJN.00510705 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 107LH UT WOS:000242172600006 PM 17699209 ER PT J AU Kimby, E Treon, SP Anagnostopoulos, A Dimopoulos, M Garcia-Sanz, R Gertz, MA Johnson, S LeBlond, V Fermand, JP Maloney, DG Merlini, G Morel, P Morra, E Nichols, G Ocio, EM Owen, R Stone, M Blade, J AF Kimby, E Treon, SP Anagnostopoulos, A Dimopoulos, M Garcia-Sanz, R Gertz, MA Johnson, S LeBlond, V Fermand, JP Maloney, DG Merlini, G Morel, P Morra, E Nichols, G Ocio, EM Owen, R Stone, M Blade, J TI Update on recommendations for assessing response from the Third International Workshop on Waldenstrom's Macroglobulinemia SO CLINICAL LYMPHOMA & MYELOMA LA English DT Article DE Bence Jones protein; disease progression; immunoglobulin M; relapse ID CONSENSUS PANEL RECOMMENDATIONS; COOPERATIVE-ONCOLOGY-GROUP; RITUXIMAB THERAPY; SERUM IGM; CRITERIA AB This report by an international consensus panel updates current recommendations for defining clinical response in Waldenstrom's macroglobulinemia (WM). The previously published response criteria incorporated parameters for monoclonal protein reduction and/or improvement of marrow and nodal involvement, and included definitions of complete and partial remissions. The criteria have been updated to include minor response and stable disease categories. In addition, the criteria now recognize that delayed responses after treatment with nucleoside analogues and biologic agents and the time point for assessing response in patients with WM should be considered so as to not miss or miscategorize a response. The new criteria should therefore help in better delineating responses to therapy in patients with WM, particularly with the wide use of nucleoside analogues and biologically based agents for this disease. C1 Harvard Univ, Sch Med,Dana Farber Canc Ins, Bing Program Waldenstroms Macroglobulinemia, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Karolinska Univ Hosp, Stockholm, Sweden. Univ Athens, Sch Med, GR-10679 Athens, Greece. Univ Salamanca Hosp, Salamanca, Spain. Mayo Clin, Rochester, MN USA. Taunton & Somerset Hosp, Somerset, NJ USA. Hop La Pitie Salpetriere, Paris, France. Hop St Louis, Paris, France. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Policlin San Matteo, Inst Sci, I-27100 Pavia, Italy. Hosp Schaffner, Lens, France. Osped Niguarda Ca Granda, Milan, Italy. Columbia Univ, New York, NY USA. Leeds Gen Infirm, Leeds, W Yorkshire, England. Baylor Sammons Canc Ctr, Dallas, TX USA. Hosp Clin Hematol, Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain. RP Treon, SP (reprint author), Harvard Univ, Sch Med,Dana Farber Canc Ins, Bing Program Waldenstroms Macroglobulinemia, Bing Ctr Waldenstroms Macroglobulinemia, M548A,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Merlini, Giampaolo/A-3817-2008; Garcia-Sanz, Ramon/B-7986-2017 OI Merlini, Giampaolo/0000-0001-7680-3254; Garcia-Sanz, Ramon/0000-0003-4120-2787 NR 17 TC 80 Z9 83 U1 0 U2 1 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD MAR PY 2006 VL 6 IS 5 BP 380 EP 383 DI 10.3816/CLM.2006.n.013 PG 4 WC Oncology SC Oncology GA 050MC UT WOS:000238090700004 PM 16640813 ER PT J AU Pardasaney, PK Sullivan, PE Portney, LG Mankin, HJ AF Pardasaney, Poonam K. Sullivan, Patricia E. Portney, Leslie G. Mankin, Henry J. TI Advantage of limb salvage over amputation for proximal lower extremity tumors SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID QUALITY-OF-LIFE; SOFT-TISSUE SARCOMA; BONE-TUMORS; ENERGY-COST; ENDOPROSTHETIC REPLACEMENT; OSTEOARTICULAR ALLOGRAFTS; OSTEOGENIC SARCOMA; CLINICAL-TRIALS; DISTAL END; RECONSTRUCTION AB Although function after lower extremity amputation and limb salvage has been compared, no study has assessed individual functional variables by surgical level. Our aim was to determine whether risks of long-term psychologic and physical limitations were associated with amputation or limb salvage at four levels: below-knee, above-knee, hip, and pelvis. We included 408 patients with sarcomas and postoperative followup of 2 years or greater who had completed a quality-of-life self-report questionnaire. The mean length of followup was 8.91 +/- 5.15 years (range, 2-27 years). Relative risk analysis was done on 12 dichotomous general health, psychologic, and physical function variables. At the below-knee level, outcomes were similar after both procedures. At the above-knee level, amputation was associated with increased risk of limp (RR = 1.6), walking aid use (RR = 2.1), anxiety (RR = 2.4), and inability to drive (RR = 3), and decreased risk of muscle weakness (RR = 0.57). At the hip and pelvic levels, outcomes were descriptively compared because of the small number of amputations. At these higher levels, limitations were more common after amputation. The difference in results between the below-knee and above-knee levels supports the importance of distinguishing surgical levels. Limb salvage offers a functional advantage at proximal tumor locations. C1 MHG Inst Hlth Profess, Grad Programs Phys Therapy, Boston, MA 02129 USA. Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Pardasaney, PK (reprint author), MHG Inst Hlth Profess, Grad Programs Phys Therapy, Charlestown Navy Yard,36 1st Ave, Boston, MA 02129 USA. EM ppardasaney@partners.org NR 44 TC 16 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2006 IS 444 BP 201 EP 208 DI 10.1097/01.blo.0000195413.16150.bc PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119NY UT WOS:000243020200029 PM 16449916 ER PT J AU Schottenbauer, MA Arnkoff, DB Glass, CR Gray, SH AF Schottenbauer, MA Arnkoff, DB Glass, CR Gray, SH TI Psychotherapy for PTSD in the community: Reported prototypical treatments SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; INTERVENTIONS AB Therapists who identified themselves primarily with psychodynamic/psychoanalytic or cognitive-behavioral theoretical orientations were recruited through professional organization online listservs. They were randomly presented one of four brief case studies, describing variations on traumatic stress. Participants then completed a Psychotherapy Process Q-sort to describe quantitatively their ideal treatment of the given patient. Results indicated significant heterogeneity among clinicians. Among clinicians who indicated that their primary theoretical orientation was psychodynamic, three prototypical treatments were discovered, and among clinicians who indicated that their primary theoretical orientation was cognitive-behavioral, four prototypical treatments were found. Overall, the prototypes in the current study were correlated with, but not identical to, prototypes of psychodynamic, cognitive-behavioral or interpersonal therapy developed in previous studies based on experts' ratings. Our findings suggest that there may be much greater heterogeneity in treatment of trauma among clinicians in the community than might be assumed by the theoretical orientations they espouse. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Catholic Univ Amer, Washington, DC 20064 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Schottenbauer, MA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM mschottenbauer@partners.org NR 34 TC 8 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1063-3995 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD MAR-APR PY 2006 VL 13 IS 2 BP 108 EP 122 DI 10.1002/cpp.480 PG 15 WC Psychology, Clinical SC Psychology GA 039XE UT WOS:000237340700003 ER PT J AU Spencer, TJ Abikoff, HB Connor, DF Biederman, J Pliszka, SR Boellner, S Read, SC Pratt, R AF Spencer, TJ Abikoff, HB Connor, DF Biederman, J Pliszka, SR Boellner, S Read, SC Pratt, R TI Efficacy and safety of mixed amphetamine salts extended release (Adderall XR) in the management of oppositional defiant disorder with or without comorbid attention-deficit/hyperactivity disorder in school-aged children and adolescents: A 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study SO CLINICAL THERAPEUTICS LA English DT Article DE oppositional defiant disorder; ODD; Adderall XR; MAS XR; mixed amphetamine salts extended release; attention-deficit/hyperactivity disorder; ADHD ID DEFICIT-HYPERACTIVITY DISORDER; CONDUCT DISORDER; ADHD; SAMPLE; MTA; METHYLPHENIDATE; PREVALENCE; SYMPTOMS; STRESS AB Background: Oppositional defiant disorder (ODD) is associated with a high degree of impairment in social skills, family interaction, and academic functioning. Comorbid ODD is reportedly present in 40% to 70% of children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Objective: The goal of this study was to assess the efficacy and safety of mixed amphetamine salts extended release (MAS XR) for the treatment of ODD in children and adolescents aged 6 to 17 years. Methods: This was a 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study. Patients were randomized to receive active treatment with MAS XR 10, 20, 30, or 40 mg/d or placebo. The primary efficacy end point was the ODD subscale of the Swanson, Nolan, and Pelham-IV (SNAP-IV) parent rating. Primary safety measures included adverse events recorded at each visit and for 30 days after study drug discontinuation, and changes in vital signs, 12-lead electrocardiographic (ECG) findings, laboratory tests and physical examinations, and body weight. A post hoc efficacy reanalysis was completed based on the results for the per-protocol population. For this analysis, patients were divided into high and low baseline severity categories according to the dichotomized baseline ODD parent or teacher score or dichotomized baseline ADHD parent or teacher score (high defined as scores at the median or greater and low defined as scores less than the median). Results: A total of 308 children and adolescents (age range, 6-17 years; 213 males, 95 females) were randomized to receive active treatment with MAS XR 10 mg/d (n = 60) 20 mg/d (n = 58), 30 mg/d (n = 69), or 40 mg/d (n = 61) or placebo (n = 60). Of the 308 study patients, 244 (79.2%) had comorbid ADHD. A significant change from baseline in the ODD symptoms measured with the SNAP-IV parent rating subscale was found for the MAS XR 30-mg/d (-0.52; P < 0.001) and 40-mg/d (-0.56; P = 0.002) groups in the per-protocol analysis and for the MAS XR 30-mg/d group in the intent-to-treat analysis (-0.42; P < 0.005). Throughout the study, MAS XR was well tolerated in these children and adolescents with ODD, and most adverse events were mild to moderate in intensity. The most frequently reported adverse events occurring in MAS XR-treated patients were anorexia/decreased appetite (25.3%), insomnia (19.5%), headache (18.5%), and abdominal pain (10.7%). Statistically, but not clinically, significant decreases in body weight were seen with MAS XR (range, -1.1 to -3.5 lb; P < 0.001 vs placebo). Changes in laboratory values, ECG measurements, and physical and other vital signs were also not clinically significant. The post hoc reanalysis was based on the per-protocol population (n = 229). An assessment of the high baseline symptom severity subgroups showed a good response to MAS XR treatment for the SNAP-IV parent and teacher rating scales (both, P < 0.05). Conclusion: This study found that higher doses of MAS XR (30 and 40 mg) were effective and well tolerated in the management of ODD in these school-aged children and adolescents in the presence or absence of ADHD. C1 Harvard Univ, Sch Med,Yawkey Ctr Outpatient Care, Massachusetts Gen Hosp,Clin & Res Program, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. NYU, Sch Med, New York, NY USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Clin Study Ctr, Little Rock, AR USA. Shire Pharmaceut Inc, Wayne, PA USA. RP Spencer, TJ (reprint author), Harvard Univ, Sch Med,Yawkey Ctr Outpatient Care, Massachusetts Gen Hosp,Clin & Res Program, Pediat Psychopharmacol Res Unit, YAW-4-4A,32 Fruit St, Boston, MA 02114 USA. EM tspencer@partners.org NR 30 TC 43 Z9 44 U1 1 U2 12 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD MAR PY 2006 VL 28 IS 3 BP 402 EP 418 DI 10.1016/j.clinthera.2006.03.006 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 031FO UT WOS:000236690000009 PM 16750455 ER PT J AU Al-Mutawa, SA Shyama, M Al-Duwairi, Y Soparkar, P AF Al-Mutawa, SA Shyama, M Al-Duwairi, Y Soparkar, P TI Dental caries experience of Kuwaiti schoolchildren SO COMMUNITY DENTAL HEALTH LA English DT Article DE dental caries; Kuwait; schoolchildren ID SAUDI-ARABIA; ORAL-HEALTH; SCHOOL-CHILDREN; PREVALENCE; DECLINE; TRENDS AB This study was designed to measure the dental caries experience of Kuwaiti schoolchildren. Methods A national epidemiologic survey of the 5-14 year old children (n = 4,588) was conducted in the 5 governorates of Kuwait in 2001. Eight trained and calibrated dentists examined the children. Dental caries was scored using WHO criteria. Results In the primary dentition, the percentage of 5- and 6-year-old children with dft = 0 was 12.6% and 14.4% respectively. The corresponding mean dft/dfs for 5- and 6-year-olds were 4.6/9.7 and 4.6/9.9. For the permanent dentition, the percentage of 12- and 14-year-old children with DMFT = 0 was 26.4% and 21.7% respectively The corresponding mean DMFT/DFS figures for 12- and 14-year-olds were 2.6/3.4 and 3.9/4.2. The d/D component was the major contributor to these mean scores. Poor oral hygiene (OR = 2.0-1 95% CI = 1.7 - 2.4) and increasing age (OR = 1.4; 95% CI = 1.3 - 1.5) were significantly associated with caries risk in the permanent dentition. Conclusions Caries levels are similar to those in neighbouring and other Middle East countries. There is a clear need for expanding the national school oral health programme to reach those children who are not yet receiving systematic preventive and curative services. Further studies are required to monitor the effect of the extensive caries preventive programme now in place in Kuwait. C1 Forsyth Inst, Boston, MA USA. RP Shyama, M (reprint author), POB 1952, Salmiya 22020, Kuwait. EM mshyama@yahoo.com NR 31 TC 21 Z9 23 U1 1 U2 1 PU F D I WORLD DENTAL PRESS LTD PI LOWESTOFT PA 5 BATTERY GREEN RD, LOWESTOFT NR32 1 DE, SUFFOLK, ENGLAND SN 0265-539X J9 COMMUNITY DENT HLTH JI Community Dent. Health PD MAR PY 2006 VL 23 IS 1 BP 31 EP 36 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 021EH UT WOS:000235966000006 PM 16555717 ER PT J AU Zhou, XH Liang, H AF Zhou, XH Liang, H TI Semi-parametric single-index two-part regression models SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE logistic regression; kernel regression; skewed data; single-index model ID LIMITED DEPENDENT-VARIABLES; ESTIMATOR AB In this paper, we proposed a semi-parametric single-index two-part regression model to weaken assumptions in parametric regression methods that were frequently used in the analysis of skewed data with additional zero values. The estimation procedure for the parameters of interest in the model was easily implemented. The proposed estimators were shown to be consistent and asymptotically normal. Through a simulation study, we showed that the proposed estimators have reasonable finite-sample performance. We illustrated the application of the proposed method in one real study on the analysis of health care costs. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Washington, Biostat Unit, NW HSR Ctr Excellence, Vet Affairs Puget Sound Hlth Care Syst,Dept Biost, Seattle, WA 98108 USA. St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. RP Zhou, XH (reprint author), Univ Washington, Biostat Unit, NW HSR Ctr Excellence, Vet Affairs Puget Sound Hlth Care Syst,Dept Biost, 1660 S Columbian Way, Seattle, WA 98108 USA. EM azhou@u.washington.edu FU AHRQ HHS [R01 HS013105]; NIAID NIH HHS [R01 AI062247, R01 AI059773-01A2] NR 18 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 EI 1872-7352 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD MAR 1 PY 2006 VL 50 IS 5 BP 1378 EP 1390 DI 10.1016/j.csda.2004.12.001 PG 13 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 007AS UT WOS:000234940200012 PM 20191094 ER PT J AU Huang, W Fileta, J Guo, Y Grosskreutz, CL AF Huang, W Fileta, J Guo, Y Grosskreutz, CL TI Downregulation of Thy1 in retinal ganglion cells in experimental glaucoma SO CURRENT EYE RESEARCH LA English DT Article DE experimental glaucoma; laser capture microdissection; qRCR; Thy1 mRNA ID MESSENGER-RNA LEVELS; INTRAOCULAR-PRESSURE; GENE-EXPRESSION; TRANSGENIC MICE; RAT RETINA; PROMOTER; ASTROCYTES; INTEGRIN; BETA(3); DAMAGE AB Purpose: Thy1 is a surface glycoprotein uniquely expressed in retinal ganglion cells (RGCs) in retina. The aim of this study was to investigate the expression change of Thy1 in a model of experimental glaucoma. Methods: The change of protein and mRNA levels of Thy1 in the retina were studied using stereological counts of back-labeled RGCs, Western blot analysis, immunohistochemistry, and laser capture microdissection (LCM) of RGCs with quantitative PCR analysis of mRNA in a model of experimental glaucoma. LCM after optic nerve crush was also performed to evaluate Thy1 mRNA levels after a different injury. Results: After 10 days of elevated IOP, there was a 34% loss of RGC number, Thy1 protein decreased 60% in eyes with elevated intraocular pressure (IOP), and Thy1 mRNA levels decreased 51% in RGCs. Both protein and mRNA level change of Thy1 is to a much greater extent than RGC number loss. Conclusions: The current results confirm that Thy 1 mRNA levels do not reflect the number of RGCs present and extend this to include a parallel decrease in Thy1 protein levels. These results suggest that Thy1 serves as an early marker of RGC stress, but not a marker of RGC loss, in models of retinal damage. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu FU NEI NIH HHS [P30EY14104, R01EY13399] NR 23 TC 66 Z9 68 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAR PY 2006 VL 31 IS 3 BP 265 EP 271 DI 10.1080/02713680500545671 PG 7 WC Ophthalmology SC Ophthalmology GA 021AA UT WOS:000235953500007 PM 16531284 ER PT J AU Harris, LA Chang, L AF Harris, LA Chang, L TI Irritable bowel syndrome: new and emerging therapies SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE irritable bowel syndrome; pathophysiology; therapy ID FUNCTIONAL GASTROINTESTINAL DISORDERS; INTESTINAL BACTERIAL OVERGROWTH; CORTICOTROPIN-RELEASING HORMONE; RANDOMIZED CONTROLLED-TRIAL; OPIOID RECEPTOR AGONISTS; PREDOMINANCE IBS-D; DOUBLE-BLIND; DIARRHEA-PREDOMINANT; RECTAL DISTENSION; ANTAGONIST ALOSETRON AB Purpose of review Irritable bowel syndrome refers to abdominal discomfort associated with altered bowel habits. Recent evidence suggests that the primary pathophysiologic mechanism is brain-gut dysregulation. Many central and peripheral factors are involved. This article will review important pathophysiologic mechanisms with a focus on new and emerging therapies. Recent findings Prior gastroenteritis and small intestinal bacterial overgrowth may be important for treatment of irritable bowel syndrome. Understanding of serotonergic receptors in gastrointestinal function has led to the development of serotonergic agents such as alosetron and tegaserod. Novel agents targeting other receptor sites include neurokinin and neurohormonal modulators, chloride channels and opioid receptors. Other therapeutic approaches - behavioral treatments, probiotics, antibiotics and alternative therapies - have developing roles in the treatment of irritable bowel syndrome. Summary A better understanding of pathophysiologic mechanisms has resulted in therapeutic advances. Prokinetic therapies may have a role in nondiarrhea predominant irritable bowel syndrome. Antidepressants are used to modulate pain and treat comorbid psychological distress. Newer agents target various receptor sites. Advances in psychological/behavioral treatments and alternative modalities hold promise for the future. C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis, Los Angeles, CA 90073 USA. Mayo Clin, Coll Med, Scottsdale, AZ USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Chang, L (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis, CURE Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM linchang@mednet.ucla.edu NR 88 TC 4 Z9 4 U1 3 U2 3 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 MAR PY 2006 VL 22 IS 2 BP 128 EP 135 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 026DP UT WOS:000236317300008 PM 16462168 ER PT J AU Cutler, C Antin, JH AF Cutler, C Antin, JH TI Chronic graft-versus-host disease SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE allogeneic stem cell transplantation; chronic graft-versus-host disease; graft-versus-leukemia effect ID STEM-CELL TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGENS; MONOCLONAL-ANTIBODY TREATMENT; CHRONIC LYMPHOCYTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; RANDOMIZED CLINICAL-TRIAL; MYCOPHENOLATE-MOFETIL; EXTRACORPOREAL PHOTOPHERESIS; CHRONIC GVHD; CYCLOSPORINE PROPHYLAXIS AB Purpose of review Chronic graft-versus-host disease is an important cause of late morbidity and mortality after allogeneic stem cell transplantation. With the renewed interest in its pathophysiology and treatment, this review discusses recent clinical and laboratory advances in this disease. Advances in pathophysiology, the relationship between chronic graft-versus-host disease and relapse incidence, and recent developments in the prophylaxis, initial therapy, and therapy for refractory disease are discussed. Recent findings A better understanding of the pathophysiology of chronic graft-versus-host disease, including the potential role of a coordinated B-cell and T-cell response, is demonstrated. Corticosteroids and cyclosporine or tacrolimus remain the standard as initial therapy. This combination is effective in the majority of affected patients, although therapy is often required for longer than 1 year. Although no strategy has been demonstrated to be effective in specifically preventing chronic graft-versus-host disease, several drugs have recently been demonstrated to be effective therapeutic agents for steroid-refractory disease. Agents such as mycophenolate mofetil, sirolimus, and rituximab have demonstrated response rates of greater than 60% in patients with steroid-refractory disease. Summary Renewed interest and understanding of chronic graft-versus-host disease have led to novel treatment strategies for steroid-refractory disease. A focus on the initial therapy and prophylaxis against chronic graft-versus-host disease is now warranted. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu NR 56 TC 25 Z9 26 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAR PY 2006 VL 18 IS 2 BP 126 EP 131 DI 10.1097/01.cco.0000208784.07195.84 PG 6 WC Oncology SC Oncology GA 035KE UT WOS:000236998900004 PM 16462180 ER PT J AU Goldfine, AB Crunkhorn, S Costello, M Gami, H Landaker, EJ Niinobe, M Yoshikawa, K Lo, D Warren, A Jimenez-Chillaron, J Patti, ME AF Goldfine, AB Crunkhorn, S Costello, M Gami, H Landaker, EJ Niinobe, M Yoshikawa, K Lo, D Warren, A Jimenez-Chillaron, J Patti, ME TI Necdin and E2F4 are modulated by rosiglitazone therapy in human adipose and muscle tissue SO DIABETES LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; PRADER-WILLI-SYNDROME; GENE-EXPRESSION; ADIPOCYTE DIFFERENTIATION; INSULIN-RESISTANCE; PPAR-GAMMA; GROWTH SUPPRESSOR; THIAZOLIDINEDIONES; FAMILY; INTERACTS AB To identify novel pathways mediating molecular mechanisms of thiazolidinediones (TZDs) in humans, we assessed gene expression in adipose and muscle tissue from six subjects with type 2 diabetes before and after 8 weeks of treatment with rosiglitazone. mRNA was analyzed using Total Gene Expression Analysis (TOGA), an automated restriction-based cDNA display method with quantitative analysis of PCR products. The expression of cell cycle regulatory transcription factors E2F4 and the MAGE protein necdin were similarly altered in all subjects after rosiglitazone treatment. E2F4 expression was decreased by 10-fold in muscle and 2.5-fold in adipose tissue; necdin was identified in adipose tissue only and increased 1.8-fold after TZD treatment. To determine whether changes were related to an effect of the drug or adipogenesis, we evaluated the impact of rosiglitazone and differentiation independently in 3T3-L1 adipocytes. While treatment of differentiated adipocytes with rosiglitazone did not alter E2F4 or necdin, expression of both genes was significantly altered during differentiation. Differentiation was associated with increased cytosolic localization of E2F4. Moreover, necdin overexpression potently inhibited adipocyte differentiation and cell cycle progression. These data suggest that changes in necdin and E2F4 expression after rosiglitazone exposure in humans are associated with altered adipocyte differentiation and may contribute to improved insulin sensitivity in humans treated with TZDs. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Osaka Univ, Inst Prot Res, Div Regulat Macromol Funct, Osaka, Japan. Digital Gene Technol Neurome, La Jolla, CA USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu RI Jimenez-Chillaron, Josep/L-5854-2015 FU NCRR NIH HHS [M01-RR-01032]; NIDDK NIH HHS [R01-DK-45935, R01-DK-060837, P30-DK-36836, K23-DK-02795, K08-DK-02526, R01-DK-33201, R01-DK-62948] NR 50 TC 10 Z9 10 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2006 VL 55 IS 3 BP 640 EP 650 DI 10.2337/diabetes.55.03.06.db05-1015 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018IL UT WOS:000235757600010 PM 16505226 ER PT J AU Naruse, K Rask-Madsen, C Takahara, N Ha, SW Suzuma, K Way, KJ Jacobs, JRC Clermont, AC Ueki, K Ohshiro, Y Zhang, JQ Goldfine, AB King, GL AF Naruse, K Rask-Madsen, C Takahara, N Ha, SW Suzuma, K Way, KJ Jacobs, JRC Clermont, AC Ueki, K Ohshiro, Y Zhang, JQ Goldfine, AB King, GL TI Activation of vascular protein kinase C-beta inhibits Akt-dependent endothelial nitric oxide synthase function in obesity-associated insulin resistance SO DIABETES LA English DT Article ID DIABETIC-RATS; CELLS; EXPRESSION; GROWTH; FATTY; DIACYLGLYCEROL; AMELIORATION; VASODILATION; ISOFORMS; MUSCLE AB Activation of protein kinase C (PKC) in vascular tissue is associated with endothelial dysfunction and insulin resistance. However, the effect of vascular PKC activation on insulin-stimulated endothelial nitric oxide (NO) synthase (eNOS) regulation has not been characterized in obesity-associated insulin resistance. Diacylglycerol (DAG) concentration and PKC activity were increased in the aorta of Zucker fatty compared with Zucker lean rats. Insulin-stimulated increases in Akt phosphorylation and cGMP concentration (a measure of NO bioavailability) after euglycemic-hyperinsulinemic clamp were blunted in the aorta of fatty compared with lean rats but were partly normalized after 2 weeks of treatment with the PKC beta inhibitor ruboxistaurin (LY333531). In endothelial cell culture, overexpression of PKC beta 1 and -beta 2, but not PKC alpha, -delta, or -zeta, decreased insulin-stimulated Akt phosphorylation and eNOS expression. Overexpression of PKC beta 1 and -beta 2, but not PKC alpha or -delta, also decreased Akt phosphorylation stimulated by vascular endothelial growth factor (VEGF). In microvessels isolated from transgenic mice overexpressing PKC beta 2 only in vascular cells, Akt phosphorylation stimulated by insulin was decreased compared with wild-type mice. Thus, activation of PKC beta in endothelial cells and vascular tissue inhibits Akt activation by insulin and VEGF, inhibits Nkt-dependent eNOS regulation by insulin, and causes endothelial dysfunction in obesity-associated insulin resistance. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Aichi Gakuin Univ, Sch Dent, Dept Internal Med, Chikusa Ku, Nagoya, Aichi 464, Japan. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl,Room 4504, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu FU NIDDK NIH HHS [R01-DK-53105] NR 28 TC 111 Z9 121 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2006 VL 55 IS 3 BP 691 EP 698 DI 10.2337/diabetes.55.03.06.db05-0771 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018IL UT WOS:000235757600016 PM 16505232 ER PT J AU Sun, MW Lee, JY de Bakker, PIW Burtt, NP Almgren, P Rastam, L Tuomi, T Gaudet, D Daly, MJ Hirschhorn, JN Altshuler, D Groop, L Florez, JC AF Sun, MW Lee, JY de Bakker, PIW Burtt, NP Almgren, P Rastam, L Tuomi, T Gaudet, D Daly, MJ Hirschhorn, JN Altshuler, D Groop, L Florez, JC TI Haplotype structures and large-scale association testing of the 5 ' AMP-activated protein kinase genes PRK4A2, PRKAB1, and PRK4B1 with type 2 diabetes SO DIABETES LA English DT Article ID HUMAN SKELETAL-MUSCLE; GENOME-WIDE SEARCH; SUSCEPTIBILITY GENES; INSULIN SENSITIVITY; GLUCOSE-TRANSPORT; METABOLIC STRESS; COMPLEX TRAITS; 7,883 PEOPLE; AMP KINASE; SIB PAIRS AB AMP-activated protein kinase (AMPK) is a key molecular regulator of cellular metabolism, and its activity is induced by both metformin and thiazolidinedione antidiabetic medications. It has therefore been proposed both as a putative agent in the pathophysiology of type 2 diabetes and as a valid target for therapeutic intervention. Thus, the genes that encode the various AMPK subunits are intriguing candidates for the inherited basis of type 2 diabetes. We therefore set out to test for the association of common variants in the genes that encode three selected AMPK subunits with type 2 diabetes and related phenotypes. Of the seven genes that encode AMPK isoforms, we initially chose PRKAA2, PRKAB1, and PRKAB2 because of their higher prior probability of association with type 2 diabetes, based on previous reports of genetic linkage, functional molecular studies, expression patterns, and pharmacological evidence. We determined their haplotype structure, selected a subset of tag single nucleotide polymorphisms that comprehensively capture the extent of common genetic variation in these genes, and genotyped them in family-based and case/control samples comprising 4,206 individuals. Analysis of single-marker and multi-marker tests revealed no association with type 2 diabetes, fasting plasma glucose, or insulin sensitivity. Several nominal associations of variants in PRKAA2 and PRKAB1 with BMI appear to be consistent with statistical noise. C1 Massachusetts Gen Hosp, Dept Mol Biol, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Lund Univ, Univ Hosp MAS, Dept Endocrinol, Malmo, Sweden. Lund Univ, Univ Hosp MAS, Dept Clin Sci, Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med,Folkhalsan Genet Inst, Folkhalsan Res Ctr, Helsinki, Finland. Univ Helsinki, Res Program Mol Med, Helsinki, Finland. Univ Montreal, Community Genom Ctr, Chicoutimi Hosp, Quebec City, PQ, Canada. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Diabet Unit, Boston, MA 02114 USA. EM jcflorez@partners.org 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 FU NIDDK NIH HHS [1 K23 DK65978-02] NR 49 TC 12 Z9 14 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2006 VL 55 IS 3 BP 849 EP 855 DI 10.2337/diabetes.55.03.06.db05-1418 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018IL UT WOS:000235757600038 PM 16505254 ER PT J AU Izumi, Y Satterfield, K Lee, S Harkless, LB AF Izumi, Y Satterfield, K Lee, S Harkless, LB TI Risk of reamputation in diabetic patients stratified by limb and level of amputation - A 10-year observation SO DIABETES CARE LA English DT Article ID LOWER-EXTREMITY AMPUTATION; TRANSMETATARSAL AMPUTATION; MEXICAN-AMERICANS; ETHNICITY; MELLITUS; DISEASE; COHORT AB OBJECTIVE - This study examined the risk of reamputation, stratified by original level of amputation, in a population of diabetic patients. We also illustrated reamputation rates by ipsilateral and contralateral limbs. RESEARCH DESIGN AND METHODS - The study population included 277 diabetic patients with a first lower-extremity amputation performed between 1993 and 1997 at University Hospital in San Antonio, Texas. Reamputation episodes for the ipsilateral and contralateral limbs were recorded through 2003. Using a cumulative incidence curve analysis, we compare the reamputation rate by limb. Cumulative rates of reamputation were calculated for each limb at each amputation level at 1, 3, and 5 years. RESULTS - Cumulative rates of reamputation per person were 26.7% at 1 year, 48.3% at 3 years, and 60.7% at 5 years. lpsilateral reamputation per amputation level at the 1-, 3-, and 5-year points were toe: 22.8, 39.6, and 52.3%; ray: 28.7, 41.2, and 50%; midfoot: 18.8, 33.3, and 42.9%, and major: 4.7, 11.8, and 13.3%. For contralateral reamputation, the rates at 1, 3, and 5 years were toe: 3.5, 18.8, and 29.5%; ray: 9.3, 21.6, and 29.2%; midfoot: 9.4, 18.5, and 33.3%; and major: 11.6, 44.1, and 53.3%. CONCLUSIONS - This study showed that a patient is at greatest risk for further same-limb amputation in the 6 months after the initial amputation. Although risk to the contralateral limb rises steadily, it never meets the level of that of the ipsilateral limb. This finding will help clinicians focus preventive efforts and medical resources during individualized at-risk periods for diabetic patients undergoing first-time amputations. C1 Univ Texas, Hlth Sci Ctr, Dept Orthoped, San Antonio, TX 78229 USA. Natl Hosp Org, WHO Collaborating Ctr Diabet Treatment & Educ, Kyoto Med Ctr, Kyoto, Japan. S Texas Vet Hlth Care Syst, Res & Dev Serv, Audie L Murphy Div, San Antonio, TX USA. RP Izumi, Y (reprint author), Univ Texas, Hlth Sci Ctr, Dept Orthoped, Mail Code 776,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM dfootjapan@hotmail.co.jp NR 29 TC 53 Z9 58 U1 0 U2 4 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 MAR PY 2006 VL 29 IS 3 BP 566 EP 570 DI 10.2337/diacare.29.03.06.dc05-1992 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018KW UT WOS:000235764100014 PM 16505507 ER PT J AU Laffel, LMB Wentzell, K Loughlin, C Tovar, A Moltz, K Brink, S AF Laffel, LMB Wentzell, K Loughlin, C Tovar, A Moltz, K Brink, S TI Sick day management using blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: a randomized clinical trial SO DIABETIC MEDICINE LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the American-Diabetes-Association CY 2002 CL San Francisco, CA SP Amer Diabetes Assoc DE Type 1 diabetes; diabetic ketoacidosis; beta-hydroxybutyrate; urine ketones; sick day management ID DIABETIC-KETOACIDOSIS; BETA-HYDROXYBUTYRATE; ELECTROCHEMICAL SENSOR; ACUTE COMPLICATIONS; ADVERSE OUTCOMES; CEREBRAL EDEMA; KINETIC METHOD; CHILDREN; ADOLESCENTS; PREDICTORS AB Aims Diabetic ketoacidosis (DKA), a life-threatening acute complication of Type 1 diabetes, may be preventable with frequent monitoring of glycaemia and ketosis along with timely supplemental insulin. This prospective, two-centre study assessed sick day management using blood 3-hydroxybutyrate (3-OHB) monitoring compared with traditional urine ketone testing, aimed at averting emergency assessment and hospitalization. Methods One hundred and twenty-three children, adolescents and young adults, aged 3-22 years, and their families received sick day education. Participants were randomized to receive either a blood glucose monitor that also measures blood 3-OHB (blood ketone group, n = 62) or a monitor plus urine ketone strips (urine ketone group, n = 61). All were encouraged to check glucose levels >= 3 times daily and to check ketones during acute illness or stress, when glucose levels were consistently elevated (>= 13.9 mmol/l on two consecutive readings), or when symptoms of DKA were present. Frequency of sick days, hyperglycaemia, ketosis, and hospitalization/emergency assessment were ascertained prospectively for 6 months. Results There were 578 sick days during 21 548 days of follow-up. Participants in the blood ketone group checked ketones significantly more during sick days (276 of 304 episodes, 90.8%) than participants in the urine ketone group (168 of 274 episodes, 61.3%) (P < 0.001). The incidence of hospitalization/emergency assessment was significantly lower in the blood ketone group (38/100 patient-years) compared with the urine ketone group (75/100 patient-years) (P = 0.05). Conclusions Blood ketone monitoring during sick days appears acceptable to and preferred by young people with Type 1 diabetes. Routine implementation of blood 3-OHB monitoring for the management of sick days and impending DKA can potentially reduce hospitalization/emergency assessment compared with urine ketone testing and offers potential cost savings. C1 Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect, Boston, MA 02215 USA. New England Diabest & Endocrinol Ctr, Waltham, MA USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM Lori.laffel@joslin.harvard.edu NR 35 TC 51 Z9 53 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAR PY 2006 VL 23 IS 3 BP 278 EP 284 DI 10.1111/j.1464-5491.2005.01771.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 012WB UT WOS:000235370500010 PM 16492211 ER PT J AU Bhavnani, SM Ambrose, PG Craig, WA Dudley, MN Jones, RN AF Bhavnani, SM Ambrose, PG Craig, WA Dudley, MN Jones, RN TI Outcomes evaluation of patients with ESBL- and non-ESBL-producing Escherichia coli and Klebsiella species as defined by CLSI reference methods: report from the SENTRY Antimicrobial Surveillance Program SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article; Proceedings Paper CT 44th Interscience Conference on Antimicrobial Agents and Chemotherapy CY OCT 30-NOV 02, 2004 CL Washington, DC DE extended-spectrum beta-lactamase; Klebsiella species; Enterobacteriaceae; Escherichia coli ID SPECTRUM-BETA-LACTAMASE; BLOOD-STREAM INFECTIONS; RISK-FACTORS; PNEUMONIAE BACTEREMIA; ORGANISMS; CEFEPIME; CHILDREN; STRAINS AB As extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae continue to emerge worldwide, selection of empiric treatment modalities is an increasing challenge. Data describing the clinical outcomes associated with different treatment regimens have been limited. Using data froth centers with continued ESBL- and non-ESBL-producing Escherichia coli and Klebsiella species isolates in North America, Latin America, and Europe, potential risk factors for the occurrence of invasive ESBL- and non-ESBL-producing Enterobacteriaceae infections and factors associated with clinical outcome were evaluated. Of the 175 cases considered evaluable, 77% were ESBL-producing organisms. Underlying comorbidities and potential risk factors were generally similar between ESBL and non-ESBL cases with a statistically greater proportion of ESBL cases requiring gastrostomy or jejunostomy tubes, ventilatory assistance, or care in the intensive care unit before culture (P <= 0.008). Among ESBL cases, carbapenem monotherapy and combination therapy were often selected for treatment (32.6% and 13.3%, respectively). Among non-ESBL cases, fluoroquinolones and beta-lactam/beta-lactamase inhibitor combination agents accounted for the highest proportion of treatment regimens (25.0% and 22.5%, respectively), whereas cephalosporin monotherapy and combination therapy were each used as treatment for 10% of cases. Clinical success was similar between patients with ESBL and non-ESBL-producing isolates (83% and 80%, respectively). Although infections arising from E. coli and Klebsiella species are associated with significant mortality, ESBL production alone did not appear to be an independent risk factor for treatment failure. (C) 2006 Elsevier Inc. All rights reserved. C1 Ordway Res Inst, Inst Clin Pharmacodynam, Albany, NY 12208 USA. SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharm Practice, Buffalo, NY 14260 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Med, Clin Pharmacol Sect, Madison, WI 53705 USA. Mpex Pharmaceut, San Diego, CA 92109 USA. JMI Labs, N Liberty, IA 52317 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Bhavnani, SM (reprint author), Ordway Res Inst, Inst Clin Pharmacodynam, Albany, NY 12208 USA. EM sbhavnani-icpd@ordwayresearch.org NR 28 TC 45 Z9 48 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAR PY 2006 VL 54 IS 3 BP 231 EP 236 DI 10.1016/j.diagmicrobio.2005.09.011 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 024VK UT WOS:000236224200013 PM 16423491 ER PT J AU McGory, ML Zingmond, DS Sekeris, E Bastani, R Ko, CY AF McGory, ML Zingmond, DS Sekeris, E Bastani, R Ko, CY TI A patient's race/ethnicity does not explain the underuse of appropriate adjuvant therapy in colorectal cancer SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY APR 30-MAY 05, 2005 CL Philadelphia, PA SP Amer Soc Colon & Rectal Surg DE colorectal cancer; race/ethnicity; disparities; adjuvant therapy; chemotherapy; radiation therapy ID RECTAL-CANCER; COMORBIDITY INDEX; COLON-CANCER; SURVIVAL; RACE; CHEMOTHERAPY; SURVEILLANCE; DISPARITIES; OUTCOMES; QUALITY AB Introduction: To improve colorectal cancer outcomes, appropriate adjuvant therapy (chemotherapy, radiation therapy) should be given. Numerous studies have demonstrated underuse of adjuvant therapy in colorectal cancer. The current study examines variables associated with underuse of adjuvant therapy. methods: Three population-based databases were linked: California Cancer Registry, California Patient Discharge Database, 2000 Census. All colorectal cancer patients diagnosed from 1994 to 2001 were studied. Patient characteristics (age, gender, race/ethnicity, comorbidities, payer, diagnosis year, socioeconomic status) were used in five multivariate regression analyses to predict receipt of chemotherapy for Stage III colon cancer, and receipt of chemotherapy and radiation therapy for Stages II, III rectal cancer. Results: The overall cohort was 18,649 Stage III colon cancer and Stages II, III rectal cancer patients. Mean age was 68.9 years, 50 percent male, 74 percent non-Hispanic white, 6 percent black, 11 percent Hispanic, 9 percent Asian, and 65 percent had no significant comorbid disease. Receipt of chemotherapy was 48 percent for Stage III colon cancer, 48 percent for Stage II rectal cancer, and 66 percent for Stage III rectal cancer. Receipt of radiation therapy was 52 percent for Stage II rectal cancer and 66 percent for Stage III rectal cancer. In all five models, low socioeconomic status predicted underuse of chemotherapy or radiation therapy (P < 0.016). Race/ethnicity was not statistically associated with underuse in any of the models. Conclusions: Most literature identifies race/ethnicity as the reason for disparate receipt of adjuvant therapy in colorectal cancer. Using a more robust database of three population-based sources, our analysis demonstrates that socioeconomic status is a more important predictor of (in)appropriate care than race/ethnicity. Explicit measures to improve care to the poor with colorectal cancer are needed. C1 Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Ctr Hlth Sci 72 215, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Gen Internal Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Hlth Serv Res, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP McGory, ML (reprint author), Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Ctr Hlth Sci 72 215, 10833 Le Conte Ave,Box 956904, Los Angeles, CA 90095 USA. EM mmcgory@mednet.ucla.edu FU NCI NIH HHS [5U01CA086322-06] NR 26 TC 36 Z9 37 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD MAR PY 2006 VL 49 IS 3 BP 319 EP 329 DI 10.1007/s10350-005-0283-6 PG 11 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 020YJ UT WOS:000235949000004 PM 16475031 ER PT J AU Caballero, AE AF Caballero, AE TI Building cultural bridges: Understanding ethnicity to improve acceptance of insulin therapy in patients with type 2 diabetes SO ETHNICITY & DISEASE LA English DT Review DE culture; Hispanic; insulin; Latino; type 2 diabetes ID NUTRITION EXAMINATION SURVEY; ACUTE MYOCARDIAL-INFARCTION; UNITED-STATES POPULATION; 3RD NATIONAL-HEALTH; NON-HISPANIC WHITES; MEXICAN-AMERICANS; NPH INSULIN; SPEAKING PATIENTS; US ADULTS; MELLITUS AB Objectives: Type 2 diabetes is a significant healthcare problem in the Latino/Hispanic community. As with most patients with type 2 diabetes, Latino patients will eventually require insulin therapy to maintain glycemic control. Some cultural barriers to starting insulin therapy among Latino patients have been reported. This review explores the implications of the increasing prevalence of type 2 diabetes in Latino patients, defines cultural values and differences that may affect acceptance of insulin therapy, and reviews available strategies that may facilitate initiation of insulin treatment in this group. Methods: A literature search was conducted for publications related to Hispanic Americans, Latino persons, type 2 diabetes, and insulin therapy by using PubMed/National Center for Biotechnology information. Results: Despite evidence that earlier initiation of insulin therapy improves outcomes in patients with type 2 diabetes, Latino patients appear to be more resistant to insulin therapy than non-Hispanic Whites. Physician challenges associated with addressing the negative perceptions about insulin therapy are further compounded by cultural and language barriers often encountered when treating Latino patients. Scarce information regarding specific insulin regimens in Latino patients is available. Conclusions: Increased cultural awareness and competence among healthcare providers and increased use of Spanish-speaking diabetes educators seem to improve diabetes outcomes among Latino patients. Also, implementation of simpler insulin regimens may increase acceptance of insulin therapy and improve clinical outcomes in Latino patients. A relatively simple titration regimen using oncedaily bedtime basal insulin glargine has demonstrated efficacy for improving glycemic control in many patients with type 2 diabetes and is a strategy that may also be useful for Latinos as an introduction to insulin therapy and as the foundation of a more comprehensive insulin regimen in the future. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Caballero, AE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM enrique.caballero@joslin.harvard.edu NR 45 TC 15 Z9 15 U1 1 U2 7 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 SPR PY 2006 VL 16 IS 2 BP 559 EP 568 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 039YU UT WOS:000237345700034 PM 17682263 ER PT J AU Strumberg, D Awada, A Hirte, H Clark, JW Seeber, S Piccart, P Hofstra, E Voliotis, D Christensen, O Brueckner, A Schwartz, B AF Strumberg, D Awada, A Hirte, H Clark, JW Seeber, S Piccart, P Hofstra, E Voliotis, D Christensen, O Brueckner, A Schwartz, B TI Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome? SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE BAY 43-9006; sorafenib; refractory solid tumours; raf kinase inhibition; VEGFR inhibitor; PDGFR inhibitor; pooled analysis; phase I studiesy ID RECEPTOR TYROSINE KINASES; GROWTH-FACTOR RECEPTOR; RAF KINASE; INHIBITOR BAY-43-9006; CANCER-THERAPY; PHASE-I; ANTITUMOR; BRAF; ANGIOGENESIS; ACTIVATION AB In this analysis of the safety and efficacy of BAY 43-9006 (sorafenib) - a novel, oral multikinase inhibitor with effects on tumour and its vasculature - pooled data were obtained from four phase I dose-escalation trials. Time to progression (TTP) was compared in patients with/without >= grade 2 skin toxicity/diarrhoea. Grade 3 hand-foot skin reactions (HFS; 8%) and diarrhoea (6%) were common. At the recommended 400 mg bid dose for phase II/III trials (RDP), 15% of patients experienced grade 2/3 HFS, and 24% experienced grade 2/3 diarrhoea. Sorafenib induced stable disease for >= 6 months in 12% of patients (6% stabilized for >= 1 year). Patients receiving sorafenib doses at or close to the RDP, who experienced skin toxicity/diarrhoea, had a significantly increased TTP compared with patients without such toxicity (P < 0.05). Sorafenib was well tolerated at the RDP, and induced sustained disease stabilization, particularly in patients with skin toxicity/ diarrhoea. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Med Sch Essen, W German Canc Ctr, Dept Internal Med & Med Oncol, Essen, Germany. Inst Jules Bordet, B-1000 Brussels, Belgium. Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Bochum, Marienhosp Herne, Dept Hematol & Med Oncol, D-44621 Herne, Germany. Bayer Ag, Wuppertal, Germany. Bayer HealthCare AG, Wuppertal, Germany. Bayer Pharmaceut Corp, West Haven, CT USA. RP Strumberg, D (reprint author), Univ Med Sch Essen, W German Canc Ctr, Dept Internal Med & Med Oncol, Essen, Germany. EM dirk.strumberg@marienhospital-herne.de NR 30 TC 108 Z9 128 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2006 VL 42 IS 4 BP 548 EP 556 DI 10.1016/j.ejca.2005.11.014 PG 9 WC Oncology SC Oncology GA 019RN UT WOS:000235854500031 PM 16426838 ER PT J AU Krutzfeldt, M Broceno, C Ellis, M Weekes, DB Bull, JJ Sellers, WR Eilers, M Vivanco, MM Mittnacht, S AF Krutzfeldt, M Broceno, C Ellis, M Weekes, DB Bull, JJ Sellers, WR Eilers, M Vivanco, MM Mittnacht, S TI Selective ablation of retinoblastoma protein function by the RET finger protein SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the German Society for Cell Biology CY MAR 29-APR 01, 2006 CL Braunschweig, GERMANY C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Marburg, Inst Mol Biol & Tumorforsch, D-3550 Marburg, Germany. EM Sibylle.mittnacht@icr.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAR PY 2006 VL 85 SU 56 BP 98 EP 98 PG 1 WC Cell Biology SC Cell Biology GA 037DS UT WOS:000237127500216 ER PT J AU Mitchell, GF Arnold, JMO Dunlap, ME O'Brien, TX Marchiori, G Warner, E Granger, CB Desai, SS Pfeffer, MA AF Mitchell, GF Arnold, JMO Dunlap, ME O'Brien, TX Marchiori, G Warner, E Granger, CB Desai, SS Pfeffer, MA TI Pulsatile hemodynamic effects of candesartan in patients with chronic heart failure: The CHARM Program SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE hemodynamics; pulse pressure; aorta; vascular stiffness; angiotensin receptor blocker; candesartan ID AORTIC INPUT IMPEDANCE; ANGIOTENSIN-CONVERTING ENZYME; LEFT-VENTRICULAR DYSFUNCTION; PULSE PRESSURE; SYSTOLIC HYPERTENSION; ARTERIAL COMPLIANCE; THERAPY; DISTENSIBILITY; DETERMINANTS; HYPERTROPHY AB Background: Abnormal large artery function and increased pulsatile load are exacerbated by excess angiotensin-II acting through the AT(1) receptor and contribute to the pathogenesis and progression of chronic heart failure (CHF). Aims: To evaluate effects of the AT(1) receptor blocker candesartan (N=30) or placebo (N=34) on pulsatile hemodynamics in participants with CHF in the CHAR-M program. Methods and results: Noninvasive hemodynamics were assessed following 6 and 14 months of treatment and averaged. Using calibrated tonometry and aortic outflow Doppler, characteristic impedance was calculated as the ratio of the change in carotid pressure and aortic flow in early systole. Total arterial compliance was calculated by the diastolic area method. Brachial blood pressure, cardiac output and peripheral resistance did not differ between groups. Lower central pulse pressure in the candesartan group (57 +/- 20 vs. 67 +/- 17 mmHg, P=0.043) was accompanied by lower characteristic impedance (200 +/- 78 vs. 240 +/- 74 dyne s/cm(5), P=0.039) and higher total arterial compliance (1.87 +/- 0.70 vs. 1.47 +/- 0,48 ml/mmHg, P=0.008). Similar favorable differences were seen when analyses were stratified for ejection firaction (<= 0.40 vs. > 0.40) and baseline angiotensin converting enzyme inhibitor use. Conclusions: Candesartan has a favorable effect on large artery function in patients with chronic heart failure. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Cardiovasc Engn Inc, Holliston, MA 01746 USA. London Hlth Sci Ctr, London, ON, Canada. Louis Stokes VA Med Ctr, Cleveland, OH USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, Univ Off Pk,Bldg 2,51 Sawyer Rd,Suite 100, Waltham, MA 02453 USA. EM GaryFMitchell@mindspring.com RI Granger, Christopher/D-3458-2014 OI Granger, Christopher/0000-0002-0045-3291 NR 32 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAR PY 2006 VL 8 IS 2 BP 191 EP 197 DI 10.1016/j.ejheart.2005.07.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 029ZJ UT WOS:000236602600013 PM 16188495 ER PT J AU Lee, YH Harley, JB Nath, SK AF Lee, YH Harley, JB Nath, SK TI Meta-analysis of TNF-alpha promoter-308 A/G polymorphism and SLE susceptibility SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE meta-analysis; TNF-alpha; SLE ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR-ALPHA; MAJOR HISTOCOMPATIBILITY COMPLEX; GENE POLYMORPHISM; ASSOCIATION; NEPHRITIS; DISEASE; ALLELE; POPULATION; CONTRIBUTE AB Alleles of tumor necrosis factor-alpha (TNF-alpha) gene have been inconsistently associated with systemic lupus erythematosus (SLE), particularly the 308-A/G functional promoter polymorphism. To generate large-scale evidence on whether 308-A/G promoter polymorphism is associated with SLE susceptibility we have conducted a meta-analysis. We have identified 21 studies of this polymorphism and SLE using MEDLINE search. Meta-analysis was performed for genotypes A/A (recessive effect), A/A+A/G (dominant effect), and A allele in fixed or random effects models. All control samples were in Hardy-Weinberg proportion. The overall odds ratio ( OR) of the A/A genotype was 3.2 (95% CI = 2.0-5.3, P < 0.001). Stratification by ethnicity indicated that the A/A genotype was associated with SLE in European-derived population (OR 4.0, CI = 2.5-6.4, P < 0.001). No association was detected in Asian-derived population (OR, 1.3, CI = 0.3-6.3, P = 0.76). The overall OR for the risk genotypes (A/A and A/G) was 2.0 (CI = 1.3-3.1, P < 0.001). Similar results were found between the risk allele A and SLE where a significant association was found in European population (OR = 2.1, CI = 1.6-2.7, P < 0.001), but not in Asian (OR = 1.4, CI = 0.8-2.3, P = 0.2) or African (OR = 1.2, CI = 0.6-2.5, P = 0.59) populations. In summary, this meta-analysis demonstrates that the TNF-alpha promoter -308 A/G polymorphism may confer susceptibility to SLE, especially in European-derived population. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Res Program, Oklahoma City, OK 73104 USA. Korea Univ, Div Rheumatol, Seoul 136701, South Korea. Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Nath, SK (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM swapan-nath@omrf.ouhsc.edu FU NCRR NIH HHS [RR01577, RR14467, RR020143]; NIAID NIH HHS [AI063622, AI24717, AI053747]; NIAMS NIH HHS [AR048940, AR049084, AR42460, AR12253, AR048928]; NIDCR NIH HHS [DE15223] NR 45 TC 132 Z9 139 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAR PY 2006 VL 14 IS 3 BP 364 EP 371 DI 10.1038/sj.ejhg.5201556 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 014SD UT WOS:000235499300018 PM 16418737 ER PT J AU Hoffmann, U Butler, J AF Hoffmann, U Butler, J TI MDCT-based coronary angiography: A Rosetta stone for understanding coronary disease? SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Div Cardiol, Nashville, TN USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 165 Charles River Plaza 400, Boston, MA 02114 USA. EM uhoffman@partners.org NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 329 EP 330 DI 10.1016/j.ejrad.2005.12.031 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000002 PM 16442258 ER PT J AU Achenbach, S Ropers, D Kuettner, A Flohr, T Ohnesorge, B Bruder, H Theessen, H Karakaya, M Daniel, WG Bautz, W Kalender, WA Anders, K AF Achenbach, S Ropers, D Kuettner, A Flohr, T Ohnesorge, B Bruder, H Theessen, H Karakaya, M Daniel, WG Bautz, W Kalender, WA Anders, K TI Contrast-enhanced coronary artery visualization by dual-source computed tomography - Initial experience SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE computed tomography; coronary arteries; coronary angiography ID MULTISLICE SPIRAL CT; FLYING FOCAL SPOT; IMAGE-RECONSTRUCTION; HEART-RATE; MULTIDETECTOR-CT; ROW CT; ANGIOGRAPHY; STENOSES; QUALITY AB Multi-detector computed tomography (CT) scanners, by virtue of their high temporal and spatial resolution, permit imaging of the coronary arteries. However, motion artifacts, especially in patients with higher heart rates, can impair image quality. We thus evaluated the performance of a new dual-source CT (DSCT) with a heart rate independent temporal resolution of 83 ms for the visualization of the coronary arteries in 14 consecutive patients. Methods: Fourteen patients (mean age 61 years, mean heart rate 71 min(-1)) were studied by DSCT. The system combines two arrays of an X-ray tube plus detector (64 slices) mounted on a single gantry at an angle of 90 degrees With a rotation speed of 330 ms, a temporal resolution of 83 ms (one-quarter rotation) can be achieved independent of heart rate. For data acquisition, intraveous contrast agent was injected at a rate of 5 ml/s. Images were reconstructed with 0.75 slice thickness and 0.5 mm increment. The data sets were evaluated concerning visibility of the coronary arteries and occurrence of motion artifact. Results: Visualization of the coronary arteries was successful in all patients. Most frequently, image reconstruction at 70% of the cardiac cycle provided for optimal image quality (50% of patients). Of a total of 226 coronary artery segments, 222 (98%) were visualized free of motion artifact. In summary, DSCT constitutes a promising new concept for cardiac CT. High and heart rate independent temporal resolution permits imaging of the coronary arteries without motion artifacts in a substantially increased number of patients as compared to earlier scanner generations. Larger and appropriately designed studies will need to determine the method's accuracy for detection of coronary artery stenoses. (C) 2005 Published by Elsevier Ireland Ltd. C1 Univ Erlangen Nurnberg, Dept Cardiol, D-91054 Erlangen, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Inst Diagnost Radiol, D-91054 Erlangen, Germany. Siemens Med Solut, Forchheim, Germany. Univ Erlangen Nurnberg, Inst Med Phys, D-91054 Erlangen, Germany. RP Achenbach, S (reprint author), Univ Erlangen Nurnberg, Dept Cardiol, Ulmenweg 18, D-91054 Erlangen, Germany. EM stephan.achenbach@med2.med.uni-erlangen.de NR 16 TC 271 Z9 308 U1 1 U2 18 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 331 EP 335 DI 10.1016/j.ejrad.2005.12.017 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000003 PM 16426789 ER PT J AU Cury, RC Ferencik, M Achenbach, S Pomerantsev, E Nieman, K Moselewski, F Abbara, S Jang, IK Brady, TJ Hoffmann, U AF Cury, RC Ferencik, M Achenbach, S Pomerantsev, E Nieman, K Moselewski, F Abbara, S Jang, IK Brady, TJ Hoffmann, U TI Accuracy of 16-slice multi-detector CT to quantify the degree of coronary artery stenosis: Assessment of cross-sectional and longitudinal vessel reconstructions SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE computed tomography; atherosclerosis; coronary artery disease ID SPIRAL COMPUTED-TOMOGRAPHY; DIAGNOSTIC-ACCURACY; INTRAVASCULAR ULTRASOUND; ANGIOGRAPHY; LESIONS AB Background: Sixteen-slice multi-detector computed tomography (MDCT) permits reliable noninvasive detection of significant coronary stenosis based on qualitative visual assessment. The purpose of this study was to determine the accuracy of MDCT to quantify the degree of coronary stenosis as compared to quantitative coronary angiography (QCA) using two different reconstruction methods. Methods: We studied 69 coronary artery lesions from 38 consecutive patients that underwent 16-slice MDCT as a part of research study; which enrolled consecutive subjects scheduled for clinically indicated invasive coronary angiography. Nine coronary artery lesions with motion artifacts, heavily calcified plaques or stents were excluded from the analysis. The degree of stenosis was calculated by two independent readers non-blinded to the location of the stenosis, but blinded to the results of the QCA. MDCT luminal diameters were measured in cross-sectional multi-planar reformatted (CS-MPR) images created perpendicular to the centerline of the vessel and in 5 mm thin-slab maximum intensity projections (MIP) parallel to the long axis of the vessel. Both MDCT methods were compared against QCA. Results: The mean degree of stenosis as measured by MDCT was closely correlated to QCA for both methods (CS-MPR versus QCA: 61 +/- 23% versus 64 +/- 29%; r(2) = 0.83, p < 0.001 and MIP versus QCA: 64 +/- 22% versus 64 +/- 29%; r(2) = 0.84, p < 0.001 for MIP. Bland-Altman analysis demonstrated a negative bias of the degree of stenosis of -2.8 +/- 12% using CS-MPR and a minimally positive bias of 0.6 +/- 12% for MIP. In stratified analysis for lesion severity (mild, 0-40%; moderate, 41-70% or severe, >70%) the agreement between both CS-MPR and MIP was high when compared to QCA (kappa = 0.74 and 0.71, respectively). Conclusion: Multi-detector spiral CT permits accurate quantitative assessment of the degree of coronary stenosis in selected data sets of sufficient quality using both cross-sectional and longitudinal vessel reconstructions. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Internal Med 2, D-8520 Erlangen, Germany. RP Cury, RC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM rcury@partners.org FU NHLBI NIH HHS [1 T32 HL076136-02] NR 16 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 345 EP 350 DI 10.1016/j.ejrad.2005.12.019 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000005 PM 16442256 ER PT J AU Lembcke, A Hein, PA Enzweiler, CNH Hoffmann, U Klessen, C Dohmen, PM AF Lembcke, A Hein, PA Enzweiler, CNH Hoffmann, U Klessen, C Dohmen, PM TI Acute myocardial ischemia after aortic valve replacement: A comprehensive diagnostic evaluation using dynamic multislice spiral computed tomography SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE acute myocardial ischemia; MSCT; aortic valve; cardiac surgery; cardiac imaging ID NONINVASIVE CORONARY-ANGIOGRAPHY; ACTIVE INFECTIVE ENDOCARDITIS; IMAGE QUALITY; ROW CT; RECONSTRUCTION; ECHOCARDIOGRAPHY; RESOLUTION; ALGORITHM; ABSCESS; PHANTOM AB We describe the case of a 72-year-old man presenting with endocarditis and clinical signs of acute myocardial ischemia after biological aortic valve replacement. A comprehensive cardiac dynamic multislice spiral computed tomography demonstrated: (1) an endocarditic vegetation of the aortic valve; (2) a subvalvular leakage feeding a paravalvular pseudoaneurysm based on an aortic root abscess with subsequent compromise of the systolic blood flow in the left main coronary artery and the resulting myocardial perfusion deficit. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Free Univ Berlin, Charite Univ Med Berlin, Dept Radiol, D-10098 Berlin, Germany. Humboldt Univ, Berlin, Germany. Free Univ Berlin, Charite Univ Med Berlin, Dept Cardiovasc Surg, D-10098 Berlin, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lembcke, A (reprint author), Free Univ Berlin, Charite Univ Med Berlin, Dept Radiol, Schumannstr 20-21, D-10098 Berlin, Germany. EM alexander.lembcke@gmx.de NR 15 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 351 EP 355 DI 10.1016/j.ejrad.2005.12.020 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000006 PM 16446071 ER PT J AU Lembcke, A Hein, PA Dohmen, PM Klessen, C Wiese, TH Hoffmann, U Hamm, B Enzweiler, CNH AF Lembcke, A Hein, PA Dohmen, PM Klessen, C Wiese, TH Hoffmann, U Hamm, B Enzweiler, CNH TI Pictorial review: Electron beam computed tomography and multislice spiral computed tomography for cardiac imaging SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Review DE computed tomography; coronary angiography; coronary calcium scoring; cardiac function analysis; image quality ID NONINVASIVE CORONARY-ANGIOGRAPHY; MULTIDETECTOR ROW CT; ARTERY STENOSES; ANIMAL-MODEL; SUBMILLIMETER; HEART; COLLIMATION; ACCURACY; CALCIUM; QUALITY AB Electron beam computed tomography (EBCT) revolutionized cardiac imaging by combining a constant high temporal resolution with prospective ECG triggering. For years, EBCT was the primary technique for some non-invasive diagnostic cardiac procedures such as calcium scoring and non-invasive angiography of the coronary arteries. Multislice spiral computed tomography (MSCT) on the other hand significantly advanced cardiac imaging through high volume coverage, improved spatial resolution and retrospective ECG gating. This pictorial review will illustrate the basic differences between both modalities with special emphasis to their image quality. Several experimental and clinical examples demonstrate the strengths and limitations of both imaging modalities in an intraindividual comparison for a broad range of diagnostic applications such as coronary artery calcium scoring, coronary angiography including stent visualization as well as functional assessment of the cardiac ventricles and valves. In general, our examples indicate that EBCT suffers from a number of shortcomings such as limited spatial resolution and a low contrast-to-noise ratio. Thus, EBCT should now only be used in selected cases where a constant high temporal resolution is a crucial issue, such as dynamic (cine) imaging. Due to isotropic submillimeter spatial resolution and retrospective data selection MSCT seems to be the non-invasive method of choice for cardiac imaging in general, and for assessment of the coronary arteries in particular. However, technical developments are still needed to further improve the temporal resolution in MSCT and to reduce the substantial radiation exposure. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Free Univ Berlin, Charite Univ Med Berlin, Dept Radiol, D-1000 Berlin, Germany. Humboldt Univ, Berlin, Germany. Augusta Hosp, Dept Radiol, Bochum, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lembcke, A (reprint author), Free Univ Berlin, Charite Univ Med Berlin, Dept Radiol, Campus Mitte, D-1000 Berlin, Germany. EM Alexander.Lembcke@gmx.de NR 21 TC 12 Z9 14 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 356 EP 367 DI 10.1016/j.ejrad.2005.12.021 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000007 PM 16427236 ER PT J AU Ferencik, M Nomura, CH Maurovich-Horvat, P Hoffmann, U Pena, AJ Cury, RC Abbara, S Nieman, K Fatima, U Achenbach, S Brady, TJ AF Ferencik, M Nomura, CH Maurovich-Horvat, P Hoffmann, U Pena, AJ Cury, RC Abbara, S Nieman, K Fatima, U Achenbach, S Brady, TJ TI Quantitative parameters of image quality in 64-slice computed tomography angiography of the coronary arteries SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE CT; CT-angiography; cardiac; arteries ID MAGNETIC-RESONANCE ANGIOGRAPHY; ELECTRON-BEAM CT; HEART-RATE; DIAGNOSTIC-ACCURACY; STENOSES; RECONSTRUCTION; VISUALIZATION; TECHNOLOGY; MOTION AB We explored quantitative parameters of image quality in consecutive patients undergoing 64-slice multi-detector computed tomography (MDCT) coronary angiography for clinical reasons. Forty-two patients (36 men, mean age 61 +/- 11 years, mean heart rate 63 +/- 10 bpm) underwent contrast-enhanced MDCT coronary angiography with a 64-slice scanner (Siemens Sensation 64, 64 mm x 0.6 mm collimation, 330 ms tube rotation, 850 mAs, 120 kV). Two independent observers measured the overall visualized vessel length and the length of the coronary arteries visualized without motion artifacts in curved multiplanar reformatted images. Contrast-to-noise ratio was measured in the proximal and distal segments of the coronary arteries. The mean length of visualized coronary arteries was: left main 12 +/- 6 mm, left anterior descending 149 +/- 25 mm, left circumflex 89 +/- 30 mm, and right coronary artery 161 +/- 38 mm. On average, 97 +/- 5% of the total visualized vessel length was depicted without motion artifacts (left main 100 +/- 0%, left anterior descending 97 +/- 6%, left circumflex 98 5%, and right coronary artery 95 +/- 6%). In 27 patients with a heart rate <65 bpm, 98 +/- 4% of the overall visualized vessel length was imaged without motion artifacts, whereas 96 +/- 6% of the overall visualized vessel length was imaged without motion artifacts in 15 patients with a heart rate >65 bpm (p < 0.001). The mean contrast-to-noise ratio in all measured coronary arteries was 14.6 +/- 4.7 (proximal coronary segments: range 15.1 +/- 4.4 to 16.1 +/- 5.0, distal coronary segments: range 11.4 +/- 4.2 to 15.9 +/- 4.9). In conclusion, 64-slice MDCT permits reliable visualization of the coronary arteries with minimal motion artifacts and high CNR in consecutive patients referred for non-invasive MDCT coronary angiography. Low heart rate is an important prerequisite for excellent image quality. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Erlangen Nurnberg, Dept Internal Med 2, Erlangen, Germany. RP Ferencik, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM maros_ferencjk@hms.harvard.edu RI Nomura, Cesar/H-1636-2012; OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU NHLBI NIH HHS [1 T32 HL076136-02] NR 27 TC 74 Z9 85 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 373 EP 379 DI 10.1016/j.ejrad.2005.12.023 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000009 PM 16439091 ER PT J AU Ferencik, M Lisauskas, JB Cury, RC Hoffmann, U Abbara, S Achenbach, S Karl, WC Brady, TJ Chan, RC AF Ferencik, M Lisauskas, JB Cury, RC Hoffmann, U Abbara, S Achenbach, S Karl, WC Brady, TJ Chan, RC TI Improved vessel morphology measurements in contrast-enhanced multi-detector computed tomography coronary angiography with non-linear post-processing SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE CT; CT-angiography; cardiac; arteries; arteriosclerosis ID INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE; DIAGNOSTIC-ACCURACY; STENOSES; LESIONS AB Multi-detector computed tomography (MDCT) permits detection of coronary plaque. However, noise and blurring impair accuracy and precision of plaque measurements. The aim of the study was to evaluate MDCT post-processing based on non-linear image deblurring and edge-preserving noise suppression for measurements of plaque size. Contrast-enhanced MDCT coronary angiography was performed in four subjects (mean age 55 +/- 5 years, mean heart rate 54 +/- 5 bpm) using a 16-slice scanner (Siemens Sensation 16, collimation 16 x 0.75 mm, gantry rotation 420 ins, tube voltage 120 kV, tube current 550 mAs, 80 mL of contrast). Intravascular ultrasound (IVUS; 40 MHz probe) was performed in one vessel in each patient and served as a reference standard. MDCT vessel cross-sectional images (1 mm thickness) were created perpendicular to centerline and aligned with corresponding IVUS images. MDCT images were processed using a deblurring and edge-preserving noise suppression algorithm. Then, three independent blinded observers segmented lumen and outer vessel boundaries in each modality to obtain vessel cross-sectional area and wall area in the unprocessed MDCT cross-sections, post-processed MDCT cross-sections and corresponding IVUS. The wall area measurement difference for unprocessed and post-processed MDCT images relative to IVUS was 0.4 +/- 3.8 mm(2) and -0.2 +/- 2.2 mm(2) (p < 0.05), respectively. Similarly, Bland-Altman analysis of vessel cross-sectional area from unprocessed and post-processed MDCT images relative to IVUS showed a measurement difference of 1.0 +/- 4.4 and 0.6 +/- 4.8 mm(2), respectively. In conclusion, MDCT permitted accurate in vivo measurement of wall area and vessel cross-sectional area as compared to IVUS. Post-processing to reduce blurring and noise reduced variability of wall area measurements and reduced measurement bias for both wall area and vessel cross-sectional area. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Med 2, Erlangen, Germany. Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. RP Ferencik, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM maros_ferencik@hms.harvard.edu FU NHLBI NIH HHS [1 T32 HL076136-02] NR 16 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 380 EP 383 DI 10.1016/j.ejrad.2005.12.024 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000010 PM 16442768 ER PT J AU Moselewski, F Ferencik, M Achenbach, S Abbara, S Cury, RC Booth, SL Jang, IK Brady, TJ Hoffmann, U AF Moselewski, F Ferencik, M Achenbach, S Abbara, S Cury, RC Booth, SL Jang, IK Brady, TJ Hoffmann, U TI Threshold-dependent variability of coronary artery calcification measurements - implications for contrast-enhanced multi-detector row-computed tomography SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE computed tomography (CT); experimental studies; coronary vessels; calcification ID ELECTRON-BEAM TOMOGRAPHY; IN-VITRO; VASCULAR CALCIFICATION; IMAGE QUALITY; CALCIUM; DISEASE; CT; QUANTIFICATION; VIVO; REPRODUCIBILITY AB Introduction: The present study investigated the threshold-dependent variability of coronary artery calcification (CAC) measurements and the potential to quantify CAC in contrast-enhanced multi-detector row-computed tomography (MDCT). Methods: We compared the mean CT attenuation of CAC to luminal contrast enhancement of the coronary arteries in 30 patients (n = 30) undergoing standard coronary contrast-enhanced spiral MDCT. The modified Agatston score [AS], calcified plaque volume [CV], and mineral mass [MM]) at four different thresholds (130, 200, 300, and 400 HU) were measured in 50 patients who underwent non-contrast-enhanced MDCT. Results: Mean CT attenuation of CAC was similar to the attenuation of the contrast-enhanced coronary lumen (CAC 297.1 +/- 68.7 HU versus 295 +/- 65 HU (p < 0.0001), respectively). Above a threshold of 300 HU CAC measurements significantly varied to standard measurements obtained at a threshold of 130 HU (p < 0.0001). The threshold-dependent variation of MM measurements was significantly smaller than for AS and CV (130 HU versus 400 HU: 63, 75, and 8 1, respectively; p < 0.001). These differences resulted in a change of age and gender based percentile category for AS in 78% of subjects. Discussion: We demonstrated that CAC measurements are threshold dependent with MM measurements having significantly less variation than AS or CV. Due to the similarity of mean CT attenuation of CAC and the contrast-enhanced coronary lumen accurate quantification of CAC may be difficult in standard coronary contrast-enhanced spiral MDCT. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Erlangen Nurnberg, Dept Internal Med Cardiol 2, D-8520 Erlangen, Germany. Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Charles River Plaza Suite 400, Boston, MA 02114 USA. EM uhoffman@partners.org FU NHLBI NIH HHS [HL69272]; NIA NIH HHS [AG19147] NR 27 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 390 EP 395 DI 10.1016/j.ejrad.2005.12.026 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000012 PM 16431067 ER PT J AU Hoffmann, U Siebert, U Bull-Stewart, A Achenbach, S Ferencik, M Moselewski, F Brady, TJ Massaro, JM O'Donnell, CJ AF Hoffmann, U Siebert, U Bull-Stewart, A Achenbach, S Ferencik, M Moselewski, F Brady, TJ Massaro, JM O'Donnell, CJ TI Evidence for lower variability of coronary artery calcium mineral mass measurements by multi-detector computed tomography in a community-based cohort - Consequences for progression studies SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE multi-detector computed tomography; coronary artery calcification; coronary artery disease; measurement variability ID ELECTRON-BEAM TOMOGRAPHY; HEART-DISEASE EVENTS; ROW CT; CALCIFIED PLAQUE; CARDIAC CT; QUANTIFICATION; PREDICTION; REPRODUCIBILITY; CALCIFICATION; QUANTITATION AB Purpose: To compare the measurement variability for coronary artery calcium (CAC) measurements using mineral mass compared with a modified Agatston score (AS) or volume score (VS) with multi-detector CT (MDCT) scanning, and to estimate the potential impact of these methods on the design of CAC progression studies. Materials and methods: We studied 162 consecutive subjects (83 women, 79 men, mean age 51 11 years) from a general Caucasian community-based cohort (Framingham Heart Study) with duplicate runs of prospective electrocardiographically-triggered MDCT scanning. Each scan was independently evaluated for the presence of CAC by four experienced observers who determined a "modified" AS, VS and mineral mass. Results: Of the 162 subjects, CAC was detected in both scans in 69 (42%) and no CAC was detected in either scan in 72 (45%). Calcium scores were low in the 21/162 subjects (12%) for whom CAC was present in one but not the other scan (modified AS <20 in 20/21 subjects, mean AS 4.6 +/- 1.9). For all three quantification algorithms, the inter- and intraobserver correlation were excellent (r > 0.96). However, the mean interscan variability was significantly different between mineral mass, modified AS, and VS (coefficient of variation 26 +/- 19%, 41 +/- 28% and 34 +/- 25%, respectively; p < 0.04), with significantly smaller mean differences in pair-wise comparisons for mineral mass compared with modified AS (p < 0.002) or with VS (p < 0.03). The amount of CAC but not heart rate was an independent predictor of interscan variability (r = -0.638, -0.614 and -0.577 for AS, VS, and mineral mass, respectively; all p < 0.0001). The decreased interscan variability of mineral mass would allow a sample size reduction of 5.5% compared with modified AS for observational studies of CAC progression and for randomized clinical trials. Conclusion: There is significantly reduced interscan variability of CAC measurements with mineral mass compared with the modified AS or VS. However, the measurement variability of all quantification methods is predicted by the amount of CAC and is inversely correlated to the extent of partial volume artifacts. Moreover, the improvement of measurement reproducibility leads to a modest reduction in sample size for observational epidemiological studies or randomized clinical trials to assess the progression of CAC. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NHLBIs, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza Suite 400, Boston, MA 02114 USA. EM uhoffman@partners.org OI Massaro, Joseph/0000-0002-2682-4812 NR 35 TC 66 Z9 69 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 396 EP 402 DI 10.1016/j.ejrad.2005.12.027 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000013 PM 16434160 ER PT J AU Hinton, DP Cury, RC Chan, RC Wald, LL Sherwood, JB Furie, KL Pitts, JT Schmitt, F AF Hinton, DP Cury, RC Chan, RC Wald, LL Sherwood, JB Furie, KL Pitts, JT Schmitt, F TI Bright and black blood imaging of the carotid bifurcation at 3.0 T SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE 3.0T MRI; vessel wall imaging; carotid artery; atherosclerosis; black blood ID MAGNETIC-RESONANCE; HIGH-RESOLUTION; IN-VIVO; ATHEROSCLEROTIC LESIONS; INITIAL-EXPERIENCE; 3 TESLA; PLAQUE; MRI; REGRESSION; ARTERIES AB Purpose: The aim of this study was to evaluate our preliminary experience at 3.0T with imaging of the carotid bifurcation in healthy and atherosclerotic subjects. Application at 3.0T is motivated by the signal-to-noise gain for improving spatial resolution and reducing signal averaging requirements. Materials and methods: We utilized a dual phased array coil and applied 2D, 3D time of flight (TOF) and turbo spin echo (TSE) sequences with comparison of two lumen signal suppression methods for black blood (BB) TSE imaging including double inversion preparation (DIR) and spatial presaturation pulses. The signal-to-noise ratios (SNR) of healthy carotid vessel walls were compared in 2D and 3D BB TSE acquisitions. The bright and black blood multi-contrast exam was demonstrated for a complex carotid plaque. Results: Contrast-to-noise (CNR) greater than 150 was achieved between the lumen and suppressed background for 3D TOF. For BB, both methods provided sufficient lumen signal suppression but slight residual flow artifacts remained at the bifurcation level. As expected 3D TSE images had higher SNR compared to 2D, but increased motion sensitivity is a significant issue for 3D at high field. For multi-contrast imaging of atherosclerotic plaque, fibrous, calcified and lipid components were resolved. The CNR ratio of fibrous (bright on PDW, T2W) and calcified (dark in T1W, T2W, PDW) plaque components was maximal in the T2W images. The 3D TOF angiogram indicating a 40% stenosis was complemented by 3D multi-planar reformat of BB images that displayed plaque extent. Detection of intimal thickening, the earliest change associated with atherosclerotic progression was observed in BB PDW images at 3.0 T. Conclusions: High SNR and CNR images have been demonstrated for the healthy and diseased carotid. Improvements in RF coils along with pulse sequence optimization, and evaluation of endogenous and exogenous contrast mechanisms will further enhance carotid imaging at 3.0T. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, MGH MIT HMS, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. In Vivo Diagnost, Pewaukee, WI 53072 USA. Siemens Med Solut Inc, Erlangen, Germany. RP Hinton, DP (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, MGH MIT HMS, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM denise@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 FU NCRR NIH HHS [P41RR14075]; NHLBI NIH HHS [R01HL61862] NR 29 TC 16 Z9 21 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 403 EP 411 DI 10.1016/j.ejrad.2005.12.028 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000014 PM 16443343 ER PT J AU Abbara, S Desai, JC Cury, RC Butler, J Nieman, K Reddy, V AF Abbara, S Desai, JC Cury, RC Butler, J Nieman, K Reddy, V TI Mapping epicardial fat with multi-detector computed tomography to facilitate percutaneous transepicardial arrhythmia ablation SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE radiofrequency ablation; percutaneous ablation; epicardial fat; computed tomography; arrhythmias ID CATHETER ABLATION; ECHOCARDIOGRAPHY; TISSUE; HEART AB A sizable portion of ventricular tachycardia circuits are epicardial, especially in patients with non-ischemic cardiomyopathy, e.g. Chagas disease. Thus there is a growing interest among the electrophysiologists in transepicardial mapping and myocardial ablation for treatment of arrhythmias. However, increased epicardial fat can be a significant hindrance in procedural success as it can mimic infarct during mapping and can also decrease the effectiviness of ablation. Quantitative knowledge of epicardial fat pre-procedure can potentially significantly facilitate the conduct and outcomes of these procedures. In this study we assessed the epicardial fat distribution and thickness in vivo in 59 patients who underwent multi-detector computed tomography (MDCT) for coronary artery assessment using a 16-slice scanner. Multiplanar reconstructions were obtained in the ventricular short axis at the basal, mid ventricular, and near the apex level, and in a four-chamber view. In the short axis slices, we measured epicardial fat diameter in nine segments, and in the four-chamber view, it was measured in five segments. In grooved segments the maximum fat thickness was recorded, while in non-grooved segments thickness at three equally spaced points were averaged. The results were as follows starting clockwise: superior inter-ventricular (IV) groove (all measurements are in mm, in basal, mid ventricular, and apical levels, respectively) (11.2, 8.6, 7.3), left ventricular (LV) superior lateral wall (1.0, 1.5, 1.7), LV inferior lateral wall (1.3, 2.2, 3.5), inferior IV groove (9.2, 6.5, 6.1), right ventricular (RV) diaphragmatic wall (1.4, 0.2, 1.0), acute margin (9.2, 7.3, 7.8), RV anterior free wall inferior (6.8, 4.0, 4.7), RV anterior free wall superior (6.5, 3.2, 3.1), RV superior wall (5.6, 2.7, 4.0), We measured the following four-chamber segments: LV apex (2.8 mm), left atrio-ventricular (AV) groove (12.7), right AV groove (14.8), RV apex (4.8), and anterior IV groove (7.7). The mean epicardial fat thickness for all cases was 5.3 mm (S.D. 1.6). The mean total epicardial fat for patients over 65 was 22% greater than younger patients, with a 36% increase along the RV anterior free wall, 57% along the RV diaphragmatic wall and 38% along the LV lateral wall. Women averaged 17% more total epicardial fat. In conclusion, this study was designed to provide an epicardial fat map for physicians performing percutaneous epicardial mapping and interventions. While the acute margin and RV anterior free wall tend to have high epicardial fat, and the LV lateral wall and RV diaphragmatic wall tend to have little to no fat, there is significant variation between patients. MDCT is a reliable modality for visualizing epicardial fat, and should be considered prior to undergoing procedures that are affected by epicardial fat content, especially in elderly and female populations. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Abbara, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM Sabbara@partners.org NR 12 TC 69 Z9 70 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAR PY 2006 VL 57 IS 3 BP 417 EP 422 DI 10.1016/j.ejrad.2005.12.030 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 021GF UT WOS:000235971000016 PM 16434161 ER PT J AU Chiappelli, F Prolo, P Rosenblum, M Edgerton, M Cajulis, OS AF Chiappelli, F Prolo, P Rosenblum, M Edgerton, M Cajulis, OS TI Evidence-based research in complementary and alternative medicine II: The process of evidence-based research SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article DE evidence-based research; systematic review; consolidated standards of randomized trials; Markov model; complementary and alternative medicine ID EVALUATING COMPLEMENTARY; CLINICAL-TRIALS; METAANALYSIS; CAM; EPIDEMIOLOGY AB It is a common practice in contemporary medicine to follow stringently the scientific method in the process of validating efficacy and effectiveness of new or improved modes of treatment intervention. It follows that these complementary or alternative interventions must be validated by stringent research before they can be reliably integrated into Western medicine. The next decades will witness an increasing number of evidence-based research directed at establishing the best available evidence in complementary and alternative medicine (CAM). This second paper in this lecture series examines the process of evidence-based research (EBR) in the context of CAM. We outline the fundamental principles, process and relevance of EBR, and its implication to CAM. We underscore areas of future development in EBR. We note that the main problem of applying EBR to CAM at present has to do with the fact that the contribution of EBR can be significant only to the extent to which studies used in the process of EBR are of good quality. All too often CAM research is not of sufficient quality to warrant the generation of a consensus statement. EBR, nevertheless, can contribute to CAM by identifying current weaknesses of CAM research. We present a revised instrument to assess quality of the literature. C1 Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Northridge, CA USA. Psychoneuroimmunol Grp Inc, Northridge, CA USA. Calif State Univ Northridge, Northridge, CA 91330 USA. RP Chiappelli, F (reprint author), Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, CHS 63-090, Los Angeles, CA 90095 USA. EM chiappelli@dent.uclia.edu NR 29 TC 35 Z9 37 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PD MAR PY 2006 VL 3 IS 1 BP 3 EP 12 DI 10.1093/ecam/nek017 PG 10 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 020VF UT WOS:000235940300002 PM 16550218 ER PT J AU Robertson, P Means, TK Luster, AD Scadden, DT AF Robertson, P Means, TK Luster, AD Scadden, DT TI CXCR4 and CCR5 mediate homing of primitive bone marrow-derived hematopoietic cells to the postnatal thymus SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID T-CELL; CHEMOKINE RECEPTOR; PROGENITOR CELLS; PRECURSOR CELLS; HIV-1 ENTRY; MICE; PROTHYMOCYTES; FETAL; STEM; DIFFERENTIATION AB Factors governing the entry of cells into the postnatal thymus are poorly understood. We aimed to define molecular mechanisms mediating the homing of bone marrow cells to the thymus using a sublethally irradiated in vivo murine model. Entry of unfractionated and lineage-depleted bone marrow cells to the thymus, but not bone marrow, was a God-mediated phenomenon. Lineage-depleted cells that had homed to the thymus expressed abundant CXCR4 and CCR5 mRNA, alone of 17 chemokine receptors evaluated by QPCR. Thymic-homed cells were distinct from cells that had homed to bone marrow in expression of CXCR4 and CCR5 by mRNA quantification and cell-surface expression of protein. Abrogation of CXCR4 and CCR5 function by genetic, antibody, or pharmacologic means impaired homing of lineage-depleted cells to the thymus, although not in a synergistic manner, implying interdependency of these receptors in the homing process. Competitive repopulation experiments demonstrated that inhibiting CXCR4-mediated homing adversely affected the double-negative cell pool at 2 weeks, suggesting that cells with prothymocytic activity may in part home via CXCR4. Overall, our data demonstrate differential homing mechanisms governing entry of unfractionated and lineage-depleted cells to irradiated bone marrow or thymus, with thymic homing of immature cells being pertussis-sensitive and mediated by the chemokine receptors CXCR4 and CCR5. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, 185 Cambridge St,CP2N-4265A, Boston, MA 02114 USA. EM dscadden@partners.org NR 47 TC 14 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2006 VL 34 IS 3 BP 308 EP 319 DI 10.1016/j.exphem.2005.11.017 PG 12 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 033HS UT WOS:000236838400007 PM 16543065 ER PT J AU Taneja, SS Smith, MR Dalton, JT Raghow, S Barnette, G AF Taneja, SS Smith, MR Dalton, JT Raghow, S Barnette, G TI Toremifene - a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE androgen deprivation therapy; androgen receptor; carcinoma; estrogen receptor; gonadotropin-releasing hormone; high-grade prostate intraepithelial neoplasia; osteoclast; osteoporosis; prostate cancer; resorption; selective estrogen receptor modulator; toremifene ID ESTROGEN-RECEPTOR-BETA; BONE-MINERAL DENSITY; ADVANCED BREAST-CANCER; RANDOMIZED CONTROLLED-TRIAL; ENDOGENOUS SEX-HORMONES; OSTEOBLAST-LIKE CELLS; HIGH-DOSE TOREMIFENE; INTRAEPITHELIAL NEOPLASIA; ER-BETA; POSTMENOPAUSAL WOMEN AB Deregulation of the estrogen axis in humans prompts a series of tissue-specific events. in the breast and prostate, alterations in estrogen signalling lead to genotypic and phenotypic molecular alterations that result in dysplastic cellular appearance, deregulated cell growth and carcinoma. In bone, decreased estrogen leads to increased osteoclastogenesis and bone resorption, decreased bone mineral density and a significant fracture risk. Toremifene is a selective estrogen receptor modulator that exerts pharmacological activity in the breast, bone and prostate. An intense interest in developing this agent for prostate cancer chemoprevention is based on the reduction of premalignant and malignant prostate lesions in a transgenic model of prostate cancer. Biological and clinical activity was demonstrated in Phase II trials by the prevention of progression to prostate cancer in men with high-grade prostate intraepithelial neoplasia and through suppression of bone turnover biomarkers and increased bone mineral density in men on androgen deprivation therapy for prostate cancer. C1 NYU, Sch Med, New York, NY 10016 USA. GTx Inc, Memphis, TN 38163 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Taneja, SS (reprint author), GTx Inc, 3 N Dunlap,3rd Floor Van Vleet Bldg, Memphis, TN 38163 USA. EM kveverka@gtxinc.com OI dalton, James T/0000-0002-3915-7326 NR 151 TC 14 Z9 14 U1 0 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD MAR PY 2006 VL 15 IS 3 BP 293 EP 305 DI 10.1517/13543784.15.3.293 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 020QY UT WOS:000235926400011 PM 16503765 ER PT J AU Pandolfino, JE El-Serag, HB Zhang, Q Shah, N Ghosh, SK Kahrilas, PJ AF Pandolfino, JE El-Serag, HB Zhang, Q Shah, N Ghosh, SK Kahrilas, PJ TI Obesity: A challenge to esophagogastric junction integrity SO GASTROENTEROLOGY LA English DT Article ID LOWER ESOPHAGEAL SPHINCTER; GASTROESOPHAGEAL-REFLUX; HIATAL-HERNIA; INTRAABDOMINAL PRESSURE; BODY-MASS; SYMPTOMS; ASSOCIATION; PREVALENCE; GERD AB Background & Aims: The aim of the current study was to analyze the relationship between obesity and the morphology of the esophagogastric junction (EGJ) pressure segment using high-resolution manometry. Methods: Two hundred eighty-five patients (108 men, aged 18-87) were studied. A solid-state manometric assembly with 36 circumferential sensors spaced 1 cm apart was placed transnasally, and simultaneous intra-esophageal and intragastric pressures were measured over 6-8 respiratory cycles. Separation of the lower esophageal sphincter (LES) and crural diaphragm was quantified by measuring the distance between the two EGJ elements during inspiration. The association between anthropometric variables and pressure values were examined using univariate and multivariate analysis. Results: There was a significant correlation of body mass index (BMI) and waist circumference (WC) with intragastric pressure (inspiration, BMI [r = 0.57], WC [r = 0.62] P <.0001; expiration, BMI [r = 0,581, WC [r = 0.64], P <.0001) and gastroesophageal pressure gradient (GEPG) (inspiration, BMI [r 0.37], WC [r = 0,43], P <.0001; expiration, BMI [r = 0.24], WC [r = 0.26], P <.0001). Multivariate analysis adjusting for age, gender, and patient type did not alter the direction or magnitude of this relationship. In addition, obesity was associated with separation of the EGJ pressure components (BMI, r = 0.17, P <.005; WC, r = 0.21, P <.001). Conclusions: Obese subjects are more likely to have EGJ disruption (leading to hiatal hernia) and an augmented GEPG providing a perfect scenario for reflux to occur. Whether or not weight loss can reverse these abnormalities is unknown. C1 Northwestern Univ, Feinberg Sch Med, Dept Med, Div Gastroenterol, Chicago, IL 60611 USA. Baylor Coll Med, Houston VA Med Ctr, Dept Med, Houston, TX 77030 USA. RP Northwestern Univ, Feinberg Sch Med, Dept Med, Div Gastroenterol, 676 N St Clair St,Suite 1400, Chicago, IL 60611 USA. EM j-pandolfino@northwestern.edu FU NIDCD NIH HHS [R01 DC00646]; NIDDK NIH HHS [K23 DK062170-01] NR 23 TC 234 Z9 245 U1 2 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2006 VL 130 IS 3 BP 639 EP 649 DI 10.1053/j.gastro.2005.12.016 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 024QC UT WOS:000236210100006 PM 16530504 ER PT J AU Rosenfeld, K AF Rosenfeld, K TI Palliative care assessment: What are we looking for? SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID OF-LIFE CARE; KARNOFSKY PERFORMANCE STATUS; CANCER-PATIENTS; END; SCALE; PERSPECTIVES; MULTICENTER; PHYSICIANS; CISPLATIN; DISTRESS AB This article provides an overview of palliative care assessment for the gastroenterologic specialist. An evidence-based conceptual model of high-quality end-of-life care is proposed, and an approach to assessment is offered, recognizing that comprehensive palliative assessment generally requires participation of an interdisciplinary team with expertise in each of the important palliative domains. The gastroenterologist has the opportunity and responsibility to screen for problems in each domain, refer the patient to appropriate team members for a more detailed assessment, and integrate data to collaboratively develop a management plan. Because the relief of suffering and the cure of disease are dual obligations, in situations in which cure is no longer possible, alleviating suffering in patients and their caregivers must be emphasized. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Vet Integrated Palliat Program, Los Angeles, CA 90037 USA. RP Rosenfeld, K (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, Vet Integrated Palliat Program, 11301 Wilshire Blvd, Los Angeles, CA 90037 USA. EM Kenneth.rosenfeld@med.va.gov NR 43 TC 7 Z9 7 U1 6 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 2006 VL 35 IS 1 BP 23 EP + DI 10.1016/j.gtc.2005.12.002 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027ME UT WOS:000236418900003 PM 16530108 ER PT J AU Dykxhoorn, DM Palliser, D Lieberman, J AF Dykxhoorn, DM Palliser, D Lieberman, J TI The silent treatment: siRNAs as small molecule drugs SO GENE THERAPY LA English DT Review DE RNA interference; small interfering RNA; therapy; drug development ID SMALL INTERFERING RNA; HEPATITIS-B-VIRUS; ENDOTHELIAL GROWTH-FACTOR; SMALL INHIBITORY RNA; SHORT HAIRPIN RNAS; FAS PROTECTS MICE; IN-VIVO DELIVERY; GENE-EXPRESSION; MAMMALIAN-CELLS; MESSENGER-RNA AB As soon as RNA interference (RNAi) was found to work in mammalian cells, research quickly focused on harnessing this powerful endogenous and specific mechanism of gene silencing for human therapy. RNAi uses small RNAs, less than 30 nucleotides in length, to suppress expression of genes with complementary sequences. Two strategies can introduce small RNAs into the cytoplasm of cells, where they are active - a drug approach where double-stranded RNAs are administered in complexes designed for intracellular delivery and a gene therapy approach to express precursor RNAs from viral vectors. Phase I clinical studies have already begun to test the therapeutic potential of small RNA drugs that silence disease-related genes by RNAi. This review will discuss progress in developing and testing small RNAi-based drugs and potential obstacles. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU NIAID NIH HHS [AI056900, AI058695] NR 128 TC 226 Z9 233 U1 4 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 2006 VL 13 IS 6 BP 541 EP 552 DI 10.1038/sj.gt.3302703 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 019LB UT WOS:000235836000011 PM 16397510 ER PT J AU Kaplowitz, RA Scranton, RE Gagnon, DR Cantillon, C Cantillon, C Levenson, JW Sesso, HD Fiore, LD Gaziano, JM AF Kaplowitz, RA Scranton, RE Gagnon, DR Cantillon, C Cantillon, C Levenson, JW Sesso, HD Fiore, LD Gaziano, JM TI Health care utilization and receipt of cholesterol testing by veterans with and those without mental illness SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE health care utilization; hyperlipidemia; mental disorders; prevention ID CARDIOVASCULAR RISK-FACTORS; MEDICAL-CARE; MYOCARDIAL-INFARCTION; AFFECTIVE-DISORDER; SERUM-CHOLESTEROL; QUALITY; SERVICES; SUICIDE; SCHIZOPHRENIA; METAANALYSIS AB Objective: We examined the relationship between mental illness, health care utilization and rates of cholesterol testing. Methods: We conducted a retrospective cohort study using Veterans Affairs (VA) administrative data on 64,490 United States veterans who used VA New England Health Care System outpatient services between January 1998 and June 2001. A total of 10,100 veterans (15.7%) had a mental illness treated with medication. We examined the interaction between mental illness and outpatient service utilization with respect to the likelihood of receiving a cholesterol test, adjusting for major demographic and clinical covariates. Results: Among veterans using VA outpatient services infrequently, those with mental illness were less likely than non-mentally in control subjects to receive a cholesterol test during the study period (first quartile adjusted OR=0.45, 95% CI=0.37-0.54; second quartile adjusted OR=0.50, 95% CI=0.45-0.57). Mentally ill subjects with more frequent utilization of VA services were as likely as (third quartile adjusted OR=1.01, 95% CI=0.91-1.13) or more likely than (fourth quartile adjusted OR=2.73, 95% CI=2.46-3.03) non-mentally ill subjects to receive cholesterol testing. Conclusions: Mental illness was associated with a lower likelihood of cholesterol testing in subjects who used fewer VA outpatient services. The observed disparity attenuated at higher levels of service utilization. (c) 2006 Elsevier Inc. All rights reserved. C1 MAVERIC, VA Boston Healthcare Syst, Boston, MA 02130 USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. RP Kaplowitz, RA (reprint author), MAVERIC, VA Boston Healthcare Syst, 151 MAV, Boston, MA 02130 USA. EM rebekah.kaplowitz@med.va.gov OI Gagnon, David/0000-0002-6367-3179 NR 34 TC 6 Z9 6 U1 5 U2 8 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 MAR-APR PY 2006 VL 28 IS 2 BP 137 EP 144 DI 10.1016/j.genhosppsych.2005.10.002 PG 8 WC Psychiatry SC Psychiatry GA 026DZ UT WOS:000236318300009 PM 16516064 ER PT J AU Moran, JL Bolton, AD Tran, PV Brown, A Dwyer, ND Manning, DK Bjork, BC Li, C Montgomery, K Siepka, SM Vitaterna, MH Takahashi, JS Wiltshire, T Kwiatkowski, DJ Kucherlapati, R Beier, DR AF Moran, JL Bolton, AD Tran, PV Brown, A Dwyer, ND Manning, DK Bjork, BC Li, C Montgomery, K Siepka, SM Vitaterna, MH Takahashi, JS Wiltshire, T Kwiatkowski, DJ Kucherlapati, R Beier, DR TI Utilization of a whole genome SNP panel for efficient genetic mapping in the mouse SO GENOME RESEARCH LA English DT Article ID POLYMORPHISMS; EXPRESSION; MUTATIONS; DISEASE; MICE AB Phenotype-driven genetics can be used to create mouse models of human disease and birth defects. However, the utility of these mutant models is limited without identification of the causal gene. To facilitate genetic mapping, we developed a fixed single nucleotide polymorphism (SNP) panel of 394 SNPs as an alternative to analyses using simple sequence length polymorphism (SSLP) marker mapping. With the SNP panel, chromosomal locations for 22 monogenic mutants were identified. The average number of affected progeny genotyped for mapped monogenic mutations is nine. Map locations for several mutants have been obtained with as few as four affected progeny. The average size of genetic intervals obtained for these mutants is 43 Mb, with a range of 17-83 Mb. Thus, our SNP panel allows for identification of moderate resolution map position with small numbers of mice in a high-through put manner. Importantly, the panel is Suitable for mapping crosses from many inbred and wild-derived inbred strain combinations. The chromosomal localizations obtained with the SNP panel allow one to quickly distinguish between potentially novel loci or remutations in known genes, and facilitates fine mapping and positional cloning. By using this approach, we identified DNA sequence changes in two ethylnitrosourea-induced mutants. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Partners Ctr Genet & Genom, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Computat Biol, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Boston, MA 02115 USA. Northwestern Univ, Ctr Funct Genom, Evanston, IL 60208 USA. Northwestern Univ, Howard Hughes Med Inst, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. Genom Inst, San Diego, CA 92121 USA. Novartis Res Fdn, San Diego, CA 92121 USA. RP Beier, DR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. EM beier@receptor.med.harvard.edu RI Takahashi, Joseph/E-8482-2012; OI Takahashi, Joseph/0000-0003-0384-8878; Moran, Jennifer/0000-0002-5664-4716 FU Howard Hughes Medical Institute; NICHD NIH HHS [U01 HD043430, U01HD43430] NR 17 TC 75 Z9 75 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 2006 VL 16 IS 3 BP 436 EP 440 DI 10.1101/gr.4563306 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 018CZ UT WOS:000235742700017 PM 16461637 ER PT J AU Parker, PA Kudelka, A Basen-Engquist, K Kavanagh, J de Moor, J Cohen, L AF Parker, PA Kudelka, A Basen-Engquist, K Kavanagh, J de Moor, J Cohen, L TI The associations between knowledge, CA125 preoccupation, and distress in women with epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE neoplasm; knowledge; distress; depressive symptoms; worry ID QUALITY-OF-LIFE; STUDIES DEPRESSION SCALE; BREAST-CANCER; TUMOR-MARKERS; CHEMOTHERAPY; SYMPTOMS; ANXIETY; GUIDELINES; EVALUATE; RE AB Objective. The goal of the current study was to determine how much women with ovarian cancer know about their cancer and CA125 testing and how much women focus on or are preoccupied with their CA125 levels. We also examined the direct and moderating effects of knowledge and CA125 preoccupation on two measures of distress (depressive symptoms and anxiety). Methods. Participants were 126 women with epithelial ovarian cancer. Patients completed questionnaires of knowledge, CA125 preoccupation, and distress at the beginning of the first or a new round of chemotherapy. Results. Both knowledge and preoccupation with CA125 levels were associated with depressive and anxiety symptoms. More importantly, knowledge appeared to moderate the association between CA125 preoccupation and depressive symptoms. That is, for patients with lower levels of knowledge, more CA125 preoccupation was associated with more depressive symptoms. However, there was no such association in women with higher levels of knowledge. Conclusion. Our results suggest that it may be possible to decrease depressive symptoms in women who are overly preoccupied or worried about their CA125 levels by improving their knowledge of aspects of their disease and the surveillance process. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Unit 1330, Houston, TX 77230 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Med Oncol, Houston, TX 77030 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Palliat Care & Rehabil Med, Houston, TX 77030 USA. RP Parker, PA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Unit 1330, POB 301439, Houston, TX 77230 USA. EM pparker@mdanderson.org NR 31 TC 32 Z9 32 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2006 VL 100 IS 3 BP 495 EP 500 DI 10.1016/j.ygyno.2005.08.057 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 018BV UT WOS:000235738800008 PM 16242759 ER PT J AU Baergen, RN Rutgers, JL Young, RH Osann, K Scully, RE AF Baergen, RN Rutgers, JL Young, RH Osann, K Scully, RE TI Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance SO GYNECOLOGIC ONCOLOGY LA English DT Review DE gestational trophoblastic disease; placental site trophoblastic tumor; extravillous trophoblast; intermediate trophoblast; uterus ID DISTINCTIVE GLOMERULAR LESION; HUMAN CHORIONIC-GONADOTROPIN; CLINICAL-EXPERIENCE; PSEUDO-TUMOR; LUNG METASTASES; MR APPEARANCE; DNA ANALYSIS; CHEMOTHERAPY; UTERUS; DISEASE AB Objective. The placental site trophoblastic tumor is a rare form of gestational trophoblastic disease. Fifteen percent of reported cases have been fatal, but predicting behavior in individual patients has been challenging. Methods. The clinical, gross and histopathological features of 55 cases and 180 cases in the literature were analyzed for their effect on survival and in relation to tumor stage. Results. The 55 patients in our series were 20 to 62 (average 32) years of age. The tumors occurred on an average of 34 months after the last known gestation. 84% were stage I, 2% stage II, 5% stage III, and 9% stage IV. Serum levels of human chorionic gonadotropin (hCG) were elevated (average 691 mlU/ml) in 77% of the cases. The tumors were on average 5 em in greatest dimension and were composed microscopically of infiltrative sheets of intermediate (extravillous) trophoblastic cells. The mitotic rate ranged from 0 to 20 (average 5.0) per 10 high power fields. The follow-up interval averaged 4.6 years. Eight patients (15%) died from metastatic tumor, and nine additional patients had metastases or a recurrence but were alive at last contact. The most common metastatic sites were the lungs, liver, and vagina. Conclusions. Significant factors associated with adverse survival in the present series were age over 35 years (P = 0.025), interval since the last pregnancy of over 2 years (P = 0.014), deep myometrial invasion (P = 0.006), stage III or IV (P < 0.0005), maximum hCG level >1000 mlU/mI (P = 0.034), extensive coagulative necrosis (P = 0.024), high mitotic rate (P = 0.005), and the presence of cells with clear cytoplasm (P < 0.0005). Only stage and clear cytoplasm were independent predictors of overall survival, while stage and age were the only independent predictors of time to recurrence or disease-free survival. In the literature, factors associated with survival were stage (P < 0.005), interval from preceding pregnancy of over 2 years (P = 0.029), previous term pregnancy (P = 0.046), high mitotic rate (P < 0.0005), and high hCG level (P = 0.037). (C) 2005 Elsevier Inc. All rights reserved. C1 New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY 10021 USA. Long Beach Mem Med Ctr, Todd Canc Inst, Long Beach, CA 90806 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92612 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP Baergen, RN (reprint author), New York Presbyterian Hosp, Weill Cornell Med Ctr, 520 E 70th St,Starr 1002, New York, NY 10021 USA. EM rbaergen@med.cornell.edu NR 119 TC 73 Z9 79 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2006 VL 100 IS 3 BP 511 EP 520 DI 10.1016/j.ygyno.2005.08.058 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 018BV UT WOS:000235738800011 PM 16246400 ER PT J AU Roffman, JL Weiss, AP Goff, DC Rauch, SL Weinberger, DR AF Roffman, JL Weiss, AP Goff, DC Rauch, SL Weinberger, DR TI Neuroimaging-genetic paradigms: A new approach to investigate the pathophysiology and treatment of cognitive deficits in schizophrenia SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE cognitive impairment; genetics; neuroimaging; schizophrenia ID CATECHOL-O-METHYLTRANSFERASE; DORSOLATERAL PREFRONTAL CORTEX; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; FACTOR VAL66MET POLYMORPHISM; BIPOLAR AFFECTIVE-DISORDER; VAL(108/158) MET GENOTYPE; NEUROTROPHIC FACTOR; WORKING-MEMORY; ALZHEIMERS-DISEASE AB Cognitive impairment is a prominent and debilitating feature of schizophrenia. Genetic predisposition likely accounts for a large proportion of these cognitive deficits. Direct associations between candidate genes and cognitive dysfunction have been difficult to establish, however, largely due to the subtle effects of these genes on observable behavior. Neuroimaging techniques can provide a sensitive means to bridge the neurobiology of genes and behavior. Here we illustrate the use of neuroimaging-genetics paradigms to elaborate the relationship between genes and cognitive dysfunction in schizophrenia. After reviewing principles important for the selection of genes, neuroimaging techniques, and subjects, we describe how imaging-genetics investigations have helped clarify the contribution of five candidate genes (COMT, GRM3, G72, DISC1, and BDNF) to cognitive deficits in schizophrenia. The potential of this approach for improving patient care will depend on its ability to predict outcomes with greater accuracy and sensitivity than current clinical measures. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,CNY 2625,Hosp E, Charlestown, MA 02129 USA. EM jroffman@partners.org NR 126 TC 35 Z9 35 U1 3 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2006 VL 14 IS 2 BP 78 EP 91 DI 10.1080/10673220600642945 PG 14 WC Psychiatry SC Psychiatry GA 039WA UT WOS:000237337200004 PM 16603474 ER PT J AU Jones, DS Perlis, RH AF Jones, DS Perlis, RH TI Pharmacogenetics, race, and psychiatry: Prospects and challenges SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE ethnicity; genetics; HapMap; history; pharmacogenetics; pharmacogenomics; psycho-pharmacology; race ID SEROTONIN TRANSPORTER GENE; ANTIDEPRESSANT-INDUCED MANIA; INDUCED WEIGHT-GAIN; CHARCOAL-BROILED BEEF; 5-HT2C RECEPTOR GENE; DRUG RESPONSE; BIPOLAR DISORDER; ETHNIC-DIFFERENCES; FUNCTIONAL POLYMORPHISM; CLINICAL CONSEQUENCES AB Although the field of pharmacogenetics has existed for nearly 50 years, it has begun to enter mainstream clinical practice only recently. Researchers and clinicians have now demonstrated that a wide assortment of genetic variants influence how individuals respond to medications. Many of these variants are relevant for psychiatry, affecting how patients respond to most antidepressants, antipsychotics, anxiolytics, and mood stabilizers. Enthusiasts hope that pharmacogenetics will soon usher in a new era of individualized medicine. However, determining the practical relevance of pharmacogenetic variants remains difficult, in part because of problems with study design and replication, and in part because a host of nongenetic factors (including age, diet, environmental exposures, and comorbid diseases) also influence how individuals respond to medications. Since individualized pharmacogenetic assessment remains difficult, some researchers have argued that race provides a convenient proxy for individual genetic variation, and that clinicians should choose medications and doses differently for different races. This approach remains extremely controversial because of the complexity of the genetic structure of the human population, the complexity of gene-environment interactions, and the complexity of the meanings of race in the United States. C1 Harvard Univ, Sch Med, MIT, Program Sci Technol & Soc,Dept Social Med, Cambridge, MA 02138 USA. Cambridge Hosp, Dept Psychiat, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jones, DS (reprint author), 77 Massachusetts Ave E51-290, Cambridge, MA 02139 USA. EM dsjones@mit.edu NR 156 TC 23 Z9 28 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2006 VL 14 IS 2 BP 92 EP 108 DI 10.1080/10673220600642895 PG 17 WC Psychiatry SC Psychiatry GA 039WA UT WOS:000237337200005 PM 16603475 ER PT J AU Finn, CT Smoller, JW AF Finn, CT Smoller, JW TI Genetic counseling in psychiatry SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE genetic counseling; psychiatric genetics; recurrence risks ID CARDIO-FACIAL SYNDROME; 22Q11 DELETION SYNDROME; BIPOLAR DISORDER; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; BEHAVIORAL PHENOTYPES; SUSCEPTIBILITY GENES; HUNTINGTONS-DISEASE; RISK INFORMATION; FAMILY ATTITUDES AB While psychiatrists may commonly discuss family history in clinical practice, there has been little systematic research documenting the role and effectiveness of genetic counseling for psychiatric disorders. In the coming years, the expected identification of susceptibility genes for psychiatric disorders may bring new opportunities and expectations from patients and families for the clinical translation of research findings in psychiatric genetics. We review evidence for possible increasing demand for genetic counseling, particularly if specific genes related to psychiatric disorders are identified. We then explore both the potential role of genetic counseling for psychiatric disorders and the issues involved in conveying genetic information in the clinical setting. Further research regarding the effectiveness of counseling interventions, as well as additional efforts directed at genetics education for clinicians, will be needed if emerging advances in genetic research are to be incorporated into clinical practice. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Psychiat Genet Program Mood & Anxiety Disorders, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Patners Ctr Genet & Genom, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02115 USA. RP Finn, CT (reprint author), WACC 812,15 Parkman St, Boston, MA 02114 USA. EM cfinn@partners.org NR 102 TC 23 Z9 23 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2006 VL 14 IS 2 BP 109 EP 121 DI 10.1080/10673220600655723 PG 13 WC Psychiatry SC Psychiatry GA 039WA UT WOS:000237337200006 PM 16603476 ER PT J AU Gilbert, J Li, Y Pinto, HA Jennings, T Kies, MS Silverman, P Forastiere, AA AF Gilbert, J Li, Y Pinto, HA Jennings, T Kies, MS Silverman, P Forastiere, AA TI Phase II trial of taxol in salivary gland malignancies (E1394): A trial of the Eastern Cooperative Oncology Group SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE salivary gland tumor; paclitaxel taxol; mucoepidermoid; adenoid cystic; adenocarcinoma ID ADENOID CYSTIC CARCINOMA; GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; COMBINATION CHEMOTHERAPY; CISPLATIN; EXPRESSION; ORIGIN; CYCLOPHOSPHAMIDE; ADENOCARCINOMA; VINORELBINE AB Background. Malignant tumors of the salivary glands make up approximately 5% of head and neck cancers. The Eastern Cooperative Oncology Group (ECOG) initiated a phase II evaluation of paclitaxel in patients with locally recurrent or metastatic salivary gland malignancies. Methods. Chemo-naive patients with histologically confirmed recurrent or metastatic carcinoma of salivary gland origin (mucoepidermoid, adenocarcinoma, or adenoid cystic) were eligible. Patients were treated with paclitaxel, 200 mg/m(2) IV, every 21 days for a minimum of four cycles. Results. Forty-five patients were treated. Eight partial responses were seen among the 31 patients with mucoepidermoid or adenocarcinoma histologic findings for a response rate of 26%. No responses were seen in the adenoid cystic carcinoma group. No significant difference in overall survival was found among these three histologic subgroups. Conclusion. Paclitaxel demonstrates moderate activity in salivary gland tumors of mucoepidermoid and adenocarcinoma histology, The poor response rate in adenoid cystic carcinoma is consistent with prior reports in this chemoresistant histologic subtype. (c) 2006 Wiley Periodicals, Inc. C1 Louisiana State Univ, Med Ctr, New Orleans, LA 70112 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Albany Med Coll, Albany, NY 12208 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Gilbert, J (reprint author), Louisiana State Univ, Med Ctr, New Orleans, LA 70112 USA. EM jgilbe@lsuhsc.edu FU NCI NIH HHS [CA14548, CA16116, CA17145, CA21115, CA23318, CA66636] NR 24 TC 61 Z9 64 U1 0 U2 1 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 MAR PY 2006 VL 28 IS 3 BP 197 EP 204 DI 10.1002/hed.20327 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 016CZ UT WOS:000235599600002 PM 16470745 ER PT J AU Jacobson, M O'Malley, AJ Earle, CC Pakes, J Gaccione, P Newhouse, JP AF Jacobson, M O'Malley, AJ Earle, CC Pakes, J Gaccione, P Newhouse, JP TI Does reimbursement influence chemotherapy treatment for cancer patients? SO HEALTH AFFAIRS LA English DT Article; Proceedings Paper CT 115th Annual Meeting of the American-Economic-Association CY JAN 03-05, 2003 CL WASHINGTON, DC SP Amer Econ Assoc ID ADVANCED COLORECTAL-CANCER; FLUOROURACIL; LEUCOVORIN AB Before the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003, Medicare reimbursed physicians for chemotherapy drugs at rates that greatly exceeded physicians' costs for those drugs. We examined the effect of physician reimbursement on chemotherapy treatment of Medicare beneficiaries older than age sixty-five with metastatic lung, breast, colorectal, or other gastrointestinal cancers between 1995 and 1998 (9,357 patients). A physician's decision to administer chemotherapy to metastatic cancer patients was not measurably affected by higher reimbursement. Providers who were more generously reimbursed, however, prescribed more-costly chemotherapy regimens to metastatic breast, colorectal, and lung cancer patients. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. EM mgjacobs@umich.edu FU AHRQ HHS [P01-HS-10803] NR 23 TC 72 Z9 73 U1 0 U2 4 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 MAR-APR PY 2006 VL 25 IS 2 BP 437 EP 443 DI 10.1377/hlthaff.25.2.437 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 022ZK UT WOS:000236094500016 PM 16522584 ER PT J AU Brideau, J AF Brideau, J TI Lydia's story SO HEALTH AFFAIRS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brideau, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jbrideau@partners.org NR 0 TC 0 Z9 0 U1 0 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 MAR-APR PY 2006 VL 25 IS 2 BP 478 EP 480 DI 10.1377/hlthaff.25.2.478-a PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 022ZK UT WOS:000236094500022 PM 16522589 ER PT J AU Patterson, JE AF Patterson, JE TI Clinic shift SO HEALTH AFFAIRS LA English DT Editorial Material C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Patterson, JE (reprint author), Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. EM pattersonj@uthscsa.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR-APR PY 2006 VL 25 IS 2 BP 484 EP 486 DI 10.1377/hlthaff.25.2.484 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 022ZK UT WOS:000236094500028 PM 16522596 ER PT J AU Conlin, J AF Conlin, J TI Comfort story no. 2 SO HEALTH AFFAIRS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Conlin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jconlin@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR-APR PY 2006 VL 25 IS 2 BP 487 EP 488 DI 10.1377/hlthaff.25.2.487-a PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 022ZK UT WOS:000236094500031 PM 16522598 ER PT J AU Wertheimer, BZ Freedberg, KA Walensky, RP Yazdanapah, Y Losina, E AF Wertheimer, BZ Freedberg, KA Walensky, RP Yazdanapah, Y Losina, E TI Therapeutic drug monitoring in HIV treatment: A literature review SO HIV CLINICAL TRIALS LA English DT Review DE antiretroviral agents; drug monitoring; HIV ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; CONTAINING TRIPLE THERAPY; PLASMA-CONCENTRATIONS; PROTEASE INHIBITORS; HIV-1-INFECTED PATIENTS; VIROLOGICAL RESPONSE; TREATMENT FAILURE; INDINAVIR; NELFINAVIR AB Purpose: Therapeutic drug monitoring (TDM) is the practice of managing plasma drug concentrations. This intervention can potentially improve inadequate antiretroviral dosing in the treatment of HIV infection. Our objective was to review the evidence regarding TDM in HIV management. Method: We searched MEDLINE using the following key words: therapeutic drug monitoring, HIV infection, pharmacokinetics, antiretroviral therapy, protease inhibitors, antiretroviral-naive, antiretroviral-experienced, and salvage therapy. Inclusion criteria required definition of optimal concentration thresholds and measures of treatment effectiveness at these targets. Results: Our search yielded 39 studies. 11 studies met inclusion criteria. 4 studies compared efficacy of TDM to standard of care (SOC) interventions via randomized clinical trials and were grouped as "interventional." 7 studies retrospectively defined thresholds from observed differences in outcome and were grouped as "observational." 3 interventional studies targeted similar indinavir concentrations (C-min 0.10-0.15 mg/L). 2 of these studies increased achievement of target serum levels and percentages of undetectable viral load (23%-41 %, p <=.009) with TDM implementation. Conclusion: TDM can effectively target antiretroviral threshold concentrations and improve virologic suppression in some cases. Further work is needed to define plasma thresholds and assess the value of TDM in HIV management. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02115 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Ctr Hosp Tourcoing, Serv Univ Malad Infect & Voyageur, Tourcoing, France. Fac Med Lille, Lille, France. Lab Rech Econ & Sociales, CNRS, URA 362, Lille, France. RP Wertheimer, BZ (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02115 USA. EM bzw@mail.med.upenn.edu FU NIAID NIH HHS [K24 AI062476, K24AI062476, K25 AI050436, K25AI50436, R01-AI42006, R01 AI042006, K23 AI001794, P30 AI060354, K23AI01794] NR 41 TC 13 Z9 13 U1 0 U2 1 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD MAR-APR PY 2006 VL 7 IS 2 BP 59 EP 69 DI 10.1310/4CCJ-KT1T-H6PV-NLFC PG 11 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 058CG UT WOS:000238641400004 PM 16798621 ER PT J AU Walsh, EC Sabeti, P Hutcheson, HB Fry, B Schaffner, SF de Bakker, PIW Varilly, P Palma, AA Roy, J Cooper, R Winkler, C Zeng, Y de The, G Lander, ES O'Brien, S Altshuler, D AF Walsh, EC Sabeti, P Hutcheson, HB Fry, B Schaffner, SF de Bakker, PIW Varilly, P Palma, AA Roy, J Cooper, R Winkler, C Zeng, Y de The, G Lander, ES O'Brien, S Altshuler, D TI Searching for signals of evolutionary selection in 168 genes related to immune function SO HUMAN GENETICS LA English DT Article ID GENOME SEQUENCE VARIATION; SECRETOR LOCUS FUT2; LINKAGE DISEQUILIBRIUM; NATURAL-SELECTION; FUSION GENE; POPULATIONS; MAP; SIGNATURES; PATTERNS; COMPLEX AB Pathogens have played a substantial role in human evolution, with past infections shaping genetic variation at loci influencing immune function. We selected 168 genes known to be involved in the immune response, genotyped common single nucleotide polymorphisms across each gene in three population samples (CEPH Europeans from Utah, Han Chinese from Guangxi, and Yoruba Nigerians from Southwest Nigeria) and searched for evidence of selection based on four tests for non-neutral evolution: minor allele frequency (MAF), derived allele frequency (DAF), Fst versus heterozygosity and extended haplotype homozygosity (EHH). Six of the 168 genes show some evidence for non-neutral evolution in this initial screen, with two showing similar signals in independent data from the International HapMap Project. These analyses identify two loci involved in immune function that are candidates for having been subject to evolutionary selection, and highlight a number of analytical challenges in searching for selection in genome-wide polymorphism data. C1 Novartis Inst Biomed Res, Cambridge, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. NCI, Lab Gen Divers, Frederick, MD 21701 USA. Loyola Univ, Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. Inst Viral Dis Control & Prevent, Beijing, Peoples R China. Inst Pasteur, Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Walsh, EC (reprint author), Novartis Inst Biomed Res, 250 Mass Ave, Cambridge, MA 02139 USA. EM Emily.walsh@novartis.com RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011; Varilly, Patrick/C-8118-2013; de Bakker, Paul/B-8730-2009 OI Altshuler, David/0000-0002-7250-4107; Varilly, Patrick/0000-0003-4619-8174; de Bakker, Paul/0000-0001-7735-7858 FU NCI NIH HHS [N01-CO-12400] NR 36 TC 50 Z9 51 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 2006 VL 119 IS 1-2 BP 92 EP 102 DI 10.1007/s00439-005-0090-0 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 016QM UT WOS:000235635000010 PM 16362345 ER PT J AU Wang, ZGC Hill, JA Yunis, EJ Xiao, L Anderson, DJ AF Wang, ZGC Hill, JA Yunis, EJ Xiao, L Anderson, DJ TI Maternal CD46H*2 and IL1B-511*1 homozygosity in T helper 1-type immunity to trophoblast antigens in recurrent pregnancy loss SO HUMAN REPRODUCTION LA English DT Article DE CD46; IL1B; Th1 immunity; recurrent pregnancy loss ID ANTAGONIST GENE POLYMORPHISM; MEMBRANE COFACTOR PROTEIN; SPONTANEOUS-ABORTION; RECEPTOR ANTAGONIST; IN-VITRO; WOMEN; PROLIFERATION; RESTRICTION; MISCARRIAGE; EXPRESSION AB BACKGROUND: Women with recurrent pregnancy loss (RPL) and T-helper (Th)1-type immunity to trophoblast antigens have an increased frequency of the IL1B-511*1 promoter variant. Since CD46 gene products also regulate maternal immune responses including Th1 immunity, we investigated whether CD46 gene polymorphisms are also associated with RPL in women with and without Th1 immunity to trophoblast, and the possibility of a synergistic effect with the IL1B-511*1 promoter variant. METHODS: A case-controlled study was performed to document HindIII site polymorphism in intron 1 of the CD46 gene in 131 women with RPL and 72 fertile controls. Clinical information, Th1-type immune responsiveness to trophoblast in women with RPL history, and IL1B promoter allelotypes for this cohort were documented in a previous study. RESULTS: The frequency of the CD46H*2 allele and CD46H*2 homozygosity were significantly increased in women with RPL compared with fertile controls (P < 0.028 and P < 0.011). CD46H*2 homozygosity was highly associated with RPL-Th1(+) (32.4 versus 9.7% in fertile controls, P < 0.0045). Logistic regression analysis revealed that women homozygous for both the IL1B-511*1 and CD46H*2 alleles had an extremely high risk of RPL-Th1(+) [exponential coefficients (EC) = 24]. Among women with RPL, homozygosity at both alleles, but not each alone, significantly increased the risk of Th1 immunity to trophoblast antigens (EC = 16), suggesting a possible genetic interaction between these two alleles in the development of Th1 immunity. CONCLUSIONS: The combination of homozygosity for both IL1B-511*1 and CD46H*2 alleles is a high risk factor for RPL-Th1(+). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol,Sch Med, Fearing Lab, Boston, MA 02115 USA. Fertil Ctr New England, Reading, MA 01867 USA. RP Wang, ZGC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binny St,SM822, Boston, MA 02115 USA. EM zhigang_wang@dfci.harvard.edu FU NHLBI NIH HHS [HL59838, HL29583] NR 32 TC 11 Z9 13 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAR PY 2006 VL 21 IS 3 BP 818 EP 822 DI 10.1093/humrep/dei366 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 016FF UT WOS:000235605400036 PM 16253969 ER PT J AU Encke, J Geissler, M Stremmel, W Wands, JR AF Encke, Jens Geissler, Michael Stremmel, Wolfgang Wands, Jack R. TI DNA-based immunization breaks tolerance in a hepatitis C virus transgenic mouse model SO HUMAN VACCINES LA English DT Article DE hepatitis C virus; transgenic mouse; humoral immune response; cellular immune response; immunological tolerance; DNA-vaccination ID CYTOKINE-EXPRESSING PLASMIDS; HUMORAL IMMUNE-RESPONSES; ALPHA-2B PLUS RIBAVIRIN; CORE PROTEIN; HEPATOCELLULAR-CARCINOMA; NONSTRUCTURAL PROTEINS; GENETIC IMMUNIZATION; STRUCTURAL PROTEINS; INFECTION; MICE AB Chronic hepatitis C infection (HCV) is associated with high morbidity and mortality due to limited treatment options. HCV transgenic mice can be used as surrogate model of chronic HCV infection and may therefore be a small animal model for the evaluation of therapeutic vaccination strategies. We immunized transgenic mice expressing HCV structural proteins with an HCV core and a mouse IL-2 expression plasmid to study the cellular and humoral immune responses. DNA-based immunization induced a significant CD4+ T cell proliferative response and a CD8+ cytotoxic T cell response. Only low amounts of anti-HCV core antibodies were detected after genetic immunization. No liver damage was observed in the liver of immunized mice despite low level HCV core transgene expression and the presence of peripheral cellular immunity. These results demonstrate that DNA-based immunization may result in activation of previously tolerant T cells and is therefore a promising approach for treatment of chronic HCV infection. C1 Univ Heidelberg, Dept Internal Med 4, D-69115 Heidelberg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Mol Hepatol Lab, Charlestown, MA USA. Univ Freiburg, Dept Med 2, Freiburg, Germany. Rhode Isl Hosp, Liver Res Ctr, Providence, RI USA. RP Encke, J (reprint author), Univ Heidelberg, Dept Internal Med 4, Neuenheimer Feld 410, D-69115 Heidelberg, Germany. EM Jens_Encke@med.uni-heidelberg.de FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-20169, AA-02666] NR 42 TC 6 Z9 8 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1554-8619 J9 HUM VACCINES JI Hum. Vaccines PD MAR-APR PY 2006 VL 2 IS 2 BP 78 EP 83 PG 6 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 132YQ UT WOS:000243979200006 PM 17012868 ER PT J AU Okonofua, EC Simpson, KN Jesri, A Rehman, SU Durkalski, VL Egan, BM AF Okonofua, EC Simpson, KN Jesri, A Rehman, SU Durkalski, VL Egan, BM TI Therapeutic inertia is an impediment to achieving the healthy people 2010 blood pressure control goals SO HYPERTENSION LA English DT Article DE population; antihypertensive agents; blood pressure monitoring; compliance; blood pressure; hypertension, arterial ID PRIMARY-CARE PHYSICIANS; HYPERTENSION MANAGEMENT; UNITED-STATES; UNCONTROLLED HYPERTENSION; ETHNIC-DIFFERENCES; AFRICAN-AMERICANS; CLINICAL-PRACTICE; GUIDELINES; TRENDS; POPULATION AB Therapeutic inertia (TI), defined as the providers' failure to increase therapy when treatment goals are unmet, contributes to the high prevalence of uncontrolled hypertension ( >= 140/90 mm Hg), but the quantitative impact is unknown. To address this gap, a retrospective cohort study was conducted on 7253 hypertensives that had >= 4 visits and >= 1 elevated blood pressure ( BP) in 2003. A 1-year TI score was calculated for each patient as the difference between expected and observed medication change rates with higher scores reflecting greater TI. Antihypertensive therapy was increased on 13.1% of visits with uncontrolled BP. Systolic BP decreased in patients in the lowest quintile of the TI score but increased in those in the highest quintile ( - 6.8 +/- 0.5 versus + 1.8 +/- 0.6 mm Hg; P < 0.001). Individuals in the lowest TI quintile were approximate to 33 times more likely to have their BP controlled at the last visit than those in highest quintile ( odds ratio, 32.7; 95% CI, 25.1 to 42.6; P < 0.0001). By multivariable analysis, TI accounted for approximate to 19% of the variance in BP control. If TI scores were decreased approximate to 50%, that is, increasing medication dosages on approximate to 30% of visits, BP control would increase from the observed 45.1% to a projected 65.9% in 1 year. This study confirms the high rate of TI in uncontrolled hypertensive subjects. TI has a major impact on BP control in hypertensive subjects receiving regular care. Reducing TI is critical in attaining the Healthy People 2010 goal of controlling hypertension in 50% of all patients. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Okonofua, EC (reprint author), Med Univ S Carolina, 135 Rutledge Ave,Rm 1111, Charleston, SC 29425 USA. EM okonofua@musc.edu FU AHRQ HHS [P01HS1087]; NHLBI NIH HHS [HL58794, HL04290]; NIMHD NIH HHS [P60-MD00267] NR 36 TC 243 Z9 249 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2006 VL 47 IS 3 BP 345 EP 351 DI 10.1161/01.HYP.0000200702.76436.4b PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 012WT UT WOS:000235372300014 PM 16432045 ER PT J AU Mukkamala, R Reisner, AT Hojman, HM Mark, RG Cohen, RJ AF Mukkamala, R Reisner, AT Hojman, HM Mark, RG Cohen, RJ TI Continuous cardiac output monitoring by peripheral blood pressure waveform analysis SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE arterial blood pressure; arterial tree; cardiac output; distributed effects; hemodynamics; mathematical modeling; pulse contour analysis; system identification; wave reflections; Windkessel ID CENTRAL AORTIC PRESSURE; BEAT STROKE VOLUME; ARTERIAL COMPLIANCE; ELASTIC PROPERTIES; PULSE; MODEL; PARAMETERS AB A clinical method for monitoring cardiac output (CO) should be continuous, minimally invasive, and accurate. However, none of the conventional CO measurement methods possess all of these characteristics. On the other hand, peripheral arterial blood pressure (ABP) may be measured reliably and continuously with little or no invasiveness. We have developed a novel technique for continuously monitoring changes in CO by mathematical analysis of a peripheral ABP waveform. In contrast to the previous techniques, our technique analyzes the ABP waveform over time scales greater than a cardiac cycle in which the confounding effects of complex wave reflections are attenuated. The technique specifically analyzes 6-min intervals of ABP to estimate the pure exponential pressure decay that would eventually result if pulsatile activity abruptly ceased (i.e., after the high frequency wave reflections vanish). The technique then determines the time constant of this exponential decay, which equals the product of the total peripheral resistance and the nearly constant arterial compliance, and computes proportional CO via Ohm's law. To validate the technique, we performed six acute swine experiments in which peripheral ABP waveforms and aortic flow probe CO were simultaneously measured over a wide physiologic range. We report an overall CO error of 14.6%. C1 Michigan State Univ, Dept Elect & Comp Engn, E Lansing, MI 48824 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06519 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Mukkamala, R (reprint author), Michigan State Univ, Dept Elect & Comp Engn, E Lansing, MI 48824 USA. EM rama@egr.msu.edu FU NIBIB NIH HHS [R01 EB001659] NR 28 TC 67 Z9 67 U1 0 U2 11 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAR PY 2006 VL 53 IS 3 BP 459 EP 467 DI 10.1109/TBME.2005.869780 PG 9 WC Engineering, Biomedical SC Engineering GA 015OJ UT WOS:000235560400011 PM 16532772 ER PT J AU Guo, SF Grindle, GG Authier, EL Cooper, RA Fitzgerald, SG Kelleher, A Cooper, R AF Guo, SF Grindle, GG Authier, EL Cooper, RA Fitzgerald, SG Kelleher, A Cooper, R TI Development and qualitative assessment of the GAME(Cycle) exercise systern SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE cardiovascular system; exercise; games; wheelchairs ID MAXIMAL OXYGEN-CONSUMPTION; PHYSICAL-ACTIVITY; WHEELCHAIR USERS; COMPUTER GAMES; VIDEO-GAME; ERGOMETRY; PARAPLEGIA; INTERFACE AB Increased physical activity is important for reducing the risk of cardiovascular disease. However, among people with disabilities, inactivity is prevalent. In order to encourage exercise among members of this group, an exercise system combining arm ergometry with video gaming, called the GAME Cycle was previously developed. User input was received through an arm crank ergometer on a swivel, with the angular velocity of the ergometer resistance wheel controlling one axis and rotation of ergometer about the swivel controlling the other. The purpose of this study was to detail the algorithms used in this device and present novel features included in a second generation of the GAME(Cycle). The features include a wheel on base, a steering return mechanism, and wireless fire buttons. A focus group of clinicians (n = 8), wheelchair users (n = 8), and clinician wheelchair users (n = 2) was conducted to evaluate the features of the GAME(Cycle). The focus group suggested improvements to the steering mechanism and to reduce vibration in the system. However, the focus group enjoyed the GAME(Cycle) and felt that it would encourage exercise among persons with disabilities. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Ctr Assist Technol, Pittsburgh, PA 15213 USA. RP Guo, SF (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. EM sguo@pitt.edu; grindleg@herlpitt.org; authiera@herlpitt.org; rcooper@pitt.edu FU NICHD NIH HHS [1R41HD39535-01] NR 21 TC 4 Z9 4 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD MAR PY 2006 VL 14 IS 1 BP 83 EP 90 DI 10.1109/TNSRE.2006.870493 PG 8 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 028WH UT WOS:000236519000011 PM 16562635 ER PT J AU Servoss, JC Friedman, LS AF Servoss, JC Friedman, LS TI Serologic and molecular diagnosis of hepatitis B virus SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID CORE ANTIGEN; ISOLATED ANTIBODY; VIRAL-HEPATITIS; DNA; SERUM; PCR; PROMOTER; ASSAY AB Since the discovery in the 1960s of "Australia antigen," subsequently determined to be hepatitis B surface antigen, serologic assays for hepatitis B virus (HBV) have expanded and evolved. More recently, molecular biology-based techniques have allowed the detection and quantification of HBV DNA in serum. In the past decade, improvements in the sensitivity of these molecular assays have allowed the detection of as few as 10 copies of HBV DNA per milliliter of serum. The combined use of serologic and molecular assays for the diagnosis of HBV infection has resulted in more precise definitions of chronic HBV infection. Molecular assays have become essential to defining responses to antiviral treatment. C1 Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. RP Friedman, LS (reprint author), Newton Wellesley Hosp, Dept Med, 2014 Washington St, Newton, MA 02462 USA. EM lfriedman@partners.org NR 27 TC 7 Z9 9 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2006 VL 20 IS 1 BP 47 EP + DI 10.1016/j.idc.2006.01.005 PG 16 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 028WV UT WOS:000236520400004 PM 16527648 ER PT J AU Bressler, B AF Bressler, B TI Another tool in the epidemiologist's toolbox SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE C1 Massachusetts Gen Hosp, Gastrointestinal Unit, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Bressler, B (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAR PY 2006 VL 12 IS 3 BP 245 EP 246 DI 10.1097/00054725-200603000-00013 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 023NC UT WOS:000236132500013 PM 16534427 ER PT J AU Couris, R Tataronis, G McCloskey, W Oertel, L Dallal, G Dwyer, J Blumberg, JB AF Couris, Rebecca Tataronis, Gary McCloskey, William Oertel, Lynn Dallal, Gerard Dwyer, Johanna Blumberg, Jeffrey B. TI Dietary vitamin K variability affects International Normalized Ratio (INR) coagulation indices SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH LA English DT Article DE vitamin K; warfarin; coumarin; International Normalized Ratio (INR); drug-nutrient interactions ID WARFARIN RESISTANCE; ATRIAL-FIBRILLATION; DRUG-INTERACTIONS; ANTICOAGULATION; NUTRITION; THERAPY; MANAGEMENT; STABILITY; FOOD AB Background: Changes in daily vitamin K intake may contribute to marked variations in the International Normalized Ratio (INR) coagulation index in patients receiving oral warfarin anticoagulant therapy, with potentially serious adverse outcomes. Thus, patients receiving warfarin therapy are routinely counseled regarding this drug-nutrient interaction and are instructed to maintain consistent vitamin K intakes, though little quantitative information about this relationship is available. Objective: To determine the quantitative impact of variability in dietary vitamin K-1 (phylloquinone) intake, assessed by a validated patient self-monitoring instrument, on weekly INR in patients receiving warfarin anticoagulant therapy. Methods: A prospective dietary assessment study was conducted at the Massachusetts. General Hospital in Boston. Sixty outpatients (37 males and 23 females) were selected with a mean age 60.3 +/- 16.8 years, who beg gan oral warfarin anticoagulant therapy within 14 days prior to their first clinic-visit to an outpatient anticoagulation therapy unit. Exclusion criteria included more than 2 drinks of alcohol per day, inability to speak English, and concurrent disease states affecting warfarin therapy such as liver disease and terminal illness. Over the five-week study period, participants recorded daily intakes in specified amounts of all-food items appearing on a validated dietary self-assessment tool. Concomitant use of prescription and/or non-prescription medications was also obtained. Concurrent daily warfarin dose and adherence to the drug regimen, concomitant use of prescription and/or non-prescription medications known to interact with warfarin, and weekly INR were obtained. Week-to-week changes in vitamin K intake, warfarin dose, and INR were determined and cross-correlated. Results: Forty-three patients (28 males and 15 females) completed the study and 17 dropped out. Pearson's correlation coefficient revealed the variability in INR and changes in vitamin K intake were inversely correlated (r = -0.600, p < 0.01). Multiple regression analysis (r = 0.848) indicated that a weekly change of 714 mu g dietary vitamin K significantly altered weekly INR by 1 unit (p < 0.01) and a weekly change of 14.5 mg warfarin significantly altered weekly INR by 1 unit (p < 0.01) after adjustment for age, sex, weight, height, and concomitant use of medications known to interact with warfarin. Conclusions: Patients taking warfarin and consuming markedly changing amounts of vitamin K, may have, a variable weekly INR with potentially unstable anticoagulant outcomes. C1 Massachusetts Coll Pharm & Hlth Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Boston, MA 02111 USA. RP Couris, R (reprint author), Massachusetts Coll Pharm & Hlth Sci, 179 Longwood Ave, Boston, MA 02115 USA. EM rcouris@bos.mcphs.edu OI Dwyer, Johanna/0000-0002-0783-1769 NR 50 TC 38 Z9 38 U1 0 U2 1 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0300-9831 J9 INT J VITAM NUTR RES JI Int. J. Vitam. Nutr. Res. PD MAR PY 2006 VL 76 IS 2 BP 65 EP 74 DI 10.1024/0300-9831.76.2.65 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 080KF UT WOS:000240245800003 PM 16941417 ER PT J AU Delinsky, SS Wilson, GT AF Delinsky, SS Wilson, GT TI Mirror exposure for the treatment of body image disturbance SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE mirror exposure; body image disturbance; shape concerns; weight concerns ID COGNITIVE-BEHAVIOR THERAPY; BINGE-EATING DISORDER; DUAL-PATHWAY MODEL; BULIMIA-NERVOSA; PREVENTION PROGRAM; QUESTIONNAIRE; DISSATISFACTION; PSYCHOTHERAPY; INTERVIEW; CHECKING AB Objective: Body image disturbance is a risk factor for the development and persistence of eating disorders. Limitations of current treatments for body image disturbance prompted the development of a mirror exposure (ME) treatment. Method: ME involves deliberate, planned, and systematic exposure to body image. The approach is non-judgmental, holistic in focus, and mindful of present emotional experience. Complementary behavioral assignments aim to reduce avoidance and excessive checking. The current study evaluated the effectiveness of ME therapy (in a three session format) compared with a nondirective (ND) therapy for 45 women with extreme weight and shape concerns. Results: ME resulted in significant improvements at termination and follow-up in body checking and avoidance, weight and shape concerns, body dissatisfaction, dieting, depression, and self-esteem. As hypothesized, ME was significantly better than ND on many of the outcome measures. Conclusion: ME is an effective treatment for body image disturbance and should be evaluated in the context of treatments for eating disorders. (c) 2005 by Wiley Periodicals, Inc. C1 Rutgers State Univ, Piscataway, NJ USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Delinsky, SS (reprint author), Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM sdelinsky@partners.org NR 44 TC 62 Z9 64 U1 6 U2 17 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAR PY 2006 VL 39 IS 2 BP 108 EP 116 DI 10.1002/eat.20207 PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 009HE UT WOS:000235101600003 PM 16231342 ER PT J AU Yoo, RH Chuang, SK Erakat, MS Weed, M Dodson, TB AF Yoo, RH Chuang, SK Erakat, MS Weed, M Dodson, TB TI Changes in crestal bone levels for immediately loaded implants SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE crestal bone levels; dental implants; immediate loading; multivariate models; retrospective cohort studies; risk factors ID RETAINED MANDIBULAR OVERDENTURES; TITANIUM IMPLANTS; DENTAL IMPLANTS; LEVELS ADJACENT; STRATEGY; DESIGN AB Purpose: The authors' objective was to measure crestal bone level change in subjects with immediately loaded implants and to identify risk factors associated with changes in bone level. Materials and Methods: A retrospective cohort study design was used. The sample comprised subjects who had had endosseous implants placed and immediately loaded between July 2001 and July 2003. Demographic, health status-related, anatomic, implant-specific, prosthetic, and surgical variables were examined. The primary outcome variable was change in crestal bone level over time. Appropriate uni-, bi-, and multivariate statistics were computed. Results: The sample comprised 174 subjects who received 347 immediately loaded implants. The mean duration of radiographic follow-up was 6.9 +/- 4.0 months, respectively. Mean changes in radiographic bone level were -0.5 mm and -0.6 mm on the mesial and distal surfaces, respectively, after a mean of 6.9 months of radiographic follow-up. Using least squares methods, it was estimated that radiographic bone levels would be -1.0 mm and -0.8 mm on the mesial and distal surfaces, respectively, at 12 months. The multivariate model revealed that radiolucency at or adjacent to implant site was associated with an increased risk of crestal bone loss (odds ratio, 1.88; 95% Cl, 1.00 to 3.60). Twelve months after placement, 92.5% of implants had had <= 1.5 mm of crestal bone loss. Discussion: The results of this study were comparable to the results of other studies comparing immediate loading to delayed loading. Further research to estimate long-term changes in crestal bone loss and to identify risk factors for bone loss with immediate loading is recommended. Conclusion: This study suggests that crestal bone level changes with immediately loaded implants were within the recommended range for 92.5% of the evaluated implants. The mandible showed a higher risk for crestal bone loss compared to the maxilla. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Univ So Calif, Sch Dent, Los Angeles, CA 90089 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Univ Med & Dent New Jersey, Dept Oral & Maxillofacial Surg, Newark, NJ 07103 USA. Faulkner Hosp, Implant Dent Ctr, Boston, MA 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 FU NIDCR NIH HHS [K24 DE000448] NR 35 TC 20 Z9 21 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD MAR-APR PY 2006 VL 21 IS 2 BP 253 EP 261 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 033SP UT WOS:000236869800011 PM 16634496 ER PT J AU Guadagnolo, BA Li, SG Neuberg, D Ng, A Hua, L Silver, B Stevenson, MA Mauch, P AF Guadagnolo, BA Li, SG Neuberg, D Ng, A Hua, L Silver, B Stevenson, MA Mauch, P TI Long-term outcome and mortality trends in early-stage, Grade 1-2 follicular lymphoma treated with radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Meeting of the European-Society-for-Therapeutic-Radiation-Oncology/European Cancer Conference CY SEP 19-25, 2003 CL Copenhagen, DENMARK SP European Soc Therapeut Radiat Oncol DE follicular lymphoma; radiotherapy; second malignancy; cause of death ID NON-HODGKINS-LYMPHOMA; COMBINED-MODALITY THERAPY; TOTAL-BODY IRRADIATION; FOLLOW-UP; RADIOTHERAPY; CLASSIFICATION; PROGNOSIS; SURVIVAL AB Purpose: To analyze long-term outcomes and causes of death in patients receiving radiation therapy (RT) for localized, low-grade follicular lymphoma. Methods and Materials: Between 1972 and 2000, 106 patients with Stage I-II, Grade 1-2 follicular lymphoma received RT alone or radiation and chemotherapy (RT/CT). Seventy-four percent had Stage I, and 26% had Stage II disease. Seventy-six percent received RT alone, and 24% received combined RT/CT. Second malignancy rates were compared with an age- and sex-matched population. Results: Median follow-up was 12 years. Median survival time was 19 years. The 5-, 10-, and 15-year overall survival (OS) rates were 93%, 75%, and 62%, respectively. Age >= 60 was the only significant adverse prognostic factor with respect to OS. There were 35 deaths, 20 of which were attributable to lymphoma. Freedom from treatment failure (FFTF) rates at 5, 10, and 15 years were 72%, 46%, and 39%, respectively. Forty-seven patients (48%) relapsed. Tumor size >3 cm was the only significant adverse factor for FFTF. Observed incidence of second malignancy did not significantly exceed expected incidence. Conclusions: Although patients with early-stage, low-grade follicular lymphoma have long median survival, the leading cause of death remains lymphoma. However, patients receiving RT do not have significantly elevated cumulative incidence of second malignancy. (C) 2006 Elsevier Inc. C1 Harvard Radiat Oncol Residency Program, Joint Ctr Radiat Therapy, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Guadagnolo, BA (reprint author), Dept Radiat Oncol, 375 Longwood Ave, Boston, MA 02215 USA. EM aguadagnolo@lroc.harvard.edu NR 32 TC 67 Z9 69 U1 1 U2 6 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 MAR 1 PY 2006 VL 64 IS 3 BP 928 EP 934 DI 10.1016/j.ijrobp.2005.08.010 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 014KH UT WOS:000235478200038 PM 16243446 ER PT J AU Blanchfield, BB Grant, RW Estey, GA Chueh, HC Gazelle, GS Meigs, JB AF Blanchfield, BB Grant, RW Estey, GA Chueh, HC Gazelle, GS Meigs, JB TI Cost of an informatics-based diabetes management program SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE costs; disease management; quality ID POPULATION MANAGEMENT; CHRONIC ILLNESS; CARE; ADULTS; US; DISEASE AB Objectives: The relatively high cost of information technology systems may be a barrier to hospitals thinking of adopting this technology. The experiences of early adopters may facilitate decision making for hospitals less able to risk their limited resources. This study identifies the costs to design, develop, implement, and operate an innovative informatics-based registry and disease management system (POPMAN) to manage type 2 diabetes in a primary care setting. Methods: The various cost components of POPMAN were systematically identified and collected. Results: POPMAN cost $450,000 to develop and operate over 3.5 years (1999-2003). Approximately $250,000 of these costs are one-time expenditures or sunk costs. Annual operating costs are expected to range from $90,000 to $110,000 translating to approximately $90 per patient for a 1,200 patient registry. Conclusions: The cost of POPMAN is comparable to the costs of other quality-improving interventions for patients with diabetes. Modifications to POPMAN for adaptation to other chronic diseases or to interface with new electronic medical record systems will require additional investment but should not be as high as initial development costs. POPMAN provides a means of tracking progress against negotiated quality targets, allowing hospitals to negotiate pay for performance incentives with insurers that may exceed the annual operating cost of POPMAN. As a result, the quality of care of patients with diabetes through use of POPMAN could be improved at a minimal net cost to hospitals. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Blanchfield, BB (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10 Floor, Boston, MA 02114 USA. EM bblanchfield@partners.org; rgrant@partners.org; getsey@partners.org; hchueh@partners.org; scott@mgh-ita.org; jmeigs@partners.org OI Grant, Richard/0000-0002-6164-8025 NR 20 TC 2 Z9 2 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD SPR PY 2006 VL 22 IS 2 BP 249 EP 254 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 033ZN UT WOS:000236893700014 PM 16571201 ER PT J AU Oh, DJ Martin, JL Williams, AJ Peck, RE Pokorny, C Russell, P Birk, DE Rhee, DJ AF Oh, DJ Martin, JL Williams, AJ Peck, RE Pokorny, C Russell, P Birk, DE Rhee, DJ TI Analysis of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human ciliary body after latanoprost SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; SMOOTH-MUSCLE-CELLS; AQUEOUS-HUMOR DYNAMICS; CYNOMOLGUS MONKEY EYES; HUMAN FETAL MEMBRANES; CULTURED HUMAN-CELLS; INTRAOCULAR-PRESSURE; EXTRACELLULAR-MATRIX; OCULAR HYPERTENSION; UVEOSCLERAL OUTFLOW AB PURPOSE. To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the ciliary body. METHODS. Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human ciliary body tissue and explant cultures of ciliary body smooth muscle (CBSM) cells. CBSM cell cultures were treated with vehicle control or latanoprost acid for 24 hours. Quantitative RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS. The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 as well as TIMP-1 to -4 were found in ciliary body tissue and CBSM cells. MMP-9 was present after latanoprost treatment. In control CBSM cells, the relative expression of MMP mRNA was MMP-2 and -14 > MMP-24 > NIMP-1, -11, -15, -16, and -19 > MMP-3 and 17, > MMP-12. The relative expression of TIMP mRNA was TIMP-2 > TIMP- 1 > TIMP-3 > TIMP-4 Latanoprost increased MMP-3 (in three of five cultures) MMP-17 (in four of five cultures), and TIMP-3 (in all five cultures); MNIP-1, -2, -12, -14, -15, and -16 and TIMP-4 were downregulated. CONCLUSIONS. The transcription of the genes for MMP-3 and -17 is increased by latanoprost treatment. MMP-9 is present after latanoprost treatment and may also mediate ECM changes. TIMP-3 is upregulated and may compensate for the increase in MMPs. These coordinated changes could be expected to mediate the latanoprost-induced alteration of ECM in the ciliary body. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Wills Eye Hosp & Res Inst, Lab Mol Ophthalmol, Philadelphia, PA 19107 USA. NEI, Sect Aging & Ocular Dis, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com RI Birk, David/I-4072-2012 OI Birk, David/0000-0002-4865-9088 FU NEI NIH HHS [EY 13997] NR 80 TC 24 Z9 28 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2006 VL 47 IS 3 BP 953 EP 963 DI 10.1167/iovs.05-0516 PG 11 WC Ophthalmology SC Ophthalmology GA 020FR UT WOS:000235894300027 PM 16505029 ER PT J AU Koktzoglou, I Harris, KR Tang, R Kane, BJ Misselwitz, B Weinmann, HJ Lu, B Nagaraj, A Roth, SI Carroll, TJ McPherson, DD Li, DB AF Koktzoglou, I Harris, KR Tang, R Kane, BJ Misselwitz, B Weinmann, HJ Lu, B Nagaraj, A Roth, SI Carroll, TJ McPherson, DD Li, DB TI Gadofluorine-enhanced magnetic resonance imaging of carotid atherosclerosis in Yucatan miniswine SO INVESTIGATIVE RADIOLOGY LA English DT Article DE magnetic resonance imaging; vessel wall imaging; atherosclerosis; contrast agents; gadofluorine ID IN-VIVO; COMPENSATORY ENLARGEMENT; CORONARY-ARTERIES; ANIMAL-MODEL; PLAQUE; LESIONS; RABBITS; SWINE; WALL AB Objective: The aim. of this study was to determine whether gadofluorine, a paramagnetic magnetic resonance imaging (MRI) contrast agent, selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. Methods: Atherosclerotic plaques were induced in the left carotid arteries (LCA) of Yucatan miniswine (n = 3) by balloon denudation and high cholesterol diet. T1-weighted MRI was performed before and 24 hours after gadofluorine injection (at a dose of 100 mu mol/kg) to assess the enhancement of the balloon-injured LCA wall relative to healthy, uninjured right carotid artery (RCA) wall. Histopathology was performed to verify the presence and composition of the atherosclerotic plaques imaged with MRI. Results: Gadofluorine was found to enhance LCA atherosclerotic lesions relative to RCA wall by 21% (P < 0.025) 24 hours after contrast injection. Enhancement of healthy LCA wall relative to healthy RCA wall was not observed. Conclusion: Gadofluorine selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. Gadofluorine appears to be a promising MR contrast agent for detection of atherosclerotic plaques in vivo. C1 Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. Northwestern Univ, Dept Med, Chicago, IL 60611 USA. Schering AG, D-1000 Berlin, Germany. Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Koktzoglou, I (reprint author), Northwestern Univ, Dept Radiol, 448 E Ontario St,Suite 700, Chicago, IL 60611 USA. EM i-koktzoglou@northwestern.edu RI Carroll, Timothy/B-6934-2009; Li, Debiao/B-7622-2009 NR 28 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD MAR PY 2006 VL 41 IS 3 BP 299 EP 304 DI 10.1097/01.rli.0000188362.12555.62 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 016PR UT WOS:000235632800013 PM 16481913 ER PT J AU Fraguas, R Henriques, SG De Lucia, MS Iosifescu, DV Schwartz, FH Menezes, PR Gattaz, WF Martins, MA AF Fraguas, R Henriques, SG De Lucia, MS Iosifescu, DV Schwartz, FH Menezes, PR Gattaz, WF Martins, MA TI The detection of depression in medical setting: A study with PRIME-MD SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE subsyndromal; depression; primary care; diagnosis; absenteeism; screening ID PRIMARY-CARE PATIENTS; QUALITY-OF-LIFE; MENTAL-DISORDERS; SUBSYNDROMAL DEPRESSION; GENERAL-PRACTITIONERS; MAJOR DEPRESSION; SYMPTOMS; PREVALENCE; POPULATION; INVENTORY AB Background: Studies investigating the performance of instruments to detect major depressive disorder (MDD) have reported inconsistent results. Subsyndromal depression (SD) has also been associated to increased morbidity, and little is known about its detection in primary care setting. This study aimed to investigate the performance of the Primary Care Evaluation of Mental Disorders (PRIME-MD) to detect MDD and any depression (threshold at SD) in an outpatient unit of a teaching general hospital. Methods: Nineteen primary care physicians using the PRIME-MD evaluated 577 patients, 240 of them (75% female; mean age, 40.0 +/- 14.4), including all with MDD and a randomly subset of those without MDD, were evaluated by 11 psychiatrists using the Structured Clinical Interview Axis I Disorders, Patient Version (SCIDI/P) for DSM-IV as the standard instrument. Results: The kappa between the PRIME-MD and the SCID was 0.42 for the diagnosis of any depression and 0.32 for MDD. The distribution of the number of depressive symptoms per patient suggested the existence of a continuum between SD and MDD, and a high frequency of subjects with 4-6 symptoms (close to the cutoff for the diagnosis of MDD). Limitations: The sample has a modest size and is a subset of an original one. Conclusion: A continuum between SD and MDD may in part explain the relatively low agreement for the diagnosis of MDD in our sample and possibly in other studies. Studies investigating the performance of screening instruments to detect MDD, should consider the relevance of identifying SD, and the influence of the distribution of the number of depressive symptoms in their results. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, BR-05508 Sao Paulo, Brazil. Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Cambridge, MA 02138 USA. Univ Sao Paulo, Fac Med, Hosp Clin, Cent Inst,Div Psychol, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Dept Prevent Med, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Dept Gen Med, BR-05508 Sao Paulo, Brazil. RP Fraguas, R (reprint author), Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, BR-05508 Sao Paulo, Brazil. EM rfraguas@partners.org RI Menezes, Paulo/C-9985-2010; Martins, Milton/D-6658-2012; Gattaz, Wagner/C-4456-2012 OI Menezes, Paulo/0000-0001-6330-3314; NR 30 TC 34 Z9 37 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 2006 VL 91 IS 1 BP 11 EP 17 DI 10.1016/j.jad.2005.12.003 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 023VN UT WOS:000236154400002 PM 16427132 ER PT J AU Caetano, SC Olvera, RL Hunter, K Hatch, JP Najt, P Bowden, C Pliszka, S Soares, JC AF Caetano, SC Olvera, RL Hunter, K Hatch, JP Najt, P Bowden, C Pliszka, S Soares, JC TI Association of psychosis with suicidality in pediatric bipolar I, II and bipolar NOS patients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat DE bipolar disorder; psychosis; suicide; children; adolescents; hospitalization ID DISORDER; CHILDREN; ADOLESCENTS; MANIA; RISK; ONSET; MOOD; PHENOMENOLOGY; RECOVERY; BEHAVIOR AB Background: Psychosis in pediatric mood disorder patients may be related to suicidal ideation. Bipolar (BP) adolescents are at high risk of completed suicide. We examined whether pediatric BP patients with psychosis have a higher prevalence of suicidality than non-psychotic BP patients. Based on previous findings in adult BP patients, we predicted that pediatric BP patients with psychotic symptoms would have higher prevalence of suicidality, higher occurrence of lifetime psychiatric hospitalizations and worse current Global Assessment of Functioning Scale (GAF) scores compared to non-psychotic BP patients. Methods: We studied 43 BP children and adolescents (mean age +/- S.D=11.2 +/- 2.8 y, range=8-17) who did (n=17) or did not have (n=26) a lifetime history of psychotic symptoms. Indicators of suicidality (thoughts of death and Suicidal ideation, plans, and attempts), psychiatric diagnoses, psychotic symptoms, psychiatric hospitalizations and GAF scores were assessed with the KSADS-PL interview. Limitations: Small sample size, cross-sectional study and exclusion of substance abuse comorbidity. Results: Pediatric BP patients with a lifetime history of psychotic symptoms compared to BP patients without psychosis were more likely to have thoughts of death (100% versus 69.2%, p=0.01), suicidal ideation (94.1% versus 42.3%, p=0.001) and suicidal plans (64.7% versus 15.4%, p=0.002). Occurrence of psychiatric hospitalization was higher in psychotic BP patients compared to non-psychotic BP patients (82.4%, versus 46.2%, p=0.018). Conclusions: Psychotic symptoms in pediatric BP patients are associated with suicidal ideation and plans, and psychiatric hospitalizations. Psychotic symptoms are a risk factor for suicidality amongst pediatric BP patients. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr San Antonio, Div Mood & Anxiety Disorders, Dept Psychiat, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Dept Psychiat, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr San Antonio, Div Mood & Anxiety Disorders, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 FU NCRR NIH HHS [M01-RR-01346, RR020571]; NIMH NIH HHS [MH01736, MH69774] NR 24 TC 24 Z9 27 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 2006 VL 91 IS 1 BP 33 EP 37 DI 10.1016/j.jad.2005.12.008 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 023VN UT WOS:000236154400005 PM 16445989 ER PT J AU Warden, D Rush, AJ Fava, M Trivedi, MH Wisniewski, SR Nierenberg, A Hollon, SD Howland, R Zisook, S Stewart, JW Gaynes, RN AF Warden, D Rush, AJ Fava, M Trivedi, MH Wisniewski, SR Nierenberg, A Hollon, SD Howland, R Zisook, S Stewart, JW Gaynes, RN TI Treatment for depression: A sequenced treatment alternatives to relieve depression report SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Meeting Abstract C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. Hlth Univ Pittsburgh, Grad Sch Publ, Epidemiol Data Ctr, Pittsburgh, PA USA. Vanderbilt Univ, Med Ctr, Dept Psychol, Nashville, TN USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. EM diane.warden@utsouthwestern.edu RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 2006 VL 91 SU 1 BP S70 EP S71 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 025VR UT WOS:000236295600105 ER PT J AU Nurnberg, HG Fava, M Gelenberg, AJ Hensley, PL AF Nurnberg, HG Fava, M Gelenberg, AJ Hensley, PL TI Sildenafil salvage of partial- and nonresponders to double blind sildenafil or placebo treatment of serotonergic antidepressant-associated sexual dysfunction: Quantifying non-specific (placebo) treatment effects SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-of-Andrology CY APR 08-11, 2006 CL Chicago, IL SP Amer Soc Androl C1 Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ Arizona, Coll Med, Dept Psychiat, Tucson, AZ USA. Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR-APR PY 2006 SU S MA 127 BP 91 EP 91 PG 1 WC Andrology SC Endocrinology & Metabolism GA 017IV UT WOS:000235688200129 ER PT J AU Wen, Y Feng, J Scott, DR Marcus, EA Sachs, G AF Wen, Y Feng, J Scott, DR Marcus, EA Sachs, G TI Involvement of the HP0165-HP0166 two-component system in expression of some acidic-pH-upregulated genes of Helicobacter pylori SO JOURNAL OF BACTERIOLOGY LA English DT Article ID UREASE-NEGATIVE MUTANT; GASTRIC SURFACE PH; ESCHERICHIA-COLI; ALLELIC EXCHANGE; PEPTIC-ULCER; COLONIZATION; RESISTANCE; UREI; DISEASE; HYDROGENASE AB About 200 genes of the gastric pathogen Helicobacter pylori increase expression at medium pHs of 6.2, 5.5, and 4.5, an increase that is abolished or much reduced by the buffering action of urease. Genes up-regulated by a low pH include the two-component system HP0165-HP0166, suggesting a role in the regulation of some of the pH-sensitive genes. To identify targets of HP0165-HP0166, the promoter regions of genes up-regulated by a low pH were grouped based on sequence similarity. Probes for promoter sequences representing each group were subjected to electrophoretic mobility shift assays (EMSA) with recombinant HP0166-His(6) or a mutated response regulator, HP0166-D52N-HiS(6), that can specifically determine the role of phosphorylation of HP0166 in binding (including a control EMSA with in-vitro-phosphorylated HP0166-His(6)). Nineteen of 45 promoter-regulatory regions were found to interact with HP0166-His(6). Seven promoters for genes encoding alpha-carbonic anhydrase, omp11,fecD, lpp20, hypA, and two with unknown function (pHP1397-1396 and pHP0654-0675) were clustered in gene group A, which may respond to changes in the periplasmic pH at a constant cytoplasmic pH and showed phosphorylation-dependent binding in EMSA with HP0166-D52N-HiS6. Twelve promoters were clustered in groups B and C whose up-regulation likely also depends on a reduction of the cytoplasmic pH at a medium pH of 5.5 or 4.5. Most of the target promoters in groups B and C showed phosphorylation-dependent binding with HP0166-D52N-HiS6, but promoters for ompR (pHP0166-0162), pHP0682-0681, and pHP1288-1289 showed phosphorylation-independent binding. These findings, combined with DNase I footprinting, suggest that HP0165-0166 is an acid-responsive signaling system affecting the expression of pH-sensitive genes. Regulation of these genes responds either to a decrease in the periplasmic pH alone (HP0165 dependent) or also to a decrease in the cytoplasmic pH (HP0165 independent). C1 Univ Calif Los Angeles, Membrane Biol Lab, Dept Physiol, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Wen, Y (reprint author), 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM ywen@ucla.edu FU NIDDK NIH HHS [DK46917, DK53462, DK58333, R01 DK046917] NR 45 TC 29 Z9 33 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2006 VL 188 IS 5 BP 1750 EP 1761 DI 10.1128/JB.188.5.1750-1761.2006 PG 12 WC Microbiology SC Microbiology GA 019EU UT WOS:000235819200009 PM 16484186 ER PT J AU Olatunji, B McKay, D AF Olatunji, B McKay, D TI Introduction to the special series: Disgust sensitivity in anxiety disorders SO JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Fordham Univ, Bronx, NY 10458 USA. RP Olatunji, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, WAC 812,15 Parkman St, Boston, MA 02114 USA. EM bolatunji@partners.org NR 11 TC 6 Z9 6 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7916 J9 J BEHAV THER EXP PSY JI J. Behav. Ther. Exp. Psychiatry PD MAR PY 2006 VL 37 IS 1 BP 1 EP 3 DI 10.1016/j.jbtep.2005.09.006 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 003MI UT WOS:000234685900001 ER PT J AU Olatunji, BO Sawchuk, CN de Jong, PJ Lohr, JM AF Olatunji, BO Sawchuk, CN de Jong, PJ Lohr, JM TI The structural relation between disgust sensitivity and blood-injection-injury fears: A cross-cultural comparison of US and Dutch data SO JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY LA English DT Article DE disgust; blood-injection-injury; cross-cultural; core; animal reminder; fear ID SPIDER PHOBIA; INDIVIDUAL-DIFFERENCES; SYMPTOMS; EXPOSURE; LIKELIHOOD; AVOIDANCE; STIMULI; DOMAINS; IMAGERY; GENDER AB A growing body of literature has implicated the role of disgust sensitivity in blood-injection-injury (BII) phobia. The present study sought to extend this line of research by investigating the structural relation between Rozin et al.'s [(2000). Disgust. In M. Lewis, J.M. Haviland (Eds.), Handbook of emotions. New York: Guilford Publications.] theoretical model of core and animal reminder disgust as they relate to BII fears in US (N = 162) and Dutch (N = 260) samples. Using confirmatory factor analysis (CFA), the hypothesized relation between the theoretical model of disgust and BII fears demonstrated good model fit in both samples. Consistent with previous findings on the differential relation between core and animal reminder disgust and BII fears [de Jong, P. J., & Merckelbach H. (1998). Blood-injection-injury phobia and fear of spiders: Domain specific individual differences in disgust sensitivity. Personality and Individual Differences, 24, 153-158], structural equation modeling (SEM) provided support for a domain specific relationship in both samples: animal reminder disgust was specifically related. to the BII latent factor, whereas core disgust was not. The clinical and research implications regarding the relationships between disgust and 1311 fears across cultures are discussed. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Groningen, Groningen, Netherlands. Univ Arkansas, Fayetteville, AR 72701 USA. RP Olatunji, BO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM bolatunji@partners.org RI de Jong, Peter/E-9095-2014 OI de Jong, Peter/0000-0002-3512-3663 FU NIMH NIH HHS [1F31MH067519-1A1] NR 54 TC 34 Z9 34 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7916 J9 J BEHAV THER EXP PSY JI J. Behav. Ther. Exp. Psychiatry PD MAR PY 2006 VL 37 IS 1 BP 16 EP 29 DI 10.1016/j.jbtep.2005.09.002 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 003MI UT WOS:000234685900003 PM 16274661 ER PT J AU Chang, SK Marin, N Follen, M Richards-Kortum, R AF Chang, SK Marin, N Follen, M Richards-Kortum, R TI Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescence spectroscopy; diagnosis; cervical cancer ID SPATIALLY-RESOLVED FLUORESCENCE; OPTIMAL EXCITATION WAVELENGTHS; LIGHT-SCATTERING; INTRINSIC FLUORESCENCE; EPITHELIAL TISSUE; AUTOFLUORESCENCE SPECTROSCOPY; OPTICAL SPECTROSCOPY; CONFOCAL MICROSCOPY; TURBID MEDIA; NEOPLASIA AB We present a mathematical model to calculate the relative concentration of light scatterers, light absorbers, and fluorophores in the epithelium and stroma. This mathematical description is iteratively fit to the fluorescence spectra measured in vivo, yielding relative concentrations of each molecule. The mathematical model is applied to a total of 493 fluorescence measurements of normal and dysplastic cervical tissue acquired in vivo from 292 patients. The estimated parameters are compared with histopathologic diagnosis to evaluate their diagnostic potential. The mathematical model is validated using fluorescence spectra simulated with known sets of optical parameters. Subsequent application of the mathematical model to in vivo fluorescence measurements from cervical tissue yields fits that accurately describe measured data. The optical parameters estimated from 493 fluorescence measurements show an increase in epithelial flavin adenine dinucleotide (FAD) fluorescence, a decrease in epithelial keratin fluorescence, an increase in epithelial light scattering, a decrease in stromal collagen fluorescence, and an increase in stromal hemoglobin light absorption in dysplastic tissue compared to normal tissue. These changes likely reflect an increase in the metabolic activity and loss of differentiation of epithelial dysplastic cells, and stromal angiogenesis associated with dysplasia. The model presented here provides a tool to analyze clinical fluorescence spectra yielding quantitative information about molecular changes related to dysplastic transformation. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Rice Univ, Dept Bioengn, Houston, TX 77005 USA. Massachusetts Gen Hosp, Wellman Canc Photomed, Boston, MA 02114 USA. Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. Baylor Univ, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. RP Richards-Kortum, R (reprint author), Rice Univ, Dept Bioengn, 6100 Main St, Houston, TX 77005 USA. EM rkortum@rice.edu RI Richards-Kortum, Rebecca/P-4074-2014 OI Richards-Kortum, Rebecca/0000-0003-2347-9467 FU NCI NIH HHS [P01 CA82710] NR 42 TC 42 Z9 42 U1 0 U2 4 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2006 VL 11 IS 2 AR 024008 DI 10.1117/1.2187979 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 043SY UT WOS:000237623100027 PM 16674198 ER PT J AU Marcu, L Tearney, GJ Gregory, KW AF Marcu, L Tearney, GJ Gregory, KW TI Cardiovascular photonics SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Editorial Material C1 Univ Calif Davis, Davis, CA 95616 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Marcu, L (reprint author), Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2006 VL 11 IS 2 AR 021001 DI 10.1117/1.2191508 PG 1 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 043SY UT WOS:000237623100005 ER PT J AU Motz, JT Fitzmaurice, M Miller, A Gandhi, SJ Haka, AS Galindo, LH Dasari, RR Kramer, JR Feld, MS AF Motz, JT Fitzmaurice, M Miller, A Gandhi, SJ Haka, AS Galindo, LH Dasari, RR Kramer, JR Feld, MS TI In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Raman spectroscopy; in vivo diagnosis; vulnerable plaque; Raman probe; atherosclerosis ID HUMAN CORONARY ATHEROSCLEROSIS; HUMAN SKIN; SPECTROSCOPY; DISEASE; LESIONS; TISSUE; PROBE AB The rupture of vulnerable atherosclerotic plaque accounts for the majority of clinically significant acute cardiovascular events. Because stability of these culprit lesions is directly related to chemical and morphological composition, Raman spectroscopy may be a useful technique for their study. Recent developments in optical fiber probe technology have allowed for the real-time in vivo Raman spectroscopic characterization of human atherosclerotic plaque demonstrated in this work. We spectroscopically examine 74 sites during carotid endarterectomy and femoral artery bypass surgeries. Of these, 34 are surgically biopsied and examined histologically. Excellent signal-to-noise ratio spectra are obtained in only 1 s and fit with an established model, demonstrating accurate tissue characterization. We also report the first evidence that Raman spectroscopy has the potential to identify vulnerable plaque, achieving a sensitivity and specificity of 79 and 85%, respectively. These initial findings indicate that Raman spectroscopy has the potential to be a clinically relevant diagnostic tool for studying cardiovascular disease. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Wellman Ctr Photomed, Boston, MA 02140 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Metro W Med Ctr, Natick, MA 01760 USA. MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. RP Motz, JT (reprint author), Wellman Ctr Photomed, 55 Fruit St,BAR704, Boston, MA 02140 USA. EM jmotz@partners.org FU NCRR NIH HHS [P41-RR-02594]; NHLBI NIH HHS [R01-HL-64675] NR 31 TC 91 Z9 91 U1 0 U2 6 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2006 VL 11 IS 2 AR 021003 DI 10.1117/1.2190967 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 043SY UT WOS:000237623100007 PM 16674178 ER PT J AU Nadkarni, SK Bilenca, A Bouma, BE Tearney, GJ AF Nadkarni, Seemantini K. Bilenca, Alberto Bouma, Brett E. Tearney, Guillermo J. TI Measurement of fibrous cap thickness in atherosclerotic plaques by spatiotemporal analysis of laser speckle images SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE atherosclerosis; fibrous cap; diffusion; laser speckle ID HIGHLY SCATTERING TISSUES; INTRAVASCULAR ULTRASOUND; LIGHT-PROPAGATION; DIFFUSION-THEORY; CORONARY; STABILIZATION; MECHANISMS; VISUALIZATION; ATHEROMA; RUPTURE AB Necrotic-core fibroatheromas (NCFA) with thin, mechanically weak fibrous caps overlying lipid cores comprise the majority of plaques that rupture and cause acute myocardial infarction. Laser speckle imaging (LSI) has been recently demonstrated to enable atherosclerotic plaque characterization with high accuracy. We investigate spatio-temporal analysis of LSI data, in conjunction with diffusion theory and Monte Carlo modeling of light transport, to estimate fibrous cap thickness in NCFAs. Time-varying laser speckle images of 20 NCFAs are selected for analysis. Spatio-temporal intensity fluctuations are analyzed by exponential fitting of the windowed normalized cross-correlation of sequential laser speckle patterns to obtain the speckle decorrelation time constant, tau(rho), as a function of distance rho from the source entry location. The distance, rho', at which tau(rho) dropped to 65% of its maximum value is recorded. Diffusion theory and Monte Carlo models are utilized to estimate the maximum photon penetration depth, Z(max) (rho'), for a distance equal to rho', measured from LSI. Measurements of Z(max) (rho') correlate well with histological measurements of fibrous cap thickness (R = 0.78, p < 0.0001), and paired t-tests show no significant difference between the groups (p = 0.4). These results demonstrate that spatio-temporal LSI may allow the estimation of fibrous cap thickness in NCFAs, which is an important predictor of plaque stability. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Pathol, Boston, MA 02114 USA. RP Nadkarni, SK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM snadkarni@hms.harvard.edu FU NHLBI NIH HHS [R01 HL070039, R01 HL076398, R01 HL076398-01, R01-HL70039] NR 25 TC 18 Z9 18 U1 0 U2 7 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2006 VL 11 IS 2 AR 021006 DI 10.1117/1.2186046 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 043SY UT WOS:000237623100010 PM 16674181 ER PT J AU Pande, AN Kohler, RH Aikawa, E Weissleder, R Jaffer, FA AF Pande, AN Kohler, RH Aikawa, E Weissleder, R Jaffer, FA TI Detection of macrophage activity in atherosclerosis in vivo using multichannel, high-resolution laser scanning fluorescence microscopy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE atherosclerosis; near-infrared fluorescence; imaging; laser scanning microscopy; macrophage; nanoparticle ID OPTICAL COHERENCE TOMOGRAPHY; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; OXIDE-ENHANCED MRI; IRON-OXIDE; HYPERLIPIDEMIC RABBITS; APOLIPOPROTEIN-E; PLAQUES; NANOPARTICLES; INFLAMMATION; ENDOCYTOSIS AB Molecular and cellular mechanisms of atherogenesis and its treatment are largely being unraveled by in vitro techniques. We describe methodology to directly image macrophage cell activity in vivo in a murine model of atherosclerosis using laser scanning fluorescence microscopy (LSFM) and a macrophage-targeted, near-infrared fluorescent (NIRF) magnetofluorescent nanoparticle (MFNP). Atherosclerotic apolipoprotein E deficient (apoE(-/-)) mice (n = 10) are injected with MFNP or 0.9% saline, and wild-type mice (n = 4) are injected with MFNP as additional controls. After 24 h, common carotid arteries are surgically exposed and prepared for LSFM. Multichannel LSFM of MFNP-enhanced carotid atheroma (5 X 5-mu m inplane resolution) shows a strong focal NIRF signal, with a plaque target-to-background ratio of 3.9 +/- 1.8. Minimal NIRF signal is observed in control mice. Spectrally resolved indocyanine green (ICG) fluorescence angiograms confirm the intravascular location of atheroma. On ex vivo fluorescence reflectance imaging, greater NIRF plaque signal is seen in apoE(-/-) MFNP mice compared to controls (p < 0.01). The NIRF signal correlates well with immunostained macrophages, both by stained surface area (r = 0.77) and macrophage number (r = 0.86). The validated experimental methodology thus establishes a platform for investigating macrophage activity in atherosclerosis in vivo, and has implications for the detection of clinical vulnerable plaques. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Donald Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Jaffer, FA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, MGH-CMIR-149 13th St,Rm 5407, Charlestown, MA 02129 USA. EM fjaffer@partners.org OI Jaffer, Farouc/0000-0001-7980-384X FU NCI NIH HHS [P50-CA86355, R24-CA92782] NR 28 TC 35 Z9 35 U1 1 U2 8 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2006 VL 11 IS 2 AR 021009 DI 10.1117/1.2186337 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 043SY UT WOS:000237623100013 PM 16674184 ER PT J AU Scepanovic, OR Fitzmaurice, M Gardecki, JA Angheloiu, GO Awasthi, S Motz, JT Kramer, JR Dasari, RR Feld, MS AF Scepanovic, OR Fitzmaurice, M Gardecki, JA Angheloiu, GO Awasthi, S Motz, JT Kramer, JR Dasari, RR Feld, MS TI Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE atherosclerosis; vulnerable plaque; morphology; spectroscopy; multimodal ID LASER-INDUCED FLUORESCENCE; HUMAN CORONARY ATHEROSCLEROSIS; THIN FIBROUS CAP; RAMAN-SPECTROSCOPY; IN-VIVO; TURBID MEDIA; HUMAN AORTA; DIAGNOSIS; TISSUE; MODEL AB Vulnerable plaques, which are responsible for most acute ischemic events, are presently invisible to x-ray angiography. Their primary morphological features include a thin or ulcerated fibrous cap, a large necrotic core, superficial foam cells, and intraplaque hemorrhage. We present evidence that multimodal spectroscopy (MMS), a novel method that combines diffuse reflectance spectroscopy (DRS), intrinsic fluorescence spectroscopy (IFS), and Raman spectroscopy (RS), can detect these markers of plaque vulnerability. To test this concept, we perform an MMS feasibility study on 17 human carotid artery specimens. Following the acquisition of spectra, each specimen is histologically evaluated. Two parameters from DRS, hemoglobin concentration and a scattering parameter, are used to detect intraplaque hemorrhage and foam cells; an IFS parameter that relates to the amount of collagen in the topmost layers of the tissue is used to detect the presence of a thin fibrous cap; and an RS parameter related to the amount of cholesterol and necrotic material is used to detect necrotic core. Taken together, these spectral parameters can generally identify the vulnerable plaques. The results indicate that MMS provides depth-sensitive and complementary morphological information about plaque composition. A prospective in vivo study will be conducted to validate these findings. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 MIT, GR Harrison Spect Lab, Cambridge, MA 02139 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Scepanovic, OR (reprint author), MIT, GR Harrison Spect Lab, 77 Massachusetts Ave,Room NW14-1106, Cambridge, MA 02139 USA. EM obrad@mit.edu OI Awasthi, Samir/0000-0001-8392-0205 FU NCRR NIH HHS [P41-RR-02594]; NHLBI NIH HHS [R01-HL-64675] NR 48 TC 19 Z9 19 U1 0 U2 2 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2006 VL 11 IS 2 AR 021007 DI 10.1117/1.2187943 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 043SY UT WOS:000237623100011 PM 16674182 ER PT J AU Tawakol, A Castano, AP Anatelli, F Bashian, G Stern, J Zahra, T Gad, F Chirico, S Ahmadi, A Fischman, AJ Muller, JE Hamblin, MR AF Tawakol, A Castano, AP Anatelli, F Bashian, G Stern, J Zahra, T Gad, F Chirico, S Ahmadi, A Fischman, AJ Muller, JE Hamblin, MR TI Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorine(e6) SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE atherosclerosis; intravascular fluorimetry; photodynamic therapy; fluorescence; biodistribution; macrophage; scavenger receptor; chlorin(e6); vulnerable plaque ID OPTICAL COHERENCE TOMOGRAPHY; FOAM CELL-FORMATION; PHOTODYNAMIC THERAPY; SCAVENGER RECEPTORS; SIGNALING PATHWAYS; RABBITS; EXPRESSION; MORPHOLOGY; DIAGNOSIS; LIGANDS AB We have previously shown that a conjugate (MA-ce6) between maleylated serum albumin and the photosensitizer chlorin(e6) (ce6) is targeted in vitro to macrophages via class A scavenger receptors. We now report on the ability of this conjugate to localize in macrophage-rich atherosclerotic plaques in vivo. Both the conjugate and the free photosensitizer ce6 are studied after injection into New Zealand White rabbits that are rendered atherosclerotic by a combination of aortic endothelial injury and cholesterol feeding into normal rabbits. Rabbits are sacrificed at 6 and 24 h after injection and intravascular fluorescence spectroscopy is carried out by fiber-based fluorimetry in intact blood-filled arteries. Surface spectrofluorimetry of numbered excised aortic segments together with injured and normal iliac arteries is carried out, and quantified ce6 content by subsequent extraction and quantitative fluorescence determination of the arterial segments and also of nontarget organs. There is good agreement between the various techniques for quantifying ce6 localization, and high contrast between arteries from atherosclerotic and normal rabbits is obtained. Fluorescence correlates with the highest burden of plaque in the aorta and the injured iliac artery. The highest accumulation in plaques is obtained using MA-ce6 at 24 h. Free ce6 gives better accumulation at 6 h compared to 24 h. The liver, spleen, lung, and gall bladder have the highest uptake in nontarget organs. Macrophage-targeted photosensitizer conjugates may have applications in both detecting and treating inflamed vulnerable plaque. c 2006 Society of Photo-Optical Instrumentation Engineers. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol & Nucl Med, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu FU NCI NIH HHS [P01 CA084203, P01 CA084203-029002, P01CA84203]; NCRR NIH HHS [K23 RR016046, RR16046]; NIAID NIH HHS [CA/AI838801] NR 40 TC 9 Z9 10 U1 1 U2 7 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2006 VL 11 IS 2 AR 021008 DI 10.1117/1.2186039 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 043SY UT WOS:000237623100012 PM 16674183 ER PT J AU Tearney, GJ Jang, IK Bouma, BE AF Tearney, GJ Jang, IK Bouma, BE TI Optical coherence tomography for imaging the vulnerable plaque SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE medical imaging; coherence ID CORONARY-ARTERY-DISEASE; INDUCED FLUORESCENCE SPECTROSCOPY; HUMAN ATHEROSCLEROTIC PLAQUES; BEAM COMPUTED-TOMOGRAPHY; INTRAVASCULAR ULTRASOUND; IN-VIVO; LEFT MAIN; RUPTURE; THROMBOSIS; MACROPHAGE AB While our understanding of vulnerable coronary plaque is still at an early stage, the concept that certain types of plaques predispose patients to developing an acute myocardial infarction continues to be at the forefront of cardiology research. Intracoronary optical coherence tomography (OCT) has been developed to both identify and study these lesions due to its distinct resolution advantage over other imaging modalities. We review clinical research conducted at the Massachusetts General Hospital over the past five years to develop, validate, and utilize this technology to improve our understanding of vulnerable plaque. Our results show that intracoronary OCT may be safely conducted in patients and that it provides abundant information regarding plaque microscopic morphology, which is essential to the identification and study of high-risk lesions. Even though many basic biological, clinical, and technological challenges must be addressed prior to widespread use of this technology, the unique capabilities of OCT ensure that it will have a prominent role in shaping the future of cardiology. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Pathol, 50 Blossom St,BAR703, Boston, MA 02114 USA. EM gtearney@partners.org FU NHLBI NIH HHS [R01 HL076398-02, R01-HL76398, R01-HL70039, R01 HL070039, R01 HL070039-02, R01 HL076398] NR 91 TC 93 Z9 97 U1 0 U2 8 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2006 VL 11 IS 2 AR 021002 DI 10.1117/1.2192697 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 043SY UT WOS:000237623100006 PM 16674177 ER PT J AU Hendricks, KJ Harris, WH AF Hendricks, KJ Harris, WH TI Revision of failed acetabular components with use of so-called jumbo noncemented components - A concise follow-up of a previous report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL HIP-ARTHROPLASTY; CUPS; RECONSTRUCTION; REPLACEMENT; GRAFT AB Acetabular revision in the presence of major bone-stock deficiency is a difficult clinical and surgical problem. Of an original pool of twenty-four consecutive patients treated with an acetabular revision with a so-called jumbo (> 65-mm) cementless hemispherical acetabular component, fifteen were followed for an average of seven years in our previous study. The current report presents the results for the twelve patients in this group who were alive at a minimum of twelve years (mean, 13.9 years) postoperatively and agreed to return for follow-up. The average final Harris hip score was 79 points. No acetabular shell had been revised because of aseptic loosening, and none was loose as seen radiographically. The complication rate was high but was largely related to infection. In the patients without infection, the fixation of these large sockets remained excellent at the time of long-term follow-up. C1 Univ Kansas, Med Ctr, Overland Pk, KS 66210 USA. Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Hendricks, KJ (reprint author), Univ Kansas, Med Ctr, MS 1307 3905 Rainbow Blvd, Overland Pk, KS 66210 USA. EM kchendri2002@yahoo.com; wharris.obbl@partners.org NR 19 TC 20 Z9 24 U1 2 U2 2 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 MAR PY 2006 VL 88A IS 3 BP 559 EP 563 DI 10.2106/JBJS.E.00389 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 021IU UT WOS:000235977700015 PM 16510823 ER PT J AU Kurihara, N Zhou, H Reddy, SV Palacios, VG Subler, MA Dempster, DW Windle, JJ Roodman, GD AF Kurihara, N Zhou, H Reddy, SV Palacios, VG Subler, MA Dempster, DW Windle, JJ Roodman, GD TI Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE Paget's disease; osteoclast; TAF(II)-17; IL-6; measles virus nucleocapsid ID LARGE T-ANTIGEN; BCL-X-L; TRANSGENIC MICE; 1,25-DIHYDROXYVITAMIN D-3; GENETIC-HETEROGENEITY; CHROMOSOME 18Q; CELLS; PRECURSORS; ACID; HYPERPARATHYROIDISM AB We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. Introduction: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. Materials and Methods: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. Results: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. Conclusions: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo. C1 VA Pittsburgh Healthcare Syst, R&D U 151, Pittsburgh, PA 15240 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. Virginia Commonwealth Univ, Richmond, VA USA. Childrens Res Inst, Dept Pediat, Charleston, SC USA. Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, R&D U 151, Univ Dr, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu OI Windle, Jolene/0000-0001-6690-385X FU NCI NIH HHS [P30-CA16059]; NIAMS NIH HHS [P01-AR049363] NR 41 TC 53 Z9 54 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 MAR PY 2006 VL 21 IS 3 BP 446 EP 455 DI 10.1359/JBMR.051108 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 016UE UT WOS:000235645100013 PM 16491293 ER PT J AU Drake, JE Stoddard, FJ Murphy, JM Ronfeldt, H Snidman, N Kagan, J Saxe, G Sheridan, R AF Drake, JE Stoddard, FJ Murphy, JM Ronfeldt, H Snidman, N Kagan, J Saxe, G Sheridan, R TI Trauma severity influences acute stress in young burned children SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID EARLY-CHILDHOOD; PTSD; SYMPTOMS; DISORDER; ADOLESCENTS; AGREEMENT; INTERVIEW; VALIDITY; PARENT; AGE AB The purpose of this study was to assess the role of trauma severity on subsequent symptoms of posttraumatic stress disorder (PTSD) and physiological reactivity in a total of 70 children, ranging from 12 to 48 months of age, who were acutely burned. Parents were interviewed shortly after the child was admitted to the hospital. PTSD symptoms were measured using the Posttraumatic Stress Disorder Semi-Structured Interview and Observational Record for Infants and Young Children and the Diagnostic Interview for Children and Adolescents. Nurses completed a questionnaire about the child's symptoms and recorded the child's physiological data throughout the hospital stay. Significant relationships were found between severity of childhood trauma and the total number of PTSD symptoms and physiological reactivity. This study supports the hypothesis that severity of trauma experienced by young children influences psychological and physiological stress indicators after burn injuries. These findings provide new directions for the assessment and prevention of PTSD in this age group. C1 Shriners Burn Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Cambridge, MA 02138 USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. RP Stoddard, FJ (reprint author), Shriners Burn Hosp, 51 Blossom St, Boston, MA 02114 USA. OI Saxe, Glenn/0000-0002-4756-1169 NR 30 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAR-APR PY 2006 VL 27 IS 2 BP 174 EP 182 DI 10.1097/01.BCR.0000202618.51001.69 PG 9 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 044UL UT WOS:000237697800008 PM 16566561 ER PT J AU Ahmed, J Sohal, S Malchano, ZJ Holmvang, G Ruskin, JN Reddy, VY AF Ahmed, J Sohal, S Malchano, ZJ Holmvang, G Ruskin, JN Reddy, VY TI Three-dimensional analysis of pulmonary venous ostial and antral anatomy: Implications for balloon catheter-based pulmonary vein isolation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE electrophysiology; magnetic resonance imaging; left atrium; pulmonary veins; atrial fibrillation; ablation; balloon catheter ID ATRIAL-FIBRILLATION; COMPUTED-TOMOGRAPHY; ABLATION AB Background: Balloon ablation catheters using various energy sources are being developed to perform pulmonary vein (PV) isolation to treat atrial fibrillation. Prior evaluations of 2D CT/MR images are limited by the frequent elliptical shape of the PV ostia, the nonorthogonal orientation of the PVs to the left atrial (LA) chamber, and difficulty in appreciating through-slice curvature. To provide anatomical data relevant to balloon catheter ablation, 3D surface reconstructions of LA-PVs were generated and analyzed to define ostial architecture and size. Methods and Results: Using MRI datasets obtained from 101 paroxysmal AF patients, the LA-PVs were segmented to generate 3D LA-PV surface reconstructions. Using both external and endoluminal projections, the PV ostial and antral regions were identified and evaluated. In the left PVs, a common left-sided ostium was identified in 94 patients, with an ostial circumference of 95 +/- 15 mm. Branching of the left PVs occurred 0-5 mm away from the common left ostium in 43 patients (43%), 5-15 mm away from the common os in 37 patients (37%), and > 15 mm away from the common os in 14 patients (14%). In patients with either distinct left PV ostia, or common os < 15 mm (87 patients), the individual LSPV/LIPV ostial circumferences were 67 +/- 12 mm and 58 +/- 9 mm, respectively. Mean left antral circumference was 114 +/- 17 mm. In the right PVs, the ostial circumferences of the RSPV/RIPV were 68 +/- 11 mm and 66 +/- 11 mm, respectively. Mean right antral circumference was 107 +/- 19 mm. Assuming ideal deformation of the LA chamber anatomy, the minimal diameters of a balloon ablation catheter required to isolate 95% of the RSPV, RIPV, LSPV, LIPV, LCPV, left antrum, and right antrum are 29 mm, 28 mm, 29 mm, 24 mm, 40 mm, 46 mm, and 47 mm, respectively. Conclusion: Analysis of 3D surface reconstructions of LA-PV anatomy reveals that balloon catheter-based ablation of the PVs is likely feasible in most patients, but balloon ablation of the common PV antra would be problematic. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MRI Unit, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02215 USA. Michigan State Med Sch, Lansing, MI USA. RP Reddy, VY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. EM vreddy@partners.org NR 12 TC 35 Z9 36 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAR PY 2006 VL 17 IS 3 BP 251 EP 255 DI 10.1111/j.1540-8167.2005.00339.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 019MT UT WOS:000235841600006 PM 16643395 ER PT J AU Schroeder, PR Haugen, BR Pacini, F Reiners, C Schlumberger, M Sherman, SI Cooper, DS Schuff, KG Braverman, LE Skarulis, MC Davies, TF Mazzaferri, EL Daniels, GH Ross, DS Luster, M Samuels, MH Weintraub, BD Ridgway, EC Ladenson, PW AF Schroeder, PR Haugen, BR Pacini, F Reiners, C Schlumberger, M Sherman, SI Cooper, DS Schuff, KG Braverman, LE Skarulis, MC Davies, TF Mazzaferri, EL Daniels, GH Ross, DS Luster, M Samuels, MH Weintraub, BD Ridgway, EC Ladenson, PW TI A comparison of short-term changes in health-related quality of life in thyroid carcinoma patients undergoing diagnostic evaluation with recombinant human thyrotropin compared with thyroid hormone withdrawal SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the Endocrine-Society CY JUN 04-07, 2005 CL San Diego, CA SP Endocrine Soc ID SURVEY SF-36; MEDICAL OUTCOMES; CANCER; THERAPY; DISCONTINUATION; HYPOTHYROIDISM; TESTS; CARE AB Context: Thyroid carcinoma requires lifelong monitoring with serum thyroglobulin, radioactive iodine whole body scanning, and other imaging modalities. Levothyroxine (L-T(4)) withdrawal for thyroglobulin measurement and whole body scanning increases these tests' sensitivities but causes hypothyroidism. Recombinant human TSH (rhTSH) enables testing without L-T(4) withdrawal. Objective: Our objective was to examine the impact of short-term hypothyroidism on the health-related quality of life (HRQOL) of patients after rhTSH vs. L-T(4) withdrawal. Design, Setting, and Patients: In this multicenter study, the SF-36 Health Survey was administered to 228 patients at three time points: on L-T(4), after rhTSH, and after L-T(4) withdrawal. Interventions: Interventions included administration of rhTSH on L-T(4) and withdrawal from thyroid hormone. Main Outcome Measures: Mean SF-36 scores were compared during the two interventions and with the U. S. general population and patients with heart failure, depression, and migraine headache. Results: Patients had SF-36 scores at or above the norm for the general U. S. population in six of eight domains at baseline on L-T4 and in seven of eight domains after rhTSH. Patients' scores declined significantly in all eight domains after L-T(4) withdrawal when compared with the other two periods (P<0.0001). Patients' HRQOL scores while on L-T(4) and after rhTSH were at or above those for patients with heart failure, depression, and migraine in all eight domains. After L-T(4) withdrawal, patients' HRQOL scores were significantly below congestive heart failure, depression, and migraine headache norms in six, three, and six of the eight domains, respectively. Conclusions: Short-term hypothyroidism after L-T(4) withdrawal is associated with a significant decline in quality of life that is abrogated by rhTSH use. C1 Johns Hopkins Med Inst, Div Endocrinol & Metab, Baltimore, MD 21287 USA. Univ Colorado, Hlth Sci Ctr, Div Endocrinol, Denver, CO 80262 USA. Univ Siena, Div Endocrinol & Metab, I-53100 Siena, Italy. Univ Wurzburg, Nukl Med Klin & Poliklin, D-97070 Wurzburg, Germany. Inst Gustave Roussy, Nucl Med Serv, F-94805 Villejuif, France. Univ Texas, MD Anderson Canc Ctr, Dept Med Specialties, Houston, TX 77030 USA. Sinai Hosp, Div Endocrinol, Baltimore, MD 21215 USA. Oregon Hlth & Sci Univ, Div Endocrinol, Portland, OR 97201 USA. Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Div Endocrinol, New York, NY 10029 USA. Univ Florida, Shands Hosp, Div Endocrinol, Gainesville, FL 32610 USA. Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. Trophogen Inc, Rockville, MD 20850 USA. RP Ladenson, PW (reprint author), Johns Hopkins Med Inst, Div Endocrinol & Metab, 1830 E Monument St,Suite 333, Baltimore, MD 21287 USA. EM ladenson@jhmi.edu OI Sherman, Steven/0000-0002-3079-5153; Braverman, Lewis/0000-0003-1263-1099 FU NIDDK NIH HHS [T32DK62707] NR 24 TC 110 Z9 114 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2006 VL 91 IS 3 BP 878 EP 884 DI 10.1210/jc.2005-2064 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 020DX UT WOS:000235889700025 PM 16394083 ER PT J AU Hermann, TS Li, WJ Dominguez, H Ihlemann, N Rask-Madsen, C Major-Pedersen, A Nielsen, DB Hansen, KW Hawkins, M Kober, L Torp-Pedersen, C AF Hermann, TS Li, WJ Dominguez, H Ihlemann, N Rask-Madsen, C Major-Pedersen, A Nielsen, DB Hansen, KW Hawkins, M Kober, L Torp-Pedersen, C TI Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ANGIOTENSIN-CONVERTING-ENZYME; CORONARY-ARTERY-DISEASE; NITRIC-OXIDE; ACE-INHIBITION; ESSENTIAL-HYPERTENSION; RECEPTOR ANTAGONISM; HEART-DISEASE; MELLITUS; SENSITIVITY; RESISTANCE AB Objective: Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects and simultaneously increase the expression of genes that are pertinent for endothelial function and metabolism. Methods: Twenty-four type 2 diabetic subjects were randomized to receive 2 months of quinapril 20 mg daily or no treatment in an open parallel study. Endothelium-dependent and -independent vasodilation was studied during serotonin or sodium nitroprusside infusion in the diabetic patients and in 15 healthy subjects. Endothelial function, insulin-stimulated endothelial function, and insulin-stimulated glucose uptake were measured before and after quinapril treatment. Blood flow was measured by venous occlusion plethysmography. Gene expression was measured by real-time PCR. Results: Quinapril treatment increased insulin-stimulated endothelial function in the type 2 diabetic subjects (P = 0.005), whereas forearm glucose uptake was unchanged. Endothelial function was also increased by quinapril (P = 0.001). Systolic and diastolic blood pressures were reduced by quinapril (P < 0.001). Quinapril increased adiponectin gene expression in vascular tissue obtained from sc adipose biopsies. Conclusions: Quinapril treatment increases insulin-stimulated endothelial function in patients with type 2 diabetes. Increased vascular adiponectin gene expression may contribute to this beneficial effect. C1 Bispebjerg Univ Hosp, Dept Cardiol Y, DK-2400 Copenhagen, Denmark. Yeshiva Univ Albert Einstein Coll Med, Div Endocrinol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Ctr Diabet Res & Training, Bronx, NY 10461 USA. Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Boston, MA 02215 USA. Gentofte Univ Hosp, Dept Clin Biochem, DK-2900 Gentofte, Denmark. Rigshosp, Ctr Heart, Dept Cardiol B, DK-2100 Copenhagen, Denmark. RP Hermann, TS (reprint author), Bispebjerg Univ Hosp, Dept Cardiol Y, Bygning 40,Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark. EM th@heart.dk RI Torp-Pedersen, Christian/E-5931-2013; OI DOMINGUEZ, HELENA/0000-0002-7089-2636 NR 40 TC 43 Z9 50 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 MAR PY 2006 VL 91 IS 3 BP 1001 EP 1008 DI 10.1210/jc.2005-1231 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 020DX UT WOS:000235889700044 PM 16352688 ER PT J AU Misra, M Miller, KK Tsai, P Gallagher, K Lin, A Lee, N Herzog, DB Klibanski, A AF Misra, M Miller, KK Tsai, P Gallagher, K Lin, A Lee, N Herzog, DB Klibanski, A TI Elevated peptide YY levels in adolescent girls with anorexia nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RESTING ENERGY-EXPENDITURE; FOOD-INTAKE; SECRETORY DYNAMICS; HEALTHY ADOLESCENTS; BONE METABOLISM; GROWTH-HORMONE; INSULIN SENSITIVITY; NUTRITIONAL-STATUS; OBESE GENE; GHRELIN AB Background: Peptide YY (PYY) is an intestinally derived anorexigen that acts via the Y2 receptor, and Y2 receptor deletion in rodents increases bone formation. Anorexia nervosa (AN) is associated with a deliberate reduction in food intake and low bone density, but endocrine modulators of food intake in AN are not known. In addition, known regulators of bone turnover, such as GH, cortisol, and estrogen, explain only a fraction of the variability in bone turnover marker levels. Hypotheses: We hypothesized that PYY may be elevated in AN compared with controls and may contribute to decreased food intake and bone formation. Methods: Fasting PYY was examined in 23 AN girls and 21 healthy adolescents 12-18 yr old. We also examined GH, cortisol, ghrelin, and leptin (overnight frequent sampling) and fasting IGF-I, estradiol, total T(3), and bone markers. Macronutrient intake and resting energy expenditure (REE) were measured. Results: AN girls had higher PYY levels compared with controls (17.8 +/- 10.2 vs. 4.8 +/- 4.3 pg/ml; P < 0.0001). Predictors of log PYY were nutritional markers, including body mass index (r = -0.62; P < 0.0001), fat mass (r = -0.55; P = 0.0003), and REE (r = -0.51; P = 0.0006), and hormones, including GH (r = 0.38; P = 0.004) and T(3) (r = -0.59; P = 0.0001). Body mass index, fat mass, REE, GH, and T(3) explained 68% of the variability of log PYY. Log PYY predicted percentage of calories from fat (r = -0.56; P = 0.0002) and independently predicted osteocalcin (r = -0.45; P = 0.003), bone-specific alkaline phosphatase (r = -0.46; P = 0.003), N-telopeptide/creatinine (r = -0.55; P = 0.0003), and deoxypyridinoline/creatinine (r = -0.52; P = 0.001) on regression modeling. Conclusion: Elevated PYY may contribute to reduced intake and decreased bone turnover in AN. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [K23 RR018851, M01-RR-01066]; NIDDK NIH HHS [DK 062249] NR 40 TC 125 Z9 125 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2006 VL 91 IS 3 BP 1027 EP 1033 DI 10.1210/jc.2005-1878 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 020DX UT WOS:000235889700048 PM 16278259 ER PT J AU Lee, H Finkelstein, JS Miller, M Comeaux, SJ Cohen, RI Leder, BZ AF Lee, H Finkelstein, JS Miller, M Comeaux, SJ Cohen, RI Leder, BZ TI Effects of selective testosterone and estradiol withdrawal on skeletal sensitivity to parathyroid hormone in men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-RESORPTION; SEX STEROIDS; POSTMENOPAUSAL WOMEN; ANDROGEN-DEPRIVATION; ESTROGEN DEFICIENCY; PROSTATE-CANCER; ELDERLY MEN; OSTEOPROTEGERIN; OSTEOPOROSIS; EXPRESSION AB Context: Gonadal steroid withdrawal increases bone turnover and causes bone loss in men, but the underlying mechanisms have not been defined. We previously reported that gonadal steroid deprivation increases the skeletal sensitivity to the bone resorbing properties of PTH infusion in men, but it is not known whether this effect is mediated by the absence of androgens, estrogens, or both. Objective: The objective of the study was to determine the selective effects of testosterone and estradiol withdrawal on the skeletal sensitivity to PTH infusion in healthy adult men. Design and Setting: We randomly assigned 58 healthy men between the ages of 20 and 45 yr to receive treatment with combinations of a GnRH analog, an aromatase inhibitor, and hormone add-back therapy to produce the following treatment groups: group 1 (testosterone and estradiol deficient, n = 16); group 2 (testosterone sufficient but estradiol deficient, n = 12); group 3 (testosterone deficient but estradiol sufficient, n = 14); and group 4 (testosterone and estradiol sufficient, n = 16). Twenty-four-hour PTH infusions were performed at baseline and after 6 wk of therapy. Serum N-telopeptide (NTX), C-telopeptide (CTX), osteocalcin (OC), and amino-terminal propeptide of type I procollagen (P1NP) were measured every 6 h during the PTH infusions. Results: Serum testosterone levels fell into the castrate range in groups 1 and 3, whereas estradiol levels were similarly reduced in groups 1 and 2. Gonadal steroid levels in the replaced groups were unchanged from baseline. Serum NTX levels measured before PTH infusion did not change in group 4 (+T, +E) but increased significantly in all other groups. A similar pattern was observed in serum CTX, although the increase in group 2 (+T, +E) was not significant (P = 0.12). Preinfusion concentrations of both OC and P1NP fell in most groups, but these changes were significant in group 2 (+T, +E) for both OC and P1NP and group 4 (+T, +E) for P1NP only. Serum NTX and CTX increased during PTH infusions in all groups at all time points (P < 0.001). In the eugonadal group (group 4 +T+E), the increase in NTX was the same at wk 0 and 6, whereas in all the other groups, the PTH-induced increase in serum NTX was significantly greater at wk, 6 compared with wk 0. The same pattern emerged for CTX, although the difference in group 3 (+T, -E) was not significant (P = 0.12). Serum OC and P1NP levels fell during PTH infusions in all groups and at all time points (P < 0.001), but no significant differences were observed between wk 0 and 6 in any group. Conclusions: These results demonstrate that the selective suppression of testosterone, estradiol, or both hormones increases the skeletal responsiveness to the bone-resorbing effects of PTH in men. These findings underscore the importance of both androgens and estrogens in male skeletal homeostasis and suggest that changes in skeletal sensitivity to PTH may play an important role in the pathogenesis of hypogonadal bone loss in men. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-1066, K23-RR16310]; NIDDK NIH HHS [K24-DK02759] NR 32 TC 15 Z9 15 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 MAR PY 2006 VL 91 IS 3 BP 1069 EP 1075 DI 10.1210/jc.2005-2495 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 020DX UT WOS:000235889700054 PM 16352679 ER PT J AU Hart, DL Cook, KF Mioduski, JE Teal, CR Crane, PK AF Hart, DL Cook, KF Mioduski, JE Teal, CR Crane, PK TI Simulated computerized adaptive test for patients with shoulder impairments was efficient and produced valid measures of function SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE computerized adaptive testing; item response theory; rehabilitation; Flexilevel Scale of Shoulder Function ID ITEM RESPONSE THEORY; DISCRIMINANT VALIDITY; RELATIVE PRECISION; HEADACHE IMPACT; RASCH ANALYSIS; HEALTH-STATUS; SCALE PF-10; UNIDIMENSIONALITY; MODELS; OUTCOMES AB Background and Objective: To test unidimensionality and local independence of a set of shoulder functional status (SFS) items, develop a computerized adaptive test (CAT) of the items using a rating scale item response theory model (RSM), and compare discriminant validity of measures generated using all items (theta(IRT)) and measures generated using the simulated CAT (theta(CAT)). Study Design and Setting: We performed a secondary analysis of data collected prospectively during rehabilitation of 400 patients with shoulder impairments who completed 60 SFS items. Results: Factor analytic techniques supported that the 42 SFS items formed a unidimensional scale and were locally independent. Except for five items, which were deleted, the RSM fit the data well. The remaining 37 SFS items were used to generate the CAT. On average, 6 items were needed to estimate precise measures of function using the SFS CAT, compared with all 37 SFS items. The theta(IRT) and theta(CAT) measures were highly correlated (r = .96) and resulted in similar classifications of patients. Conclusion: The simulated SFS CAT was efficient and produced precise, clinically relevant measures of functional status with good discriminating ability. (C) 2006 Elsevier Inc. All rights reserved. C1 Focus Therapeut Outcomes Inc, White Stone, VA 22578 USA. US Dept Vet Affairs, Vet Affairs Measurement Excellence Training Res &, Houston, TX USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Focus Therapeut Outcomes Inc, Knoxville, TN USA. Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Washington, Sch Med, Div Gen Internal Med, Seattle, WA USA. RP Hart, DL (reprint author), Focus Therapeut Outcomes Inc, 551 Yopps Cove Rd, White Stone, VA 22578 USA. EM dsailhart@verizon.net RI Crane, Paul/C-8623-2014; OI Crane, Paul/0000-0003-4278-7465 FU NIA NIH HHS [K08 AG 022232] NR 57 TC 55 Z9 56 U1 1 U2 3 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 MAR PY 2006 VL 59 IS 3 BP 290 EP 298 DI 10.1016/j.jclinepi.2005.08.006 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 019GR UT WOS:000235824100010 PM 16488360 ER PT J AU Good, G AF Good, G TI Sick to death SO JOURNAL OF CLINICAL ETHICS LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Good, G (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM GGood@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SPR PY 2006 VL 17 IS 1 BP 80 EP 82 PG 3 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 035VZ UT WOS:000237031100011 PM 16689118 ER PT J AU Repper-DeLisi, J Kilroy, SM AF Repper-DeLisi, J Kilroy, SM TI "We need to meet" SO JOURNAL OF CLINICAL ETHICS LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Repper-DeLisi, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM JRepperDelisi@partners.org; SKilroy@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SPR PY 2006 VL 17 IS 1 BP 85 EP 89 PG 5 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 035VZ UT WOS:000237031100013 PM 16689120 ER PT J AU Dauterive, R AF Dauterive, R TI Was my patient fortunate or forsaken? SO JOURNAL OF CLINICAL ETHICS LA English DT Article C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dauterive, R (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM RDauterive@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SPR PY 2006 VL 17 IS 1 BP 90 EP 93 PG 4 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 035VZ UT WOS:000237031100014 PM 16689121 ER PT J AU Robinson, EM Good, G Burke, S AF Robinson, EM Good, G Burke, S TI Talking with Lorraine's mother and sister, five months after her death SO JOURNAL OF CLINICAL ETHICS LA English DT Article C1 Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. Cambridge Hlth Alliance Cambridge, Cambridge, MA USA. RP Robinson, EM (reprint author), Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. EM ERobinson1@partners.org; GGood@partners.org; SBurke@CHAlliance.org NR 0 TC 1 Z9 1 U1 1 U2 2 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SPR PY 2006 VL 17 IS 1 BP 94 EP 96 PG 3 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 035VZ UT WOS:000237031100015 PM 16689122 ER PT J AU Husain, Z Holodick, N Day, C Szymanski, I Alper, CA AF Husain, Z Holodick, N Day, C Szymanski, I Alper, CA TI Increased apoptosis of CD20(+) IgA(+) B cells is the basis for IgA deficiency: The molecular mechanism for correction in vitro by IL-10 and CD40L SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE immunodeficiency diseases; IgA deficiency; caspase-1; apoptosis ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; SUSCEPTIBILITY GENES; MAMMALIAN HOMOLOG; SECRETING CELLS; CASPASE-1; DEATH; DIFFERENTIATION; LYMPHOCYTES; EXPRESSION; INDUCTION AB IgA deficiency is the most common primary immunodeficiency in humans. Comparative analysis of gene expression in PBMC from IgA-deficient (IgAd) and normal donors using functional multiplex panels showed overexpression of the Caspase-1 (CASP-1) gene. Cells from all the IgAd donors (n=7) expressed 4-10-fold caspase-1 mRNA over normal controls (n=5). CD19(+) B cells from all IgAd donors produced IgA in cultures following IL-10 and CD40L with Staphylococcus aureus (Cowan) (SAC) or tetanus toxoid (TT) treatments. In CD19(+) B cells from IgAd donors, reconstitution of IgA secretion was associated with protection of the CD20(+) B cell population that underwent apoptosis in the absence of IL-10, CD40L, and TT (triple treatment). Caspase-1 gene expression was decreased in the reconstituted cells. Furthermore, treatment with a caspase-1 inhibitor also independently protected against B cell apoptosis in vitro. An apoptosis-specific cDNA array showed differential expression of 4 out of 96 genes and a shift towards survival-related gene expression from the apoptotic to the protected B cells after triple treatment. There was an increase in the expression of the IAP-2 (inhibitor of apoptosis) gene in the reconstituted cells. Upregulation of the IAP-2 gene protects B cells from deletion and allows for IgA secretion in this system. The inability to detect secreted IgA in IgAd patients could result from the loss of IgA-committed B cells that express high levels of caspase-1. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Alper, CA (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM alper@cbr.med.harvard.edu FU NHLBI NIH HHS [HL-29583] NR 55 TC 15 Z9 16 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAR PY 2006 VL 26 IS 2 BP 113 EP 125 DI 10.1007/s10875-006-9001-y PG 13 WC Immunology SC Immunology GA 051CN UT WOS:000238138200002 PM 16758339 ER PT J AU Fakhari, FD Jeong, JH Kanan, Y Dittmer, DP AF Fakhari, FD Jeong, JH Kanan, Y Dittmer, DP TI The latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus induces B cell hyperplasia and lymphoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PRIMARY EFFUSION LYMPHOMA; GENE-EXPRESSION PROFILE; SOLID LYMPHOMAS; PERIPHERAL-BLOOD; IN-VIVO; KSHV; MICE; HUMAN-HERPESVIRUS-8; INFECTION; PROMOTER AB Kaposi sarcoma-associated herpesvirus (KSHV) is a human lymphotropic herpesvirus. It is implicated in B cell neoplasias such as primary effusion lymphoma and multicentric Castleman disease in AIDS patients. The KSHV latency-associated nuclear antigen (LANA) is consistently expressed in all KSHV-associated tumor cells and was shown to bind the tumor suppressor proteins p53 and pRb. To test LANAs contribution to lymphomagenesis in vivo vie generated transgenic mice expressing LANA under the control of its own promoter, which is B cell specific. All of the transgenic mice developed splenic follicular hyperplasia due to an expansion of IgM(+)IgD(+)B cells and showed increased germinal center formation. We also observed lymphomas, implying that LANA can activate B cells and provide the first step toward lymphomagenesis. C1 Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dittmer, DP (reprint author), Univ N Carolina, Dept Microbiol & Immunol, 804 Mary Ellen Jones,CB7290, Chapel Hill, NC 27599 USA. EM ddittmer@med.unc.edu FU NCI NIH HHS [CA109232, R01 CA109232] NR 47 TC 63 Z9 70 U1 0 U2 1 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 MAR PY 2006 VL 116 IS 3 BP 735 EP 742 DI 10.1172/JCI26190 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 019RL UT WOS:000235854300024 PM 16498502 ER PT J AU Gunn, SR Reveles, XT Hamlington, JD Sadkowski, LC Johnson-Pais, TL Jorgensen, JH AF Gunn, SR Reveles, XT Hamlington, JD Sadkowski, LC Johnson-Pais, TL Jorgensen, JH TI Use of DNA sequencing analysis to confirm fungemia due to Trichosporon dermatis in a pediatric patient SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IDENTIFICATION; LOUBIERI; REGIONS AB This is the first reported case of human disease caused by Tricosporon dermatis, an organism recently transferred to the genus Trichosporon from Cryptococcus and now confirmed to be a human pathogen. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, VA Mycol Reference Lab, San Antonio, TX 78284 USA. RP Gunn, SR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM gunn@uthsesa.edu FU NCI NIH HHS [P30 CA054174, P30 CA54174] NR 11 TC 13 Z9 16 U1 0 U2 0 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 MAR PY 2006 VL 44 IS 3 BP 1175 EP 1177 DI 10.1128/JCM.44.3.1175-1177.2006 PG 3 WC Microbiology SC Microbiology GA 022ZP UT WOS:000236095000086 PM 16517924 ER PT J AU Wong, JS Kaelin, CM Troyan, SL Gadd, MA Gelman, R Lester, SC Schnitt, SJ Sgroi, DC Silver, BJ Harris, JR Smith, BL AF Wong, JS Kaelin, CM Troyan, SL Gadd, MA Gelman, R Lester, SC Schnitt, SJ Sgroi, DC Silver, BJ Harris, JR Smith, BL TI Prospective study of wide excision alone for ductal carcinoma in situ of the breast SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TX ID RANDOMIZED CONTROLLED-TRIAL; SURGICAL ADJUVANT BREAST; CANCER; TAMOXIFEN; WOMEN; RADIOTHERAPY; THERAPY; B-24 AB Purpose It has been hypothesized that wide excision alone with margins >= 1 cm may be adequate treatment for small, grade 1 or 2 ductal carcinoma in situ (DCIS). To test this hypothesis, we conducted a prospective, single-arm trial. Methods Entry criteria included DCIS of predominant grade 1 or 2 with a mammographic extent of ! 2.5 cm treated with wide excision with final margins of >= 1 cm or a re-excision without residual DCIS. Tamoxifen was not permitted. The accrual goal was 200 patients. Results In July 2002, the study closed to accrual at 158 patients because the number of local recurrences met the predetermined stopping rules. The median age was 51 and the median follow-up time was 40 months. Thirteen patients developed local recurrence as the first site of treatment failure 7 to 63 months after study entry. The rate of ipsilateral local recurrence as first site of treatment failure was 2.4% per patient-year, corresponding to a 5-year rate of 12%. Nine patients (69%) experienced recurrence of DCIS and four (31%) experienced recurrence with invasive disease. Twelve recurrences were detected marnmographically and one was palpable. Ten were in the same quadrant as the initial DCIS and three were elsewhere within the ipsilateral breast. No patient had positive axillary nodes at recurrence or subsequent metastatic disease. Conclusion Despite margins of >= 1 cm, the local recurrence rate is substantial when patients with small, grade 1 or 2 DCIS are treated with wide excision alone. This risk should be considered in assessing the possible use of radiation therapy with or without tamoxifen in these patients. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. RP Wong, JS (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,L2, Boston, MA 02115 USA. EM jwong@lroc.harvard.edu NR 11 TC 151 Z9 159 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 MAR 1 PY 2006 VL 24 IS 7 BP 1031 EP 1036 DI 10.1200/JCO.2005.02.9975 PG 6 WC Oncology SC Oncology GA 018QV UT WOS:000235780800006 PM 16461781 ER PT J AU Heinrich, MC McArthur, GA Demetri, GD Joensuu, H Bono, P Herrmann, R Hirte, H Cresta, S Koslin, DB Corless, CL Dirnhofer, S van Oosterom, AT Nikolova, Z Dimitrijevic, S Fletcher, JA AF Heinrich, MC McArthur, GA Demetri, GD Joensuu, H Bono, P Herrmann, R Hirte, H Cresta, S Koslin, DB Corless, CL Dirnhofer, S van Oosterom, AT Nikolova, Z Dimitrijevic, S Fletcher, JA TI Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; FAMILIAL ADENOMATOUS POLYPOSIS; KIT EXPRESSION; BETA; MUTATIONS; MESYLATE; EFFICACY; SAFETY; PROLIFERATION; ASSOCIATION AB Purpose To determine the clinical efficacy of imatinib in patients with advanced aggressive fibromatosis (AF) and to identify the molecular basis of response/nonresponse to this agent. Patients and Methods Nineteen patients with AF were treated with imatinib (800 mg/d) as part of a phase 11 clinical study. Tumor specimens were analyzed for mutations of KIT, PDGFRA, PDGFRB, and CTNNB1 (beta-catenin). Tumor expression of total and activated KIT, PDGFRA, and PDGFRB were assessed using immunohistochemistry and immunoblotting techniques. We also measured plasma levels of PDGF-AA and PDGF-BB in patients and normal patient controls. Results Three of 19 patients (15.7%) had a partial response to treatment, with four additional patients having stable disease that lasted more than 1 year (overall 1 year tumor control rate of 36.8%). No mutations of KIT, PDGFRA, or PDGFRB were found. Sixteen of 19 patients (84%) had mutations involving the WNT pathway (APC or CTNNB1). However, there was no correlation between WNT pathway mutations and clinical response to imatinib. AF tumors expressed minimal to null levels of KIT and PDGFRA but expressed levels of PDGFRB that are comparable with normal fibroblasts. However, PDGFRB phosphorylation was not detected, suggesting that PDGFRB is only weakly activated. AF patients had elevated levels of PDGF-AA and PDGF-BB compared with normal patient controls. Notably, the plasma level of PDGF-BB was inversely correlated with time to treatment failure. Conclusion Imatinib is an active agent in the treatment of advanced AF Imatinib response in AF patients may be mediated by inhibition of PDGFRB kinase activity. C1 Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. Peter MacCallum Canc Ctr, Melbourne, Australia. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Helsinki, Cent Hosp, Helsinki, Finland. Univ Basel Hosp, CH-4031 Basel, Switzerland. Novartis Pharma AG, Clin Res Oncol, Basel, Switzerland. Juravinski Canc Ctr, Hamilton, ON, Canada. Inst Nazl Tumori Milano, Milan, Italy. UZ Gasthuisberg Dienst Oncol, Louvain, Belgium. RP Heinrich, MC (reprint author), R&D-19,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM heinrich@ohsu.edu RI Cresta, Sara/B-8588-2017; OI Cresta, Sara/0000-0002-6830-0662; Joensuu, Heikki/0000-0003-0281-2507 FU NCI NIH HHS [5P30 CA69533-04] NR 32 TC 152 Z9 160 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 MAR 1 PY 2006 VL 24 IS 7 BP 1195 EP 1203 DI 10.1200/JCO.2005.04.0717 PG 9 WC Oncology SC Oncology GA 018QV UT WOS:000235780800027 PM 16505440 ER PT J AU Surman, CBH Randall, ET Biederman, J AF Surman, CBH Randall, ET Biederman, J TI Association between attention-deficit/hyperactivity disorder and bulimia nervosa: Analysis of 4 case-control studies SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; B PERSONALITY-DISORDER; METHYLPHENIDATE TREATMENT; COMORBIDITY; CHILDREN; GENDER; ADOLESCENTS; PREVALENCE; ANOREXIA; ADULTS AB Background: Impulsivity is a common feature of attention-deficit/hyperactivity disorder (ADHD), and evidence suggests that impulsivity traits may be an indicator of poor prognosis for individuals with bulimia nervosa. To identify whether there is an association between ADHD and bulimia nervosa, the authors systematically examined data from children and adults with and without ADHD. Method: We systematically identified rates of bulimia nervosa in individuals with and without ADHD (DSM-III-R criteria) in our 2 large pediatric and 2 large adult samples (N = 522 children, 742 adults). Subjects were assessed from the late 1980s to February 1999. Results: In the 2 samples of adults with and without ADHD, significantly greater rates of bulimia nervosa were identified in women with versus without ADHD (12% vs. 3%, p < .05 for 1 sample and 11% vs. 1%, p < .05 for the other sample). No significant differences in rates of bulimia nervosa were identified in men or children with ADHD when compared to sex-matched control subjects. Conclusion: Although preliminary and requiring further confirmation, these findings suggest that ADHD may be associated with bulimia nervosa in some women. If confirmed, this association between bulimia nervosa and ADHD could have important clinical and therapeutic implications. C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Surman, CBH (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Adult ADHD Res Program, Suite 2000,185 Alewife Brook Pkwy, Cambridge, MA 02138 USA. EM csurman@partners.org FU NIMH NIH HHS [R01 MH 57934, R01 MH-4314-01A2, R01 MH-50657-04] NR 28 TC 30 Z9 31 U1 2 U2 6 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 MAR PY 2006 VL 67 IS 3 BP 351 EP 354 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 031RL UT WOS:000236721600002 PM 16649819 ER PT J AU Simon, NM Hoge, EA Fischmann, D Worthington, JJ Christian, KM Kinrys, G Pollack, MH AF Simon, NM Hoge, EA Fischmann, D Worthington, JJ Christian, KM Kinrys, G Pollack, MH TI An open-label trial of risperidone augmentation for refractory anxiety disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; PANIC DISORDER; DOUBLE-BLIND; DEPRESSION; SCALE; OLANZAPINE; EFFICACY AB Background: There is a paucity of data to support "next-step" treatments for the many patients with anxiety disorders who remain symptomatic after initial pharmacotherapy. Method: Thirty patients with a primary diagnosis of an anxiety disorder-panic disorder (PD), social anxiety disorder (SAD), or generalized anxiety disorder (GAD)-refractory to initial pharmacotherapy with an adequate (or maximally tolerated) antidepressant and/or benzodiazepine trial of at least 8 weeks' duration prior to study initiation received open-label augmentation with flexibly dosed risperidone for 8 weeks. Participants were diagnosed using the Structured Clinical Interview for DSM-IV. Results: Risperidone augmentation at a mean +/- SD dose of 1.12 +/- 0.68 mg/day (range, 0.25-3.00 mg/day) resulted in a significant reduction in anxiety symptoms across disorders as measured by the Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale for Anxiety (HAM-A) scores and for each disorder-specific primary Outcome measure-the Panic Disorder Severity Scale, the Liebowitz Social Anxiety Scale, and HAM-A-in the intent-to-treat sample. Seventy percent (21/30) of participants completed the 8-week trial, with premature discontinuation due primarily to sedation and weight gain. Conclusions: Although conclusions are limited by the open-label, relatively brief nature of this trial, our data suggest that augmentation with low-dose risperidone may be a useful option for patients with PD, SAD, or GAD refractory to adequate initial intervention with antidepressants and/or benzodiazepines. Longer-term, controlled safety and efficacy data are needed to understand the place of risperidone augmentation in the algorithm of treatment options for refractory anxiety disorders. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Cambridge Hlth Alliance, Anxiety Disorders Res Program, Cambridge, MA USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 NR 33 TC 47 Z9 47 U1 0 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 MAR PY 2006 VL 67 IS 3 BP 381 EP 385 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 031RL UT WOS:000236721600006 PM 16649823 ER PT J AU Pollack, MH Simon, NM Fagiolini, A Pitman, R McNally, RJ Nierenberg, AA Miyahara, S Sachs, GS Perlman, C Ghaemi, SN Thase, ME Otto, MW AF Pollack, MH Simon, NM Fagiolini, A Pitman, R McNally, RJ Nierenberg, AA Miyahara, S Sachs, GS Perlman, C Ghaemi, SN Thase, ME Otto, MW TI Persistent posttraumatic stress disorder following September 11 in patients with bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; NEW-YORK-CITY; ANXIETY SENSITIVITY; TERRORIST ATTACKS; PTSD SYMPTOMS; STEP-BD; PREDICTORS; TRAUMA; PERSONALITY; PREVALENCE AB Objective: We examined the development of posttraumatic stress disorder (PTSD) following indirect exposure to the September 11. 2001, terrorist attacks in a cohort at high risk for adverse trauma-related sequelae as a result of having bipolar disorder. Method: Subjects (N = 137) were participants in the ongoing, naturalistic, longitudinal study Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) prior to September 11, 2001. The present study examined prospectively collected pre-event information about bipolar disorder and other potential predictors of PTSD, along with assessment of the level of indirect trauma exposure (i.e., via media) and peri-traumatic distress in the aftermath of September 11, and their association with 9/11-related, new-onset PTSD as assessed by a self-report measure, the Posttraumatic Stress Diagnostic Scale. Results: Posttrauma assessments were completed a mean +/- SD of 430.6 +/- 78.7 days (range, 0.5-1.5 years) after September 11. Twenty percent (N = 27) of patients reported development of new-onset PTSD in response to the September 11 attacks. Rates of PTSD were significantly associated with the presence of a hypomanic, manic, or mixed mood state at the time of trauma (chi(2) = 4.25; p < .05); 62% of patients in these states developed PTSD. Mania/hypomania remained a significant predictor of PTSD in response to the September 11 attacks after controlling for peritraumatic exposure and distress variables, suggestive of a substantial increase in risk compared with those in recovery (OR = 17; 95% CI = 2.6 to 115.6; p = .0034). Conclusions: Rates of persistent new-onset PTSD among bipolar patients were elevated in the aftermath of the September 11 attacks. Our findings suggest that the presence of a manic state may be the most critical risk factor for adverse sequelae following indirect traumatic exposure in bipolar individuals. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA. Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM mpollack@partners.org OI FAGIOLINI, ANDREA/0000-0001-5827-0853 FU NIMH NIH HHS [5 R01 MH 663901] NR 33 TC 25 Z9 25 U1 4 U2 8 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 MAR PY 2006 VL 67 IS 3 BP 394 EP 399 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 031RL UT WOS:000236721600008 PM 16649825 ER PT J AU Spencer, TJ Faraone, SV Michelson, D Adler, LA Reimherr, FW Glatt, SJ Biederman, J AF Spencer, TJ Faraone, SV Michelson, D Adler, LA Reimherr, FW Glatt, SJ Biederman, J TI Atomoxetine and adult attention-deficit/hyperactivity disorder: The effects of comorbidity SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT RESPONSE; ADHD; CHILDREN; METHYLPHENIDATE; MTA AB Objective: The objective of this study was to determine if measures of broad clinical psychopathology or neuropsychological performance could aid in the prediction of therapeutic response to the highly selective norepinephrine transporter inhibitor, atomoxetine, among adults with attention-deficit/hyperactivity disorder (ADHD). Method: We analyzed data from 2 double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256) with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomly assigned to 10 weeks of treatment with atomoxetine or placebo and were assessed with Conners' Adult ADHD Rating Scales (CAARS), the General Well-Being Schedule (GWB), the Sheehan Disability Scale, the Stroop Color-Word Test (SCWT), and the Structured Clinical Interview for DSM-IV (SCID) before and after treatment. Results: Therapeutic improvement on atomoxetine as evidenced by reduced CAARS scores was reliably predicted by the presence of a lifetime comorbid diagnosis of depression or post-traumatic stress disorder at baseline, while improvement oil subscales of the GWB and Sheehan Disability Scale were predicted by these and other SCID endorsements, such as alcohol and substance use, as well as demographics such as age and gender. In light of the exploratory nature of this work and the many comparisons that were examined in the corresponding regression models, these findings should be regarded as tentative pending replication and extension in another dataset. Conclusion: From these findings, we conclude that the variable responsiveness of individuals to atomoxetine cannot be largely accounted for by differences in broad-spectrum psychopathology or neuropsychological indicators of attentional capacity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. Univ Utah, Dept Psychiat, Salt Lake City, UT USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Spencer, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, WRM 705,55 Fruit St, Boston, MA 02114 USA. EM spencer@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 16 TC 23 Z9 23 U1 0 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 MAR PY 2006 VL 67 IS 3 BP 415 EP 420 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 031RL UT WOS:000236721600011 PM 16649828 ER PT J AU Blank, S Lenze, EJ Mulsant, BH Dew, MA Karp, JF Shear, MK Houck, PR Miller, MD Pollock, BG Tracey, B Reynolds, CF AF Blank, S Lenze, EJ Mulsant, BH Dew, MA Karp, JF Shear, MK Houck, PR Miller, MD Pollock, BG Tracey, B Reynolds, CF TI Outcomes of late-life anxiety disorders during 32 weeks of citalopram treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; CONTROLLED-TRIAL; OLDER-ADULTS; EFFICACY; PHARMACOTHERAPY; COMORBIDITY; RECOVERY; AGE AB Background: Anxiety disorders are common in later life, but little is known about the longterm benefits and risks of pharmacotherapy. Method: 30 patients aged 60 years and older, with a DSM-IV anxiety disorder, entered a 32-week trial of citalopram. Data gathered at baseline and follow-up included anxiety symptoms using Hamilton Rating Scale for Anxiety (HAM-A) scores, quality of life using the Medical Outcomes Study 36-item Short Form (SF-36), and sleep using the Pittsburgh Sleep Quality Index (PSQI). Data analysis consisted of mixed effect repeated measures models of HAM-A scores and pre-post comparison of SF-36 and PSQI scores. Results: 30 persons entered treatment: most (27/30) had a primary DSM-IV diagnosis of generalized anxiety disorder (2 had panic disorder; I had posttraurnatic stress disorder). Three subjects discontinued study medication clue to side effects. 5 were terminated because of nonresponse, and 5 dropped out of the study for other reasons; thus, 17 subjects (57%) completed 32 weeks of treatment. Subjects' HAM-A scores improved significantly, with continuing improvements up until about 20 weeks of treatment. On the basis of a criterion of reduction in HAM-A to < 10 during the trial, 60% (18/30) of subjects were responders. Those who completed the 32-week trial had significant improvements in sleep and quality of life-including social functioning, vitality, mental health, and role difficulties due to emotional problems. Conclusions: In this 32-week study of citalopram for elderly persons with anxiety disorders, 60% responded. Those who received a full course of treatment experience significant improvements in quality of life and sleep quality. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Intervent Res Ctr Late Life Mood Disorders, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Lenze, EJ (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM lenzeej@msx.upmc.edu FU NIMH NIH HHS [P30 MH 52247, T32 MH8619986, K23 MH 64196] NR 27 TC 14 Z9 15 U1 0 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 MAR PY 2006 VL 67 IS 3 BP 468 EP 472 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 031RL UT WOS:000236721600018 PM 16649835 ER PT J AU Shipp, TD Bromley, B Benacerraf, B AF Shipp, TD Bromley, B Benacerraf, B TI Is 3-dimensional volume sonography an effective alternative method to the standard 2-dimensional technique of measuring the nuchal translucency? SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE 3-dimensional ultrasound; fetus; technology assessment; nuchal translucency ID TRANSVAGINAL ULTRASOUND; THICKNESS MEASUREMENTS; DOWN-SYNDROME AB Purpose. To determine whether 3-dimensional (3D) volume scanning is an effective alternative method of measuring nuchal translucency in first-trimester fetuses compared with the standard 2-dimensional (2D) technique, and to report a standardized method of evaluation. Methods. We measured the nuchal translucency of 29 fetuses between 11.4 and 13.9 weeks of age using the standard 2D sonographic technique with the fetus in a sagittal view. We then rescanned the fetus in a coronal orientation and obtained a 3D volume of the fetal neck area from crown to rump using a consistent technique. The sagittal orientation was reconstructed, and the width of the nuchal translucency was measured electronically using the reconstructed midsagittal view. The measurements using a conventional 2D sagittal view were then compared with the 3D reconstructed sagittal view. The nuchal translucency was adequately measured in all fetuses in which the 3D assessment was attempted. Results. The nuchal translucencies of 29 consecutive fetuses were measured using both 2D and 3D multiplanar reconstruction of the fetal neck. The mean standard deviation for the standard 2D assessment of the nuchal translucency was 1.7 +/- 1.4 mm. Using 3D reconstruction of the Z plane, the measurement was 1.8 +/- 1.6 mm. This was not a statistically significant difference (P=0.4). There was a very high correlation between the two techniques (r=0.984, P<0.001). Conclusions. There is an excellent correlation between the measurements of the nuchal translucency using standard 2D scanning and those obtained from 3D multiplanar reconstruction of the Z plane. Using a consistent technique, the nuchal translucency can be accurately and reliably measured with a 3D rendering. This technique is potentially useful in fetuses that are not in an optimal position for standard 2D nuchal translucency measurement. (C) 2006 Wiley Periodicals, Inc. C1 Diagnost Ultrasound Associates PC, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol,Div Maternal Fetal Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Shipp, TD (reprint author), Diagnost Ultrasound Associates PC, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD MAR-APR PY 2006 VL 34 IS 3 BP 118 EP 122 DI 10.1002/jcu.20215 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 037UI UT WOS:000237172400003 PM 16547988 ER PT J AU Powitzky, ES Hayman, LA Bartling, SH Chau, J Gupta, R Shukla, V AF Powitzky, ES Hayman, LA Bartling, SH Chau, J Gupta, R Shukla, V TI High-resolution computed tomography of temporal bone - Part III: Axial postoperative anatomy SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE temporal bone anatomy; temporal bone computed tomography; temporal bone postoperative appearance; temporal bone surgery ID MIDDLE-EAR; OSSICULAR RECONSTRUCTION; COCHLEAR IMPLANTATION; PREOPERATIVE ANATOMY; VOLUME-CT; SURGERY AB The purpose of this 4-part series is to illustrate the nuances of temporal bone anatomy using a high-resolution (200-mu isotropic) prototype Volume computed tomography (CT) scanner. The normal anatomy in axial and coronal sections is depicted in the first and second parts. In this and the subsequent part, the structures that are removed and/or altered in 9 different surgical procedures are color coded and inscribed ill the same axial (article 111) and coronal (article IV) sections. The text stresses clinically important imaging features, including the normal postoperative appearance, and common complications after these operations. The superior resolution of the volume CT images is vital to the comprehensive and accurate representation of these operations. Minuscule intricate Structures that arc Currently only localized in the mind's eye because of the resolution limit of conventional CT are clearly seen oil these scans. This enhanced visualization, together with the information presented in the text, Should assist in interpreting temporal bone scans, Communicating with surgeons, and teaching this complex anatomy. C1 Ctr ENT, Houston, TX 77030 USA. Baylor Coll Med, Dept Otolaryngol, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX USA. Hannover Med Sch, Dept Neuroradiol, D-3000 Hannover, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Alberta, Dept Otolaryngol, Edmonton, AB, Canada. RP Powitzky, ES (reprint author), Ctr ENT, 6624 Fannin,Suite 1480, Houston, TX 77030 USA. EM epo@centerforent.com OI Powitzky, Eric/0000-0002-1747-9439 NR 17 TC 4 Z9 7 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 MAR-APR PY 2006 VL 30 IS 2 BP 337 EP 343 DI 10.1097/00004728-200603000-00034 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 028HU UT WOS:000236478600034 PM 16628060 ER PT J AU Tejerina, E Frutos-Vivar, F Restrepo, MI Anzueto, A Abroug, F Palizas, F Gonzalez, M D'Empaire, G Apezteguia, C Esteban, A AF Tejerina, E Frutos-Vivar, F Restrepo, MI Anzueto, A Abroug, F Palizas, F Gonzalez, M D'Empaire, G Apezteguia, C Esteban, A CA Int Mech Ventilation Stdy Grp TI Incidence, risk factors, and outcome of ventilator-associated pneumonia SO JOURNAL OF CRITICAL CARE LA English DT Article DE critical care; epidemiology; mechanical ventilation; ventilator-associated pneumonia; mortality; outcome ID INTENSIVE-CARE UNITS; NOSOCOMIAL PNEUMONIA; HOSPITAL STAY; MORTALITY; INFECTION; MORBIDITY; DIAGNOSIS; PROGNOSIS; COHORT; ONSET AB Objective: The purpose of this study is to determine the incidence, risk factors, and outcome of ventilator-associated pneumonia (VAP). Design: Prospective cohort. Setting: Three hundred sixty-one intensive care units (ICUs) from 20 countries. Patients and Participants: Two thousand eight hundred ninety-seven patients mechanically ventilated for more than 12 hours. Measurements and Results: Baseline demographic data, primary indication for mechanical ventilation, daily ventilator settings, multiple organ failure over the course of mechanical ventilation, and outcome were collected. Ventilator-associated pneumonia was present in 439 patients (15%). Patients with VAP were more likely to have chronic pulmonary obstructive disease, aspiration, sepsis, and acute respiratory distress syndrome. Mortality in patients with VAP was 38%. Factors associated with mortality were severity of illness, limited activity before the onset of mechanical ventilation and development of shock, acute renal failure, and worsening of hypoxemia during the period of mechanical ventilation. Casecontrol analysis showed no increased mortality in patients with VAP (38.1% vs 37.9%, P =.95) but prolonged duration of mechanical ventilation and ICU stay. Conclusion: In a large cohort of mechanically ventilated patients, VAP is more likely in patients with underlying lung disease (acute or chronic). Ventilator-associated pneumonia was associated with a significant increase in ICU length of stay but no increase in mortality. (c) 2006 Elsevier Inc. All rights reserved. C1 Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Intens Care Unit, San Antonio, TX USA. Ctr Hosp Univ Fattouma Burghuiba, Intens Care Unit, Monastir 5000, Tunisia. Clin Bazterr, Intens Care Unit, RA-1425 Buenos Aires, DF, Argentina. Hosp Gen Medellin, Intens Care Unit, Medellin, Colombia. Hosp Clin Caracas, Intens Care Unit, Caracas, Venezuela. Hosp Nacl Prof Alejandro Posadas, Intens Care Unit, RA-1706 Haedo, Argentina. RP Esteban, A (reprint author), Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. EM aesteban@ucigetafe.com OI Frutos-Vivar, Fernando/0000-0002-4648-9636 NR 24 TC 59 Z9 77 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD MAR PY 2006 VL 21 IS 1 BP 56 EP 65 DI 10.1016/j.jcrc.2005.08.005 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 036JE UT WOS:000237066600010 PM 16616625 ER PT J AU Anderson, B Mishory, A Nahas, Z Borckardt, JJ Yamanaka, K Rastogi, K George, MS AF Anderson, B Mishory, A Nahas, Z Borckardt, JJ Yamanaka, K Rastogi, K George, MS TI Tolerability and safety of high daily doses of repetitive transcranial magnetic stimulation in healthy young men SO JOURNAL OF ECT LA English DT Article DE rTMS; transcranial magnetic stimulation; safety; seizure ID HUMAN MOTOR CORTEX; RESISTANT DEPRESSION; DOUBLE-BLIND; RTMS; EFFICACY; SEIZURE; MEMORY AB Repetitive transcranial magnetic stimulation (rTMS) is an experimental technology that involves a powerful magnetic pulse applied to the scalp, which is sufficient to cause neuronal depolarization. Transcranial magnetic stimulation has been used in treatment studies for psychiatric disorders, primarily unipolar depression, and as a tool to map brain function. Although thousands of rTMS sessions have been given with few side effects, rTMS can produce serious adverse effects such as an unintended seizure. Safety guidelines for frequency, duration, and intensity of rTMS have aided in the prevention of such adverse side effects. However, the total dose (number of stimuli) able to be delivered safely to human subjects within a day or within a week has not been established. For example, previous rTMS Studies as a treatment for depression consisted of delivering 800 to 3000 magnetic pulses per day, with 8000 to 30,000 magnetic pulses over 2 to 3 weeks. This study examined whether high doses of rTMS within a day or over a week would produce significant side effects. As part of a study to examine rTMS effects in sleep deprivation, we exposed healthy men to 12,960 magnetic pulses a day for up to 3 days in I week. This equals 38,880 magnetic pulses over I week, which is likely one of the largest exposures of TMS to date. Despite this intense treatment regimen, we failed to produce significant side effects. Doses of up to 12,960 pulses per day appear safe and tolerable in healthy Young men. C1 Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. RP Anderson, B (reprint author), Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, 67 President St,502 N, Charleston, SC 29425 USA. EM andersob@musc.edu FU NCRR NIH HHS [M01 RR01070]; NIA NIH HHS [AG40956]; NIMH NIH HHS [R01-MH069896, R01-MH069887] NR 33 TC 41 Z9 44 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD MAR PY 2006 VL 22 IS 1 BP 49 EP 53 DI 10.1097/00124509-200603000-00011 PG 5 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 033BU UT WOS:000236822100011 PM 16633208 ER PT J AU Lee, K AF Lee, K TI Acute embolic stroke after electroconvulsive therapy SO JOURNAL OF ECT LA English DT Article DE acute stroke; cryptogenic stroke; electroconvulsive therapy ID ATRIAL-FIBRILLATION; SEIZURE THRESHOLD; CARDIOVERSION; ECT AB This is the case report of a 44-year-old woman presented with an acute stroke immediately after electroconvulsive therapy (ECT). The patient had no significant medical history other than chronic depression. She was taking sertraline, and she had had multiple previous ECT treatments without any complications. While being monitored in the recovery room within 10 minutes after the last ECT session, she was found to have sudden onset of left-sided flaccid hemiplegia and numbness along with slurred speech. On arrival to our hospital, she was found to have flaccid hemiplegia on the left side involving the face, ann, and leg (face and arm more than the leg involvement), severe dysarthria, and mild neglect syndrome (National Health Institute Stroke Scale of 14). Noncontrast computed tomography (CT) of the head showed no signs of early ischemia, and iodine contrast CT angiography revealed right middle cerebral artery (MCA) (distal M I segment) clot. Patient received intravenous recombinant tissue plasminogen (rt-PA) at 2.5 hours after the onset of symptoms, and then a total of 3.0 mg of intra-arterial (IA) rt-PA. Angiography at the end of the procedure showed successful recanalization of the M1 segment and normal vessel caliber with adequate distal flow. After the procedure, the patient made rapid improvements in all of her initial symptoms during the first 24 hours. An extensive stroke workup failed to reveal any cause of the stroke, including usual stroke and hypercoagulable risk factors. This was an acute embolic stroke immediately following an ECT, and without the aggressive thrombolytic therapy, the patient's outcome would have been poor because there was an M1 segment clot with a major MCA syndrome with relatively high National Institute of Health Stroke Scale. The neurological side effect profile of ECT is reported to be minimal with most common symptoms being headache, disorientation, and memory complaints. There is no clear cause-and-effect relationship in this case, and the stroke after ECT is extremely rare. In Such rare event of stroke while receiving ECT, there is an effective treatment available using both intravenous and IA thrombolysis as reported in this case. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Lee, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 9 TC 7 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD MAR PY 2006 VL 22 IS 1 BP 67 EP 69 DI 10.1097/00124509-200603000-00014 PG 3 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 033BU UT WOS:000236822100014 PM 16633211 ER PT J AU Peden-Adams, MM EuDaly, JG Heesemann, LM Smythe, J Miller, J Gilkeson, GS Keil, DE AF Peden-Adams, MM EuDaly, JG Heesemann, LM Smythe, J Miller, J Gilkeson, GS Keil, DE TI Developmental immunotoxicity of trichloroethylene (TCE): Studies in B6C3F1 mice SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING LA English DT Article DE TCE; immune; PFC; developmental immunotoxicology; DTH ID LUPUS-ERYTHEMATOSUS SLE; RISK-ASSESSMENT; AUTOIMMUNE-RESPONSE; HOST-RESISTANCE; EXPOSURE; SINGLE; IMMUNE; CELLS; WATER; HYPERSENSITIVITY AB This study assessed the developmental immunotoxicity of trichloroethylene (TCE) in B6C3F1 mice exposed via drinking water (0, 1,400, 14,000 ppb) from gestation day 0 (GD0) to either 3 or 8 weeks of age. Lymphocyte proliferation, NK cell activity, SRBC-specific IgM production (PFC response), splenic B220+ cells, and thymic and splenic T-cell immunophenotypes were assessed at 3 and 8 weeks of age. Delayed type hypersensitivity (DTH) and autoantibodies to ds-DNA were assessed in 8-week old animals only. Proliferation and NK cell activity were not affected at either age. Decreased PFC responses were noted in male offspring at both ages and both TCE treatment levels. PFC responses in female offspring were suppressed by treatment with 14,000 ppb TCE at both ages assessed and at 1,400 ppb TCE at 8 weeks of age. Splenic numbers of B220 cells were only decreased in 3-week old pups exposed to 14,000 ppb TCE. The most pronounced alteration in T-cell subpopulations were increases in all thymic (CD4+, CD8+, CD4+/CD8+, and CD4-/CD8-) T-cell types in 8-week old animals. DTH was increased in females at both TCE levels and in males at the high dose only. These results indicate that TCE may be an effective developmental immunotoxicant and suggests that additional studies are required to determine the health risks associated with developmental exposure to TCE. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29412 USA. Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29412 USA. Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29412 USA. Med Univ S Carolina, Marine Biomed & Environm Sci Ctr, Charleston, SC 29412 USA. Ralph Johnson VAMC, Med Res Serv, Charleston, SC USA. RP Peden-Adams, MM (reprint author), Med Univ S Carolina, Dept Pediat, 221 Ft Johnson Rd, Charleston, SC 29412 USA. EM pedenada@musc.edu NR 29 TC 22 Z9 23 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1093-4529 J9 J ENVIRON SCI HEAL A JI J. Environ. Sci. Health Part A-Toxic/Hazard. Subst. Environ. Eng. PD MAR PY 2006 VL 41 IS 3 BP 249 EP 271 DI 10.1080/10934520500455289 PG 23 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 012NN UT WOS:000235346000001 PM 16484062 ER PT J AU Rich-Edwards, JW Kleinman, K Abrams, A Harlow, BL McLaughlin, TJ Joffe, H Gillman, MW AF Rich-Edwards, JW Kleinman, K Abrams, A Harlow, BL McLaughlin, TJ Joffe, H Gillman, MW TI Sociodemographic predictors of antenatal and postpartum depressive symptoms among women in a medical group practice SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID SOCIAL SUPPORT; POSTNATAL DEPRESSION; MAJOR DEPRESSION; COMMUNITY SAMPLE; UNITED-STATES; RISK-FACTORS; PREGNANCY; PREVALENCE; DISORDERS; MOTHERS AB Objective: Data are scarce regarding the sociodemographic predictors of antenatal and postpartum depression. This study investigated whether race/ethnicity, age, finances, and partnership status were associated with antenatal and postpartum depressive symptoms. Setting: 1662 participants in Project Viva, a US cohort study. Design: Mothers indicated mid-pregnancy and six month postpartum depressive symptoms on the Edinburgh postpartum depression scale (EPDS). Associations of sociodemographic factors with odds of scoring > 12 on the EPDS were estimated. Main results: The prevalence of depressive symptoms was 9% at mid-pregnancy and 8% postpartum. Black and Hispanic mothers had a higher prevalence of depressive symptoms compared with non-Hispanic white mothers. These associations were explained by lower income, financial hardship, and higher incidence of poor pregnancy outcome among minority women. Young maternal age was associated with greater risk of antenatal and postpartum depressive symptoms, largely attributable to the prevalence of financial hardship, unwanted pregnancy, and lack of a partner. The strongest risk factor for antenatal depressive symptoms was a history of depression (OR = 4.07; 95% CI 3.76, 4.40), and the strongest risk for postpartum depressive symptoms was depressive symptoms during pregnancy (6.78; 4.07, 11.31) or a history of depression before pregnancy (3.82; 2.31, 6.31). Conclusions: Financial hardship and unwanted pregnancy are associated with antenatal and postpartum depressive symptoms. Women with a history of depression and those with poor pregnancy outcomes are especially vulnerable to depressive symptoms during the childbearing year. Once these factors are taken in account, minority mothers have the same risk of antenatal and postpartum depressive symptoms as white mothers. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Eoidemiol, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Div Clin Res, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Rich-Edwards, JW (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM janet_rich-edwards@hphc.org FU NHLBI NIH HHS [K24 HL068041, K24HL68041]; NIMH NIH HHS [MH068596, MH56217, R01 MH068596] NR 43 TC 212 Z9 217 U1 4 U2 22 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD MAR PY 2006 VL 60 IS 3 BP 221 EP 227 DI 10.1136/jech.2005.039370 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 012MR UT WOS:000235343800009 PM 16476752 ER PT J AU Lin, WY Kim, SS Yeung, E Chung, RT AF Lin, Wenyu Kim, Sun Suk Yeung, Elaine Chung, Raymond T. TI HCV core protein expression blocks type IIFN signal pathway by reducing P-STAT1 SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2006 VL 21 SU 2 BP A76 EP A76 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 179WG UT WOS:000247320400016 ER PT J AU McLaughlin, MA Orosz, GM Magaziner, J Hannan, EL McGinn, T Morrison, RS Hochman, T Koval, K Gilbert, M Siu, AL AF McLaughlin, MA Orosz, GM Magaziner, J Hannan, EL McGinn, T Morrison, RS Hochman, T Koval, K Gilbert, M Siu, AL TI Preoperative status and risk of complications in patients with hip fracture SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE preoperative assessment; complications; elderly; noncardiac surgery; hip fracture ID NONCARDIAC SURGERY; ELDERLY PATIENTS; CARDIAC RISK; MORTALITY; OUTCOMES; VALIDATION; INDEX; ASSOCIATION; PREDICTION; GUIDELINE AB Background: Limited information is available on preoperative status and risks for complications for older patients having surgery for hip fracture. Our objective was to identify potentially modifiable clinical findings that should be considered in decisions about the timing of surgery. Methods: We conducted a prospective cohort study with data obtained from medical records and through structured interviews with patients. A total of 571 adults with hip fracture who were admitted to 4 metropolitan hospitals were included. Results: Multiple logistic regression was used to identify risk factors (including 11 categories of physical and laboratory findings, classified as mild and severe abnormalities) for in-hospital complications. The presence of more than 1 (odds ratiol [OR] 9.7, 95% confidence interval [CI] 2.8 to 33.0) major abnormality before surgery or the presence of major abnormalities on admission that were not corrected prior to surgery (OR 2.8, 95% CI 1.2 to 6.4) was independently associated with the development of postoperative complications. We also found that minor abnormalities, while warranting correction, did not increase risk (OR 0.70, 95% CI 0.28 to 1.73). Conclusions: In this study of older adults undergoing urgent surgery, potentially reversible abnormalities in laboratory and physical examination occurred frequently and significantly increased the risk of postoperative complications. Major clinical abnormalities should be corrected prior to surgery, but patients with minor abnormalities may proceed to surgery with attention to these medical problems perioperatively. C1 CUNY, Mt Sinai Med Ctr, Mt Sinai Sch Med, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. Univ Arkansas Med Sci, Ft Smith, AR USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12222 USA. Hosp Joint Dis & Med Ctr, New York, NY USA. RP McLaughlin, MA (reprint author), CUNY, Mt Sinai Med Ctr, Mt Sinai Sch Med, Box 1030,1 Gustave L Levy Pl, New York, NY 10029 USA. EM maryann.mclaughlin@mssm.edu FU AHRQ HHS [U18 HS009459, U18HS09459-0]; NIA NIH HHS [K24 AG000918, R01 AG021992] NR 33 TC 34 Z9 44 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 IS 3 BP 219 EP 225 DI 10.1111/j.1525-1497.2006.00318.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024UY UT WOS:000236223000003 PM 16390507 ER PT J AU Palonen, KP Allison, JJ Heudebert, GR Willett, LL Kiefe, CI Wall, TC Houston, TK AF Palonen, KP Allison, JJ Heudebert, GR Willett, LL Kiefe, CI Wall, TC Houston, TK TI Measuring resident physicians' performance of preventive care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE education; medical; preventive health services; patient survey; medical record review; cost evaluation ID MEDICAL-RECORD AUDIT; QUALITY-OF-CARE; STANDARDIZED PATIENTS; PATIENT QUESTIONNAIRES; CLINICAL VIGNETTES; CHART ABSTRACTION; HEALTH-CARE; SELF-REPORT; GUIDELINES; SMOKING AB Background: The Accreditation Council for Graduate Medical Education has suggested various methods for evaluation of practice-based learning and improvement competency, but data on implementation of these methods are limited. Objective: To compare medical record review and patient surveys on evaluating physician performance in preventive services in an outpatient resident clinic. Design: Within an ongoing quality improvement project, we collected baseline performance data on preventive services provided for patients at the University of Alabama at Birmingham (UAB) Internal Medicine Residents' ambulatory clinic. Participants:eventy internal medicine and medicine-pediatrics residents from the UAB Internal Medicine Residency program. Measurements: Resident- and clinic-level comparisons of aggregated patient survey and chart documentation rates of (1) screening for smoking status, (2) advising smokers to quit, (3) cholesterol screening, (4) mammography screening, and (5) pneumonia vaccination. Results: Six hundred and fifty-nine patient surveys and 761 charts were abstracted. At the clinic level, rates for screening of smoking status, recommending mammogram, and for cholesterol screening were similar (difference < 5%) between the 2 methods. Higher rates for pneumonia vaccination (76% vs 67%) and advice to quit smoking (66% vs 52%) were seen on medical record review versus patient surveys. However, within-resident (N=70) comparison of 2 methods of estimating screening rates contained significant variability. The cost of medical record review was substantially higher ($107 vs $17/physician). Conclusions: Medical record review and patient surveys provided similar rates for selected preventive health measures at the clinic level, with the exception of pneumonia vaccination and advising to quit smoking. A large variation among individual resident providers was noted. C1 Birmingham VA Med Ctr, HSR&D Res Enhancement Award Program, Birmingham, AL USA. Univ Alabama, Dept Med, Div Gen Internal Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Vet Hlth Adm, Off Acad Affiliat, VA Natl Qual Scholars, Birmingham, AL USA. Univ Alabama, Dept Pediat, Div Gen Pediat, Birmingham, AL USA. RP Palonen, KP (reprint author), 1530 3rd Ave S,FOT 720, Birmingham, AL 35294 USA. EM palonen@uab.edu RI Houston, Thomas/F-2469-2013 NR 29 TC 12 Z9 12 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 IS 3 BP 226 EP 230 DI 10.1111/j.1525-1497.2006.00338.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024UY UT WOS:000236223000004 PM 16499544 ER PT J AU Chan, ECY Barry, MJ Vernon, SW Ahn, C AF Chan, ECY Barry, MJ Vernon, SW Ahn, C TI Brief report: Physicians and their personal prostate cancer-screening practices with prostate-specific antigen SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE prostate specific antigen; informed decision making; prostate cancer screening; physician practice ID PRIMARY-CARE PHYSICIANS; UNITED-STATES; MEN; UROLOGISTS; BELIEFS AB Background: There is inconclusive evidence that prostate cancer screening with prostate-specific antigen (PSA) reduces mortality. Although PSA testing is widespread, it is unknown how many physicians have taken the PSA test themselves. Objective: To determine the prevalence of PSA testing among physicians. Design: Cross-sectional survey. Subjects: A nationwide stratified random sample of urologists (response rate 61%, n=247), Internists (response rate 51%, n=273), and family physicians (response rate 64%, n=249) were surveyed by mail in 2000. After excluding female respondents and men who either reported a positive history of prostate cancer or did not respond to that query, there were 146 urologists, 96 Internists, and 118 family physicians. Measurements: Whether physicians had undergone prostate cancer screening with PSA. Results: Eighty-seven percent (155/178) of male physicians aged, 50 and older and 21% (31/150) of white male physicians under age 50 reported having had a PSA test. More urologists than nonurologists in both age groups reported having had a screening PSA test. Conclusions: Most physicians aged 50 and older report undergoing PSA testing. This may reflect a belief in its efficacy and contribute to its widespread use. C1 Univ Texas, Houston Med Sch, Dept Med, Div Gen Internal Med, Houston, TX 77030 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Univ Texas, Houston Med Sch, Div Hlth Promot & Behav Sci, Ctr Hlth Promot & Prevent Res, Houston, TX 77030 USA. RP Chan, ECY (reprint author), Univ Texas, Houston Med Sch, Dept Med, Div Gen Internal Med, 6431 Fannin,1-122 MSB, Houston, TX 77030 USA. EM Evelyn.C.Chan@uth.tmc.edu FU NCI NIH HHS [K08-CA78615]; NCRR NIH HHS [M01-RR02558, M01 RR002558]; PHS HHS [S1171-19/20] NR 21 TC 17 Z9 17 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 IS 3 BP 257 EP 259 DI 10.1111/j.1525-1497.2006.00327.x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 024UY UT WOS:000236223000009 PM 16637825 ER PT J AU Borrero, S Kwoh, CK Sartorius, J Ibrahim, SA AF Borrero, S Kwoh, CK Sartorius, J Ibrahim, SA TI Brief Report: Gender and total knee/hip arthroplasty utilization rate in the VA system SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE osteoarthritis; gender; arthroplasty; Veterans Administration ID TOTAL HIP-ARTHROPLASTY; MEDICARE POPULATION; UNITED-STATES; REPLACEMENT; OUTCOMES; SURGERY; WOMEN; MEN AB Objective: Osteoarthritis (OA) is a leading cause of disability and is more prevalent in women than men. Total joint arthroplasty is an effective treatment option for end-stage OA. We examined gender differences in utilization rates of total knee/hip arthroplasty in the Veterans Administration (VA) system. Methods: The sample consisted of all VA patients for fiscal year (FY) 1999, 50 years of age or older, with or without the diagnosis of OA in any joint. We calculated the odds of patients undergoing total knee/hip arthroplasty adjusting for age, comorbidities, and presence of OA. We included the hospital site as a random effects variable to adjust for clustering. Results: Of the 1,968,093 (2.3% women) VA patients in FY 1999 who were 50 years of age or older, 329,461 (2.9% women) patients carried a diagnosis of OA. For women, 2-year adjusted odds of undergoing total knee or hip arthroplasty were 0.97 (0.83 to 1.14) and 1.00 (0.79 to 1.27), respectively. Conclusion: Among patients potentially at risk for the procedure, men and women in the VA system were equally likely to undergo knee/hip arthroplasty. C1 VA Pittsburgh Hlth Care Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Hlth Care Syst, Ctr Hlth Equity Res & Promot, 151-C, Pittsburgh, PA 15240 USA. EM said.ibrahim2@med.va.gov NR 20 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S54 EP S57 DI 10.1111/j.1525-1497.2006.00375.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500011 PM 16637947 ER PT J AU Cope, JR Yano, EM Lee, ML Washington, DL AF Cope, JR Yano, EM Lee, ML Washington, DL TI Determinants of contraceptive availability at medical facilities in the department of veterans affairs SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Meeting of the Academy-of-Health-Services-Research CY JUN 06-08, 2004 CL San Diego, CA SP Acad Hlth Serv Res DE women's health; veterans; contraception; birth control; family planning; US Department of Veterans Affairs ID WOMENS HEALTH-CARE; FAMILY-PLANNING AGENCIES; UNITED-STATES; OUTPATIENT CLINICS; PERFORMANCE-MEASURES; INTRAUTERINE-DEVICE; SERVICES; PHYSICIANS; PROVISION; PREGNANCY AB Objective: To describe the variation in provision of hormonal and intrauterine contraception among Veterans Affairs (VA) facilities. Design: Key informant, cross-sectional survey of 166 VA medical facilities. Data from public use data sets and VA administrative databases were linked to facility data to further characterize their contextual environments. Participants: All VA hospital-based and affiliated community-based outpatient clinics delivering services to at least 400 unique women during fiscal year 2000. Measurements: Onsite availability of hormonal contraceptive prescription and intrauterine device (IUD) placement. Results: Ninety-seven percent of facilities offered onsite prescription and management of hormonal contraception whereas 63% offered placement of IUDs. After adjusting for facility caseload of reproductive-aged women, 3 organizational factors were independently associated with onsite IUD placement: (1) onsite gynecologist (adjusted odds ratio [OR], 20.35; 95% confidence interval [CI], 7.02 to 58.74; P <.001); (2) hospital-based in contrast to community-based practice (adjusted OR, 5.49; 95% CI, 1.16 to 26.10; P=.03); and (3) availability of a clinician providing women's health training to other clinicians (adjusted OR, 3.40; 95% CI 1.19 to 9.76; P=.02). Conclusions: VA's provision of hormonal and intrauterine contraception is in accordance with community standards, although onsite availability is not universal. Although contraception is a crucial component of a woman's health maintenance, her ability to obtain certain contraceptives from the facility where she obtains her primary care is largely influenced by the availability of a gynecologist. Further research is needed to determine how fragmentation of women's care into reproductive and nonreproductive services impacts access to contraception and the incidence of unintended pregnancy. C1 VA Greater Los Angeles HSR&D Ctr Excellenc, VA Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. Dept Hlth Serv, ValleyCare, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Yano, EM (reprint author), VA Greater Los Angeles HSR&D Ctr Excellenc, VA Sepulveda Ambulatory Care Ctr, 16111 Plummer St 152, Sepulveda, CA 91343 USA. EM Elizabeth.Yano@va.gov NR 40 TC 13 Z9 15 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S33 EP S39 DI 10.1111/j.1525-1497.2006.00372.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500008 PM 16637943 ER PT J AU Frayne, SM Parker, VA Christiansen, CL Loveland, S Seaver, MR Kazis, LE Skinner, KM AF Frayne, SM Parker, VA Christiansen, CL Loveland, S Seaver, MR Kazis, LE Skinner, KM TI Health status among 28,000 women veterans - The VA women's health program evaluation project SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women's health; veterans; health status; quality of life; social support ID POSTTRAUMATIC-STRESS-DISORDER; QUALITY-OF-LIFE; SOCIAL SUPPORT; MENTAL-HEALTH; MYOCARDIAL-INFARCTION; SOCIOECONOMIC-STATUS; FEMALE VETERANS; ALAMEDA COUNTY; SEXUAL ASSAULT; WAR VETERANS AB Background: Male veterans receiving Veterans Health Administration (VA) care have worse health than men in the general population. Less is known about health status in women veteran VA patients, a rapidly growing population. Objective: To characterize health status of women (vs men) veteran VA patients across age cohorts, and assess gender differences in the effect of social support upon health status. Design and Patients: Data came from the national 1999 Large Health Survey of Veteran Enrollees (response rate 63%) and included 28,048 women and 651,811 men who used VA in the prior 3 years. Measurements: Dimensions of health status from validated Veterans Short Form-36 instrument; social support (married, living arrangement, have someone to take patient to the doctor). Results: In each age stratum (18 to 44, 45 to 64, and >= 65 years), Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were clinically comparable by gender, except that for those aged >= 65, mean MCS was better for women than men (49.3 vs 45.9, P <.001). Patient gender had a clinically insignificant effect upon PCS and MCS after adjusting for age, race/ethnicity, and education. Women had lower levels of social support than men; in patients aged < 65, being married or living with someone benefited MCS more in men than in women. Conclusions: Women veteran VA patients have as heavy a burden of physical and mental illness as do men in VA, and are expected to require comparable intensity of health care services. Their ill health occurs in the context of poor social support, and varies by age. C1 VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. Stanford Univ, Sch Med, Div Gen Internal Med, Stanford, CA 94305 USA. VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Frayne, SM (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA. EM sfrayne@stanford.edu OI Christiansen, Cindy/0000-0001-9951-480X; Kazis, Lewis/0000-0003-1800-5849; Parker, Victoria/0000-0002-7632-9174 NR 51 TC 53 Z9 53 U1 4 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S40 EP S46 DI 10.1111/j.1525-1497.2006.00373.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500009 PM 16637944 ER PT J AU Goldzweig, CL Balekian, TM Rolon, C Yano, EM Shekelle, PG AF Goldzweig, CL Balekian, TM Rolon, C Yano, EM Shekelle, PG TI The state of women veterans' health research SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE women; veterans; systematic review ID POSTTRAUMATIC-STRESS-DISORDER; PERSIAN-GULF-WAR; FEMALE VIETNAM VETERANS; AFFAIRS MEDICAL-CENTER; US MILITARY PERSONNEL; HORMONE REPLACEMENT THERAPY; SELF-REPORTED HEALTH; MENTAL-HEALTH; SEXUAL ASSAULT; NATIONAL SAMPLE AB Objective: Assess the state of women veterans' health research. Design: Systematic review of studies that pertained specifically to or included explicit information about women veterans. A narrative synthesis of studies in 4 domains/topics was conducted: Stress of military life; Health and performance of military/VA women; Health services research/quality of care; and Psychiatric conditions. Measurements and Main Results: We identified 182 studies. Of these, 2 were randomized-controlled trials (RCTs) and the remainder used observational designs. Forty-five percent of studies were VA funded. We identified 77 studies pertaining to the stress of military life, of which 21 reported on sexual harassment or assault. Rates of harassment ranged from 55% to 79% and rates of sexual assault from 4.2% to 7.3% in active duty military women and 11% to 48% among women veterans. Forty-two studies concerned the health and performance of military/VA women, with 21 studies evaluating sexual assault and posttraumatic stress disorder (PTSD) and their effect on health. Fifty-nine studies assessed various aspects of health services research. Eight studies assessed quality of care and 5, patient satisfaction. Twenty-five studies assessed utilization and health care organization, and findings include that women veterans use the VA less than men, that gender-specific reasons for seeking care were common among female military and veteran personnel, that provision of gender-specific care increased women veterans' use of VA, and that virtually all VAs have available on-site basic women's health services. Fifty studies were classified as psychiatric; 31 of these were about the risk, prevalence, and treatment of PTSD. Conclusions: Most research on VA women's health is descriptive in nature and has concerned PTSD, sexual harassment and assault, the utilization and organization of care, and various psychiatric conditions. Experimental studies and studies of the quality of care are rare. C1 Greater Los Angeles VA Healthcare Syst, So Calif Evidence Based Practice Ctr, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. RP Goldzweig, CL (reprint author), VA W Los Angeles Healthcare Ctr, 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM caroline.goldzweig@va.gov NR 141 TC 88 Z9 89 U1 2 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S82 EP S92 DI 10.1111/j.1225-1497.2006.00380.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500016 PM 16637952 ER PT J AU Johnson, KM Nelson, KM Bradley, KA AF Johnson, KM Nelson, KM Bradley, KA TI Television viewing practices and obesity among women veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med DE obesity; television; women veterans ID POSTTRAUMATIC-STRESS-DISORDER; FEMALE VETERANS; HEALTH-PROFESSIONALS; SOCIOECONOMIC-STATUS; PHYSICAL-ACTIVITY; ACTIVITY PROGRAMS; AFFAIRS PATIENTS; OVERWEIGHT; ASSOCIATION; DEPRESSION AB Background: Obesity is epidemic in the U.S. and has been associated with television viewing. Objective: To describe the association between obesity and television viewing practices among women veterans. Design, Setting and Participants: Cross-sectional, mailed survey completed by 1,555 female veterans enrolled at the VA Puget Sound Health Care System in 2000. Measurements and Methods: We used bivariate and multivariate analyses to assess the association of obesity (body mass index > 30 kg/m(2) based on self-reported height and weight) with self-reported number of hours of television or videos viewed per day, and frequency of eating meals or snacking while watching television, controlling for other covariates. Results: Watching television > 2 hours per typical day on week days and/or weekends was associated with obesity (P <.001), as was eating or snacking while watching television (P=.003). In multivariate logistic regression analyses, watching television > 2 hours per day and eating or snacking while watching television were each associated with obesity (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1 to 1.8; and OR 1.3, 95% CI 1.0 to 1.7, respectively), after adjusting for demographic variables, smoking, physical activity, and depression. Results were similar when posttraumatic stress disorder was included in the model instead of depression. Women who both watched > 2 hours of television per day and ate or snacked while viewing were almost twice as likely to be obese (OR 1.9, 95% CI 1.4 to 2.6). Conclusions: Watching television over 2 hours per day and eating while watching television were each associated with obesity among female VA patients and may be modifiable risk factors for obesity. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. RP Johnson, KM (reprint author), VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Mailstop S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. EM Kay.Johnson2@med.va.gov FU NIAAA NIH HHS [K23 AA000313, K23AA00313] NR 37 TC 14 Z9 15 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S76 EP S81 DI 10.1111/j.1525-1497.2006.00379.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500015 PM 16637951 ER PT J AU Johnson, KM Bradley, KA Bush, K Gardella, C Dobie, DJ Laya, MB AF Johnson, KM Bradley, KA Bush, K Gardella, C Dobie, DJ Laya, MB TI Frequency of mastalgia among women veterans - Association with psychiatric conditions and unexplained pain syndromes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE mastalgia; breast pain; mastodynia; women veterans; unexplained pain syndromes ID POSTTRAUMATIC-STRESS-DISORDER; CYCLICAL MASTALGIA; FEMALE VETERANS; PRIMARY-CARE; BREAST PAIN; AFFAIRS PATIENTS; PREVALENCE; MANAGEMENT; VALIDATION; HEALTH AB Objective: To determine the prevalence and frequency of mastalgia and its association with psychiatric conditions and unexplained pain syndromes. Design, Setting and Participants: Cross-sectional mailed survey completed by 1,219 female veterans enrolled at the VA Puget Sound Health Care System in 1998. Measurements: Breast pain in the past year, unrelated to pregnancy, was categorized as infrequent (<= monthly) or frequent (>= weekly) mastalgia. Surveys assessed posttraumatic stress disorder (PTSD), depression, panic disorder, and alcohol misuse with validated screening tests, as well as self-reported past-year chronic pelvic pain, fibromyalgia, and irritable bowel syndrome. Results: The response rate was 63%. Fifty-five percent of the respondents reported past-year mastalgia. Of these, 15% reported frequent mastalgia. Compared to women without mastalgia, women reporting frequent mastalgia were more likely to screen positive for PTSD (odds ratio [OR] 5.2, 95% confidence interval [CI] 3.2 to 8.4), major depression (OR 4.2, 2.6 to 6.9), panic disorder (OR 7.1, 3.9 to 12.8), eating disorder (OR 2.6, 1.5 to 4.7), alcohol misuse (OR 1.8, 1.1 to 2.8), or domestic violence (OR 3.1, 1.9 to 5.0), and to report fibromyalgia (OR 3.9, 2.1 to 7.4), chronic pelvic pain (OR 5.4, 2.7 to 10.5), or irritable bowel syndrome (OR 2.8, 1.6 to 4.8). Women with infrequent mastalgia were also more likely than women without mastalgia to screen positive for PTSD, depression, or panic disorder, or report pelvic pain or irritable bowel syndrome, although associations were weaker than with frequent mastalgia. Conclusions: Like other unexplained pain syndromes, frequent mastalgia is strongly associated with PTSD and other psychiatric conditions. Clinicians seeing patients with frequent mastalgia should inquire about anxiety, depression, alcohol misuse, and trauma history. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Gen Internal Med, Seattle, WA USA. Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. RP Johnson, KM (reprint author), VA Puget Sound Hlth Care Syst, Mailstop S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. EM Kay.Johnson2@med.va.gov FU NIAAA NIH HHS [K23AA00313, K23 AA000313] NR 30 TC 18 Z9 19 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S70 EP S75 DI 10.1111/j.1525-1497.2006.00378.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500014 PM 16637950 ER PT J AU Murdoch, M Bradley, A Mather, SH Klein, RE Turner, CL Yano, EM AF Murdoch, M Bradley, A Mather, SH Klein, RE Turner, CL Yano, EM TI Women and war - What physicians should know SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE veterans; female; combat disorders; sexual trauma; review ID POSTTRAUMATIC-STRESS-DISORDER; PERSIAN-GULF-WAR; SEXUAL ASSAULT; VIETNAM VETERANS; MILITARY ENVIRONMENT; COMBAT VETERANS; ARMED-FORCES; RISK-FACTORS; HEALTH; FEMALE AB Most of today's 1.7 million women veterans obtain all or most of their medical care outside the VA health care system, where their veteran status is rarely recognized or acknowledged. Several aspects of women's military service have been associated with adverse psychologic and physical outcomes, and failure to assess women's veteran status, their deployment status, and military trauma history could delay identifying or treating such conditions. Yet few clinicians know of women's military history-or of military service's impact on women's subsequent health and well being. Because an individual's military service may be best understood within the historical context in which it occurred, we provide a focused historical overview of women's military contributions and their steady integration into the Armed Forces since the War for Independence. We then describe some of the medical and psychiatric conditions associated with military service. C1 Vet Adm Med Ctr, Gen Internal Med Sect, CCDOR 111 0, Minneapolis, MN 55417 USA. Univ Minnesota, Sch Med, Dept Internal Med, Minneapolis, MN 55455 USA. VA Roseburg Healthcare Syst, Roseburg, OR USA. Vet Hlth Adv, Off Publ Hlth & Environm Hazard, Washington, DC USA. Dept Vet Affairs, Off Actuary, Washington, DC USA. Vet Hlth Adm, Women Vet Hlth Program, Washington, DC USA. VA Greater Los Angeles Ctr Study Healthcare Provi, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Murdoch, M (reprint author), Vet Adm Med Ctr, Gen Internal Med Sect, CCDOR 111 0, 1 Vet Dr, Minneapolis, MN 55417 USA. EM Maureen.Murdoch@med.va.gov NR 80 TC 48 Z9 49 U1 3 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S5 EP S10 DI 10.1111/j.1525-1497.2006.00368.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500004 PM 16637946 ER PT J AU Vogt, D Bergeron, A Salgado, D Daley, J Ouimette, P Wolfe, J AF Vogt, D Bergeron, A Salgado, D Daley, J Ouimette, P Wolfe, J TI Barriers to veterans health administration care in a nationally representative sample of women veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women's health; veterans; access to care; health services research ID AFFAIRS MEDICAL-CENTER; FEMALE VETERANS; GENDER AWARENESS; SERVICES; VA; DELIVERY; PROJECT; ACCESS AB Background: Women veterans are generally less healthy than their nonveteran female counterparts or male veterans. Accumulating evidence suggests there may be barriers to women veterans' access to and use of Veterans Health Administration (VHA) care. Objective: To document perceived and/or actual barriers to care in a nationally representative sample of women veterans and examine associations with VHA use. Design: Cross-sectional telephone survey. Participants: Women who are current and former users of VHA from VA's National Registry of Women Veterans. Measurements: Assessments of perceptions of VHA care, background characteristics, and health service use. Results: Perceptions of VHA care were most positive regarding facility/physical environment characteristics and physician skill and sensitivity and least positive regarding the availability of needed services and logistics of receiving VHA care (M=0.05 and M=-0.10; M=-0.23 and M=-0.25, respectively). The most salient barrier to the use of VHA care was problems related to ease of use. Moreover, each of the barriers constructs contributed unique variance in VHA health care use above and beyond background characteristics known to differentiate current users from former VHA users (Odds ratio [OR]=4.03 for availability of services; OR=2.63 for physician sensitivity and skill: OR=2.70 for logistics of care; OR=2.30 for facility/physical environment). Few differences in barriers to care and their association with VHA health care use emerged for women with and without service-connected disabilities. Conclusions: Findings highlight several domains in which VHA decisionmakers can intervene to enhance the care available to women veterans and point to a number of areas for further investigation. C1 Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD,Womens Hlth Sci Div, Boston, MA 02130 USA. Univ Rhode Isl, Dept Psychol, Kingston, RI 02881 USA. Tenet Healthcare, Dallas, TX USA. Dartmouth Coll Sch Med, Hanover, NH USA. Syracuse VA Med Ctr, VA Ctr Integrated Healthcare, Syracuse, NY USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vogt, D (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD,Womens Hlth Sci Div, 116B-5,150 S Huntington Ave, Boston, MA 02130 USA. EM Dawne.Vogt@med.va.gov NR 32 TC 36 Z9 36 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S19 EP S25 DI 10.1111/j.1525-1497.2006.00370.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500006 PM 16637940 ER PT J AU Washington, DL Yano, EM Simon, B Sun, S AF Washington, DL Yano, EM Simon, B Sun, S TI To use or not to use - What influences why women veterans choose VA health care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women's health services; ambulatory care/utilization; hospitals; veterans/utilization; health services accessibility; decision making; choice behavior ID AFFAIRS MEDICAL-CENTER; QUALITY-OF-CARE; NATIONAL SAMPLE; FEMALE VETERANS; SERVICES; RELIABILITY; VALIDITY; PROJECT AB Background and Objective: Effects of advances in Department of Veterans Affairs (VA) women's health care on women veterans' health care decision making are unknown. Our objective was to determine why women veterans use or do not use VA health care. Desing and Participants: Cross-sectional survey of 2,174 women veteran VA users and VA-eligible nonusers throughout southern California and southern Nevada. Measurements: VA utilization, attitudes toward care, and socio-demographics. Results: Reasons cited for VA use included affordability (67.9%); women's health clinic (WHC) availability (58.8%); quality of care (54.8%); and convenience (47.9%). Reasons for choosing health care in non-VA settings included having insurance (71.0%); greater convenience of non-VA care (66.9%); lack of knowledge of VA eligibility and services (48.5%); and perceived better non-VA quality (34.5%). After adjustment for socio-demographics, health characteristics, and VA priority group, knowledge deficits about VA eligibility and services and perceived worse VA care quality predicted outside health care use. VA users were less likely than non-VA users to have after-hours access to nonemergency care, but more likely to receive both general and gender-related care from the same clinic or provider, to use a WHC for gender-related care, and to consider WHC availability very important. Conclusions: Lack of information about VA, perceptions of VA quality, and inconvenience of VA care, are deterrents to VA use for many women veterans. VA WHCs may foster VA use. Educational campaigns are needed to fill the knowledge gap regarding women veterans' VA eligibility and advances in VA quality of care, while VA managers consider solutions to after-hours access barriers. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. VA Sepulveda Ambulatory Care Ctr & Nursing Home, VA Greater Los Angeles Hlth Serv Res & Dev Ctr Ex, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM donna.washington@va.gov NR 35 TC 73 Z9 73 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S11 EP S18 DI 10.1111/j.1525-1497.2006.00369.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500005 PM 16637939 ER PT J AU Washington, DL Yano, EM Horner, RD AF Washington, DL Yano, EM Horner, RD TI The health and health care of women veterans - Perspectives, new insights, and future research directions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID AFFAIRS MEDICAL-CENTER; QUALITY C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Cincinnati, Med Ctr, Inst Study Hlth, Cincinnati, OH 45267 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA USA. EM donna.washington@va.gov NR 7 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S3 EP S4 DI 10.1111/j.1525-1497.2006.00367.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500002 ER PT J AU Yaeger, D Himmelfarb, N Cammack, A Mintz, J AF Yaeger, D Himmelfarb, N Cammack, A Mintz, J TI DSM-IV diagnosed posttraumatic stress disorder in women veterans with and without military sexual trauma SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE military sexual trauma; PTSD; women's health ID FEMALE VIETNAM VETERANS; HEALTH-CARE UTILIZATION; PREVALENCE; ASSAULT; PTSD; RISK; ASSOCIATION; OUTPATIENTS; ENVIRONMENT; PERSONNEL AB Background: This study compares rates of posttraumatic stress disorder (PTSD) in female veterans who had military sexual trauma (MST) with rates of PTSD in women veterans with all other types of trauma. Methods: Subjects were recruited at the Women's Comprehensive Healthcare Center when attending medical or psychiatric appointments or through a mailing; 230 women agreed and 196 completed the study. They completed questionnaires on health and military history, along with the Stressful Life Events Questionnaire (SLEQ). Those who met DSM-IV PTSD Criterion A completed the PTSD Symptom Scale-Interview (PSS-I) on which PTSD diagnoses were based. Results: Ninety-two percent reported at least 1 trauma. Forty-one percent had MST, alone or with other trauma, and 90% had other trauma, with or without MST. Overall, 43% of subjects with trauma had PTSD. Those with MST had higher rates of PTSD than those with other trauma. Sixty percent of those with MST had PTSD; 43% of subjects with other traumas (with or without MST) had PTSD. Military sexual trauma and other trauma both significantly predicted PTSD in regression analyses (P=.0001 and .02, respectively) but MST predicted it more strongly. Prior trauma did not contribute to the relationship between MST and PTSD. Discussion: Findings suggest that MST is common and that it is a trauma especially associated with PTSD. C1 VA Greater Los Angeles Healthcare Syst, Womens Comprehens Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. RP Yaeger, D (reprint author), VA Greater Los Angeles Healthcare Syst, Womens Comprehens Healthcare Ctr, Mailcode OQAC WC,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Deborah.Yaeger@va.gov NR 29 TC 52 Z9 52 U1 3 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S65 EP S69 DI 10.1111/j.1525-1497.2006.00377.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500013 PM 16637949 ER PT J AU Yano, EM Bastian, LA Frayne, SM Howell, AL Lipson, LR McGlynn, G Schnurr, PP Seaver, MR Spungen, AM Fihn, SD AF Yano, EM Bastian, LA Frayne, SM Howell, AL Lipson, LR McGlynn, G Schnurr, PP Seaver, MR Spungen, AM Fihn, SD TI Toward a VA women's health research agenda: Setting evidence-based priorities to improve the health and health care of women veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women's health; research and development; research priorities; veterans; health care quality; access and evaluation ID POSTTRAUMATIC-STRESS-DISORDER; FEMALE VIETNAM VETERANS; SEXUAL ASSAULT; ADMINISTRATION OUTPATIENTS; OUTCOMES; PREVALENCE; MILITARY; SYMPTOMS; CENTERS; AFFAIRS AB The expansion of women in the military is reshaping the veteran population, with women now constituting the fastest growing segment of eligible VA health care users. In recognition of the changing demographics and special health care needs of women, the VA Office of Research & Development recently sponsored the first national VA Women's Health Research Agenda-setting conference to map research priorities to the needs of women veterans and position VA as a national leader in Women's Health Research. This paper summarizes the process and outcomes of this effort, outlining VA's research priorities for biomedical, clinical, rehabilitation, and health services research. C1 VA Sepulveda Ambulatory Care Ctr, VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. VA Med Ctr, VA HSR&D Ctr Excellence, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Duke Univ, Durham, NC USA. VA Palo Alto Healthcare Syst, VA HSR&D Ctr Excellence, Ctr Healthcare Evaluat, Palo Alto, CA USA. Stanford Univ, Palo Alto, CA 94304 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. Vet Hlth Adm, VA HSR&D Serv, Washington, DC USA. VA Boston Healthcare Syst, VA HSR&D Serv, CIDER, Boston, MA USA. VA Med Ctr, VA Natl Ctr Posttraumat Stress Disorders, White River Jct, VT USA. VA Boston Healthcare Syst, Primary Care Serv Line, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. James J Peter VA Med Ctr, VA Rehabil Res & Dev, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. VA Puget Sound Healthcare Syst, VA HSR&D Ctr Excellence, NW Ctr Outcomes Res Older Adults, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. RP Yano, EM (reprint author), VA Sepulveda Ambulatory Care Ctr, VA Greater Los Angeles HSR&D Ctr Excellence, 16111 Plummer St,Mailstop 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov NR 32 TC 48 Z9 48 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2006 VL 21 SU 3 BP S93 EP S101 DI 10.1111/j.1525-1497.2006.00381.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 021AK UT WOS:000235954500017 PM 16637953 ER PT J AU Buecker, PJ Villafuerte, JE Hornicek, FJ Gebhardt, MC Mankin, HJ AF Buecker, PJ Villafuerte, JE Hornicek, FJ Gebhardt, MC Mankin, HJ TI Improved survival for sarcomas of the wrist and hand SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE sarcoma; hand; survival; wrist ID SOFT-TISSUE SARCOMAS; GIANT-CELL TUMORS; EXTREMITY PRESERVATION; METASTATIC-DISEASE; TENDON SHEATH; BONE-TUMORS; FOOT; MANAGEMENT; LESIONS; RHABDOMYOSARCOMA AB Purpose: To evaluate survival characteristics of malignant hand tumors compared with those occurring in other musculoskeletal locations over a 30-year period. Methods: Patients were identified through a computerized database maintained at the authors' institution over the past 30 years. Each patient's records were reviewed retrospectively. Diagnoses were categorized and survival data for patients with hand malignancies were compared with those of patients having similar tumors in other musculoskeletal sites by using multivariate statistical analysis. Results: The most common malignancies were epitheloid sarcoma, synovial sarcoma, and malignant fibrous histiocytoma. Improved survival during the follow-up period was found for hand malignancies versus those occurring in other musculoskeletal sites as a whole, and this difference was statistically significant. No significant survival benefit was identified for individual tumors. Conclusions: Patients presenting with primary malignancies of the hand may survive longer than those with similar tumors in other musculoskeletal locations. C1 Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Buecker, PJ (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol Serv, 55 Fruit St,Yawkey 3B, Boston, MA 02114 USA. EM pjbuecker@hotmail.com NR 33 TC 13 Z9 13 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2006 VL 31A IS 3 BP 452 EP 455 DI 10.1016/j.jhsa.2005.11.005 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 022VO UT WOS:000236084400015 PM 16516741 ER PT J AU Chen, AJW Abrams, GM D'Esposito, M AF Chen, AJW Abrams, GM D'Esposito, M TI Functional reintegration of prefrontal neural networks for enhancing recovery after brain injury SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article; Proceedings Paper CT Galveston Brain Injury Conference (GBIC) CY APR, 2005 CL Galveston, TX SP Moody Fdn DE brain injuries; craniocerebral trauma; frontal lobe; learning; magnetic resonance imaging; neuronal plasticity; prefrontal cortex; recovery of function; rehabilitation ID POSITRON-EMISSION-TOMOGRAPHY; WORKING-MEMORY IMPAIRMENT; COGNITIVE REHABILITATION; UTILIZATION BEHAVIOR; FRONTAL LOBES; FMRI DATA; CORTEX; CONNECTIVITY; REORGANIZATION; REPRESENTATION AB Functions of the prefrontal cortex (PFC) are fundamental to learning and rehabilitation after brain injuries, but the PFC is particularly vulnerable to trauma. We propose approaches to cognitive training that are hypothesized to specifically enhance PFC function. We present a theoretical framework that generates hypotheses regarding the effects of training on the functional integration of processes across distributed networks of brain regions. Specific outcome measurements that may be used to test these hypotheses in clinical trials are proposed. This neural network-level approach may guide cognitive rehabilitation and facilitate development of adjunctive biologic treatments to enhance the effects of training. C1 Univ Calif Berkeley, Brain Imaging Ctr, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Chen, AJW (reprint author), Univ Calif Berkeley, Brain Imaging Ctr, Helen Wills Neurosci Inst, 132 Barker Hall,Mailing Ctr 3190, Berkeley, CA 94720 USA. EM anthony.chen@ucsf.edu NR 56 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD MAR-APR PY 2006 VL 21 IS 2 BP 107 EP 118 PG 12 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 031PK UT WOS:000236716300003 PM 16569985 ER PT J AU Waters, EA Weinstein, ND Colditz, GA Emmons, K AF Waters, EA Weinstein, ND Colditz, GA Emmons, K TI Formats for improving risk communication in medical tradeoff decisions SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID FREQUENCY FORMATS; BREAST-CANCER; INFORMATION; PERCEPTION; PROBABILITY; INSTRUCTION; NUMERACY; INTERNET; DISPLAY; CHOICE AB To make treatment decisions, patients should consider not only a treatment option's potential consequences but also the probability of those consequences. Many lay-people, however, have difficulty using probability information. This Internet-based study ( 2,601 participants) examined a hypothetical medical tradeoff situation in which a treatment would decrease one risk but increase another. Accuracy was assessed in terms of the ability to determine correctly whether the treatment would increase or decrease the total risk. For these tradeoff problems, accuracy was greater when the following occurred: ( 1) the amount of cognitive effort required to evaluate the tradeoff was reduced; ( 2) probability information was presented as a graphical display rather than as text only; and ( 3) information was presented as percentages rather than as frequencies (n in 100). These findings provide suggestions of ways to present risk probabilities that may help patients understand their treatment options. C1 Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Human Ecol, Piscataway, NJ 08854 USA. Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Waters, EA (reprint author), Rutgers State Univ, Dept Psychol, Tillett Hall,53 Ave E,Room 102, Piscataway, NJ 08854 USA. EM waters@aesop.rutgers.edu RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Waters, Erika/0000-0001-7402-0133 NR 39 TC 73 Z9 73 U1 2 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD MAR PY 2006 VL 11 IS 2 BP 167 EP 182 DI 10.1080/10810730500526695 PG 16 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 021BL UT WOS:000235957400004 PM 16537286 ER PT J AU White-Williams, C Brown, R Kirklin, J St Clair, K Keck, S O'Donnell, J Pitts, D Van Bakel, A AF White-Williams, C Brown, R Kirklin, J St Clair, K Keck, S O'Donnell, J Pitts, D Van Bakel, A TI Improving clinical practice: Should we give influenza vaccinations to heart transplant patients? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID RECIPIENTS AB Background: Current practice recommends that immunosuppressed patients (pts) receive yearly influenza (flu) vaccinations. However, disparity exists between current recommendations and clinical practice regarding the decision to administer flu vaccinations to heart transplant (Tx) pts. The purpose of this study was to examine the common clinical practices and outcome characteristics in Tx pts in a multi-institutional database. We assess the incidence of rejection, infection and flu in the months after administration of flu vaccinations. Methods: Between 1990 and 2001, 5,581 pts underwent Tx at 28 institutions. Pts who were > 1 year post-Tx as of January 1, 2002 (N = 3,601) constituted the study group. Results: During the years 2002 and 2003, 89% of the institutions administered flu vaccines, with 7 institutions requiring pts to be > 3 months (N = 1), 6 months (N = 1) and 12 months (N = 5) post-Tx. All 25 centers that vaccinated pts used trivalent inactivated vaccines during the months of October through January. Three centers did not vaccinate Tx pts due to a purported association with increased allograft rejection. There were no significant differences in the total number of rejection episodes (0.4% vs 0.3%, p = 0.7), rejection episodes by month (January: 0.4% vs 0%, p = 0.2; February: 0.5% vs 1.5%, p = 0.08; March: 0.5% vs 0%, p = 0.14), all infections (0.7% vs 0.6%, p = 0.6) and viral infections (0.1% vs 0%, p = 0.17) between centers that administered flu vaccines and those that did not, respectively. The incidence of flu was low in both groups. Conclusions: Flu vaccinations can be given safely to heart transplant pts without an increased incidence of rejection or infection. This information provides clinicians with data to improve clinical practice. C1 Univ Alabama, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Clarian Hlth Partners, Indianapolis, IN USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP White-Williams, C (reprint author), Univ Alabama, 739 Zeigler Bldg, Birmingham, AL 35294 USA. EM cwwilli@uabmc.edu NR 11 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAR PY 2006 VL 25 IS 3 BP 320 EP 323 DI 10.1016/j.healun.2005.09.015 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 020XH UT WOS:000235946000010 PM 16507426 ER PT J AU Winawer, N Murali, M Saint, S Babaliaros, V AF Winawer, Neil Murali, Mandakolathur Saint, Sanjay Babaliaros, Vasilis TI A negative test of aneurysmal proportions SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID ACUTE AORTIC DISSECTION; DIAGNOSIS C1 [Winawer, Neil; Babaliaros, Vasilis] Emory Univ, Sch Med, Grady Mem Hosp, Dept Med,Div Gen Med, Atlanta, GA 30303 USA. [Murali, Mandakolathur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Saint, Sanjay] Ann Arbor VA Med Ctr, Hlth Serv Res & Dev, Ctr Excellence, Ann Arbor, MI USA. [Saint, Sanjay] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. RP Winawer, N (reprint author), Emory Univ, Sch Med, Grady Mem Hosp, Dept Med,Div Gen Med, 49 Jessie Hill Jr Dr, Atlanta, GA 30303 USA. EM nwinawe@emory.edu FU AHRQ HHS [P20-HS11540] NR 8 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD MAR-APR PY 2006 VL 1 IS 2 BP 113 EP 117 DI 10.1002/jhm.79 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 291PR UT WOS:000255209800007 PM 17219481 ER PT J AU Basile, JN Chrysant, S AF Basile, JN Chrysant, S TI The importance of early antihypertensive efficacy: the role of angiotensin II receptor blocker therapy SO JOURNAL OF HUMAN HYPERTENSION LA English DT Review DE angiotensin II type 1 receptor blockers; calcium channel blockers; blood pressure goal rates; early antihypertensive efficacy ID RANDOMIZED CLINICAL-TRIALS; TO-MODERATE HYPERTENSION; HIGH CARDIOVASCULAR RISK; BLOOD-PRESSURE; ELDERLY SCOPE; DOUBLE-BLIND; SYSTOLIC HYPERTENSION; COMBINATION THERAPY; STROKE PREVENTION; VALSARTAN AB Desirable features of antihypertensive agents include efficacy, tolerability, prolonged duration of action and rapid achievement of target blood pressure (BP). Recent studies have examined the relationship between the onset of antihypertensive effect and cardiovascular events. Data from the Valsartan Antihypertensive Longterm Use Evaluation (VALUE), the Study on Cognition and Prognosis in the Elderly (SCOPE), and the Systolic Hypertension in Europe (Syst-Eur) trials support the hypothesis that the time it takes to reach target BP influences cardiovascular outcomes. VALUE, which compared BP-lowering and clinical event rates between patients treated with the angiotensin II receptor blocker (ARB) valsartan or the calcium channel blocker (CCB) amlodipine as well as between those who achieved immediate or delayed BP control, provides the strongest evidence of this to date. Additional data from SCOPE and Syst-Eur suggest that delays of 3 months to 2 years in starting antihypertensive therapy can increase the risk of certain cardiovascular end points, especially stroke. These data suggest that it may be beneficial to examine the efficacy of antihypertensive agents, not only long term, but also at earlier times to assess the onset and impact of early antihypertensive effect. The ARB olmesartan medoxomil (olmesartan) and the CCB amlodipine were compared in a randomized, double-blind, placebo-controlled clinical trial, which demonstrated that the onset of antihypertensive effect of olmesartan is comparable with that of amlodipine. Another study demonstrated that more patients treated with olmesartan achieved target BPs within 2 weeks of treatment compared with the ARBs losartan, valsartan and irbesartan. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. Univ Oklahoma, Sch Med, Oklahoma City, OK 73190 USA. Oklahoma Cardiovasc & Hypertens Ctr, Oklahoma City, OK 73190 USA. RP Basile, JN (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM jan.basile@med.va.gov NR 40 TC 23 Z9 24 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD MAR PY 2006 VL 20 IS 3 BP 169 EP 175 DI 10.1038/sj.jhh.1001972 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 013JA UT WOS:000235404400001 PM 16397516 ER PT J AU Clermont, A Bursell, SE Feener, EP AF Clermont, A Bursell, SE Feener, EP TI Role of the angiotensin II type 1 receptor in the pathogenesis of diabetic retinopathy: effects of blood pressure control and beyond SO JOURNAL OF HYPERTENSION LA English DT Article; Proceedings Paper CT International Workshop on Angitension II Receptor Blockade - Vascular and Organ Protective Effects CY APR 28-30, 2005 CL Gouvieux, FRANCE DE diabetes; retinopathy; renin-angiotensin system; angiotensin II type 1 receptor ID ENDOTHELIAL GROWTH-FACTOR; CONVERTING ENZYME-INHIBITION; OCULAR-TISSUES; MICROVASCULAR COMPLICATIONS; RETINAL EXPRESSION; MESSENGER-RNA; MACULAR EDEMA; RISK-FACTORS; RATS; MELLITUS C1 Harvard Univ, Div Res, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Beetham Eye Inst, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Feener, EP (reprint author), Harvard Univ, Div Res, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU NIDDK NIH HHS [DK60165, P30 DK036836] NR 52 TC 17 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD MAR PY 2006 VL 24 SU 1 BP S73 EP S80 DI 10.1097/01.hjh.0000220410.69116.f8 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 043XE UT WOS:000237635400012 PM 16601577 ER PT J AU Vianello, F Papeta, N Chen, T Kraft, P White, N Hart, WK Kircher, MF Swart, E Rhee, S Palu, G Irimia, D Toner, M Weissleder, R Poznansky, MC AF Vianello, F Papeta, N Chen, T Kraft, P White, N Hart, WK Kircher, MF Swart, E Rhee, S Palu, G Irimia, D Toner, M Weissleder, R Poznansky, MC TI Murine B16 melanomas expressing high levels of the chemokine stromal-derived factor-1/CXCL12 induce tumor-specific T cell chemorepulsion and escape from immune control SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOID-TISSUE CHEMOKINE; HIGH ENDOTHELIAL VENULES; IN-VIVO; ACTIVE MOVEMENT; ANTITUMOR IMMUNITY; HUMAN GLIOBLASTOMA; ACTIVATION; RECEPTOR; CXCR4; IMMUNOTHERAPY AB The chemokine, stromal-derived factor-1/CXCL12, is expressed by normal and neoplastic tissues and is involved in tumor growth, metastasis, and modulation of tumor immunity. T cell-mediated tumor immunity depends on the migration and colocalization of CTL with tumor cells, a process regulated by chemokines and adhesion molecules. It has been demonstrated that T cells are repelled by high concentrations of the chemokine CXCL12 via a concentration-dependent and CXCR4 receptor-mediated mechanism, termed chemorepulsion or fugetaxis. We proposed that repulsion of tumor Ag-specific T cells from a tumor expressing high levels of CXCL12 allows the tumor to evade immune control. Murine B16/OVA melanoma cells (H2(b)) were engineered to constitutively express CXCL12. Immunization of C57BL/6 mice with B16/OVA cells lead to destruction of B16/OVA tumors expressing no or low levels of CXCL12 but not tumors expressing high levels of the chemokine. Early recruitment of adoptively transferred OVA-specific CTL into B16/OVA tumors expressing high levels of CXCL12 was significantly reduced in comparison to B16/OVA tumors, and this reduction was reversed when tumor-specific CTLs were pretreated with the specific CXCR4 antagonist, AMD3100. Memory OVA-specific CD8(+) T cells demonstrated antitumor activity against B16/OVA tumors but not B16/OVA.CXCL12-high tumors. Expression of high levels of CXCL12 by B16/OVA cells significantly reduced CTL colocalization with and killing of target cells in vitro in a CXCR4-dependent manner. The repulsion of tumor Ag-specific T cells away from melanomas expressing CXCL12 confirms the chemorepellent activity of high concentrations of CXCL12 and may represent a novel mechanism by which certain tumors evade the immune system. C1 AIDS Res Ctr, Div Infect Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Univ Padua, Dept Microbiol, Padua, Italy. Massachusetts Gen Hosp, Ctr Bioengn, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Poznansky, MC (reprint author), AIDS Res Ctr, Div Infect Dis, Bldg 149,13th St, Charlestown, MA 02129 USA. EM mpoznansky@partners.org RI Vianello, Fabrizio/M-5211-2016; OI Vianello, Fabrizio/0000-0002-7174-4651; Irimia, Daniel/0000-0001-7347-2082 FU NIAID NIH HHS [R01 AI49757, R21 AI49858]; NIBIB NIH HHS [P41 EB002503] NR 54 TC 52 Z9 54 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2006 VL 176 IS 5 BP 2902 EP 2914 PG 13 WC Immunology SC Immunology GA 059YL UT WOS:000238768000028 PM 16493048 ER PT J AU Das, S Suarez, G Beswick, EJ Sierra, JC Graham, DY Reyes, VE AF Das, S Suarez, G Beswick, EJ Sierra, JC Graham, DY Reyes, VE TI Expression of B7-H1 on gastric epithelial cells: Its potential role in regulating T cells during Helicobacter pylori infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; B7 FAMILY; LYMPHOCYTE-ACTIVATION; VACUOLATING CYTOTOXIN; IMMUNE-RESPONSES; APOPTOSIS; ANTIGEN; LIGAND; PD-1; CD4(+) AB Helicobacter pylori infection is associated with gastritis, ulcers, and gastric cancer. The infection becomes chronic as the host response is unable to clear it. Gastric epithelial cells (GEC) play an important role during the host response, and their expression of class II MHC and costimulatory molecules such as CD80 and CD86 suggests their role in local Ag presentation. Although T cells are recruited to the infected gastric mucosa, they have been reported to be hyporesponsive. In this study, we detected the expression of B7-H1 (programmed death-1 ligand 1), a member of B7 family of proteins associated with T cell inhibition on GEC. Quantitative real-time RT-PCR revealed that B7-H1 expression increased significantly on GEC after H. pylori infection. Western blot analysis showed that B7-H1 expression was induced by various H. pylori strains and was independent of H. pylori virulence factors such as Cag, VacA, and Urease. The functional role of B7-H1 in the cross talk between GEC and T cells was assessed by coculturing GEC or H. pylori-infected GEC with CD4(+) T cells isolated from peripheral blood. Using blocking Abs to B7-H1 revealed that B7-H1 was involved in the suppression of T cell proliferation and IL-2 synthesis, and thus suggested a role for B7-H1 on the epithelium as a contributor in the chronicity of H. pylori infection. C1 Univ Texas, Med Branch, Dept Pediat, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Reyes, VE (reprint author), Univ Texas, Med Branch, Childrens Hosp, Room 2-300,301 Univ Blvd, Galveston, TX 77555 USA. EM vreyes@utmb.edu FU NIDDK NIH HHS [DK50669, DK56338] NR 55 TC 67 Z9 74 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2006 VL 176 IS 5 BP 3000 EP 3009 PG 10 WC Immunology SC Immunology GA 059YL UT WOS:000238768000038 PM 16493058 ER PT J AU Taube, C Miyahara, N Ott, V Swanson, B Takeda, K Loader, J Shultz, LD Tager, AM Luster, AD Dakhama, A Gelfand, EW AF Taube, C Miyahara, N Ott, V Swanson, B Takeda, K Loader, J Shultz, LD Tager, AM Luster, AD Dakhama, A Gelfand, EW TI The leukotriene B4 receptor (BLT1) is required for effector CD8(+) T cell-mediated, mast cell-dependent airway hyperresponsiveness SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALLERGIC PULMONARY EOSINOPHILIA; ALVEOLAR MACROPHAGES; PASSIVE TRANSFER; DEFICIENT MICE; MURINE MODEL; ASTHMA MODEL; LYMPH-NODES; IN-VITRO; B-4; INFLAMMATION AB Studies in both humans and rodents have suggested that CD8(+) T cells contribute to the development of airway hyperresponsiveness (AHR) and that leukotriene B4 (LTB4) is involved in the chemotaxis of effector CD8(+) T cells (T-EFF) to the lung by virtue of their expression of BLT1, the receptor for LTB4. In the present study, we used a mast cell-CD8-dependent model of AHR to further define the role of BLT1 in CD8(+) T cell-mediated AHR. C57BL/6(+/+) and CD8-deficient (CD8(-/-)) mice were passively sensitized with anti-OVA IgE and exposed to OVA via the airways. Following passive sensitization and allergen exposure, C57BL/6(+/+) mice developed altered airway function, whereas passively sensitized and allergen-exposed CD8(-/-) mice failed to do so. CD8(-/-) mice reconstituted with CD8(+) T-EFF developed AHR in response to challenge. In contrast, CD8(-/-) mice reconstituted with BLT1-deficient effector CD8(+) T cells did not develop AHR. The induction of increased airway responsiveness following transfer of CD8(+) TEFF or in wild-type mice could be blocked by administration of an LTB4 receptor antagonist confirming the role of BLT1 in CD8(+) T cell-mediated AHR. Together, these data define the important role for mast cells and the LTB4-BLT1 pathway in the development of CD8(+) T cell-mediated allergic responses in the lung. C1 Natl Jewish Med & Res Ctr, Div Cell Biol, Dept Pediat, Denver, CO 80206 USA. Natl Jewish Med & Res Ctr, Dept Immunol, Denver, CO 80206 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. RP Gelfand, EW (reprint author), Natl Jewish Med & Res Ctr, Div Cell Biol, Dept Pediat, 1400 Jackson St, Denver, CO 80206 USA. EM gelfande@njc.org FU NHLBI NIH HHS [P01 HL036577-21A15977, HL-36577, HL-42246, HL-61005, P01 HL036577] NR 53 TC 63 Z9 66 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2006 VL 176 IS 5 BP 3157 EP 3164 PG 8 WC Immunology SC Immunology GA 059YL UT WOS:000238768000055 PM 16493075 ER PT J AU Baden, HP AF Baden, Howard P. TI Irwin Freedberg: The early years at Harvard SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Biographical-Item C1 Harvard Univ, Cutaneous Biol Res Ctr, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Baden, HP (reprint author), Harvard Univ, Cutaneous Biol Res Ctr, Sch Med, Massachusetts Gen Hosp, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM hbaden@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2006 VL 126 IS 3 BP 515 EP 516 DI 10.1038/sj.jid.5700095 PG 2 WC Dermatology SC Dermatology GA 062TW UT WOS:000238968500002 PM 16482174 ER PT J AU Freedberg, KA AF Freedberg, Kenneth A. TI The private side of the professional man - Irwin Freedberg SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Program HIV Epidemiol & Outcomes Res, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Freedberg, KA (reprint author), Massachusetts Gen Hosp, Program HIV Epidemiol & Outcomes Res, Med Practices Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM kfreedberg@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2006 VL 126 IS 3 BP 533 EP 535 DI 10.1038/sj.jid.5700196 PG 4 WC Dermatology SC Dermatology GA 062TW UT WOS:000238968500018 PM 16482190 ER PT J AU Koutkia, P Eaton, K You, SM Breu, J Grinspoon, SK AF Koutkia, P Eaton, K You, SM Breu, J Grinspoon, SK TI Growth hormone secretion among HIV-infected patients: Effects of gender, race, and fat distribution SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-Research/Midwestern-Section-of the American-Federation-for-Medical-Research CY APR 28, 2006 CL Chicago, IL SP Central Soc Clin Res, Amer Fed Med Res, Midwestern Sec C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. MIT, Gen Clin Res Ctr, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2006 VL 54 IS 2 MA 43 BP S380 EP S380 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 021QS UT WOS:000235999400140 ER PT J AU Kulig, CC Beresford, TP Everson, GT AF Kulig, CC Beresford, TP Everson, GT TI Rapid, accurate, and sensitive fatty acid ethyl ester determination by gas chromatography-mass spectrometry SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID ETHANOL-CONSUMPTION; ALCOHOL-CONSUMPTION; MARKERS; SERUM; METABOLITES; BLOOD; QUANTIFICATION; INGESTION; BIOMARKER; MECONIUM AB Background: Fatty acid ethyl esters (FAEEs) are useful markers of ongoing alcohol use and may be associated with alcohol-induced damage to the liver and pancreas. In this article, we describe a novel method for rapid determination of the three major FAEEs found in human plasma. Methods: Internal standard, ethyl heptadecanoate, was added to plasma samples, and FAEEs were isolated by acetone precipitation, hexane lipid extraction, and amino-propyl silica solid phase extraction. FAEEs were quantitated by gas chromatography-mass spectrometry (GC-MS) using a nonpolar dimethylpolysiloxane column. The accuracy, precision, specificity, and sensitivity of the assay were defined from plasma samples from recently drinking and abstinent persons, with and without the addition of FAEEs. Results: Individual FAEE peaks demonstrated excellent resolution. Instrument time was reduced by more than 60%. The lower limit of detection was 5 to 10 nM, and the lower limit of quantitation for each FAEE was 60 nM (for 22 samples with known concentration 60 nM, x +/- SD: 61 +/- 5.7, 57 +/- 5.7, and 57 +/- 5.9 nM, for ethyl palmitate, ethyl oleate, and ethyl stearate, respectively). Instrument precision (coefficient of variance, CV) for these three FAEEs was 0.3%, 0.4%, and 0.7%, respectively. Intra-assay precision (CV) for total FAEEs was less than 7%. FAEEs were absent in 49 samples from abstinent persons. FAEEs were detected in all 76 samples with associated positive blood alcohol levels. Conclusions: Our method of FAEE analysis is rapid and potentially useful in research and clinical studies. FAEE determination using this method is precise, accurate, sensitive, and specific and deserves broader application. C1 Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Mental Hlth Serv, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. RP Kulig, CC (reprint author), Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, B-158,4200 E 9th Ave, Denver, CO 80262 USA. EM clark.kulig@uchsc.edu NR 27 TC 16 Z9 16 U1 2 U2 7 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD MAR PY 2006 VL 147 IS 3 BP 133 EP 138 DI 10.1016/j.lab.2005.11.006 PG 6 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 022ZG UT WOS:000236094100005 PM 16503243 ER PT J AU Tharp, WG Yadav, R Irimia, D Upadhyaya, A Samadani, A Hurtado, O Liu, SY Munisamy, S Brainard, DM Mahon, MJ Nourshargh, S van Oudenaarden, A Toner, MG Poznansky, MC AF Tharp, William G. Yadav, R. Irimia, D. Upadhyaya, A. Samadani, A. Hurtado, O. Liu, S-Y Munisamy, S. Brainard, D. M. Mahon, M. J. Nourshargh, S. van Oudenaarden, A. Toner, M. G. Poznansky, Mark C. TI Neutrophil chemorepulsion in defined interleukin-8 gradients in vitro and in vivo SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE chemotaxis; microfluidics; gradient ID PROTEIN-COUPLED RECEPTORS; KINASE-C-ALPHA; LOCALIZED JUVENILE PERIODONTITIS; NERVE GROWTH CONES; ACTIVE MOVEMENT; CHEMOATTRACTANT RECEPTOR; ANTINOCICEPTIVE POTENCY; CHEMOTACTIC CYTOKINES; THYMOCYTE EMIGRATION; BACTERIAL CHEMOTAXIS AB We report for the first time that primary human neutrophils can undergo persistent, directionally biased movement away from a chemokine in vitro and in vivo, termed chemorepulsion or fugetaxis. Robust nentrophil chemorepulsion in microfluidic gradients of interleukin-8 (IL-8; CXC chemokine ligand 8) was dependent on the absolute concentration of chemokine, CXC chemokine receptor 2 (CXCR2), and was associated with polarization of cytoskeletal elements and signaling molecules involved in chemotaxis and leading edge formation. Like chemoattraction, chemorepulsion was pertussis toxin-sensitive and dependent on phosphoinositide-3 kinase, RhoGTPases, and associated proteins. Perturbation of nentrophil intracytoplasmic cyclic adenosine monophosphate concentrations and the activity of protein kinase C isoforms modulated directional bias and persistence of motility and could convert a chemorepellent to a chemoattractant response. Neutrophil chemorepulsion to an IL-8 ortholog was also demonstrated and quantified in a rat model of inflammation. The finding that neutrophils undergo chemorepulsion in response to continuous chemokine gradients expands the paradigm by which neutrophil migration is understood and may reveal a novel approach to our understanding of the homeostatic regulation of inflammation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. MIT, Dept Phys, Cambridge, MA 02139 USA. Hammersmith Hosp, Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst,Cardiovasc Med Unit, London W12 0HS, England. Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Sci, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Poznansky, MC (reprint author), Massachusetts Gen Hosp East, Div Infect Dis, 149 13th St,Room 5212,Charlestown Navy Yard, Boston, MA 02129 USA. EM mpoznansky@partners.org OI Irimia, Daniel/0000-0001-7347-2082 FU NIAID NIH HHS [R01 AI49757]; NIBIB NIH HHS [P41 EB002503] NR 101 TC 64 Z9 67 U1 1 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 2006 VL 79 IS 3 BP 539 EP 554 DI 10.1189/jlb.0905516 PG 16 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119LY UT WOS:000243015000014 PM 16365152 ER PT J AU Kim, JW Hills, WL Rizzo, JF Egan, RA Lessell, S AF Kim, JW Hills, WL Rizzo, JF Egan, RA Lessell, S TI Ischemic optic neuropathy following spine surgery in a 16-year-old patient and a ten-year-old patient SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID VISUAL-LOSS; RISK-FACTORS; FUSION AB Peri-operative ischemic optic neuropathy typically occurs in middle-aged or older patients. We report this condition in two patients aged 16 and 10 years. Only six other cases of peri-operative ischemic optic neuropathy have been reported in patients aged less than 30 years, all but one occurring after spinal surgery. Although the visual prognosis appears to be more favorable in younger patients, the pathogenesis of this rare complication of surgery is likely to be the same as that affecting older individuals. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Neuroophthalmol, Boston, MA 02114 USA. Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. Univ Calif Irvine, Dept Ophthalmol, Irvine, CA USA. RP Lessell, S (reprint author), 243 Charles St, Boston, MA 02114 USA. EM simmons_lessel@meei.harvard.edu NR 21 TC 14 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD MAR PY 2006 VL 26 IS 1 BP 30 EP 33 DI 10.1097/01.wno.0000205980.32023.2d PG 4 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 020TB UT WOS:000235932200006 PM 16518163 ER PT J AU Martinez-Monedero, R Corrales, CE Cuajungco, MP Heller, S Edge, ASB AF Martinez-Monedero, R Corrales, CE Cuajungco, MP Heller, S Edge, ASB TI Reinnervation of hair cells by auditory neurons after selective removal of spiral ganglion neurons SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE beta-bungarotoxin; apoptosis; spiral ganglion; transplantation ID EAR SENSORY NEURONS; INNER-EAR; BETA-BUNGAROTOXIN; HIPPOCAMPAL-NEURONS; NERVE-TERMINALS; TRANSGENIC MICE; NEUROTROPHIN-3; INNERVATION; APOPTOSIS; SURVIVAL AB Hearing loss can be caused by primary degeneration of spiral ganglion neurons or by secondary degeneration of these neurons after hair cell loss. The replacement of auditory neurons would be an important step in any attempt to restore auditory function in patients with damaged inner ear neurons or hair cells. Application of beta-bungarotoxin, a toxin derived from snake venom, to an explant of the cochlea eradicates spiral ganglion neurons while sparing the other cochlear cell types. The toxin was found to bind to the neurons and to cause apoptotic cell death without affecting hair cells or other inner ear cell types as indicated by TUNEL staining, and, thus, the toxin provides a highly specific means of deafferentation of hair cells. We therefore used the denervated organ of Corti for the study of neuronal regeneration and synaptogenesis with hair cells and found that spiral ganglion neurons obtained from the cochlea of an untreated newborn mouse reinnervated hair cells in the toxin-treated organ of Corti and expressed synaptic vesicle markers at points of contact with hair cells. These findings suggest that it may be possible to replace degenerated neurons by grafting new cells into the organ of Corti. (c) 2006 Wiley Periodicals, Inc. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Tillotson Unit Cell Biol Inner Ear, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. RP Edge, ASB (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM albert_edge@meei.harvard.edu RI Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 FU NIDCD NIH HHS [R01 DC007174, F33 DC006789, P30 DC005209, P30 DC05209, R01 DC006167, R01 DC007174-02] NR 46 TC 45 Z9 48 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAR PY 2006 VL 66 IS 4 BP 319 EP 331 DI 10.1002/neu.20232 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 015YH UT WOS:000235587000001 PM 16408287 ER PT J AU Xie, Z Dong, Y Maeda, U Romano, DM Tanzi, RE AF Xie, Z Dong, Y Maeda, U Romano, DM Tanzi, RE TI RNAi silencing of APP adaptor proteins attenuates a beta levels via differential effects on APP processing SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 14 EP 14 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900033 ER PT J AU Neuwelt, EA Wu, J Varallyay, C Muldoon, L Jones, R AF Neuwelt, EA Wu, J Varallyay, C Muldoon, L Jones, R TI In vivo leukocyte iron labeling with intravenous ferumoxides and protamine sulfate for cellular magnetic resonance imaging SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 43 EP 43 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900112 ER PT J AU Ying, W Lu, H Zhu, K Swanson, RA AF Ying, W Lu, H Zhu, K Swanson, RA TI NADH transport in murine astrocytes is mediated by P2X7 receptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 UCSF, Dept Neurol, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 103 EP 103 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900258 ER PT J AU Prasad, R Giri, S Nath, N Singh, I Singh, AK AF Prasad, R Giri, S Nath, N Singh, I Singh, AK TI 5-Aminoimidazole-4-carboxamide ribonucleoside attenuates EAE via modulation of endothelial-monocyte interaction SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Charleston, SC USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 107 EP 107 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900269 ER PT J AU Prasad, R Giri, S Singh, I Singh, AK AF Prasad, R Giri, S Singh, I Singh, AK TI GSNO attenuates EAE disease by S-nitrosylation mediated modulation of endothelial-monocyte interactions SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Charleston, SC USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 108 EP 108 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900272 ER PT J AU Yao, JK Thomas, EA AF Yao, JK Thomas, EA TI Antipsychotic drug-induced changes in membrane lipids of mouse brain lacking apolipoprotein d SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. Scripps Res Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 115 EP 115 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900293 ER PT J AU Baek, RC Broekman, ML Comer, LA Seyfried, TN Sena-Esteves, M AF Baek, RC Broekman, ML Comer, LA Seyfried, TN Sena-Esteves, M TI Adeno-virus mediated correction of beta-galactosidase deficiency & glycosphingolipid accumulation in brain of GM1 gangliosidosis mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Dept Neurol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 126 EP 126 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900322 ER PT J AU Denny, CA Chalifoux, JR Alroy, J Pawlyk, BS Sandberg, MA Seyfried, TN AF Denny, CA Chalifoux, JR Alroy, J Pawlyk, BS Sandberg, MA Seyfried, TN TI Neurochemical, neurophysiological, and morphological abnormalities in retinas of sandhoff and GM1 gangliosidosis mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. RI Denny, Christine Ann/I-5235-2015 OI Denny, Christine Ann/0000-0002-6926-2020 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 126 EP 126 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900323 ER PT J AU Sarkey, JP Richards, MP Stubbs, EB AF Sarkey, JP Richards, MP Stubbs, EB TI Therapeutic potential of lovastatin for the treatment of experimental autoimmune neuritis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res & Neurol Serv, Hines, IL 60141 USA. Loyola Univ, Program Neurosci, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 131 EP 131 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900338 ER PT J AU Lo, EH AF Lo, EH TI Neurovascular coupling in health and disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Neurochemistry CY MAR 11-15, 2006 CL Portland, OR SP Amer Soc Neurochem C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2006 VL 96 SU 1 BP 135 EP 135 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021KU UT WOS:000235982900348 ER PT J AU Venneman, S Leuchter, A Bartzokis, G Beckson, M Simon, SL Schaefer, M Rawson, R Newton, T Cook, IA Uijtdehaage, S Ling, W AF Venneman, S Leuchter, A Bartzokis, G Beckson, M Simon, SL Schaefer, M Rawson, R Newton, T Cook, IA Uijtdehaage, S Ling, W TI Variation in neurophysiological function and evidence of quantitative electroencephalogram discordance: Predicting cocaine-dependent treatment attrition SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID DOUBLE-BLIND; CEREBRAL PERFUSION; CONTROLLED TRIAL; BRAIN-FUNCTION; PLACEBO; ABNORMALITIES; DESIPRAMINE; EFFICACY; ABUSE; INDIVIDUALS AB Cocaine treatment trials suffer from a high rate of attrition. We examined pretreatment neurophysiological factors to identify participants at greatest risk. Twenty-five participants were divided into concordant and discordant groups following electroencephalogram ( EEG) measures recorded prior to a double-blind, placebo-controlled treatment trial. Three possible outcomes were examined: successful completion, dropout, and removal. Concordant ( high perfusion correlate) participants had an 85% rate of successful completion, while discordant participants had a 15% rate of successful completion. Twenty-five percent of dropouts and 50% of participants removed were discordant ( low perfusion correlate), while only 25% of those who completed were discordant. Failure to complete the trial was not explained by depression, craving, benzoylecgonine levels or quantitative electroencephalogram ( QEEG) power; thus cordance may help identify attrition risk. C1 Univ Houston Victoria, Dept Psychol, Victoria, TX 77901 USA. W Los Angeles VA Med Ctr, Medicat Dev Unit, Res Serv, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Psychiat Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Quantitat EEG Lab, Los Angeles Neuropsychiat Inst & Hosp, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Venneman, S (reprint author), Univ Houston Victoria, Dept Biol, 3007 Ben Wilson, Victoria, TX 77901 USA. EM VennemanS@uhv.edu RI Bartzokis, George/K-2409-2013; OI newton, thomas/0000-0002-3198-5901; Uijtdehaage, Sebastian/0000-0001-8598-4683 FU NIDA NIH HHS [1 Y01 DA 50038]; NIMH NIH HHS [1 K02 MH 01165]; PHS HHS [1R01 40705-09] NR 39 TC 6 Z9 6 U1 2 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2006 VL 18 IS 2 BP 208 EP 216 DI 10.1176/appi.neuropsych.18.2.208 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 044KU UT WOS:000237672000010 PM 16720798 ER PT J AU Beltran, D Faquin, WC Gallagher, G August, M AF Beltran, D Faquin, WC Gallagher, G August, M TI Selective immunohistochemical comparison of polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID SALIVARY-GLAND TUMORS; SMOOTH-MUSCLE ACTIN; EPITHELIAL-MYOEPITHELIAL CARCINOMA; C-KIT EXPRESSION; PROLIFERATIVE ACTIVITY; CELL-PROLIFERATION; PARAFFIN SECTIONS; MIB-1 ANTIBODY; ORIGIN; KI-67 AB Purpose: Polymorphous low-grade adenocarcinoma (PLGA) is a salivary gland malignancy characterized by indolent growth and a low rate of metastasis. PLGA shares histological features with adenoid cystic carcinoma (ACC), including infiltrating solid and cribriform patterns, presence of cystic spaces, and neurotropism. The degree of polymorphism of PLGA presents diagnostic challenges, particularly in small biopsy specimens. Immunohistochemical reactions to differentiate PLGA from the more aggressive ACC would be extremely valuable but controversy exists in the current literature regarding their utility. This study examines the potential use of c-kit, Ki-67, smooth muscle actin (SMA), and muscle-specific actin (MSA) as ancillary markers for distinguishing PLGA from ACC. Patients and Methods: Medical records of 20 cases of PLGA treated at the Massachusetts General Hospital were reviewed. Patient demographic data and tumor-specific information were elicited. Formalin-fixed paraffin-embedded sections from 10 of these cases and 12 comparison cases of ACC were accessed. The histologic diagnoses were confirmed and immunohistochemical staining using antibodies to c-kit, Ki-67, SMA, and MSA was employed to determine differences in staining. Results: PLGA showed a significantly weaker immunohistochemical expression of c-kit compared with ACC (P = < .001). Ki-67, correlating with proliferative behavior, was more weakly expressed in PLGA (P = .091). The exuberant myoepithelial component of ACC resulted in stronger staining with SMA and MSA (P = .047; P = .065, respectively). Conclusions: Statistically significant immunohistochemical staining patterns using c-kit and SMA in this study support their potential use as markers to differentiate PLGA from ACC in cases where the diagnosis can be challenging. (c) 2006 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Boston Univ, Goldman Sch Dent Med, Dept Oral & Maxillofacial Pathol, Boston, MA USA. RP August, M (reprint author), Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Dent Med, Massachusetts Gen Hosp, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM maugust@partners.org NR 48 TC 23 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2006 VL 64 IS 3 BP 415 EP 423 DI 10.1016/j.joms.2005.11.027 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 018TD UT WOS:000235786800011 PM 16487803 ER PT J AU Ring, D AF Ring, D TI Selective screw placement in forearm compression plating: Results of 75 consecutive fractures stabilized with 4 cortices of screw fixation on either side of the fracture - Invited commentary SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Editorial Material ID RADIUS; ULNA C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD MAR PY 2006 VL 20 IS 3 BP 162 EP 163 PG 2 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 030UZ UT WOS:000236661800002 ER PT J AU Tholouli, E Di Vizio, D O'Connel, F Twomey, D Ligon, K Levenson, R Hoyland, JA Yin, JAL Golub, TR Loda, M Byers, RJ AF Tholouli, E Di Vizio, D O'Connel, F Twomey, D Ligon, K Levenson, R Hoyland, JA Yin, JAL Golub, TR Loda, M Byers, RJ TI Quantum dot based multiplex hybridisation for in-situ gene expression profiling in clinical samples SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract CT 189th Meeting of the Pathological-Society-of-Great-Britain-and-Ireland CY JAN 04-06, 2006 CL Robinson Coll, Cambridge, ENGLAND SP Patholog Soc Great Britain Ireland HO Robinson Coll C1 Univ Dept Haematol, Manchester, Lancs, England. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. MIT, Broad Inst, Boston, MA USA. CRI, Boston, MA USA. Univ Manchester, Div Lab & Regenerat Med, Manchester, Lancs, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAR PY 2006 VL 208 SU S BP 1A EP 1A PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 019OU UT WOS:000235847400005 ER PT J AU Polyak, K AF Polyak, K TI The role of the tumor microenvironment in breast cancer SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract CT 189th Meeting of the Pathological-Society-of-Great-Britain-and-Ireland CY JAN 04-06, 2006 CL Robinson Coll, Cambridge, ENGLAND SP Patholog Soc Great Britain Ireland HO Robinson Coll C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAR PY 2006 VL 208 SU S BP 33A EP 33A PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 019OU UT WOS:000235847400130 ER PT J AU Davis, EP Townsend, EL Gunnar, MR Guiang, SF Lussky, RC Cifuentes, RF Georgieff, MK AF Davis, E. P. Townsend, E. L. Gunnar, M. R. Guiang, S. F. Lussky, R. C. Cifuentes, R. F. Georgieff, M. K. TI Antenatal betamethasone treatment has a persisting influence on infant HPA axis regulation SO JOURNAL OF PERINATOLOGY LA English DT Article DE cortisol; stress; glucocorticoid treatment; prematurity; prenatal exposure ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; SALIVARY CORTISOL; PREMATURE-INFANTS; PRENATAL EXPOSURE; GLUCOCORTICOIDS; THERAPY; FETAL; DEXAMETHASONE; REACTIVITY AB Objective: To examine the consequences of antenatal betamethasone ( AB) exposure on postnatal stress regulation. Study design: Fourteen AB exposed infants born at 28 - 30 weeks' gestation were assessed in the NICU during postnatal week 1 and at 34 weeks postconception. Nine infants born at 34 weeks gestation without AB treatment were evaluated as a postconceptional age comparison group. Salivary cortisol, heart rate, and behavior were measured at baseline and in response to a heelstick blood draw. Results: Repeated measures ANOVAs revealed that both groups displayed an increase in heart rate and behavioral distress in response to the stressor. The cortisol response, however, was blunted in AB-treated infants at both assessments. Conclusion: AB treatment has consequences for hypothalamic pituitary - adrenal (HPA) axis regulation that persist for at least four to six weeks after birth, indicating that studies of long-term effects are warranted. C1 Univ Calif Irvine, Dept Psychiat & Human Behav, Orange, CA 92868 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Univ Minnesota, Inst Child Dev, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Neurobehav Dev, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Hennepin Cty Med Ctr, Dept Pediat, Minneapolis, MN 55415 USA. RP Davis, EP (reprint author), Univ Calif Irvine, Dept Psychiat & Human Behav, 333 City Blvd W,Suite 1200, Orange, CA 92868 USA. EM edavis@uci.edu NR 29 TC 42 Z9 43 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD MAR PY 2006 VL 26 IS 3 BP 147 EP 153 DI 10.1038/sj.jp.7211447 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 102WD UT WOS:000241843100003 PM 16467857 ER PT J AU Witt, AE Hines, LM Collins, NL Hu, YH Gunawardane, RN Moreira, D Raphael, J Jepson, D Koundinya, M Rolfs, A Taron, B Isakoff, SJ Brugge, JS LaBaer, J AF Witt, AE Hines, LM Collins, NL Hu, YH Gunawardane, RN Moreira, D Raphael, J Jepson, D Koundinya, M Rolfs, A Taron, B Isakoff, SJ Brugge, JS LaBaer, J TI Functional proteomics approach to investigate the biological activities of cDNAs implicated in breast cancer SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE functional proteomics; breast cancer; cell-based assay; cDNA expression; proliferation; migration; invasion; acinar morphogenesis; BC1000; high-throughput ID MAMMARY EPITHELIAL-CELLS; COMPARATIVE GENOMIC HYBRIDIZATION; BASEMENT-MEMBRANE CULTURES; GROWTH-FACTOR BETA-1; RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; TUMOR PROGRESSION; MAMMALIAN-CELLS; NUCLEAR ANTIGEN; CDK INHIBITORS AB Functional proteomics approaches that comprehensively evaluate the biological activities of human cDNAs may provide novel insights into disease pathogenesis. To systematically investigate the functional activity of cDNAs that have been implicated in breast carcinogenesis, we generated a collection of cDNAs relevant to breast cancer, the Breast Cancer 1000 (BC1000), and conducted screens to identify proteins that induce phenotypic changes that resemble events which occur during tumor initiation and progression. Genes were selected for this set using bioinformatics and data mining tools that identify genes associated with breast cancer. Greater than 1000 cDNAs were assembled and sequence verified with high-throughput recombination-based cloning. To our knowledge, the BC1000 represents the first publicly available sequence-validated human disease gene collection. The functional activity of a subset of the BC1000 collection was evaluated in cell-based assays that monitor changes in cell proliferation, migration, and morphogenesis in MCF-10A mammary epithelial cells expressing a variant of ErbB2 that can be inducibly activated through dimerization. Using this approach, we identified many cDNAs, encoding diverse classes of cellular proteins, that displayed activity in one or more of the assays, thus providing insights into a large set of cellular proteins capable of inducing functional alterations associated with breast cancer development. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Proteom, Cambridge, MA 02141 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM joan_brugge@hms.harvard.edu FU NCI NIH HHS [P01 CA080111-069001, P01 CA080111-099001, P01 CA080111, CA099191, P01 CA080111-109001, P01 CA080111-079001, CA080111, CA089393, P01 CA080111-089001]; NIGMS NIH HHS [U54 GM64346-04] NR 73 TC 48 Z9 50 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAR PY 2006 VL 5 IS 3 BP 599 EP 610 DI 10.1021/pr050395i PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 020GP UT WOS:000235897000016 PM 16512675 ER PT J AU Buhlmann, U Etcoff, NL Wilhelm, S AF Buhlmann, U Etcoff, NL Wilhelm, S TI Emotion recognition bias for contempt and anger in body dysmorphic disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE body dysmorphic disorder; emotion recognition; facial expression; self-referent; other-referent; contempt ID OBSESSIVE-COMPULSIVE SCALE; RELIABILITY; FACES AB Body dysmorphic disorder (BDD) patients are preoccupied with imagined defects or flaws in appearance (e.g., size or shape of nose). They are afraid of negative evaluations by others and often suffer significant morbidity including hospitalization and suicide attempts. Many patients experience ideas of reference, e.g., they often believe others take special notice of their "flaw". Facial expressions play an important role in conveying negative or positive feelings, and sympathy or rejection. In this study, we investigated emotion recognition deficits in 18 BDD patients and 18 healthy controls. Participants were presented with two questionnaires accompanying facial photographs. One questionnaire included self-referent scenarios ("Imagine that the bank teller is looking at you. What is his facial expression like?"), whereas the other one included other-referent scenarios ("Imagine that the bank teller is looking at a friend of yours," etc.), and participants were asked to identify the corresponding emotion (e.g., anger, contempt, neutral, or surprise). Overall, BDD patients, relative to controls, had difficulty identifying emotional expressions in self-referent scenarios. They misinterpreted more expressions as contemptuous and angry in self-referent scenarios than did controls. However, they did not have significantly more difficulties identifying emotional expressions in other-referent scenarios than controls. Thus, poor insight and ideas of reference, common in BDD, might be related to a bias for misinterpreting other people's emotional expressions as negative. Perceiving others as rejecting might reinforce concerns about one's personal perceived ugliness and social desirability. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Body Dysmorph Disorder Clin, Bldg 149 13th St, Charlestown, MA 02129 USA. EM wilhelm@psych.mgh.harvard.edu NR 22 TC 53 Z9 55 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAR PY 2006 VL 40 IS 2 BP 105 EP 111 DI 10.1016/j.jpsychires.2005.03.006 PG 7 WC Psychiatry SC Psychiatry GA 016SS UT WOS:000235641200002 PM 15904932 ER PT J AU Cook, JM Walser, RD Kane, V Ruzek, JI Woody, G AF Cook, JM Walser, RD Kane, V Ruzek, JI Woody, G TI Dissemination and feasibility of a cognitive-behavioral treatment for substance use disorders and posttraumatic stress disorder in the veterans administration SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE posttraumatic stress disorder; PTSD; substance-related disorders; therapy; trauma ID DUAL DIAGNOSIS; WOMEN; INTERVENTIONS; PSYCHOTHERAPY; OUTCOMES AB This article describes a small dissemination effort and provides initial efficacy data for use of Seeking Safety, a cognitive-behavioral treatment for comorbid substance use disorders (SUD) and posttraumatic stress disorder (PTSD), in a VA setting. After providing a daylong interactive training in Seeking Safety to front-line clinicians, a cotherapist group practice model was implemented. Following 14 months of clinician training and an uncontrolled pilot study of four groups with 18 veterans, initial efficacy data indicate significant symptom reduction for patients and acceptability to clinicians. Findings are encouraging in that Seeking Safety treatment appears to have the potential to be beneficial for veterans with SUD-PTSD and also appeal to clinicians. Dissemination of Seeking Safety is feasible in the VA, yet there are likely barriers to sustaining it as a routine treatment. Recommendations for future dissemination are proposed, including ways VA administration can facilitate this process. C1 Columbia Univ, New York State Psychiat Inst, Med Ctr, New York, NY 10032 USA. Natl Ctr PTSD & VISN 21 MIRECC, VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, VISN MIRECC 4, Behav Hlth Serv, Philadelphia, PA USA. RP Cook, JM (reprint author), Columbia Univ, New York State Psychiat Inst, Med Ctr, 1051 Riverside Drve,Box 69, New York, NY 10032 USA. EM jc2676@columbia.edu NR 20 TC 29 Z9 29 U1 1 U2 4 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 MAR PY 2006 VL 38 IS 1 BP 89 EP 92 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 032NE UT WOS:000236780500010 PM 16681179 ER PT J AU Hirai, M Stanley, MA Novy, DM AF Hirai, M Stanley, MA Novy, DM TI Generalized anxiety disorder in hispanics: Symptom characteristics and prediction of severity SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE generalized anxiety disorder; hispanic; adult ID DSM-III-R; STATE WORRY QUESTIONNAIRE; PSYCHOMETRIC PROPERTIES; PRIMARY-CARE; PSYCHIATRIC-DISORDERS; MEXICAN-AMERICANS; OLDER ADULTS; LANGUAGE; PREVALENCE; LIFETIME AB Literature suggests that an increasing number of Hispanic people suffer with GAD, and possible associated problems include high costs for treatment and elevated risk of severe impairment. The current study examined components of anxiety, as measured by currently available assessment instruments in both English and Spanish languages, among bilingual Hispanic individuals with GAD. Participants completed all instruments in both languages. Relations between these self-report measures and clinician-rated GAD severity were also studied. In factor analyses, the Spanish measures yielded two factors, the first of which included all instruments assessing physiological components of anxiety and one content specific measure of worry. The second factor included one worry scale and one trait anxiety scale. The English measures yielded a single factor solution. Regression analyses revealed that for the English measures, the BAI and PSWQ were statistically significant predictors of GAD severity. For the Spanish measures, the BAI was the only statistically significant predictor. C1 Washington State Univ, Dept Psychol, Pullman, WA 99164 USA. Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Univ Texas, Sch Med, Dept Anesthesiol, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Hirai, M (reprint author), Washington State Univ, Dept Psychol, POB 644820, Pullman, WA 99164 USA. EM hiraim@wsu.edu NR 46 TC 17 Z9 17 U1 5 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD MAR PY 2006 VL 28 IS 1 BP 49 EP 56 DI 10.1007/s10862-006-4541-2 PG 8 WC Psychology, Clinical SC Psychology GA 966JY UT WOS:000232017200007 ER PT J AU Johnston, MV Pogach, L Rajan, M Mitchinson, A Krein, SL Bonacker, K Reiber, G AF Johnston, Mark V. Pogach, Leonard Rajan, Mangala Mitchinson, Allison Krein, Sarah L. Bonacker, Kristin Reiber, Gayle TI Personal and treatment factors associated with foot self-care among veterans with diabetes SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE diabetes; diabetic foot; healthcare quality; health education; minority; outcome assessment; podiatry; primary healthcare; self-care; veterans ID COST-EFFECTIVENESS; CONTROLLED-TRIAL; ULCER; PREVENTION; AMPUTATION; OUTCOMES; RISK; BENEFICIARIES; MORTALITY; SERVICES AB We developed and validated a survey of foot selfcare education and behaviors in 772 diabetic patients with high-risk feet at eight Department of Veterans Affairs medical centers. Principal components analysis identified six subscales with satisfactory internal consistency: basic foot-care education, extended foot-care education, basic professional foot care, extended professional foot care, basic foot self-care, and extended foot self-care (alpha = 0.77-0.91). Despite high illness burden, adherence to foot self-care recommendations was less than optimal; only 32.2% of participants reported looking at the bottom of their feet daily. Independent predictors of greater adherence to basic foot self-care practices included African-American or Hispanic background, perceived neuropathy, foot ulcers in the last year, prior amputation (beta = 0.080.12, p < 0.04-0.001), and provision of greater basic and extended education (beta = 0. 16, p < 0.004, and beta = 0. 15, p < 0.007). The survey subscales can now be used for evaluating foot care and education needs for persons with high-risk feet. C1 Univ Wisconsin, Sch Med, Dept Internal Med, Milwaukee, WI 53201 USA. VA New Jersey Hlth Care Syst, Dept Vet Affairs, Ctr Healthcare Knowledge Management, E Orange, NJ USA. Kessler Med Rehabil Res & Educ Corp, W Orange, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. HSR&D, Ctr Practice Management & Outcomes Res, VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. HSR&D, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Hlth Serv & Epidemiol, Seattle, WA USA. RP Johnston, MV (reprint author), Univ Wisconsin, Sch Med, Dept Internal Med, POB 413, Milwaukee, WI 53201 USA. EM johnsto@uwm.edu RI Krein, Sarah/E-2742-2014 OI Krein, Sarah/0000-0003-2111-8131 NR 49 TC 15 Z9 15 U1 1 U2 10 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAR-APR PY 2006 VL 43 IS 2 BP 227 EP 238 DI 10.1682/JRRD.2005.06.0106 PG 12 WC Rehabilitation SC Rehabilitation GA 070TT UT WOS:000239548200011 PM 16847789 ER PT J AU Welsh, AH Zhou, XH AF Welsh, AH Zhou, XH TI Estimating the retransformed mean in a heteroscedastic two-part model SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE extra zeros; health care costs; heteroscedastic regression model; retransformation; skewed data; smearing; two-part model ID SAMPLES AB Two distribution-free estimators are proposed to estimate the mean of a dependent variable after fitting a semiparametric two-part heteroscedastic regression model to a transformation of the dependent variable. We show that the proposed estimators are consistent and have asymptotic normal distributions. We also compare their finite-sample performance in a simulation study. Finally, we illustrate the proposed methods in a real-world example of predicting in-patient health care costs. (c) 2004 Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA. Univ Southampton, Fac Math Studies, Southampton SO17 1BJ, Hants, England. VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence 152, Seattle, WA 98108 USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Sch Publ Hlth, F600 Hlth Sci,POB 357232, Seattle, WA 98195 USA. EM azhou@u.washington.edu NR 15 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD MAR 1 PY 2006 VL 136 IS 3 BP 860 EP 881 DI 10.1016/j.jspi.2004.07.009 PG 22 WC Statistics & Probability SC Mathematics GA 989TT UT WOS:000233697500015 ER PT J AU Sawicki, MP AF Sawicki, MP TI Knocking out answers to diabetes: Role of SSTR5 SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID SOMATOSTATIN; GENE; SECRETION; ABLATION; RECEPTOR; MICE C1 Greater Los Angeles VA Med Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Sawicki, MP (reprint author), Greater Los Angeles VA Med Ctr, CHS 72-215,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM msawicki@mednet.ucla.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAR PY 2006 VL 131 IS 1 BP 131 EP 132 DI 10.1016/j.jss.2005.09.015 PG 2 WC Surgery SC Surgery GA 018NM UT WOS:000235771200019 PM 16297405 ER PT J AU Kratochvil, CJ Vitiello, B Brent, D Bostic, JQ Naylor, MW AF Kratochvil, CJ Vitiello, B Brent, D Bostic, JQ Naylor, MW TI Selecting an antidepressant for the treatment of pediatric depression SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID CONTROLLED-TRIAL; FLUOXETINE; ADOLESCENTS; CHILDREN C1 Univ Nebraska, Med Ctr, Dept Psychiat, Omaha, NE 68198 USA. NIMH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Illinois, Chicago, IL USA. RP Kratochvil, CJ (reprint author), Univ Nebraska, Med Ctr, Dept Psychiat, 985581 Nebraska Med Ctr, Omaha, NE 68198 USA. EM ckratoch@unmc.edu NR 7 TC 4 Z9 4 U1 0 U2 0 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 MAR PY 2006 VL 45 IS 3 BP 371 EP 373 DI 10.1097/01.chi.0000197029.87378.1c PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 017VZ UT WOS:000235722700014 PM 16540823 ER PT J AU Astner, S Burnett, N Ruis-Diaz, F Doukas, AG Gonzalez, S Gonzalez, E AF Astner, S Burnett, N Ruis-Diaz, F Doukas, AG Gonzalez, S Gonzalez, E TI Irritant contact dermatitis induced by a common household irritant: A noninvasive evaluation of ethnic variability in skin response SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SCANNING LASER MICROSCOPY; FLUORESCENCE EXCITATION SPECTROSCOPY; REFLECTANCE CONFOCAL MICROSCOPY; INDUCED CUTANEOUS IRRITATION; IN-VIVO; STRATUM-CORNEUM; RACIAL-DIFFERENCES; BARRIER FUNCTION; BLACK; WHITE AB Objective. This study was undertaken to investigate the ethnic Susceptibility to irritant contact dermatitis induced by a common dishwashing liquid using noninvasive technologies. Methods: A total of 30 participants (15 Caucasian, 15 African American) were patch tested to graded concentrations of a common household irritant and evaluated using clinical scoring, reflectance confocal microscopy, transepidermal water loss, and fluorescence excitation spectroscopy. Results: At 24 hours, the concentration thresholds for clinically perceptible irritancy were significantly higher for African American compared with Caucasian participants. Reflectance confocal microscopy showed stratum corneum disruption, parakeratosis, and spongiosis; these features were more severe in Caucasian participants (P <= .002). Mean values for transepidermal water loss were significantly higher in the Caucasian group at comparable clinical scores (P <= .005). Fluorescence excitation spectroscopy showed a broad excitation band at 300 urn (emission 340 nm) and values in both groups returned to baseline by day 7. Limitations: This pilot study was limited in scope and larger studies are needed to further evaluate ethnic differences in irritant contact dermatitis and to demonstrate the applicability Of Our findings for other irritants. Conclusion: Clinical evaluation, reflectance confocal microscopy, and transepidermal water loss showed significant differences in the cutaneous irritant response between both groups suggesting a superior barrier function of African American skin. Fluorescence excitation spectroscopy on the other hand demonstrated no differences in the hyperproliferative response after irritant exposure and indicated similar kinetics for the two groups. C1 Mem Sloan Kettering Canc Ctr, Dermatol Serv, New York, NY 10022 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Ctr Photomed, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Dermatol, Contact Dermatitis Unit, Boston, MA 02114 USA. RP Gonzalez, S (reprint author), Mem Sloan Kettering Canc Ctr, Dermatol Serv, Rockefeller Outpatient Pavil,160 E 53rd St, New York, NY 10022 USA. EM gonzals6@mskcc.org NR 49 TC 25 Z9 29 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2006 VL 54 IS 3 BP 458 EP 465 DI 10.1016/j.jaad.2005.11.1099 PG 8 WC Dermatology SC Dermatology GA 017VF UT WOS:000235720700011 PM 16488297 ER PT J AU Blyumin, M Brown, K Kimball, A AF Blyumin, M Brown, K Kimball, A TI Awareness of the qualifications and scope of practice of nonphysician clinicians SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Dermatology CY MAR 03-07, 2006 CL San Francisco, CA SP Amer Acad Dermatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2006 VL 54 IS 3 SU S BP AB117 EP AB117 PG 1 WC Dermatology SC Dermatology GA 017VI UT WOS:000235721000457 ER PT J AU Brown, K Kimball, A AF Brown, K Kimball, A TI Stock market fluctuations and the numbers of US medical school applicants SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Dermatology CY MAR 03-07, 2006 CL San Francisco, CA SP Amer Acad Dermatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2006 VL 54 IS 3 SU S BP AB120 EP AB120 PG 1 WC Dermatology SC Dermatology GA 017VI UT WOS:000235721000470 ER PT J AU Kazanis, M Kimball, A AF Kazanis, M Kimball, A TI Bathing practices and emollient use among psoriasis patients SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Dermatology CY MAR 03-07, 2006 CL San Francisco, CA SP Amer Acad Dermatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2006 VL 54 IS 3 SU S BP AB200 EP AB200 PG 1 WC Dermatology SC Dermatology GA 017VI UT WOS:000235721001314 ER PT J AU Kimball, A Matts, P AF Kimball, A Matts, P TI Characterizing hyperpigmented facial lesions using clinical evaluation and a new chromophore-mapping technique SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Dermatology CY MAR 03-07, 2006 CL San Francisco, CA SP Amer Acad Dermatol C1 Massachusetts Gen Hosp, Clin Unit Res Trials Skin, Boston, MA 02114 USA. Brigham & Womens Hosp, Clin Unit Res Trials Skin, Boston, MA 02115 USA. Procter & Gamble Co, Egham, Surrey, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2006 VL 54 IS 3 SU S BP AB40 EP AB40 PG 1 WC Dermatology SC Dermatology GA 017VI UT WOS:000235721000153 ER PT J AU Salter, S AF Salter, S TI Can striae be used to predict pelvic relaxation? SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Dermatology CY MAR 03-07, 2006 CL San Francisco, CA SP Amer Acad Dermatol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2006 VL 54 IS 3 SU S BP AB78 EP AB78 PG 1 WC Dermatology SC Dermatology GA 017VI UT WOS:000235721000301 ER PT J AU Yoo, J Kimball, A AF Yoo, J Kimball, A TI Workforce characteristics of osteopathic dermatologists in the US SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Dermatology CY MAR 03-07, 2006 CL San Francisco, CA SP Amer Acad Dermatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2006 VL 54 IS 3 SU S BP AB121 EP AB121 PG 1 WC Dermatology SC Dermatology GA 017VI UT WOS:000235721001004 ER PT J AU Yoo, J Kimball, A AF Yoo, J Kimball, A TI Wait times in dermatology SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Dermatology CY MAR 03-07, 2006 CL San Francisco, CA SP Amer Acad Dermatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2006 VL 54 IS 3 SU S BP AB121 EP AB121 PG 1 WC Dermatology SC Dermatology GA 017VI UT WOS:000235721001002 ER PT J AU MacDonald, JH Agarwal, S Lorei, MP Johanson, NA Freiberg, AA AF MacDonald, JH Agarwal, S Lorei, MP Johanson, NA Freiberg, AA TI Knee arthrodesis SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID INTRAMEDULLARY NAIL; RESECTION-ARTHRODESIS; COMPRESSION ARTHRODESIS; SALVAGE PROCEDURE; ARTHROPLASTY; INFECTION; FIXATION; FUSION; REPLACEMENT; FRAME AB Arthrodesis is one of the last options available to obtain a stable, painless knee in a patient with a damaged knee joint that is not amenable to reconstructive measures. Common indications for knee arthrodesis include failed total knee arthroplasty, periarticular tumor, posttraumatic arthritis, and chronic sepsis. The primary contraindications to knee fusion are bilateral involvement or an ipsilateral hip arthrodesis. A variety of techniques has been described, including external fixation, internal fixation by compression plates, intramedullary fixation through the knee with a modular nail, and antegrade nailing through the piriformis fossa. Allograft or autograft may be necessary to restore lost bone stock or to augment fusion. For the carefully selected patient with realistic expectations, knee arthrodesis may relieve pain and obviate the need for additional surgery or extensive postoperative rehabilitation. C1 Leeds Gen Infirm, Leeds Orthopaed Program, Leeds, W Yorkshire, England. Drexel Coll Med, Philadelphia, PA USA. Massachusetts Gen Hosp, Arthroplasty Serv, Boston, MA 02114 USA. RP MacDonald, JH (reprint author), Orthopaed & Sports Med Ctr, 108 Forbes St, Annapolis, MD 21401 USA. NR 46 TC 25 Z9 27 U1 0 U2 1 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD MAR PY 2006 VL 14 IS 3 BP 154 EP 163 PG 10 WC Orthopedics SC Orthopedics GA 021VG UT WOS:000236013400006 PM 16520366 ER PT J AU Collins, TC Suarez-Almazor, M Bush, RL Petersen, NJ AF Collins, TC Suarez-Almazor, M Bush, RL Petersen, NJ TI Gender and peripheral arterial disease SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article ID ADULTS; POPULATION; PREVALENCE; MORTALITY; QUALITY; WOMEN AB Objective: The aim of this study is to determine gender differences in the risk factor profile and leg symptoms of peripheral arterial disease ( PAD). Methods: We identified men and women with PAD from a cohort of patients within a primary care clinic setting. We screened patients 50 years of age and older. We diagnosed PAD based on an ankle-brachial index (ABI) level of less than 0.9; the ABI is the ratio of ankle and arm systolic blood pressure measurements. Patients completed 4 questionnaires, one of which was used to ascertain leg symptoms related to compromised blood flow, the San Diego Claudication Questionnaire (SDCQ). Additional questionnaires were used to determine the patient's medical history, walking impairment, and health-related quality of life. Results: We enrolled 403 patients stratified by race and gender including 55 white women, 82 African American women, and 71 Hispanic women. There were no significant differences by gender in the prevalence of disease. The prevalence of PAD was 9.1% in white women, 21.9% in African American women, and 14.1% in Hispanic women (P = .11). Risk factors for PAD were the same for women and men (ie, diabetes mellitus, current smoking, and use of blood pressure medication). Walking impairment subscale scores were lower for women with PAD when compared with women without PAD and to men with disease. Scores for physical function and general health were lower for women versus men with PAD. Conclusions: The prevalence of PAD, a common disease within primary care clinics, does not vary by gender. Women with PAD are at greater risk for a compromise in daily function and quality of life. Future research is needed to prevent walking impairment and improve limb functioning in patients, particularly women, with PAD. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. RP Collins, TC (reprint author), Dept Vet Affairs, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM tcollins@bcm.tmc.edu NR 22 TC 34 Z9 35 U1 1 U2 2 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 MAR-APR PY 2006 VL 19 IS 2 BP 132 EP 140 PG 9 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 046IG UT WOS:000237804300004 PM 16513901 ER PT J AU Friedlander, AH Norman, DC AF Friedlander, AH Norman, DC TI Geriatric alcoholism - Pathophysiology and dental implications SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Review DE alcoholism; aging; metabolism ID TUMOR-NECROSIS-FACTOR; SUBSTANCE USE DISORDERS; LATE-LIFE; LIVER-DISEASE; ORAL HYGIENE; OLDER-ADULTS; RISK-FACTORS; PERIODONTAL-DISEASE; TREATMENT ADHERENCE; GENERAL-POPULATION AB Background.. The authors reviewed the clinical features, epidemiology, diagnosis, medical treatment, orofacial findings and dental treatment of geriatric patients with alcoholism. Types of Studies Reviewed. The authors conducted MEDLINE searches for the period 1995 through 2004 using the terms "alcoholism," "geriatric," "pathophysiology," "treatment" and "dentistry." They selected reports published in English in peer-reviewed journals for further review. Results. Physiological changes associated with aging permit the harmful effects of drinking alcohol to arise at lower levels of consumption than in younger people. Excessive use of alcohol exacerbates the medical and emotional problems associated with aging and predisposes the person to adverse drug reactions with medications controlling these illnesses. Clinical Implications. The incidence of dental disease in this population is extensive because of diminished salivary flow and a disinterest in performing appropriate oral hygiene techniques. Concurrent abuse of tobacco products worsens dental disease and heightens the risk of developing oral cancer. Identification of patients who abuse alcohol, a cancer-screening examination, preventive dental education, and use of saliva substitutes and anticaries agents are indicated. Clinicians must take precautions when performing surgery and when prescribing or administering analgesics, antibiotics or sedative agents that are likely to have an adverse interaction with alcohol. C1 VA Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Grad Med Educ, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 100 TC 8 Z9 12 U1 4 U2 10 PU AMER DENTAL ASSN 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 MAR PY 2006 VL 137 IS 3 BP 330 EP 338 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 022UO UT WOS:000236081800024 PM 16570466 ER PT J AU Casarett, D Van Ness, PH O'Leary, JR Fried, TR AF Casarett, D Van Ness, PH O'Leary, JR Fried, TR TI Are patient preferences for life-sustaining treatment really a barrier to hospice enrollment for older adults with serious illness? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospice; end-of-life care; hospice preferences ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE PROXIES; OF-LIFE; NURSING-HOMES; PALLIATIVE CARE; END; PHYSICIANS; COMPLETION; DECISIONS; CANCER AB OBJECTIVES: To determine whether patient preferences are a barrier to hospice enrollment. DESIGN: Prospective cohort study. SETTING: Fifteen ambulatory primary care and specialty clinics and three general medicine inpatient units. PARTICIPANTS: Two hundred three seriously ill patients with cancer (n=65, 32%), congestive heart failure (n=77, 38%), and chronic obstructive pulmonary disease (n=61, 30%) completed multiple interviews over a period of up to 24 months. MEASUREMENTS: Preferences for high- and low-burden life-sustaining treatment and site of death and concern about being kept alive by machines. RESULTS: Patients were more likely to enroll in hospice after interviews at which they said that they did not want low-burden treatment (3 patients enrolled/16 interviews at which patients did not want low-burden treatment vs 47 patients enrolled/841 interviews at which patients wanted low-burden treatment; relative risk (RR)=3.36, 95% confidence interval (CI)=1.17-9.66), as were interviews at which patients said they would not want high-burden treatment (5/28 vs 45/826; RR=3.28, 95% CI=1.14-7.62), although most patients whose preferences were consistent with hospice did not enroll before the next interview. In multivariable Cox regression models, patients with noncancer diagnoses who desired low-burden treatment (hazard ratio (HR)=0.46, 95% CI=0.33-0.68) were less likely to enroll in hospice, and those who were concerned that they would be kept alive by machines were more likely to enroll (HR=5.46, 95% CI=1.86-15.88), although in patients with cancer, neither preferences nor concerns about receiving excessive treatment were associated with hospice enrollment. Preference for site of death was not associated with hospice enrollment. CONCLUSION: Overall, few patients had treatment preferences that would make them eligible for hospice, although even in patients whose preferences were consistent with hospice, few enrolled. Efforts to improve end-of-life care should offer alternatives to hospice that do not require patients to give up life-sustaining treatment, as well as interventions to improve communication about patients' preferences. C1 Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Div Geriatr Med, Philadelphia, PA 19104 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Program Aging, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Dept Vet Affairs Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, New Haven, CT USA. RP Casarett, D (reprint author), 3615 Chestnut St, Philadelphia, PA 19104 USA. EM Casarett@mail.med.upenn.edu FU NIA NIH HHS [K02 AG020113, K02 AG020113-01, K02 AG20113, R01 AG019769, R01 AG019769-01A1, R01 AG19769] NR 44 TC 33 Z9 33 U1 2 U2 10 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 MAR PY 2006 VL 54 IS 3 BP 472 EP 478 DI 10.1111/j.1532-5415.2005.00628.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 017ZB UT WOS:000235731000012 PM 16551315 ER PT J AU Min, LC Elliott, MN Wenger, NS Saliba, D AF Min, LC Elliott, MN Wenger, NS Saliba, D TI Higher vulnerable elders survey scores predict death and functional decline in vulnerable older people SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE mortality; functional decline; screening tool ID MORTALITY; COMMUNITY; ASSOCIATION; POPULATION; CARE; IMPAIRMENT; DEMENTIA; OUTCOMES; FAILURE; PROGRAM AB OBJECTIVES: To examine whether the Vulnerable Elders Survey (VES-13) score predicts risk of death and functional decline in vulnerable older adults. DESIGN: Longitudinal evaluation with mean follow-up of 11 months (range 8-14 months). SETTING: Two managed care organizations in the United States. PARTICIPANTS: Four hundred twenty community-dwelling older people identified as having moderate to high risk of death and functional decline based on a VES-13 score of 3 or higher. These older people were enrolled in the Assessing Care of Vulnerable Elders observational study. MEASUREMENTS: Baseline: VES-13 score, sex, income, cognitive score, and number of medical diagnoses. Outcome measures: functional decline and death. RESULTS: VES-13 scores strongly predicted death and functional decline (P <.001, area under the receiver operating curve=0.66). The estimated combined risk of death and decline rose with VES-13 score, increasing from 23% for older people with a VES-13 score of 3 to 60% for those with a score of 10. Other measures (sex, comorbidity) were not significant predictors of death or decline over this period after controlling for VES-13 score. CONCLUSION: The VES-13 score is useful as a screening tool to detect risk of health deterioration in already vulnerable older populations, and higher scores reflect greater risk over a short follow-up period. C1 Univ Calif Los Angeles, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. RAND, Santa Monica, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Min, LC (reprint author), Univ Calif Los Angeles, Dept Med, Div Geriatr, 10945 Le Conte Ave,Suite 2339,Box 951687, Los Angeles, CA 90095 USA. EM lmin@mednet.ucla.edu NR 29 TC 70 Z9 70 U1 2 U2 3 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 MAR PY 2006 VL 54 IS 3 BP 507 EP 511 DI 10.1111/j.1532-5415.2005.00615.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 017ZB UT WOS:000235731000018 PM 16551321 ER PT J AU Rosen, J Mittal, V Degenholtz, H Castle, N Mulsant, BH Hulland, S Nace, D Rubin, F AF Rosen, Jules Mittal, Vikas Degenholtz, Howard Castle, Nick Mulsant, Benoit H. Hulland, Shelley Nace, David Rubin, Fred TI Ability, incentives, and management feedback: Organizational change to reduce pressure ulcers in a nursing home SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE nursing home; pressure ulcer; quality improvement; organization ID BRADEN-SCALE; SORE RISK; QUALITY; PREVENTION AB Objective: Quality improvement (QI) processes in nursing homes are highly variable and often ineffective. This study evaluated an innovative QI process to reduce pressure ulcers (PUs) in a nursing home with a high rate of PUs. Design: This was a 48-week, longitudinal study comparing the incidence of PUs during 12-week baseline and intervention and post-intervention periods. Setting: Not-for-profit, 136-bed nursing home in urban Western Pennsylvania. Patients or Other Participants: All residents and all staff at the nursing home participated in this study. Interventions: The intervention consisted of 3 components: Ability enhancement, incentivization, and management feedback. To enhance ability, all staff members completed a computer-based interactive video education program on PU prevention and were mandated to use penlights to promote early detection. Incentivization included $75 for each staff member if the desired reduction in PU incidence was achieved. Management feedback provided real-time information of staff"s adherence to the mandated training. Main Outcome Measures: Outcome measures consisted of staff's adherence to mandated training and the incidence of new PUs during the baseline period compared to the intervention and post-intervention periods. Results: Management responded to noncompliance with training with both rewards and stepped discipline. Adherence to protocol, as measured by training compliance, was 100%. There was a significant reduction (P < .05) in the incidence of stage 2 or worse PUs during the intervention period. During the post-intervention periods, the effect was lost. Conclusion: An innovative QI initiative resulted in a significant decrease in PUs in 1 facility. This intervention was not sustainable when the 3 components of the QI intervention were no longer actively maintained. C1 Univ Pittsburgh, Sch Med, WPIC, Dept Psychiat, Pittsburgh, PA 15241 USA. Univ Pittsburgh, Katz Grad Sch Business, Pittsburgh, PA 15241 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15241 USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Internal Med, Pittsburgh, PA USA. RP Rosen, J (reprint author), Univ Pittsburgh, Sch Med, WPIC, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15241 USA. EM rosenji@upmc.edu RI Nace, David/D-2638-2014; OI Degenholtz, Howard/0000-0003-1986-7360 FU AHRQ HHS [HS11976]; NIMH NIH HHS [MH01613, MH52247] NR 25 TC 17 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 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD MAR PY 2006 VL 7 IS 3 BP 141 EP 146 DI 10.1016/j.jamda.2005.08.003 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 081JV UT WOS:000240314800002 PM 16503306 ER PT J AU Babnett, GO AF Babnett, GO TI Report to the National Institutes of Health Division of Research Grants Computer Research Study Section on computer applications in medical communication and information retrieval systems as related to the improvement of patient care and the medical record - September 26, 1966 SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID FIELD-LENGTH FORMAT; DIGITAL COMPUTER; LABORATORY DATA; DIAGNOSIS; EXPERIENCE; COMPUTATION; MANAGEMENT; AUTOMATION; PROGRESS; THERAPY C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP Babnett, GO (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, 50 Staniford St, Boston, MA 02114 USA. EM obarnett@partners.org NR 62 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 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 2006 VL 13 IS 2 BP 127 EP 135 DI 10.1197/jamia.M2009 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 023HQ UT WOS:000236118000002 ER PT J AU Berner, ES Houston, TK Ray, MN Allison, JJ Heudebert, GR Chatham, WW Kennedy, JI Glandon, GL Norton, PA Cawford, MA Maisiak, RS AF Berner, ES Houston, TK Ray, MN Allison, JJ Heudebert, GR Chatham, WW Kennedy, JI Glandon, GL Norton, PA Cawford, MA Maisiak, RS TI Improving ambulatory prescribing safety with a handheld decision support system: A randomized controlled trail SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS; PROSPECTIVE VALIDATION; SIMPLE QUESTIONNAIRE; CONTROLLED-TRIAL; RISK; PERFORMANCE; PATIENT; THROMBOEMBOLISM AB Objective: To evaluate the effectiveness of a personal digital assistant (PDA)-based clinical decision support system (CDSS) on nonsteroidal anti-inflammatory drug (NSAID) prescribing safety in the outpatient setting. Design: The design was a randomized, controlled trial conducted in a university-based resident clinic. Internal medicine residents received a PDA-based CDSS suite. For intervention residents, the CDSS included a prediction rule for NSAID-related gastrointestinal risk assessment and treatment recommendations. Unannounced standardized patients (SPs) trained to portray musculoskeletal symptoms presented to study physicians. Safety outcomes were assessed from the prescriptions given to the SPs. Each prescription was reviewed by a committee of clinicians blinded to participant, intervention group assignment, and baseline or follow-up status. Measurements: Prescriptions were judged as safe or unsafe. The main outcome measure was the differential change in unsafe prescribing of NSAIDs for the intervention versus the control group. Results: At baseline, the mean proportion of cases per physician with unsafe prescriptions for the two groups was similar (0.27 vs. 0.29, p > 0.05). Controlling for baseline performance, intervention participants prescribed more safely than controls after receiving the CDSS (0.23 vs. 0.45 [F = 4.24, p < 0.05]). With the CDSS, intervention participants documented more complete assessment of patient gastrointestinal risk from NSAIDs. Conclusion: Participants provided with a PDA-based CDSS for NSAID prescribing made fewer unsafe treatment decisions than participants without the CDSS. C1 Univ Alabama, Dept Hlth Serv Adm, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL USA. RP Berner, ES (reprint author), Univ Alabama, Dept Hlth Serv Adm, 1675 Univ Blvd,Room 544, Birmingham, AL 35294 USA. EM eberner@uab.edu RI Houston, Thomas/F-2469-2013; OI Berner, Eta/0000-0003-4319-2949 FU AHRQ HHS [R18 HS011820, R18 HS 11820] NR 52 TC 46 Z9 46 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 2006 VL 13 IS 2 BP 171 EP 179 DI 10.1197/jamia.M1961 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 023HQ UT WOS:000236118000008 PM 16357350 ER PT J AU Fiorina, P Ansari, MJ Jurewicz, M Barry, M Ricchiuti, V Smith, RN Shea, S Means, TK Auchincloss, H Luster, AD Sayegh, MH Abdi, R AF Fiorina, Paolo Ansari, Mohammed Javeed Jurewicz, Mollie Barry, Mark Ricchiuti, Vincent Smith, Rex Neal Shea, Susan Means, Terry K. Auchincloss, Hugh, Jr. Luster, Andrew D. Sayegh, Mohamed H. Abdi, Reza TI Role of CXC chemokine receptor 3 pathway in renal ischemic injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID T-CELL; REPERFUSION INJURY; ISCHEMIA/REPERFUSION INJURY; ALLOGRAFT-REJECTION; ADHESION MOLECULES; FAILURE; KIDNEY; DYSFUNCTION; BLOCKADE; INNATE AB Chemokines play a major role in the recruitment of leukocytes in inflammation and in the regulation of T helper 1 (Th1)/Th2 immune responses. These mechanisms have been recognized to be important in the pathogenesis of renal ischemia-reperfusion (I/R) injury. The interaction of the CXC chemokine receptor 3 (CXCR3) receptor with its ligands is a key pathogenic pathway in promoting inflammation and in enhancing Th1 immune responses. After the induction of ischemia in the mouse model of renal ischemia, an increase in intrarenal expression of CXCR3 and its ligands was observed. Compared with the wild-type (WT) mice, CXCR3-deficient mice (CXCR3(-/-)) had significantly lower serum creatinine levels, better survival rate, and significantly less acute tubular necrosis and cellular infiltrates. In the kidney, intracellular staining of infiltrating cells that were recovered from kidneys revealed a lower percentage of CD4(+)IFN-gamma(+) cells in the CXCR3(-/-) mice compared with the WT mice. Furthermore, adoptive transfer of WT CD3(+) cells into CXCR3(-/-) mice before induction of I/R injury abrogated the protection of CXCR3(-/-) mice from I/R injury. It is concluded that CXCR3 plays an important role in orchestrating the recruitment of Thl cells to the ischemic kidney and in mediating I/R injury and therefore may serve as a novel target for the therapy of I/R injury. C1 Harvard Univ, Sch Med, Transplantat Res Ctr, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Endocrinol Core Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol & Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Abdi, R (reprint author), Harvard Univ, Sch Med, Transplantat Res Ctr, Childrens Hosp, 221 Longwood Ave, Boston, MA 02115 USA. EM rabdi@rics.bwh.harvard.edu NR 48 TC 49 Z9 52 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 2006 VL 17 IS 3 BP 716 EP 723 DI 10.1681/ASN.2005090954 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 106SF UT WOS:000242120400017 PM 16481416 ER PT J AU Liu, MC Chien, CC Burne-Taney, M Molls, RR Racusen, LC Colvin, RB Rabb, H AF Liu, Manchang Chien, Chu-Chun Burne-Taney, Melissa Molls, Roshni R. Racusen, Lorraine C. Colvin, Robert B. Rabb, Hamid TI A pathophysiologic role for T lymphocytes in murine acute cisplatin nephrotoxicity SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Nephrology CY NOV 08-13, 2005 CL Philadelphia, PA SP Amer Soc Nephrol ID ACUTE-RENAL-FAILURE; ISCHEMIA-REPERFUSION INJURY; PPAR-ALPHA LIGAND; ADRIAMYCIN NEPHROPATHY; INFLAMMATORY RESPONSES; TUBULE CELLS; RAT; NECROSIS; INHIBITION; APOPTOSIS AB Recent evidence supports a role for an inflammatory pathogenesis of cisplatin nephrotoxicity, but immune cell-mediated mechanisms in this disease are still largely unknown. The role for T lymphocytes on cisplatin-induced acute kidney injury was examined with C57BL/6 T cell-deficient (nu/nu) mice and CD4- or CD8-deficient mice and their wild-type (WT) littermates. All mice received a single dose of cisplatin at 40 mg/kg (intraperitoneally) and were followed up for 72 h. At 72 h after cisplatin administration, T cell-deficient mice had a marked attenuation in renal dysfunction (serum creatinine 3.2 +/- 0.5 versus 0.8 +/- 0.1 mg/dl; P = 0.007), kidney tubular injury (scores 1.44 +/- 0.15 versus 0.22 +/- 0.08; P < 0.0001), and survival. Adoptive transfer of T cells into nu/nu mice followed by cisplatin enhanced renal dysfunction and tubular injury. The increase in renal myeloperoxidase activity after cisplatin administration was blunted in nu/nu mice. Renal TNF-alpha, IL-1 beta, and keratinocyte-derived chemokine protein expression was increased in WT mice but not in nu/nu mice after cisplatin administration. T cell levels significantly increased in kidneys of WT mice after cisplatin administration as early as at 1 h, peaked at 12 h, and declined by 24 h. CD4- and, to a lesser degree, CD8-deficient mice were relatively protected from cisplatin-induced mortality and renal dysfunction compared with WT mice. These data demonstrate that T lymphocytes are direct mediators of experimental cisplatin nephrotoxicity. Targeting T lymphocytes could lead to improved ways to administer cisplatin safely to cancer patients. C1 Johns Hopkins Univ, Sch Med, Div Nephrol, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rabb, H (reprint author), Johns Hopkins Univ, Sch Med, Div Nephrol, Dept Med, 720 Rutland Ave,Ross 965, Baltimore, MD 21205 USA. EM hrabb1@jhmi.edu NR 29 TC 79 Z9 84 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 2006 VL 17 IS 3 BP 765 EP 774 DI 10.1681/ASN.2005010102 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 106SF UT WOS:000242120400022 PM 16481417 ER PT J AU Edwards, C Whitfield, K Sudhakar, S Pearce, M Byrd, G Wood, M Feliu, M Leach-Beale, B DeCastro, L Whitworth, E Abrams, M Jonassaint, J Harrison, MO Mathis, M Scott, L Johnson, S Durant, L Holmes, A Presnell, K Bennett, G Shelby, R Robinson, E AF Edwards, C Whitfield, K Sudhakar, S Pearce, M Byrd, G Wood, M Feliu, M Leach-Beale, B DeCastro, L Whitworth, E Abrams, M Jonassaint, J Harrison, MO Mathis, M Scott, L Johnson, S Durant, L Holmes, A Presnell, K Bennett, G Shelby, R Robinson, E TI Parental substance abuse, reports of chronic pain and coping in adult patients with sickle cell disease SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE pain; sickle cell disease; substance abuse ID MUSCULOSKELETAL PAIN; FAMILY HISTORY; ALCOHOL-ABUSE; RISK-FACTORS; CHILDREN; PERSONALITY; ADOLESCENTS; EXPERIENCE; DISORDERS; PSYCHOPATHOLOGY AB There is increasing interest from a social learning perspective in understanding the role of parental factors on adult health behaviors and health outcomes. Our review revealed no studies, to date, that have evaluated the effects of parental substance abuse on reports of chronic pain and coping in adult patients with sickle cell disease (SCD). We explored the effects of parental substance (alcohol or drug) abuse on reports of the sensory, affective and summary indices of pain in 67 adult patients, mean age 38.9 (13.5), with SCID. We also explored the effects of parental substance abuse on psychopathology associated with pain and active coping. Twenty-four percent of patients reported that their parent(s) abused substances. Patients whose parent(s) were characterized as substance abusers reported greater sensory (p=0.02), affective (p=0.01) and summary (VAS; p=0.02) indices of pain as compared to their counterparts, whose parent(s) were not characterized as substance abusers. Patients did not differ in average age, education or the propensity to respond in a socially acceptable manner. There was a significant trend towards patients who characterized their parents as abusers scoring higher than their counterparts on active coping. We propose a Social Learning Theory to explain the current findings and suggest a need for additional prospective research to simultaneously explore biological (genetic) and social factors that influence the interpretation, experience and reporting of chronic pain in adult patients with chronic disease. C1 Duke Univ, Med Ctr, Biofeedback Lab, Dept Psychiat,Div Med Psychol, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Med, Div Hematol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Pains & Palliat Care Ctr, Duke Addict Program, Durham, NC 27710 USA. Penn State Univ, Biobehav Hlth, University Pk, PA 16802 USA. Drexel Univ, Sch Med, Philadelphia, PA 19104 USA. A&T State Univ, Dept Biol, Greensboro, NC USA. Xavier Univ, New Orleans, LA 70125 USA. N Carolina Cent Univ, Dept Psychol, Durham, NC USA. Johns Hopkins Univ, Alzheimers Dis Res Ctr, Baltimore, MD USA. Gen Baptist State Convent N Carolina, Raleigh, NC USA. So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Edwards, C (reprint author), Duke Univ, Med Ctr, Biofeedback Lab, Dept Psychiat,Div Med Psychol, 932 Morreene Rd,Room 170, Durham, NC 27705 USA. EM cledwa00@acpub.duke.edu NR 75 TC 10 Z9 10 U1 4 U2 9 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD MAR PY 2006 VL 98 IS 3 BP 420 EP 428 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 020RP UT WOS:000235928300016 PM 16573309 ER PT J AU Shi, AA Digumarthy, SR Temel, JS Halpern, EF Kuester, LB Aquino, SL AF Shi, Ann A. Digumarthy, Subba R. Temel, Jennifer S. Halpern, Elkan F. Kuester, Landon B. Aquino, Suzanne L. TI Does initial staging or tumor histology better identify asymptomatic brain metastases in patients with non-small cell lung cancer? SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE non-small cell lung cancer; imaging; brain metastasis; staging ID COMPUTED-TOMOGRAPHY; BRONCHOGENIC-CARCINOMA; FREQUENCY; SURVIVAL; CT AB Background: To determine whether the distribution, staging features, or tumor histology of non-small cell lung cancer (NSCLC) distinguishes neurologically symptomatic from asymptomatic patients initially diagnosed with lung cancer, and to determine whether these factors may predict the presence of brain metastasis. Methods: We performed a retrospective review of 809 patients with NSCLC and brain metastases who were treated in our institution between January 1996 and March 2003. Patients who had brain metastasis on initial staging were included. Thoracic computed tomographic scans were reviewed for lung tumor features and staging. Neurological computed tomographic or magnetic resonance image scans were assessed for distribution of brain metastases. Medical records were reviewed for comprehensive staging, tumor histology, and neurological symptoms. Fisher's exact test was used to determine any differences among tumor histology, staging, and imaging features among patients with or without neurological symptoms. Results: Of the 809 patients, 181 had brain metastasis at initial staging. Among these 181 patients, 120 (66%) presented with neurological symptoms (group 1); 61 (34%) patients were asymptomatic (group 2). Patients with adenocarcinoma and large-cell carcinoma had greater odds of brain metastases than patients with squamous cell carcinoma (p = 0.001). There were 106 (58.6%) patients with adenocarcinoma, 32 (17.7%) with large cell carcinoma, and 18 (9.9%) with squamous cell carcinoma. In both groups, most lung cancers were in the right lung with upper lobe dominance. No significant difference in tumor histology or T stage was found between groups, although group 2 was more likely to have a higher N stage. Of the 181 patients with brain metastasis, 60 (33.1%) had NO disease. 51 (28.2%) had T1 disease, and 23 (19.2%) had no other metastasis. There was no correlation between number/distribution of brain metastases and tumor histology, although patients with disease in the cerebellum or temporal lobes had a greater likelihood of neurological symptoms (odds ratio 3.7). Conclusion: There was no significant difference in tumor histology, staging, or distribution between symptomatic or asymptomatic patients with NSCLC with brain metastases. The odds of brain metastases were greater in those with adenocarcinoma or large-cell carcinoma. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM saquino@partners.org NR 30 TC 26 Z9 27 U1 1 U2 2 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 MAR PY 2006 VL 1 IS 3 BP 205 EP 210 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 064UD UT WOS:000239113700004 PM 17409858 ER PT J AU Velmahos, GC Gervasini, A Petrovick, L Dorer, DJ Doran, ME Spaniolas, K Alam, HB De Moya, M Borges, LF Conn, AK AF Velmahos, GC Gervasini, A Petrovick, L Dorer, DJ Doran, ME Spaniolas, K Alam, HB De Moya, M Borges, LF Conn, AK TI Routine repeat head CT for minimal head injury is unnecessary SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 64th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 22, 2005 CL Atlanta, GA SP Amer Assoc Surg Trauma DE head injury; cat scan; minimal; Glasgow Coma Scale; repeat ID COMPUTED-TOMOGRAPHY; TRAUMA; SCAN AB Background. Patients with MHI and a positive head computed tomography (CT) scan frequently have a routine repeat head CT (RRHCT) to identify possible evolution of the head injury requiring intervention. RRHCT is ordered based on the premise that significant injury progression may take place in the absence of clinical deterioration. Methods: In a Level I urban trauma center with a policy of RRHCT, we reviewed the records of 692 consecutive trauma patients with Glasgow Coma Scale scores of 13-15 and a head CT (October 2004 through October 2005). The need for medical or surgical neurologic intervention after RRHCT was recorded. Patients with a worse and unchanged RRHCT were compared, and independent predictors of a worse RRHCT were identified by stepwise logistic regression. Results: There were 179 patients with MHI and RRHCT ordered. Of them, 37 (21%) showed signs of injury evolution on RRHCT and 7 (4%) required intervention. All 7 had clinical deterioration preceding RRHCT. In no patient without clinical deterioration did RRHCT prompt a change in management. A Glasgow Coma Scale score less than 15 (13 or 14), age higher than 65 years, multiple traumatic lesions found on first head CT, and interval shorter than 90 minutes from arrival to first head CT predicted independently a worse RRHCT. Conclusions: RRHCT is unnecessary in patients with MHL Clinical examination identifies accurately the few who will show significant evolution and require intervention. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM g.velmahos@partners.org NR 10 TC 51 Z9 54 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAR PY 2006 VL 60 IS 3 BP 494 EP 499 DI 10.1097/01.ta.0000203546.14824.0d PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 026WX UT WOS:000236374900005 PM 16531845 ER PT J AU Briggs, SM AF Briggs, SM TI Terrorism preparedness: Web-based resource management and the TOPOFF 3 exercise - Editorial comments SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Briggs, SM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAR PY 2006 VL 60 IS 3 BP 572 EP 572 PG 1 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 026WX UT WOS:000236374900023 ER PT J AU Soares, GM Murphy, TP Singha, MS Parada, A Jaff, M AF Soares, GM Murphy, TP Singha, MS Parada, A Jaff, M TI Renal artery duplex ultrasonography as a screening and surveillance tool to detect renal artery stenosis - A comparison with current reference standard Imaging SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE duplex ultrasonography; renal artery; stenosis ID RENOVASCULAR DISEASE; DIAGNOSIS; ANGIOGRAPHY; DOPPLER; RECONSTRUCTION; SONOGRAPHY; ULTRASOUND; BRANCHES; UTILITY AB Objective. Digital subtraction angiography quantitative vessel analysis (QVA) to assess percent renal arterial stenosis (RAS) is the reference standard. Quantitative vessel analysis is not ideal for screening purposes. Renal artery duplex ultrasonography (RADUS) is a noninvasive method to screen for RAS using well-known parameters. We investigated the direct correlation between several RADUS parameters and QVA to evaluate the acceptability of RADUS as a RAS screening and surveillance tool. Methods. We performed a multicenter retrospective study. Stenoses were evaluated in all patients with arteriograms and RADUS examinations within 30 days of each other in the span of 1 year. Percent stenosis of each stenotic renal artery segment was calculated digitally with QVA and correlated with the corresponding peak systolic velocity (PSV) and renal-aortic ratio (RAR) obtained with RADUS. Descriptive statistics and receiver operating characteristic curves were calculated. Correlation of percent stenosis, PSV, and RAR was performed. Sensitivity specificity, and accuracy of diagnostic cut points for each RADUS parameter were calculated. Results. Sixty-seven renal arteries were included. Thirty-three arteries had less than 60% stenosis; 34 had stenosis of 60% or greater. The mean values were PSV 272.791 cm/s; RAR, 3.716; and angiographic percent stenosis, 51.731%. Receiver operating characteristic curves showed higher accuracy for RAR with stenoses of 60% or greater versus PSV. Conclusions. Renal artery duplex ultrasonographic parameters for 60% or greater RAS correlate well with QVA. For detecting stenosis of 60% or greater, RAR is the most accurate parameter at a threshold of 2.5. Renal-aortic ratio is more accurate than PSV Peak systolic velocity may be a useful RADUS alternative parameter for hemodynamically important stenoses in the setting of aortic disease when aortic velocities are less than 40 or greater than 100 cm/s. C1 Brown Univ, Dept Vasc & Intervent Radiol, Providence, RI 02903 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Soares, GM (reprint author), Brown Univ, Dept Vasc & Intervent Radiol, 593 Eddy St, Providence, RI 02903 USA. EM gsoares@lifespan.org NR 20 TC 13 Z9 15 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2006 VL 25 IS 3 BP 293 EP 298 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 017MK UT WOS:000235697500001 PM 16495488 ER PT J AU Heinzerling, KG Etzioni, DA Hurley, B Holtom, P Bluthenthal, RN Asch, SM AF Heinzerling, KG Etzioni, DA Hurley, B Holtom, P Bluthenthal, RN Asch, SM TI Hospital utilization for injection drug use-related soft tissue infections in urban versus rural counties in California SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE hospital utilization; injection drug use; Medicaid; soft tissue infection; urban; rural ID SAN-FRANCISCO; UNITED-STATES; RISK-FACTORS; ABSCESSES; SKIN; PREVALENCE AB Drug related-soft tissue infections (DR-STIs) are a significant source of hospital utilization in inner-city urban areas where injection drug use is common but the magnitude of hospital utilization for DR-STIs outside of inner-city urban areas is not known. We described the magnitude and characteristics of hospital utilization for DR-STIs in urban versus rural counties in California. All discharges from all nonfederal hospitals in California in 2000 with ICD-9 codes for a soft tissue infection and for drug dependence/abuse were abstracted from the California Office of Statewide Health Planning and Development discharge database. There were 4,152 DR-STI discharges in 2000 from hospitals in 49 of California's 58 counties. Residents of 12 large metropolitan counties accounted for 3,598 discharges (87% of total). The majority of DR-STI discharges were from urban safety net hospitals with county indigent programs and Medicaid as the expected payment source and opiate related discharge diagnoses. Hospital utilization for DR-STIs in California is highest in large urban metropolitan counties, although DR-STI discharges are widespread. Increased access to harm reduction services and drug treatment may reduce government health care expenditures by preventing unnecessary hospital utilization for DR-STIs. C1 Univ Calif Los Angeles, Dept Family Med, Sch Med, Los Angeles, CA 90025 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Surg, Sch Med, Los Angeles, CA 90025 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. RAND, Hlth Program, Santa Monica, CA 90406 USA. RAND, Drug Policy Res Ctr, Santa Monica, CA 90406 USA. RP Heinzerling, KG (reprint author), Univ Calif Los Angeles, Dept Family Med, Sch Med, 11075 Santa Monica Blvd,Suite 200, Los Angeles, CA 90025 USA. EM heinzk@ucla.edu OI Bluthenthal, Ricky/0000-0003-3491-1702 FU NIDA NIH HHS [K23 DA023558] NR 18 TC 6 Z9 6 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD MAR PY 2006 VL 83 IS 2 BP 176 EP 181 DI 10.1007/s11524-005-9021-6 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 039OO UT WOS:000237316300006 PM 16736367 ER PT J AU Galper, SL Chen, MH Catalona, WJ Roehl, KA Richie, JP D'Amico, AV AF Galper, SL Chen, MH Catalona, WJ Roehl, KA Richie, JP D'Amico, AV TI Evidence to support a continued stage migration and decrease in prostate cancer specific mortality SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; prostatectomy; mass screening; treatment failure ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; ANTIGEN ERA; SURVIVAL; PROGRESSION AB Purpose: We evaluated whether the proportion of patients with a postoperative PSA-DT less than 3 months, a surrogate for PCSM, decreased significantly during the PSA era. Materials and Methods: Between July 1988 and July 2002, 3,719 men with clinically localized prostate cancer treated with RP comprised the study cohort. A chi-square metric was used to compare the preoperative and postoperative characteristics, 5-year actual PSA failure rates, and PSA-DTs for patients treated during the 2 equally divided eras of the early PSA era, July 1988 to July 1995 and the late PSA era, August 1995 to July 2002. Results: Patients presenting in the more recent PSA era were of younger age (p < 0.0001), with earlier stage (p < 0.0001) and lower grade disease (p = 0.01). Similarly, patients had lower grade (p < 0.001), stage (p < 0.0001), and positive margin (p < 0.0001) and lymph node rates (p = 0.0002) at RP. The 5-year actual PSA failure rates decreased from 14.3% in the early PSA era to 2.5% in the later PSA era (p < 0.0001). There was a 37% reduction in the proportion of patients with a PSA-DT less than 3 months, corresponding to a decrease in absolute magnitude from 9% to 5.7% between the 2 eras. Absolute reductions of 3.1% and 9% were also noted for the proportion of PSA-DTs of 3 to 5.99 months and 6 to 11.99 months, respectively, whereas PSA-DTs of 12 months or greater increased by 15.3%. Conclusions: During the recent PSA era, postoperative PSA failure has significantly decreased and PSA-DTs have increased, suggesting that PCSM will continue to decrease. C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Galper, SL (reprint author), 483 Washington St 2, Brookline, MA 02446 USA. EM shiragalper@yahoo.com NR 20 TC 58 Z9 58 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2006 VL 175 IS 3 BP 907 EP 912 DI 10.1016/S0022-5347(05)00419-2 PN 1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 011SW UT WOS:000235289400024 PM 16469577 ER PT J AU Spurgeon, SEF Hsieh, YC Rivadinera, A Beer, TM Mori, M Garzotto, M AF Spurgeon, SEF Hsieh, YC Rivadinera, A Beer, TM Mori, M Garzotto, M TI Classification and regression tree analysis for the prediction of aggressive prostate cancer on biopsy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen; risk; biopsy ID DIGITAL RECTAL EXAMINATION; RADICAL PROSTATECTOMY; NATURAL-HISTORY; ANTIGEN; MEN; PROBABILITY; NOMOGRAM; DISEASE; GRADE; RISK AB Purpose: Prostate cancer screening allows early cancer detection but not all patients benefit from subsequent therapy. Thus, identifying patients who are likely to harbor aggressive cancer could significantly decrease the number of prostate biopsies performed. Materials and Methods: Data were collected on 1,563 consecutive referred men with serum PSA 10 ng/ml or less who underwent an initial prostate biopsy. Predictors of aggressive cancer (Gleason sum 7 or greater) were identified using CART analysis. Model building was done in a randomly selected training set (70% of the data) and validation was completed using the remaining data. Results: Cancer was detected in 406 men (26.1%). Gleason 7 or greater cancer was found in 130 men (8.3%). CART created a decision tree that identified certain groups at risk for aggressive cancer, namely 1) PSAD greater than 0.165 ng/ml/cc, and 2) PSAD greater than 0.058 to 0.165 ng/rnl/cc or less, age greater than 57.5 years and prostate volume greater than 22.7 cc. The incidence of aggressive prostate cancer was 1.1% when PSAD was 0.058 ng/ml/cc or less in the validation set. The sensitivity and specificity of CART for identifying men with aggressive cancer were 100% and 31.8% for model building data, and 91.5% and 33.5% for the validation data set, respectively. Conclusions: CART identified groups at risk for aggressive prostate cancer. Application of this CART could decrease unnecessary biopsies by 33.5% when only a diagnosis of high grade prostate cancer would lead to subsequent therapy. C1 Portland Vet Affairs Med Ctr, Urol Sect, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR USA. Oregon Hlth & Sci Univ, Div Urol, Portland, OR USA. Oregon Hlth & Sci Univ, Inst Canc, Biostat Shared Resource, Portland, OR USA. RP Garzotto, M (reprint author), Portland Vet Affairs Med Ctr, Urol Sect, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM garzotto@ohsu.edu NR 20 TC 8 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2006 VL 175 IS 3 BP 918 EP 922 DI 10.1016/S0022-5347(05)00353-8 PN 1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 011SW UT WOS:000235289400027 PM 16469580 ER PT J AU Hiasa, Y Blackard, JT Lin, WY Kamegaya, Y Horiike, N Onji, M Schmidt, EV Chung, RT AF Hiasa, Y Blackard, JT Lin, WY Kamegaya, Y Horiike, N Onji, M Schmidt, EV Chung, RT TI Cell-based models of sustained, interferon-sensitive hepatitis C virus genotype 1 replication SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE hepatitis C virus; HCV; replication; genotype 1; adenovirus vector; Huh-T7 ID BLOOD MONONUCLEAR-CELLS; RECOMBINANT VACCINIA VIRUS; PROTEIN-KINASE; VIRAL-RNA; EXTRAHEPATIC REPLICATION; ALPHA-INTERFERON; IN-VITRO; MUTATIONS; CULTURE; GENOME AB We have previously reported hepatitis C virus (HCV) replication using a novel binary expression system in which mammalian cells were transfected with a T7 polymerase-driven full-length genotype 1 a HCV cDNA plasmid (pT7-flHCV-Rz) and infected with vaccinia-T7 polymerase. We hypothesized that the use of replication-defective adenoviral vectors expressing T7 (Ad-T7pol) or cell lines stably transfected with T7 (Huh-T7) would alleviate cell toxicity and allow for more Sustained HCV replication. CV-1. Huh7, and Huh-T7 cells were transfected with pT7-flHCV-Rz and treated with Ad-T7pol (CV-1 and Huh7 only). Protein and RNA were harvested from cells on days 1, 2, 3, 5, 7, and 9 post-infection. No cytotoxicity was observed at 9 days post-infection in any cell type. HCV positive- and negative-strand RNA expression were strongest during days 1-3 post-infection; however, HCV RNA remained detectable throughout the 9-day observation period. Furthermore, transfection with a replication-incompetent plasmid Suggested that efficient HCV replication is dependent upon NS5B gene expression. Finally, after 1-2 days of IFN treatment, HCV positive-strand levels decreased significantly compared to HCV-infected but untreated samples (p < 0.05). In conclusion, these refined binary systems offer more durable and authentic models for identification of host cellular processes critical to HCV replication and will permit longer-term analysis of virus-host interactions critical to HCV pathogenesis and the treatment of genotype 1 infections. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. Ehime Univ, Sch Med, Dept Internal Med 3, Toon, Ehime 7910295, Japan. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 816,55 Fruit St, Boston, MA 02114 USA. EM hiasa@ni.ehime-u.ac.jp; jblackard@partners.org; wlin1@partners.org; ykamegaya@partners.org; horiike@m.ehime-u.ac.jp; onjimori@m.ehime-u.ac.jp; eschmidt@partners.org; rtchung@partners.org FU NIAID NIH HHS [R01 AI043478-03, R01 AI43478]; NIDDK NIH HHS [R01 DK057857, R01 DK57857] NR 33 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAR PY 2006 VL 132 IS 1-2 BP 195 EP 203 DI 10.1016/j.jviromet.2005.10.014 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 019RP UT WOS:000235854700026 PM 16313977 ER PT J AU Agopian, K Wei, BL Garcia, JV Gabuzda, D AF Agopian, K Wei, BL Garcia, JV Gabuzda, D TI A hydrophobic binding surface on the human immunodeficiency virus type 1 Nef core is critical for association with p21-activated kinase 2 SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR SERINE KINASE; CD4 DOWN-REGULATION; PAK-RELATED KINASE; HIV-1 NEF; T-CELLS; RHESUS MACAQUES; SH3 DOMAIN; LYMPHOCYTE-ACTIVATION; CRYSTAL-STRUCTURE; DILEUCINE MOTIF AB The interaction of human immunodeficiency virus type 1 (HIV-1) Nef with p21-activated kinase 2 (Pak2) has been proposed to play an important role in T-cell activation and disease progression during viral infection. However, the mechanism by which Nef activates Pak2 is poorly understood. Mutations in most Nef motifs previously reported to be required for Pak2 activation (G(2), PxxP(72), and RR105) also affect other Nef functions, such as CD4 or major histocompatibility complex class I (MHC-I) downregulation. To better understand Nef interactions with Pak2, we performed mutational analysis of three primary HIV-1 Nef clones that exhibited similar capacities for downregulation of CD4 and MHC-I but variable abilities to associate with activated Pak2. Our results demonstrate that Nef amino acids at positions 85, 89, 187, 188, and 191 (L, H, S, R, and F in the clade B consensus, respectively) are critical for Pak2 association. Mutation of these Nef residues dramatically altered association with Pak2 without affecting Nef expression levels or CD4 and MHC-I downregulation. Furthermore, compensation occurred at positions 89 and 191 when both amino acids were substituted. Since residues 85, 89, 187, 188, and 191 cluster on the surface of the Nef core domain in a region distinct from the dimerization and SH3-binding domains, we propose that these Nef residues form part of a unique binding surface specifically involved in association with Pak2. This binding surface includes exposed and recessed hydrophobic residues and may participate in an as-yet-unidentified protein-protein interaction to facilitate Pak2 activation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Div Infect Dis, Dallas, TX 75390 USA. RP Gabuzda, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 816,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIAID NIH HHS [AI33331, R01 AI033331]; NINDS NIH HHS [NS35734, R01 NS035734] NR 67 TC 39 Z9 39 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2006 VL 80 IS 6 BP 3050 EP 3061 DI 10.1128/JVI.80.6.3050-3061.2006 PG 12 WC Virology SC Virology GA 023MS UT WOS:000236131400046 PM 16501114 ER PT J AU Zuniga, R Lucchetti, A Galvan, P Sanchez, S Sanchez, C Hernandez, A Sanchez, H Frahm, N Linde, CH Hewitt, HS Hildebrand, W Altfeld, M Allen, TM Walker, BD Korber, BT Leitner, T Sanchez, J Brander, C AF Zuniga, R Lucchetti, A Galvan, P Sanchez, S Sanchez, C Hernandez, A Sanchez, H Frahm, N Linde, CH Hewitt, HS Hildebrand, W Altfeld, M Allen, TM Walker, BD Korber, BT Leitner, T Sanchez, J Brander, C TI Relative dominance of Gag p24-specific cytotoxic T lymphocytes is associated with human immunodeficiency virus control SO JOURNAL OF VIROLOGY LA English DT Article ID PLASMA VIRAL LOAD; TYPE-1 SUBTYPE-C; CELL RESPONSES; HIV-INFECTION; IMMUNODOMINANT REGIONS; ESCAPE MUTATION; CD8(+); TRANSMISSION; HLA; MAGNITUDE AB Conflicting data on the role of total virus- and protein-specific cytotoxic-T-lymphocyte (CTL) responses in the control of human immunodeficiency virus (HIV) disease progression exist. We present data generated from a Peruvian cohort of untreated, clade B-infected subjects, demonstrating that the proportion of Gag-specific, and in particular p24-reactive, CTL responses among the total virus-specific CTL activity is associated with individuals' CD4 counts and viral loads. Analyses in a second cohort in the United States confirm these findings and point towards a dominant role of Gag-specific immunity in effective control of HIV infection, providing important guidance for HIV vaccine development. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Asociac Civil IMPACTA Salud & Educ, Lima, Peru. Univ Oklahoma, Norman, OK 73019 USA. Los Alamos Natl Lab, Los Alamos, NM USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Brander, C (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 5th Floor,MGH E,5239,149 13th St, Charlestown, MA 02129 USA. EM cbrander@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [N01-AI-15422, N01AI30024] NR 23 TC 196 Z9 204 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2006 VL 80 IS 6 BP 3122 EP 3125 DI 10.1128/JVI.80.6.3122-3125.2006 PG 4 WC Virology SC Virology GA 023MS UT WOS:000236131400058 PM 16501126 ER PT J AU Delmonico, FL AF Delmonico, FL TI What is the system failure? SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID ORGAN AB As a result of the increasing use of live organ donors, international conferences have been held in Amsterdam and Vancouver to address the transplant community's concern for the well-being of such donors. Congress has considered arguments to permit a regulated market of organ sales but has rejected such a proposal, in part because of a fundamental ethical principle: selling one's kidney or any other part of one's body violates the dignity of the human person. The "system failure" is not only at the doorstep of organ donation. The expansion of the waiting list for kidney transplants is heavily composed of the elderly who could have benefited by preventive medical care. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Delmonico, FL (reprint author), Massachusetts Gen Hosp, White 505, Boston, MA 02114 USA. EM francis_delmonico@neob.org NR 6 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2006 VL 69 IS 6 BP 954 EP 955 DI 10.1038/sj.ki.5000278 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 026LJ UT WOS:000236340100004 PM 16528241 ER PT J AU Hsieh, TJ Chen, R Zhang, SL Liu, F Brezniceanu, ML Whiteside, CI Fantus, IG Ingelfinger, JR Hamet, P Chan, JSD AF Hsieh, TJ Chen, R Zhang, SL Liu, F Brezniceanu, ML Whiteside, CI Fantus, IG Ingelfinger, JR Hamet, P Chan, JSD TI Upregulation of osteopontin gene expression in diabetic rat proximal tubular cells revealed by microarray profiling SO KIDNEY INTERNATIONAL LA English DT Article DE osteopontin; high glucose; renin-angiotensin system ID KINASE-C ISOFORMS; PROTEIN-KINASE; HIGH GLUCOSE; TUBULOINTERSTITIAL INJURY; GROWTH-FACTOR; MACROPHAGE RECRUITMENT; EPITHELIAL-CELLS; KIDNEY GROWTH; BB RAT; ANGIOTENSINOGEN AB Progression of diabetic nephropathy appears directly related to renal tubulointerstitial injury, but the involved genes are incompletely delineated. To identify such genes, DNA microarray analysis was performed with RNA from renal proximal tubules (RPTs) of streptozotocin-induced diabetic Wistar rats, spontaneously diabetic BioBreeding rats, and rat immortalized renal proximal tubular cells (IRPTCs) exposed to high glucose (25 mM) medium for 2 weeks. Osteopontin (OPN) mRNA expression was quantified by real time-quantitative polymerase chain reaction (RT-qPCR) or conventional reverse transcriptase-polymerase chain reaction (RT-PCR). OPN mRNA expression was upregulated (5-70-fold increase) in diabetic rat RPTs and in IRPTCs chronically exposed to high glucose compared to control RPTs and IRPTCs. High glucose, angiotensin II, phorbol 12-myristate 13-acetate and transforming growth factor-beta 1 (TGF-beta(1)) stimulated OPN mRNA expression in IRPTCs in a dose- and time-dependent manner. This effect was inhibited by tiron, taurine, diphenylene iodinium, losartan, perindopril, calphostin C, or LY 379196 but not PD123319. IRPTCs overexpressing dominant-negative protein kinase C-beta 1 (PKC-beta(1)) cDNA or antisense TGF-beta(1) cDNA prevented the high glucose effect on OPN mRNA expression. We concluded that high glucose-mediated increases in OPN gene expression in diabetic rat RPTs and IRPTCs are mediated, at least in part, via reactive oxygen species generation, intrarenal rennin-angiotensin system activation, TGF-beta(1) expression, and PKC-beta(1) signaling. C1 CHUM, Hotel Dieu, Res Ctr, Montreal, PQ H2W 1T8, Canada. Mt Sinai Hosp, Univ Hlth Network, Dept Med, Toronto, ON M5G 1X5, Canada. Harvard Univ, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA USA. RP Chan, JSD (reprint author), CHUM, Hotel Dieu, Res Ctr, 3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU NHLBI NIH HHS [HL-48455] NR 51 TC 31 Z9 37 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2006 VL 69 IS 6 BP 1005 EP 1015 DI 10.1038/sj.ki.5000206 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 026LJ UT WOS:000236340100014 PM 16528250 ER PT J AU Sachetelli, S Liu, Q Zhang, SL Liu, F Hsieh, TJ Brezniceanu, ML Guo, DF Filep, JG Ingelfinger, JR Sigmund, CD Hamet, P Chan, JSD AF Sachetelli, S Liu, Q Zhang, SL Liu, F Hsieh, TJ Brezniceanu, ML Guo, DF Filep, JG Ingelfinger, JR Sigmund, CD Hamet, P Chan, JSD TI RAS blockade decreases blood pressure and proteinuria in transgenic mice overexpressing rat angiotensinogen gene in the kidney SO KIDNEY INTERNATIONAL LA English DT Article DE angiotensinogen; hypertension; proteinuria; transgenic mice ID PROXIMAL TUBULAR CELLS; CORTICAL COLLECTING DUCT; RENIN-ANGIOTENSIN; HIGH GLUCOSE; HYPERTENSIVE-RATS; EXPRESSION; SYSTEM; HYPERTROPHY; HYBRIDIZATION; INDUCTION AB Angiotensinogen (ANG) is the sole substrate of the renin-angiotensin system (RAS). Clinical studies have shown that RAS activation may lead to hypertension, a major cardiovascular and renal risk factor. To delineate the underlying mechanisms of hypertension-induced nephropathy, we generated transgenic mice that overexpress rat ANG (rANG) in the kidney to establish whether intrarenal RAS activation alone can evoke hypertension and kidney damage and whether RAS blockade can reverse these effects. Transgenic mice overexpressing renal rANG were generated by employing the kidney-specific, androgen-regulated protein promoter linked to rANG cDNA. This promoter targets rANG cDNA to renal proximal tubules and responds to androgen stimulation. Transgenic mice displayed kidney-specific expression of rANG, significantly increased blood pressure (BP) and albuminuria in comparison to non-transgenic littermates. Administration of losartan (an angiotensin II (type 1)-receptor antagonist) or perindopril (an angiotensin-converting enzyme inhibitor) reversed these abnormalities in transgenic animals. Renal injury was evident on examination of the kidneys in transgenic mice, and attenuated by losartan and perindopril treatment. We conclude that the overproduction of ANG alone in the kidney induces an increase in systemic BP, proteinuria, and renal injury. RAS blockers prevent these abnormalities. These data support the role of the intrarenal RAS in the development of hypertension and renal injury. C1 CHUM Hotel Dieu, Res Ctr, Montreal, PQ, Canada. Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. Univ Iowa, Sch Med, Dept Internal Med & Physiol & Biophys, Iowa City, IA 52242 USA. RP Chan, JSD (reprint author), Hop Hotel Dieu, CHUM, Res Ctr, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca OI Sigmund, Curt/0000-0002-1453-0921 FU NHLBI NIH HHS [HL-48455] NR 31 TC 80 Z9 80 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2006 VL 69 IS 6 BP 1016 EP 1023 DI 10.1038/sj.ki.5000210 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 026LJ UT WOS:000236340100015 PM 16528251 ER PT J AU Irimia, D Toner, M AF Irimia, D Toner, M TI Cell handling using microstructured membranes SO LAB ON A CHIP LA English DT Article ID ON-A-CHIP; MICROFLUIDIC DEVICES; DIELECTROPHORETIC TRAPS; CLINICAL DIAGNOSTICS; SOFT LITHOGRAPHY; VALVES; POLY(DIMETHYLSILOXANE); CENTRIFUGATION; SUSPENSIONS; SEPARATION AB Gentle and precise handling of cell suspensions is essential for scientific research and clinical diagnostic applications. Although different techniques for cell analysis at the micro-scale have been proposed, many still require that preliminary sample preparation steps be performed off the chip. Here we present a microstructured membrane as a new microfluidic design concept, enabling the implementation of common sample preparation procedures for suspensions of eukaryotic cells in lab-on-a-chip devices. We demonstrate the novel capabilities for sample preparation procedures by the implementation of metered sampling of nanoliter volumes of whole blood, concentration increase up to three orders of magnitude of sparse cell suspension, and circumferentially uniform, sequential exposure of cells to reagents. We implemented these functions by using microstructured membranes that are pneumatically actuated and allowed to reversibly decouple the flow of fluids and the displacement of eukaryotic cells in suspensions. Furthermore, by integrating multiple structures on the same membrane, complex sequential procedures are possible using a limited number of control steps. C1 Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU NIBIB NIH HHS [P41 EB002503] NR 36 TC 58 Z9 59 U1 1 U2 17 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PD MAR PY 2006 VL 6 IS 3 BP 345 EP 352 DI 10.1039/b515983k PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 021OZ UT WOS:000235993800002 PM 16511616 ER PT J AU Chen, JWY Wasterlain, CG AF Chen, JWY Wasterlain, CG TI Status epilepticus: pathophysiology and management in adults SO LANCET NEUROLOGY LA English DT Review ID CONVULSIVE STATUS EPILEPTICUS; REFRACTORY STATUS EPILEPTICUS; SUSTAINING STATUS EPILEPTICUS; TEMPORAL-LOBE EPILEPSY; NONCONVULSIVE STATUS EPILEPTICUS; SPONTANEOUS RECURRENT SEIZURES; CHILDHOOD STATUS EPILEPTICUS; LIMBIC STATUS EPILEPTICUS; NEURON-SPECIFIC ENOLASE; ACID-INDUCED SEIZURES AB As in Clark and Prout's classic work, we identify three phases of generalised convulsive status epilepticus, which we call impending, established, and subtle. We review physiological and subcellular changes that might play a part in the transition from single seizures to status epilepticus and in the development of time-dependent pharmacoresistance. We review the principles underlying the treatment of status epilepticus and suggest that prehospital treatment is beneficial, that therapeutic drugs should be used in rapid sequence according to a defined protocol, and that refractory status epilepticus should be treated with general anaesthesia. We comment on our preference for drugs with a short elimination half-life and discuss some therapeutic choices. C1 Univ Calif Los Angeles, Geffen Sch Med, Dept Neurol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90073 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Wasterlain, CG (reprint author), Univ Calif Los Angeles, Geffen Sch Med, Dept Neurol, Los Angeles, CA 90073 USA. EM wasteria@ucla.edu FU NINDS NIH HHS [NS13515, NS42708] NR 163 TC 186 Z9 194 U1 1 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD MAR PY 2006 VL 5 IS 3 BP 246 EP 256 DI 10.1016/S1474-4422(06)70374-X PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 016PS UT WOS:000235632900019 PM 16488380 ER PT J AU Domchek, SM Friebel, TM Neuhausen, SL Wagner, T Evans, G Isaacs, C Garber, JE Daly, M Eeles, R Matloff, E Tomlinson, GE Van't Veer, L Lynch, HT Olopade, O Weber, BL Rebbeck, TR AF Domchek, SM Friebel, TM Neuhausen, SL Wagner, T Evans, G Isaacs, C Garber, JE Daly, M Eeles, R Matloff, E Tomlinson, GE Van't Veer, L Lynch, HT Olopade, O Weber, BL Rebbeck, TR TI Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study SO LANCET ONCOLOGY LA English DT Article ID BREAST-CANCER RISK; PROPHYLACTIC OOPHORECTOMY; OVARIAN-CANCER; WOMEN; SURGERY; BIAS AB Background Bilateral prophylactic salpingo-cophorectomy (BPSO) is used widely used to reduce the risk of breast and ovarian cancer in women with BRCA1 and BRCA2 mutations. However, the reduction in mortality after this surgery is unclear. We aimed to assess whether BPSO improves overall mortality or cancer-specific mortality in BRCA1 and BRCA2 mutation carriers. Methods We identified a prospective cohort of 666 women with disease-associated gem-dine mutations in BRCA1 or BRCA2 and no previous cancer diagnosis. in our primary analysis, we compared 155 women who had had BPSO and 271 women matched for age at BPSO who had not had BPSO. In our secondary analysis, we compared 188 women who had had BPSO with 478 women who had not. In both analyses, we compared overall mortality and cancer-specific mortality. All analyses were adjusted for Centre, mutation (BRCA1 vs BRCA2), and birth year. Findings In the primary analysis, mean follow-up from BPSO to censoring was 3.1 years [SD 2(.)4] in the BPSO group and 2(.)1 years [2(.)0] in the non-BPSO group. The hazard ratio (HR) for overall mortality was 0(.)24 (95% CI 0(.)08-0(.)71), for breast-cancer-specific mortality was 0(.)10(0(.)02-0(.)71), and for ovarian-cancer-specific mortality was 0(.)05 (0(.)01-0(.)46) for women who had BPSO compared with those who had not. In secondary analysis, BPSO was associated with reduced overall mortality (HR 0(.)28 [95% Cl 0(.)10-0(.)74]), but not with breast-cancer-specific mortality (0(.)15 [0-02-1-18] or ovarian-cancer-specific mortality (0(.)23 [0(.)02-1(.)87]. When regarded as a time-dependent covariate, BPSO was not associated significantly with mortality. Interpretation if confirmed, the finding that BPSO improves overall survival and cancer-specific survival in women with BRCA mutations will complement our existing knowledge of cancer-risk reduction associated with BPSO. Together, these data could give information to women who are considering genetic testing. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA USA. Univ Vienna, Dept Obstet & Gynaecol, Div Senol, Vienna, Austria. St Marys Hosp, Dept Clin Genet, Manchester M13 0JH, Lancs, England. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Med, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Oncol, Washington, DC 20007 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Inst Canc Res, Sutton, Surrey, England. Royal Marsden Natl Hlth Serv Trust, Sutton, Surrey, England. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Ctr Canc, New Haven, CT 06510 USA. Univ Texas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX USA. Univ Texas, Dept Paediat, Dallas, TX USA. Netherlands Canc Inst, Dept Pathol, NL-1066 CX Amsterdam, Netherlands. Creighton Univ, Dept Med, Omaha, NE 68178 USA. Creighton Univ, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. GlaxoSmithKline, Merion, PA USA. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Abramson Canc Ctr, 904 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM trebbeck@cceb.med.upenn.edu FU NCI NIH HHS [N01-CN-6700, CA74415, R01-CA83855] NR 14 TC 150 Z9 156 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2006 VL 7 IS 3 BP 223 EP 229 DI 10.1016/S1470-2045(06) PG 7 WC Oncology SC Oncology GA 026ML UT WOS:000236342900026 PM 16510331 ER PT J AU Mikulec, AA Poe, DS AF Mikulec, AA Poe, DS TI Operative management of a posterior semicircular canal dehiscence SO LARYNGOSCOPE LA English DT Article DE posterior semicircular canal dehiscence; high jugular bulb; labyrinthine fistula; canal plugging ID CONDUCTIVE HEARING-LOSS; VERTIGO; SURGERY; EAR AB Objective: The objective of this study was to describe the operative management of posterior canal dehiscence. Methods: A transmastoid approach to and plugging of the posterior canal was performed for posterior semicircular canal dehiscence (PSCD). Results: Postoperatively, the patient exhibited improvement in conductive hearing loss and vestibular symptoms. Conclusions: PSCD can cause symptoms identical to that of superior semicircular canal dehiscence. Successful PSCD plugging can be performed without visualization of the actual area of dehiscence. C1 Childrens Hosp Boston, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Poe, DS (reprint author), Childrens Hosp Boston, Dept Otolaryngol, Zero Emerson Pl,Suite 2C, Boston, MA 02114 USA. EM dpoe@massmed.org NR 16 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2006 VL 116 IS 3 BP 375 EP 378 DI 10.1097/01.mlg.0000200358.93385.5c PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 020PE UT WOS:000235921100006 PM 16540892 ER PT J AU Chng, WJ Winkler, JM Greipp, PR Jalal, SM Bergsagel, PL Chesi, M Trendle, MC Ahmann, GJ Henderson, K Blood, E Oken, MM Hulbert, A Van Wier, SA Santana-Davila, R Kyle, RA Gertz, MA Lacy, MQ Dispenzieri, A Fonseca, R AF Chng, WJ Winkler, JM Greipp, PR Jalal, SM Bergsagel, PL Chesi, M Trendle, MC Ahmann, GJ Henderson, K Blood, E Oken, MM Hulbert, A Van Wier, SA Santana-Davila, R Kyle, RA Gertz, MA Lacy, MQ Dispenzieri, A Fonseca, R TI Ploidy status rarely changes in myeloma patients at disease progression SO LEUKEMIA RESEARCH LA English DT Article DE ploidy; myeloma; disease progression; DNA index; flow cytometry ID MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; IN-SITU; IGH TRANSLOCATIONS; CHROMOSOME 13Q; BREAST-CANCER; PLASMA-CELLS; K-RAS; ABNORMALITIES AB Hyperdiploid and non-hyperdiploid multiple myeloma represents distinct biological entities characterized by different patterns of genetic changes. We sought to determine whether ploidy category (non-hyperdiploid versus hyperdiploid) remains stable over time from diagnosis to progression. Of the 43 patients studied (39 by flow cytometry DNA index and 4 by a FISH-based index), only five (12%) altered their ploidy status at progression. In three of these patients, the change may possibly be attributable to technical artifacts because of the low absolute change in DNA index. For those who retain their ploidy subtypes, the DNA index change minimally (3.75 +/- 4.87%). It would appear that the initiating genetic events underlying hyperdiploid and non-hyperdiploid MM that marks them out as distinct entities continue to dominate and persist during disease evolution and progression. (c) 2005 Elsevier Ltd. All rights reserved. C1 Mayo Clin Scottsdale, Ctr Comprehens Canc, Div Haematol Oncol, Scottsdale, AZ 85259 USA. Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Ctr Stat, Boston, MA USA. Minneapolis VA Med Ctr, Minneapolis, MN USA. Nalt Univ hosp, Dept Hematol Oncol, Singapore, Singapore. RP Fonseca, R (reprint author), Mayo Clin Scottsdale, Ctr Comprehens Canc, Div Haematol Oncol, Johnson Res Bldg,13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM fonseca.rafael@mayo.edu RI Bergsagel, Peter/A-7842-2011; OI Bergsagel, Peter/0000-0003-1523-7388; Fonseca, Rafael/0000-0002-5938-3769; Dispenzieri, Angela/0000-0001-8780-9512 FU NCI NIH HHS [P01 CA62242, P50 CA100707-01, R01 CA83724-01] NR 29 TC 20 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAR PY 2006 VL 30 IS 3 BP 266 EP 271 DI 10.1016/j.leukres.2005.07.004 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 008KP UT WOS:000235039900004 PM 16111750 ER PT J AU Ruan, PK Gray, RJ AF Ruan, PK Gray, RJ TI A method for analyzing disease-specific mortality with missing cause of death information SO LIFETIME DATA ANALYSIS LA English DT Article DE competing risks; log-rank test; cumulative incidence function; missing failure type; Nelson-Aalen estimator ID EARLY BREAST-CANCER; COMPETING RISKS; RANDOMIZED-TRIALS; SURVIVAL-DATA; FAILURE DATA; INFERENCE; MODEL AB In this paper, we examine a method for analyzing competing risks data where the failure type of interest is missing or incomplete, but where there is an intermediate event, and only patients who experience the intermediate event can die of the cause of interest. In some applications, a method called "log-rank subtraction" has been applied to these problems. There has been no systematic study of this methodology, though. We investigate the statistical properties of the method and further propose a modified method by including a weight function in the construction of the test statistic to correct for potential biases. A class of tests is then proposed for comparing the disease-specific mortality in the two groups. The tests are based on comparing the difference of weighted log-rank scores for the failure type of interest. We derive the asymptotic properties for the modified test procedure. Simulation studies indicate that the tests are unbiased and have reasonable power. The results are also illustrated with data from a breast cancer study. C1 Harvard Univ, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Ruan, PK (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. EM pruan@hsph.harvard.edu; gray@jimmy.harvard.edu NR 14 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2006 VL 12 IS 1 BP 35 EP 51 DI 10.1007/s10985-005-7219-2 PG 17 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 028UX UT WOS:000236515400003 PM 16583298 ER PT J AU Liu, F Xu, DX Ferguson, MS Chu, BC Saam, T Takaya, N Hatsukami, TS Yuan, C Kerwin, WS AF Liu, F Xu, DX Ferguson, MS Chu, BC Saam, T Takaya, N Hatsukami, TS Yuan, C Kerwin, WS TI Automated in vivo segmentation of carotid plaque MRI with morphology-enhanced probability maps SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE in vivo; carotid artery; multi-contrast MR; plaque composition; naive-Bayesian network ID LEVEL SET APPROACH; QUANTITATIVE ASSESSMENT; ACCURACY; IMAGES; ATHEROSCLEROSIS; MODEL AB MRI is a promising noninvasive technique for characterizing atherosclerotic plaque composition in vivo, with an end-goal of assessing plaque vulnerability. Because of limitations arising from acquisition time, achievable resolution, contrast-to-noise ratio, patient motion, and the effects of blood flow, automatically identifying plaque composition remains a challenging task in vivo. In this article, a segmentation method using maximum a posteriori probability Bayesian theory is presented that divides axial, multi-contrast-weighted images into regions of necrotic core, calcification, loose matrix, and fibrous tissue. Key advantages of the method are that it utilizes morphologic information, such as local wall thickness, and coupled active contours to limit the impact from noise and artifacts associated with in vivo imaging. In experiments involving 142 sets of multi-contrast images from 26 subjects undergoing carotid endarterectomy, segmented areas of each of these tissues per slice agreed with histologically confirmed areas with correlations (R-2) of 0.78, 0.83, 0.41, and 0.82, respectively. In comparison, manually identifying areas blinded to histology yielded correlations of 0.71, 0.76, 0.33, and 0.78, respectively. These results show that in vivo automatic segmentation of carotid MRI is feasible and comparable to or possibly more accurate than manual review for quantifying plaque composition. Magn Reson Med 55: 659-668, 2006. Published 2006 Wiley-Liss, lnc. C1 Univ Washington, Vasc Imaging Lab, Seattle, WA 98109 USA. Univ Washington, Dept Radiol, Seattle, WA 98109 USA. VA Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA USA. RP Univ Washington, Vasc Imaging Lab, 815 Mercer St,Box 358050, Seattle, WA 98109 USA. EM feil@u.washington.edu FU NHLBI NIH HHS [R44-HL070576, R01-HL056784] NR 27 TC 79 Z9 83 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAR PY 2006 VL 55 IS 3 BP 659 EP 668 DI 10.1002/mrm.20814 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 019TA UT WOS:000235858400025 PM 16470594 ER PT J AU Fishman, JM Casarett, D AF Fishman, JM Casarett, D TI Mass media and medicine: When the most trusted media mislead SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID CULTIVATION; PERSPECTIVE; TELEVISION C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Ctr Bioeth, Div Geriatr Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Fishman, JM (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 711 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jfishman@cceb.med.upenn.upenn.edu NR 17 TC 6 Z9 6 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAR PY 2006 VL 81 IS 3 BP 291 EP 293 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 018CG UT WOS:000235740700002 PM 16529129 ER PT J AU Mansouri, A Muller, FL Liu, YH Ng, R Faulkner, J Hamilton, M Richardson, A Huang, TT Epstein, CJ Van Remmen, H AF Mansouri, A Muller, FL Liu, YH Ng, R Faulkner, J Hamilton, M Richardson, A Huang, TT Epstein, CJ Van Remmen, H TI Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE mitochondrial function; hydrogen peroxide generation; oxidative damage; skeletal muscle ID FREE-RADICAL PRODUCTION; CALORIC RESTRICTION; HEART-MITOCHONDRIA; PROTEIN COMPLEXES; KNOCKOUT MICE; AGE; GENERATION; OXYGEN; RAT; DNA AB Mitochondrial function, hydrogen peroxide generation and oxidative damage were measured in hind-limb skeletal muscle from young (6-8 month) and old (27-29 month) wildtype and heterozygous Mn-superoxide dismutase (MnSOD) knockout mice (Sod2(+/-)). The reduction in MnSOD activity in the Sod2(+/-) mice makes these mice a good model to examine the implications of life-long elevated endogenous mitochondrial oxidative stress on mitochondrial function. ATP production was reduced approximately 30% with age in skeletal muscle mitochondria isolated from wildtype mice, and reduced 40-45% in mitochondria from both young and old Sod2(+/-) mice compared to the young wildtype mice. Release of hydrogen peroxide from skeletal muscle mitochondria increased 40-50% with age in both wildtype and Sod2(+/-) but was not higher ill mitochondria from Sod2(+/-) mice. Activities of electron transport Complexes I and V were decreased 25-30% in both young and old Sod2(+/-) mice compared to wildtype mice, and were 25-30% lower in mitochondria from old wildtype and old Sod2(+/-) mice. DNA oxidative damage (oxo8dG levels) increased more than 45% with age and over 130% in the young Sod(+/-) mice compared to the wildtype mice. These data show that mitochondrial oxidative stress in mouse skeletal muscle is increased with age, leading to alterations in mitochondrial function. In addition, increased oxidative stress generated by reduced activity of MnSOD does not exacerbate these alterations during aging. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Van Remmen, H (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu OI Mansouri, Abdellah/0000-0003-3856-5771 FU NIA NIH HHS [5T3-AG021890-02, AG-08938, P01 AG20591] NR 45 TC 125 Z9 127 U1 2 U2 6 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 MAR PY 2006 VL 127 IS 3 BP 298 EP 306 DI 10.1016/j.mad.2005.11.004 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 019TU UT WOS:000235860400010 PM 16405961 ER PT J AU Liu, JM Ball, SL Yang, Y Mei, PC Zhang, L Shi, HN Kaminski, HJ Lemmon, VP Hu, HY AF Liu, JM Ball, SL Yang, Y Mei, PC Zhang, L Shi, HN Kaminski, HJ Lemmon, VP Hu, HY TI A genetic model for muscle-eye-brain disease in mice lacking protein O-mannose 1,2-N-acetylglucosaminyltransferase (POMGnT1) SO MECHANISMS OF DEVELOPMENT LA English DT Article DE POMGnT1; muscle-eye-brain disease; neuronal migration; electrorctinogram; alpha-dystroglycan; mouse model; OmniBank ID CONGENITAL MUSCULAR-DYSTROPHY; WALKER-WARBURG-SYNDROME; ALPHA-DYSTROGLYCAN; NEURONAL MIGRATION; FUKUYAMA-TYPE; GLYCOPROTEIN COMPLEX; EXTRACELLULAR-MATRIX; GLYCOSYLATION; LAMININ; MOUSE AB Protein O-mannose beta 1,2-N-acetyglucosaminyltransferase l (POMGnTI) is an enzyme involved in the synthesis of O-mannosyl glycans. Mutations of POMGnTl in humans result in the muscle-eye-brain (MEB) disease. In this study, we have characterized a null mutation generated by gene trapping with a retroviral vector inserted into the second exon of the mouse POMGnTl locus. Expression of POMGnTI mRNA was abolished in mutant mice. Glycosylation of alpha-dystroglycan was also reduced. POMGnTI mutant mice were viable with multiple developmental defects in muscle, eye, and brain, similar to the phenotypes observed in human MEB disease. The present study provides the first genetic animal model to further dissect the roles of POMGnTI in MEB disease. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. Case Western Reserve Univ, Vet Adm Med Ctr, Dept Psychol, Res Serv, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Univ Miami, Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA. RP SUNY Upstate Med Univ, Dept Neurosci & Physiol, 650 E Adams St, Syracuse, NY 13210 USA. EM huh@upstate.edu RI Lemmon, Vance/A-2565-2008; Lemmon, Vance/A-7410-2010 OI Ball, Sherry/0000-0002-2362-9499; Lemmon, Vance/0000-0003-3550-7576 FU NEI NIH HHS [R01 EY005285]; NICHD NIH HHS [HD044011, R01 HD039884] NR 43 TC 75 Z9 76 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 EI 1872-6356 J9 MECH DEVELOP JI Mech. Dev. PD MAR PY 2006 VL 123 IS 3 BP 228 EP 240 DI 10.1016/j.mod.2005.12.003 PG 13 WC Developmental Biology SC Developmental Biology GA 036UU UT WOS:000237102200003 PM 16458488 ER PT J AU Kertesz, SG Larson, MJ Cheng, DM Tucker, JA Winter, M Mullins, A Saitz, R Samet, JH AF Kertesz, SG Larson, MJ Cheng, DM Tucker, JA Winter, M Mullins, A Saitz, R Samet, JH TI Need and non-need factors associated with addiction treatment utilization in a cohort of homeless and housed urban poor SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 14, 2004 CL San Juan, PR SP Coll Problems Drug Dependence DE homelessness; substance abuse; utilization; longitudinal ID SUBSTANCE-ABUSE TREATMENT; HELP-SEEKING; MEDICAL-CARE; BEHAVIORAL-MODEL; SEVERITY INDEX; MENTAL-HEALTH; ALCOHOL; ADULTS; OUTCOMES; DETOXIFICATION AB Background: Research on addiction treatment utilization in indigent samples mainly has been retrospective, without measures of addictive consequences, social network influences, and motivation. Prospective assessment of factors influencing utilization could inform policy and clinical care. Objective: We sought to identify factors associated with utilization of addiction treatment and mutual help groups among substance-dependent persons with high rates of homelessness. Research and Methods: This was a prospective cohort of patients detoxified from alcohol or drugs at baseline who were followed for 2 years in a randomized clinical trial of linkage to primary care (n = 274). Outcomes included utilization of Inpatient/Residential, Outpatient, Any Treatment, and Mutual Help Groups. Predictor variables in longitudinal regression analyses came from the literature and clinical experience, organized according to theoretical categories of Need, and non-Need (eg, Predisposing and Enabling). Results: Many subjects used Inpatient/Residential (72%), Outpatient (62%), Any Treatment (88%) or Mutual Help Groups (93%) at least once. In multivariable analyses, addictive consequences (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.12-1.71), motivation (OR 1.32, 95% CI 1.09-1.60), and female gender (OR 1.80, 95% CI 1.13-2.86) were associated with most treatment types (ORs are for Any Treatment). Homelessness was associated with Residential/Inpatient (for Chronically Homeless vs. Housed, OR 1.75, 95% CI 1.04-2.94). Living with one's children (OR 0.51, 95% CI 0.31-0.84) and substance-abusing social environment (OR 0.65, 95% CI 0.43-0.98) were negatively associated with Any Treatment. Conclusions: In this cohort of substance-dependent persons, addictive consequences, social network variables, and motivation were associated with treatment utilization. Non-need factors, including living with one's children and gender, also were significant. C1 Univ Alabama, Sch Med, Div Prevent Med, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Div Gen Internal Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. New England Res Inst, Inst Hlth Serv Res & Policy, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Univ Alabama, Sch Publ Hlth, Dept Hlth Behav, Birmingham, AL 35294 USA. Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02215 USA. Wright Inst, Berkeley, CA USA. Boston Univ, Sch Med, Boston Med Ctr, Gen Internal Med Sect, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA. RP Kertesz, SG (reprint author), Univ Alabama, Sch Med, Div Prevent Med, 1530 3rd Ave S,MT608, Birmingham, AL 35294 USA. EM skertesz@uab.edu OI Kertesz, Stefan/0000-0001-6101-8421 FU NCRR NIH HHS [M01-RR00533]; NIDA NIH HHS [K23-DA15847]; PHS HHS [R01-10019, R01-10870] NR 49 TC 20 Z9 20 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2006 VL 44 IS 3 BP 225 EP 233 DI 10.1097/01.mlr.0000199649.19464.8f PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 018VJ UT WOS:000235792600005 PM 16501393 ER PT J AU Landon, BE Reschovsky, JD Pham, HH Blumenthal, D AF Landon, BE Reschovsky, JD Pham, HH Blumenthal, D TI Leaving medicine - The consequences of physician dissatisfaction SO MEDICAL CARE LA English DT Article DE managed care; physician satisfaction; physician behavior; workforce ID JOB-SATISFACTION; PRIMARY-CARE; PROFESSIONAL SATISFACTION; MANAGED CARE; STRESS; HEALTH; TURNOVER; WORKLIFE; QUALITY; TRENDS AB Background: During the past decade, a confluence of forces has changed the practice of medicine in unprecedented ways. Anecdotal reports suggest that, in response, some physicians are leaving the practice of medicine or retiring earlier than they otherwise would have. Objective: We sought to examine how physician demographic characteristics, practice characteristics, and career satisfaction are related to physician decisions to leave the practice of medicine or substantially cut back their practice hours. Design: Data for this study are from the first 2 rounds of the Community Tracking Study (CTS) Physician Survey, a series of nationally representative telephone surveys of physicians first conducted in 1996. Subsequent rounds of the survey included physicians sampled in the previous round, which allowed us to ascertain their career status 2 years after their initial interviews. Subjects: Primary care and specialist physicians initially spending at least 20 hours per week in direct patient care activities were studied. Main Outcomes Measures: Physicians cutting back their practice hours to less than 20 hours per week or leaving the practice of medicine altogether. Results: Of the 16,681 physicians interviewed for whom we also had information about their career status 2 years later, 462 (2.8%) had retired and 499 (3.0%) had reduced time spent in patient care to less than 20 hours per week. In multinomial logistic analyses that examined both outcomes, full- or part-owners of practices were both less likely to retire and to cut back hours. Internal medicine specialists and psychiatrists were less likely to retire (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.48-0.99 and OR 0.33, 95% CI 0.18-0.60 respectively) whereas surgical specialists were more likely to retire (OR 1.6, 95% CI 1.1-2.2). Physician satisfaction was strongly related to both outcomes. For instance, very dissatisfied physicians were both more likely to retire (OR 2.34, 95% CI 1.6-3.5) and cut back on their hours (OR 3.6, 95% CI 2.32-5.6). Conclusions: Our findings demonstrate that dissatisfied physicians were 2 to 3 times more likely to leave medicine than satisfied physicians. These findings have implications for physician manpower projections and quality of care. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Massachusetts Gen Hosp, Partners HealthCare Syst, Inst Hlth Care Policy, Boston, MA 02114 USA. Ctr Studying Hlth Syst Change, Washington, DC USA. RP Landon, BE (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM landon@hcp.med.harvard.edu FU AHRQ HHS [P0-1-HS-10803] NR 26 TC 130 Z9 132 U1 0 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2006 VL 44 IS 3 BP 234 EP 242 DI 10.1097/01.mlr.0000199848.17133.9b PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 018VJ UT WOS:000235792600006 PM 16501394 ER PT J AU Glassman, PA Belperio, P Simon, B Lanto, A Lee, M AF Glassman, PA Belperio, P Simon, B Lanto, A Lee, M TI Exposure to automated drug alerts over time - Effects on clinicians' knowledge and perceptions SO MEDICAL CARE LA English DT Article DE drug therapy; computer assisted; medication errors; attitude of health personnel; attitude to computers; medical record systems; computerized ID PHYSICIAN ORDER ENTRY; INTERVENTION; BENEFITS; BARRIERS; SYSTEMS; ERRORS AB Objective: We tested whether interval exposure to an automated drug alert system that included approximately 2000 drug-drug interaction alerts increased recognition of selected interacting drug pairs. We also examined other perceptions about computerized order entry. Research Design: We administered cross-sectional surveys in 2000 and 2002 that included more than 260 eligible clinicians in each time period. Subjects: We studied clinicians practicing in ambulatory settings within a Southern California Veterans Affairs Healthcare System and who responded to both surveys (97 respondents). Measures: We sought to measure (1) recognition of selected drug-drug and drug-condition interactions and (2) other benefits and barriers to using automated drug alerts. Results: Clinicians correctly categorized similar percentages of the 7 interacting drug-drug pairs at baseline and follow-up (53% vs. 54%, P = 0.51) but improved their overall recognition of the 3 contraindicated drug-drug pairs (51% vs. 60%, P = 0.01). No significant changes from baseline to follow-up were found for the 8 interacting drug-condition pairs (60% vs. 62%, P = 0.43) or the 4 contraindicated drug-condition pairs (52% vs. 56%, P = 0.24). More providers preferred using order entry at follow-up than baseline (63% vs. 45%, P < 0.001). Signal-to-noise ratio remained the biggest reported problem at follow-up and baseline (54 vs. 57%, P = 0.75). In 2002, clinicians reported seeing a median of 5 drug alerts per week (representing approximately 12.5% of prescriptions entered), with a median 5% reportedly leading to an action. Conclusions: Interval exposure to automated drug alerts had little to no effect on recognition of selected drug-drug interactions. The primary perceived barrier to effective utilization of drug alerts remained the same over time. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA 90073 USA. VA HSR&D Ctr Excellence Study Healthcare Provider, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. VA Ctr Qual Management Publ Hlth, Palo Alto, CA USA. RP Glassman, PA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, 111G,W Los Angeles Campus,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Peter.Glassman@med.va.gov NR 22 TC 39 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2006 VL 44 IS 3 BP 250 EP 256 DI 10.1097/01.mlr.0000199849.08389.91 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 018VJ UT WOS:000235792600008 PM 16501396 ER PT J AU Bachand, F Lackner, DH Bahler, J Silver, PA AF Bachand, F Lackner, DH Bahler, J Silver, PA TI Autoregulation of ribosome biosynthesis by a translational response in fission yeast SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MASS-SPECTROMETRIC ANALYSIS; SACCHAROMYCES-CEREVISIAE; ARGININE METHYLATION; PROTEIN SYNTHESIS; MESSENGER-RNAS; ENVIRONMENTAL-CHANGES; PRE-RIBOSOMES; GENE; METHYLTRANSFERASE; BIOGENESIS AB Maintaining the appropriate balance between the small and large ribosomal subunits is critical for translation and cell growth. We previously identified the 40S ribosomal protein S2 (rpS2) as a substrate of the protein arginine methyltransferase 3 (RMT3) and reported a misregulation of the 40S/60S ratio in rmt3 deletion mutants of Schizosaccharomyces pombe. For this study, using DNA microarrays, we have investigated the genome-wide biological response of rmt3-null cells to this ribosomal subunit imbalance. Whereas little change was observed at the transcriptional level, a number of genes showed significant alterations in their polysomal-to-monosomal ratios in rmt3 Delta mutants. Importantly, nearly all of the 40S ribosomal protein-encoding mRNAs showed increased ribosome density in rmt3 disruptants. Sucrose gradient analysis also revealed that the ribosomal subunit imbalance detected in rmt3-null cells is due to a deficit in small-subunit levels and can be rescued by rpS2 overexpression. Our results indicate that rmt3-null fission yeast compensate for the reduced levels of small ribosomal subunits by increasing the ribosome density, and likely the translation efficiency, of 40S ribosomal protein-encoding mRNAs. Our findings support the existence of autoregulatory mechanisms that control ribosome biosynthesis and translation as an important layer of gene regulation. C1 Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ, Canada. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bachand, F (reprint author), Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ, Canada. EM f.bachand@usherbrooke.ca RI Bahler, Jurg/B-4572-2009 OI Bahler, Jurg/0000-0003-4036-1532 FU Cancer Research UK [A6517]; Wellcome Trust [077118] NR 67 TC 36 Z9 37 U1 0 U2 2 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 MAR PY 2006 VL 26 IS 5 BP 1731 EP 1742 DI 10.1128/MCB.26.5.1731-1742.2006 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 016EE UT WOS:000235602700015 PM 16478994 ER PT J AU Boumil, RM Ogawa, Y Sun, BK Huynh, KD Lee, JT AF Boumil, RM Ogawa, Y Sun, BK Huynh, KD Lee, JT TI Differential methylation of Xite and CTCF sites in Tsix mirrors the pattern of X-inactivation choice in mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID REPRESSIVE HISTONE METHYLATION; IMPRINTED XIST EXPRESSION; CHROMOSOME INACTIVATION; DNA METHYLATION; MOUSE EMBRYOS; GENE; HYPOMETHYLATION; MAMMALS AB During mammalian dosage compensation, one of two X-chromosomes in female cells is inactivated. The choice of which X is silenced can be imprinted or stochastic. Although genetic loci influencing the choice decision have been identified, the primary marks for imprinting and random selection remain undefined. Here, we examined the role of DNA methylation, a mechanism known to regulate imprinting in autosomal loci, and sought to determine whether differential methylation on the two Xs might predict their fates. To identify differentially methylated domains (DMDs) at the X-inactivation center, we used bisulfite sequencing and methylation-sensitive restriction enzyme analyses. We found DMDs in Tsix and Xite, two genes previously shown to influence choice. Interestingly, the DMDs in Tsix lie within CTCF binding sites. Allelic methylation differences occur in gametes and are erased in embryonic stem cells carrying two active Xs. Because the pattern of DNA methylation mirrors events of X-inactivation, we propose that differential methylation of DMDs in Tsix and Xite constitute a primary mark for epigenetic regulation. The discovery of DMDs in CTCF sites draws further parallels between X-inactivation and autosomal imprinting. C1 Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Simches 6-624,185 Cambridge St, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Sun, Bryan/0000-0002-0740-0125 FU NICHD NIH HHS [5F32-HD08541, F32 HD008541]; NIGMS NIH HHS [R01 GM058839, R01-GM58839] NR 41 TC 40 Z9 44 U1 0 U2 3 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 MAR PY 2006 VL 26 IS 6 BP 2109 EP 2117 DI 10.1128/MCB.26.6.2109-2117.2006 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 020NE UT WOS:000235915400009 PM 16507990 ER PT J AU Burkart, AD Mukherjee, A Mayo, KE AF Burkart, AD Mukherjee, A Mayo, KE TI Mechanism of repression of the inhibin alpha-subunit gene by inducible 3 ' 5 '-cyclic adenosine monophosphate early repressor SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ELEMENT-BINDING-PROTEIN; CAMP EARLY REPRESSOR; RAT GRANULOSA-CELLS; FOLLICLE-STIMULATING-HORMONE; TRANSCRIPTION FACTOR CREB; RNA-POLYMERASE-II; LONG-TERM DESENSITIZATION; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; OVARIAN FOLLICLES; DNA-BINDING AB The rodent ovary is regulated throughout the reproductive cycle to maintain normal cyclicity. Ovarian follicular development is controlled by changes in gene expression in response to the gonadotropins FSH and LH. The inhibin alpha-subunit gene belongs to a group of genes that is positively regulated by FSH and negatively regulated by LH. Previous studies established an important role for inducible cAMP early repressor (ICER) in repression of alpha- inhibin. These current studies investigate the mechanisms of repression by ICER. It is not clear whether all four ICER isoforms expressed in the ovary can act as repressors of the inhibin alpha-subunit gene. EMSAs demonstrate binding of all isoforms to the inhibin alpha-subunit CRE ( cAMP response element), and transfection studies demonstrate that all isoforms can repress the inhibin alpha-subunit gene. Repression by ICER is dependent on its binding to DNA as demonstrated by mutations to ICER's DNA-binding domain. These mutational studies also demonstrate that repression by ICER is not dependent on heterodimerization with CREB (CRE-binding protein). Competitive EMSAs show that ICER effectively competes with CREB for binding to the inhibin alpha CRE in vitro. Chromatin immunoprecipitation assays demonstrate a replacement of CREB dimers bound to the inhibin alpha CRE by ICER dimers in ovarian granulosa cells in response to LH signaling. Thus, there is a temporal association of transcription factors bound to the inhibin alpha-CRE controlling inhibin alpha-subunit gene expression. C1 Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. Northwestern Univ, Ctr Reprod Sci, Evanston, IL 60208 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Mayo, KE (reprint author), Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, 2153 Sheridan Rd, Evanston, IL 60208 USA. EM k-mayo@northwestern.edu FU NICHD NIH HHS [P01-HD-21921, U54 HD41857]; NIGMS NIH HHS [T32 GM 08061, T32 GM008061] NR 65 TC 25 Z9 26 U1 0 U2 0 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 MAR PY 2006 VL 20 IS 3 BP 584 EP 597 DI 10.1210/me.2005-0204 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 014SW UT WOS:000235501300010 PM 16269517 ER PT J AU Waterman, WR Xu, LL Tetradis, S Motyckova, G Tsukada, J Saito, K Webb, AC Robinson, DR Auron, PE AF Waterman, WR Xu, LL Tetradis, S Motyckova, G Tsukada, J Saito, K Webb, AC Robinson, DR Auron, PE TI Glucocorticoid inhibits the human pro-interleukin 1 beta gene (ILIB) by decreasing DNA binding of transactivators to the signal-responsive enhancer SO MOLECULAR IMMUNOLOGY LA English DT Article DE interleukin-1beta; enhancer/promoter elements; gene transcription; glucocorticoid; inflammation ID HUMAN PROINTERLEUKIN-1-BETA GENE; ALPHA-1-ACID GLYCOPROTEIN GENE; HUMAN INTERLEUKIN-1-BETA GENE; PROTEIN-PROTEIN-INTERACTION; NF-KAPPA-B; NUCLEAR FACTOR; TRANSCRIPTIONAL ACTIVATION; REGULATORY ELEMENTS; EXPRESSION NF-IL6; HUMAN MONOCYTES AB Elucidating the role of glucocorticoid in regulating gene expression is crucial to developing effective strategies against inflammatory diseases such as arthritis. In this report we demonstrate that glucocorticoid inhibits transcription directed by the IL-1 beta gene (IL1B) upstream induction sequence (UIS) enhancer, and to a much lesser extent by the tissue-specific basal promoter. Within the enhancer. three transcription factor binding sites, previously demonstrated by LIS to be important for the induction of IL1B by lipopolysaccharide. are now shown to be directly inhibited by the synthetic glucocorticoid, dexamethasone. We also previously showed that one of these sites could bind a novel STAT-like factor, while the other two bound heterodimers containing NF-IL6(C/EBP beta). Although it has been reported by others that NF-IL6 homodimers can interact with glucocorticoid receptor (GR) to enhance transcription of the alpha 1-acid glycoprotein gene, it now appears that glucocorticoid represses DNA binding of NF-IL6 heterodimers as well as the novel STAT-like factor to the critical sites within the IL1B UIS. Thus, GR likely disrupts the DNA binding capability of critical IL1B factors via transrepression. (C) 2005 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Philadelphia Coll Osteopath Med, Dept Neurosurg, Philadelphia, PA 19131 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ Occupat & Environm Hlth, Dept Internal Med 1, Kitakyushu, Fukuoka 807, Japan. Wellesley Coll, Dept Biol Sci, Wellesley, MA 02181 USA. RP Auron, PE (reprint author), Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, 200 Lothrop St,Room BSTWR-W1142, Pittsburgh, PA 15261 USA. EM auron@pitt.edu FU NCI NIH HHS [CA68544]; NIAMS NIH HHS [AR43518] NR 55 TC 12 Z9 12 U1 0 U2 4 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 MAR PY 2006 VL 43 IS 7 BP 773 EP 782 DI 10.1016/j.molimm.2005.07.003 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 013UM UT WOS:000235435300001 PM 16095699 ER PT J AU Norris, PJ Stone, JD Anikeeva, N Heitman, JW Wilson, IC Hirschkorn, DF Clark, MJ Moffett, HF Cameron, TO Sykulev, Y Stern, LJ Walker, BD AF Norris, PJ Stone, JD Anikeeva, N Heitman, JW Wilson, IC Hirschkorn, DF Clark, MJ Moffett, HF Cameron, TO Sykulev, Y Stern, LJ Walker, BD TI Antagonism of HIV-specific CD4+ T cells by C-terminal truncation of a minimum epitope SO MOLECULAR IMMUNOLOGY LA English DT Article DE HIV; CD4+T cell; T cell epitope; T cell antagonism; class II tetramer ID PEPTIDE-MHC COMPLEXES; TCR ANTAGONISM; CLASS-II; RECEPTOR ANTAGONISM; CUTTING EDGE; FUNCTIONAL CONSEQUENCES; IMMUNOLOGICAL SYNAPSE; CRYSTAL-STRUCTURE; NEGATIVE SIGNAL; LIGANDS AB Antagonism of T cell responses by variants of the cognate peptide is a potential mechanism of viral escape from immune responses and may play a role in the ability of HIV to evade immune control. We show here a rarely described mechanism of antagonism by a peptide shorter than the minimum length epitope for an HIV p24-specific CD4+ T cell clone. The shorter antagonist peptide-MHC complex bound the T cell receptor (TCR), albeit with lower affinity than the full-length agonist peptide. Prior work showing the crystal structure of the peptide-MHC complex revealed a unique glycine hinge near the C-terminus of the agonist peptide, allowing the generation of full-length antagonist peptide lacking the hinge. These results confirm the dependence of productive TCR engagement on residues spilling out from the C-terminus of the MHC binding groove and show that partial engagement of the TCR with a truncated, low-affinity ligand can result in T cell antagonism. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Calif San Francisco, Blood Syst Res Inst, Dept Lab Med, San Francisco, CA 94118 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Div Infect Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. MIT, Dept Chem, Cambridge, MA 01239 USA. Thomas Jefferson Univ, Dept Immunol & Microbiol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Kimmel Canc Inst, Philadelphia, PA 19107 USA. NYU, Coll Med, Skirball Inst, New York, NY 10016 USA. Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Biochem, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Norris, PJ (reprint author), Univ Calif San Francisco, Blood Syst Res Inst, Dept Lab Med, 270 Masonic Ave, San Francisco, CA 94118 USA. EM pnorris@bloodsystems.org FU NIAID NIH HHS [K08 AI001698, K08 AI001698-06, AI-01698]; PHS HHS [R01 28568] NR 53 TC 11 Z9 11 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 MAR PY 2006 VL 43 IS 9 BP 1349 EP 1357 DI 10.1016/j.molimm.2005.09.004 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 022JT UT WOS:000236052500006 PM 16216327 ER PT J AU Quinti, L Weissleder, R Tung, CH AF Quinti, L Weissleder, R Tung, CH TI A fluorescent nanosensor for apoptotic cells SO NANO LETTERS LA English DT Article ID FLOW-CYTOMETRIC DETECTION; LABELED ANNEXIN-V; PHOSPHATIDYLSERINE EXPRESSION; ARTIFICIAL RECEPTORS; MEMBRANE SURFACES; AQUEOUS-SOLUTION; RECOGNITION; PEPTIDE AB A biocompatible surface-functionalized nanoparticle was designed to sense phosphatidylserine exposed on apoptotic cells. We conjugated synthetic artificial phosphatidylserine binding ligands in a multivalent fashion onto magnetofluorescent nanoparticles. Our results show that (1) the synthetic nanoparticles bind to apoptotic cells, (2) there is excellent correlation with annexin V staining by microscopy, and (3) FACS analysis with nanoparticles allows the measurement of therapeutic apoptosis induction. The described nanomaterials should be useful for a variety of biomedical applications including in vivo imaging of apoptosis. C1 Harvard Univ, Ctr Mol Imaging Res, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Ctr Mol Imaging Res, Massachusetts Gen Hosp, Sch Med, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01 CA99385, R21 CA114149] NR 14 TC 66 Z9 69 U1 2 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD MAR PY 2006 VL 6 IS 3 BP 488 EP 490 DI 10.1021/nl0524694 PG 3 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 022IV UT WOS:000236049800030 PM 16522048 ER PT J AU Low, AF Tearney, GJ Bouma, BE Jang, IK AF Low, AF Tearney, GJ Bouma, BE Jang, IK TI Technology insight: optical coherence tomography - current status and future development SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Review DE coronary artery disease; intravascular ultrasound; optical coherence tomography; vulnerable plaque ID RISK-ASSESSMENT STRATEGIES; VULNERABLE PLAQUE; INTRAVASCULAR ULTRASOUND; IN-VIVO; ATHEROSCLEROTIC PLAQUES; CORONARY-ARTERY; ELASTOGRAPHY; VISUALIZATION; DEFINITIONS; ENDOSCOPE AB The understanding of concepts in coronary artery disease, such as the vulnerable or high-risk plaque, which accounts for many acute coronary events arising from non-flow-limiting coronary lesions, has advanced remarkably. Although coronary angiography is an established imaging technique for visualizing atherosclerotic disease, it is limited by its two-dimensional imaging aspect and a low sensitivity for identifying lesions in the presence of positive remodeling and diffuse disease. Moreover, coronary atherosclerotic plaques cannot be characterized. Although intravascular ultrasound is currently the most commonly employed adjunctive method to better define lesions, it is limited by low resolution. The development of new technologies for improved coronary plaque characterization has, thus, been desired. Optical coherence tomography is a developing technique that uses near-infrared light for the cross-sectional visualization of the vessel wall at the microscopic level. It enables excellent resolution of coronary architecture and precise characterization of plaque architecture. Quantification of macrophages within the plaque is also possible. These capabilities allow precise identification of the most common type of vulnerable plaque, the thin-cap fibroatheroma. Here, we discuss results from clinical studies which indicate that optical coherence tomography is a promising imaging technique for improved characterization of the coronary atherosclerotic plaque. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 42 TC 64 Z9 68 U1 0 U2 9 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 MAR PY 2006 VL 3 IS 3 BP 154 EP 162 DI 10.1038/ncpcardio0482 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 014FE UT WOS:000235463800011 PM 16505861 ER PT J AU McDougal, WS AF McDougal, WS TI Conservative surgery for penile cancer: what surgical excision margins are needed to achieve oncologic control? SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Editorial Material DE conservative surgery; excision margin; penile cancer ID CARCINOMA C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA USA. RP McDougal, WS (reprint author), 55 Fruit St,GRB 1102, Boston, MA 02114 USA. EM wmcdougal@partners.org NR 2 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD MAR PY 2006 VL 3 IS 3 BP 132 EP 133 DI 10.1038/ncpuro0437 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 019NX UT WOS:000235845100006 ER PT J AU Morgan, BA AF Morgan, BA TI Upending the hair follicle SO NATURE GENETICS LA English DT Editorial Material ID SMALL RNAS; C-ELEGANS; MICRORNAS; EVOLUTION; LIN-14; IMPACT AB A new study profiles microRNA (miRNA) expression in mouse epidermis and hair follicles and examines the requirement for these miRNAs during normal embryonic development. In the absence of Dicer-dependent miRNA production, hair follicles evaginate rather than invaginate, revealing an unexpected role for miRNAs in regulating hair follicle morphogenesis. C1 Massachusetts Gen Hosp, Cuteneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cuteneous Biol Res Ctr, Charlestown, MA 02129 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu NR 12 TC 3 Z9 3 U1 0 U2 2 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 MAR PY 2006 VL 38 IS 3 BP 273 EP 274 DI 10.1038/ng0306-273 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 015ZG UT WOS:000235589600003 PM 16501553 ER PT J AU Mak, HY Nelson, LS Basson, M Johnson, CD Ruvkun, G AF Mak, HY Nelson, LS Basson, M Johnson, CD Ruvkun, G TI Polygenic control of Caenorhabditis elegans fat storage SO NATURE GENETICS LA English DT Article ID C-ELEGANS; CHEMOSENSORY NEURONS; SENSORY PERCEPTION; LARVAL DEVELOPMENT; GENE FAMILY; TUBBY; PROTEIN; MUTATION; HOMOLOG; INSULIN AB Tubby mice(1) and individuals with Bardet-Biedl syndrome(2) have defects in ciliated neuron function and obesity, suggesting an as-yet unknown metabolic signaling axis from ciliated neurons to fat storage tissues. Here we show coordinate regulation of Caenorhabditis elegans fat storage by orthologues of these genes acting in ciliated neurons and by a 3-ketoacyl-coA thiolase (encoded by kat-1) that acts in fat storage tissue. A genetic screen for markedly enhanced fat storage in tub-1 mutants led to the isolation only of kat-1 alleles, which impair fatty acid beta-oxidation. kat-1 acts in the intestine, the major C. elegans fat storage tissue, and is transcriptionally upregulated in animals with high fat storage. A genetic screen for synergistic increase in fat storage of a kat-1 mutant identified bbs-1. bbs-1 acts in 15 ciliated neurons that are poised to sense external and internal nutrient levels, supporting a model in which bbs-1 and tub-1 in ciliated neurons form part of an ancient, conserved neuroendocrine axis. This pathway also includes genes encoding intraflagellar transport proteins and cyclic nucleotide gated channels, demonstrating that C. elegans fat storage is under polygenic control. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Axys Pharmaceut, San Francisco, CA 94080 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Mak, Ho Yi/0000-0002-1500-5328 FU NIDDK NIH HHS [R01 DK070147] NR 30 TC 110 Z9 124 U1 5 U2 17 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 MAR PY 2006 VL 38 IS 3 BP 363 EP 368 DI 10.1038/ng1739 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 015ZG UT WOS:000235589600020 PM 16462744 ER PT J AU Rollins, BJ AF Rollins, BJ TI Release the hounds! A chemokine elicits monocytes from bone marrow SO NATURE IMMUNOLOGY LA English DT Editorial Material ID BACTERIAL-INFECTION; MICE; RESPONSES; ATHEROSCLEROSIS; RECRUITMENT; BINDING; CXCR4; CELLS C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02116 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02116 USA. Harvard Univ, Sch Med, Boston, MA 02116 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02116 USA. EM barrett_rollins@dfci.harvard.edu NR 14 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2006 VL 7 IS 3 BP 230 EP 232 DI 10.1038/ni0306-230 PG 4 WC Immunology SC Immunology GA 012SR UT WOS:000235360400006 PM 16482169 ER PT J AU Binstadt, BA Patel, PR Alencar, H Nigrovic, PA Lee, DM Mahmood, U Weissleder, R Mathis, D Benoist, C AF Binstadt, BA Patel, PR Alencar, H Nigrovic, PA Lee, DM Mahmood, U Weissleder, R Mathis, D Benoist, C TI Particularities of the vasculature can promote the organ specificity of autoimmune attack SO NATURE IMMUNOLOGY LA English DT Article ID MAST-CELLS; INDUCED ARTHRITIS; ARTHUS REACTION; DEFICIENT MICE; INFLAMMATORY RESPONSES; RHEUMATOID-ARTHRITIS; ENDOTHELIAL-CELLS; IMMUNE-COMPLEXES; INNATE IMMUNE; DOMINANT ROLE AB How certain autoimmune diseases target specific organs remains obscure. In the 'K/BxN' arthritis model, autoantibodies to a ubiquitous antigen elicit joint-restricted pathology. Here we have used intravital imaging to demonstrate that transfer of arthritogenic antibodies caused macromolecular vasopermeability localized to sites destined to develop arthritis, augmenting its severity. Vasopermeability depended on mast cells, neutrophils and Fc gamma RIII but not complement, tumor necrosis factor or interleukin 1. Unexpectedly, radioresistant FcR gamma-expressing cells in an organ distant from the joint were required. Histamine and serotonin were critical, and systemic administration of these vasoactive amines recapitulated the joint localization of immune complex-triggered vasopermeability. We propose that regionally distinct vascular properties 'interface' with immune effector pathways to foster organ-specific autoimmune damage, perhaps explaining why arthritis accompanies many human infectious and autoimmune disorders. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. Childrens Hosp, Rheumatol Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM cbdm@joslin.harvard.edu; cbdm@joslin.harvard.edu RI Binstadt, Bryce/N-1305-2013 OI Binstadt, Bryce/0000-0003-3127-3856 FU NCI NIH HHS [R24 CA92782, R33 CA91007, P50 CA86355]; NIAID NIH HHS [P01 AI54904]; NIAMS NIH HHS [R01 AR046580] NR 49 TC 109 Z9 112 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2006 VL 7 IS 3 BP 284 EP 292 DI 10.1038/ni1306 PG 9 WC Immunology SC Immunology GA 012SR UT WOS:000235360400013 PM 16444258 ER PT J AU Zamboni, DS Kobayashi, KS Kohlsdorf, T Ogura, Y Long, EM Vance, RE Kuida, K Mariathasan, S Dixit, VM Flavell, RA Dietrich, WF Roy, CR AF Zamboni, DS Kobayashi, KS Kohlsdorf, T Ogura, Y Long, EM Vance, RE Kuida, K Mariathasan, S Dixit, VM Flavell, RA Dietrich, WF Roy, CR TI The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection SO NATURE IMMUNOLOGY LA English DT Article ID APOPTOSIS INHIBITORY PROTEIN; INTRACELLULAR GROWTH; MACROPHAGE APOPTOSIS; VIRULENCE SYSTEM; GENE; MICE; LGN1; SUSCEPTIBILITY; ACTIVATION; RESISTANCE AB Baculovirus inhibitor of apoptosis repeat-containing 1 (Birc1) proteins have homology to several germline-encoded receptors of the innate immune system. However, their function in immune surveillance is not clear. Here we describe a Birc1e-dependent signaling pathway that restricted replication of the intracellular pathogen Legionella pneumophila in mouse macrophages. Translocation of bacterial products into host-cell cytosol was essential for Birc1e-mediated control of bacterial replication. Caspase-1 was required for Birc1e-dependent antibacterial responses ex vivo in macrophages and in a mouse model of Legionnaires' disease. The interleukin 1 beta converting enzyme-protease-activating factor was necessary for L. pneumophila growth restriction, but interleukin 1 beta was not required. These results establish Birc1e as a nucleotide-binding oligomerization-leucine-rich repeat protein involved in the detection and control of intracellular L. pneumophila. C1 Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Ecol & Evolutionary Biol, New Haven, CT 06510 USA. Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02115 USA. Vertex Pharmaceut, Cambridge, MA 02139 USA. Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA. RP Roy, CR (reprint author), Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA. EM craig.roy@yale.edu RI dixit, vishva/A-4496-2012; Kohlsdorf, Tiana/C-3463-2012; Zamboni, Dario/D-3024-2012; OI dixit, vishva/0000-0001-6983-0326; Kohlsdorf, Tiana/0000-0002-3873-2042; Zamboni, Dario/0000-0002-7856-7512; Roy, Craig/0000-0003-4490-440X FU NIAID NIH HHS [AI41699, AI049987, AI48770, AI062017] NR 34 TC 320 Z9 331 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2006 VL 7 IS 3 BP 318 EP 325 DI 10.1038/ni1305 PG 8 WC Immunology SC Immunology GA 012SR UT WOS:000235360400017 PM 16444259 ER PT J AU Rukstalis, JM Habener, JF AF Rukstalis, JM Habener, JF TI Islets break off from the mainland SO NATURE MEDICINE LA English DT Editorial Material ID PANCREATIC BETA-CELLS; DIFFERENTIATION; PLASTICITY; TISSUE; MICE C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Rukstalis, JM (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. EM jmrukstalis@partners.org; jhabener@partners.org NR 14 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2006 VL 12 IS 3 BP 273 EP 274 DI 10.1038/nm0306-273 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 018ZA UT WOS:000235802900017 PM 16520767 ER PT J AU Polyak, K Hahn, WC AF Polyak, K Hahn, WC TI Roots and stems: stem cells in cancer SO NATURE MEDICINE LA English DT Review ID BREAST-CANCER; SELF-RENEWAL; SIDE POPULATION; THERAPEUTIC IMPLICATIONS; COLORECTAL-CANCER; TELOMERASE; IDENTIFICATION; PROLIFERATION; LINES; TRANSPLANTATION AB Cancer develops from normal tissues through the accumulation of genetic alterations that act in concert to confer malignant phenotypes. Although we have now identified some of the genes that when mutated initiate tumor formation and drive cancer progression, the identity of the cell population(s) susceptible to such transforming events remains undefined for the majority of human cancers. Recent work indicates that a small population of cells endowed with unique self-renewal properties and tumorigenic potential is present in some, and perhaps all, tumors. Although our understanding of the biology of these putative cancer stem cells remains rudimentary, the existence of such cells has implications for current conceptualizations of malignant transformation and therapeutic approaches to cancer. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Broad Inst Harvard, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. RP Polyak, K (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu FU NCI NIH HHS [P50 CA89393, R01 CA94074]; NIA NIH HHS [R01 AG23145]; PHS HHS [K01 94223] NR 63 TC 226 Z9 245 U1 4 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2006 VL 12 IS 3 BP 296 EP 300 DI 10.1038/nm1379 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 018ZA UT WOS:000235802900026 PM 16520777 ER PT J AU Korzenik, JR Podolsky, DK AF Korzenik, JR Podolsky, DK TI Evolving knowledge and therapy of inflammatory bowel disease SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID ACTIVE CROHNS-DISEASE; PLACEBO-CONTROLLED TRIAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; SIDED ULCERATIVE-COLITIS; NECROSIS-FACTOR-ALPHA; OPEN-LABEL TRIAL; RECOMBINANT HUMAN INTERLEUKIN-10; HUMANIZED MONOCLONAL-ANTIBODY; INTESTINAL EPITHELIAL-CELLS; COLONY-STIMULATING FACTOR AB With recent advances in the understanding of its pathophysiology, inflammatory bowel disease has become a very active area for the development of novel therapeutic agents. New targets for biologics include cytokines involved in T-cell activation, with antibodies directed against IL-12 and interferon-gamma. Selective adhesion molecule blockade has produced promising, though mixed, results. Recombinant human granulocyte-macrophage colony-stimulating factor might be effective in active Crohn's disease, presumably through stimulation of intestinal innate immune responses. With increasing evidence for a crucial role for luminal flora in maintaining the health of the bowel, strategies to manipulate intestinal bacteria using probiotics and prebiotics are being actively investigated as well. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. EM dpodolsky@partners.org NR 120 TC 96 Z9 106 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD MAR PY 2006 VL 5 IS 3 BP 197 EP 209 DI 10.1038/nrd1986 PG 13 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 019LD UT WOS:000235836300016 PM 16518373 ER PT J AU de Gelder, B AF de Gelder, B TI Towards the neurobiology of emotional body language SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID HUMAN AMYGDALA; AFFECTIVE BLINDSIGHT; BIOLOGICAL MOTION; SOCIAL-BEHAVIOR; NEURAL SYSTEMS; SUPERIOR COLLICULUS; FACIAL EXPRESSIONS; LIGHT DISPLAYS; IMPLIED MOTION; POINT-LIGHT AB People's faces show fear in many different circumstances. However, when people are terrified, as well as showing emotion, they run for cover. When we see a bodily expression of emotion, we immediately know what specific action is associated with a particular emotion, leaving little need for interpretation of the signal, as is the case for facial expressions. Research on emotional body language is rapidly emerging as a new field in cognitive and affective neuroscience. This article reviews how whole-body signals are automatically perceived and understood, and their role in emotional communication and decision-making. C1 Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. EM degelder@nmr.mgh.harvard.edu NR 108 TC 264 Z9 264 U1 11 U2 81 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 MAR PY 2006 VL 7 IS 3 BP 242 EP 249 DI 10.1038/nrn1872 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 015FJ UT WOS:000235537000018 PM 16495945 ER PT J AU Tegeder, I Costigan, M Griffin, RS Abele, A Belfer, I Schmidt, H Ehnert, C Scholz, J Wu, T Allchorne, A Diatchenko, L Sama, S Atlas, SJ Fillingim, RB Maixner, W Geisslinger, G Max, MB Woolf, CJ AF Tegeder, I Costigan, M Griffin, RS Abele, A Belfer, I Schmidt, H Ehnert, C Scholz, J Wu, T Allchorne, A Diatchenko, L Sama, S Atlas, SJ Fillingim, RB Maixner, W Geisslinger, G Max, MB Woolf, CJ TI GTP-cyclohydrolase, the rate-limiting enzyme in tetrahydrobiopterin biosynthesis, regulates pain sensitivity and persistence SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 47th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie CY APR 04-06, 2006 CL Mainz, GERMANY SP Deutsch Gesell Expt & Klin Pharmakol & Toxikol C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Frankfurt, Pharmazentrum Frankfurt, D-6000 Frankfurt, Germany. NIH, Neurogenet Lab, Rockville, MD USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC USA. Univ Florida, Coll Dent, Gainesville, FL USA. Gainesville VA Med Ctr, Gainesville, FL USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 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 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2006 VL 372 SU 1 MA S2 BP 13 EP 13 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 037DL UT WOS:000237126800003 ER PT J AU Woolf, CJ AF Woolf, CJ TI Neuro-immune interactions and pain SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 47th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie CY APR 04-06, 2006 CL Mainz, GERMANY SP Deutsch Gesell Expt & Klin Pharmakol & Toxikol C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 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 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2006 VL 372 SU 1 MA S1 BP 13 EP 13 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 037DL UT WOS:000237126800002 ER PT J AU Vetter, T Lohse, MJ Vilardaga, JP AF Vetter, T Lohse, MJ Vilardaga, JP TI beta-Arrestin2 binding to the PTH1 receptor is not dependant on receptor phosphorylation SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 47th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie CY APR 04-06, 2006 CL Mainz, GERMANY SP Deutsch Gesell Expt & Klin Pharmakol & Toxikol C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Wurzburg, Inst Pharmacol & Toxicol, D-97078 Wurzburg, Germany. 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 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2006 VL 372 SU 1 MA 100 BP 37 EP 37 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 037DL UT WOS:000237126800106 ER PT J AU Abele, A Scholz, J Haussler, A Marian, C Woolf, CJ Tegeder, I AF Abele, A Scholz, J Haussler, A Marian, C Woolf, CJ Tegeder, I TI Targeting microglia proliferation as a novel strategy in the treatment of neuropathic pain SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 47th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie CY APR 04-06, 2006 CL Mainz, GERMANY SP Deutsch Gesell Expt & Klin Pharmakol & Toxikol C1 Univ Frankfurt, Klin Pharmakol, D-6000 Frankfurt, Germany. Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA 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 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2006 VL 372 SU 1 MA 545 BP 140 EP 140 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 037DL UT WOS:000237126800550 ER PT J AU Montet, X Montet-Abou, K Reynolds, F Weissleder, R Josephson, L AF Montet, Xavier Montet-Abou, Karin Reynolds, Fred Weissleder, Ralph Josephson, Lee TI Nanoparticle imaging of integrins on tumor cells SO NEOPLASIA LA English DT Article DE nanoparticle; imaging; RGD; peptide; integrin ID SUPERPARAMAGNETIC IRON-OXIDE; FLUORESCENT SILICA NANOPARTICLES; TAT PEPTIDE; MULTIMODAL NANOPARTICLE; ATHEROSCLEROTIC PLAQUES; CYCLIC PENTAPEPTIDES; CONTRAST AGENT; DRUG-DELIVERY; RGD PEPTIDES; ANGIOGENESIS AB Nanoparticles 10 to 100 nm in size can deliver large payloads to molecular targets, but undergo slow diffusion and/or slow transport through delivery barriers. To examine the feasibility of nanoparticles targeting a marker expressed in tumor cells, we used the binding of cyclic arginine-glycine-aspartic acid (RGD) nanoparticle targeting integrins on BT-20 tumor as a model system. The goals of this study were: 1) to use nanoparticles to image alpha V beta(3) integrins expressed in BT-20 tumor cells by fluorescence-based imaging and magnetic resonance imaging, and, 2) to identify factors associated with the ability of nanoparticles to target tumor cell integrins. Three factors were identified: 1) tumor cell integrin expression ( the alpha v beta(3) integrin was expressed in BT-20 cells, but not in 9L cells); 2) nanoparticle pharmacokinetics ( the cyclic RGD peptide cross-linked iron oxide had a blood half-life of 180 minutes and was able to escape from the vasculature over its long circulation time); and 3) tumor vascularization ( the tumor had a dense capillary bed, with distances of < 100 mu m between capillaries). These results suggest that nanoparticles could be targeted to the cell surface markers expressed in tumor cells, at least in the case wherein the nanoparticles and the tumor model have characteristics similar to those of the BT-20 tumor employed here. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,5406, Charlestown, MA 02129 USA. EM ljosephson@partners.org OI Montet, Xavier/0000-0003-2442-5866 FU NCI NIH HHS [P50 CA086355, P50 CA86355, R24 CA092782, R24 CA92782]; NIBIB NIH HHS [R01 EB000662, R01 EB00662] NR 57 TC 170 Z9 175 U1 6 U2 47 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAR PY 2006 VL 8 IS 3 BP 214 EP 222 DI 10.1593/neo.05769 PG 9 WC Oncology SC Oncology GA 067DV UT WOS:000239282800007 PM 16611415 ER PT J AU Brown, D AF Brown, Dennis TI Imaging protein trafficking SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE protein trafficking; spinning disk confocal microscopy, applications; TIRF microscopy; real-time imaging systems ID REFLECTION FLUORESCENCE MICROSCOPY; LIVING CELLS; INTRACELLULAR-TRANSPORT; MEMBRANE-FUSION; PLASMA-MEMBRANE; MICROTUBULES; GOLGI; VASOPRESSIN; DYNAMICS; DISEASES AB The need to understand complex intracellular trafficking mechanisms from both a basic and disease-oriented perspective has stimulated considerable interest in the development of real-time microscopy tools. Recent advances in instrumentation and the development of molecular bioprobes, such as green fluorescent protein and its derivatives, have opened up a new era in our ability to perform close to real-time imaging of cellular events with high spatial and temporal resolution, and with high sensitivity. This review briefly introduces and discusses some of the systems and methodologies that are available from several manufacturers, including laser scanning and spinning disk confocal microscopy, and total internal reflectance microscopy. Copyright (c) 2006 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Simches Res Bldg N,Suite 8202,185 Cambridge St, Boston, MA 02114 USA. EM brown@receptor.mgh.harvard.edu FU NCRR NIH HHS [S10RR117972] NR 32 TC 5 Z9 5 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PD MAR PY 2006 VL 103 IS 2 BP E55 EP E61 DI 10.1159/000090617 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 163QK UT WOS:000246176700005 PM 16543765 ER PT J AU Reger, MA Watson, GS Frey, WH Baker, LD Cholerton, B Keeling, ML Belongia, DA Fishel, MA Plymate, SR Schellenberg, GD Cherrier, MM Craft, S AF Reger, MA Watson, GS Frey, WH Baker, LD Cholerton, B Keeling, ML Belongia, DA Fishel, MA Plymate, SR Schellenberg, GD Cherrier, MM Craft, S TI Effects of intranasal insulin on cognition in memory-impaired older adults: Modulation by APOE genotype SO NEUROBIOLOGY OF AGING LA English DT Article DE cognition; Alzheimer's disease; diabetes; memory; glucose ID CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR-I; APOLIPOPROTEIN-E GENOTYPE; AMYLOID PRECURSOR PROTEIN; CENTRAL CHOLINERGIC MECHANISM; BLOOD-BRAIN-BARRIER; OBESE ZUCKER RATS; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; HABITUATION RESPONSE AB Raising insulin acutely in the periphery and in brain improves verbal memory. Intranasal insulin administration, which raises insulin acutely in the CNS without raising plasma insulin levels, provides an opportunity to determine whether these effects are mediated by central insulin or peripheral processes. Based on prior research with intravenous insulin, we predicted that the treatment response would differ between subjects with (epsilon 4+) and without (epsilon 4-) the APOE-epsilon 4 allele. On separate mornings, 26 memory-impaired subjects (13 with early Alzheimer's disease and 13 with amnestic mild cognitive impairment) and 35 normal controls each underwent three intranasal treatment conditions consisting of saline (placebo) or insulin (20 or 40 1U). Cognition was tested 15 min post-treatment, and blood was acquired at baseline and 45 min after treatment. Intranasal insulin treatment did not change plasma insulin or glusose levels. Insulin treatment facilitated recall on two measures of verbal memory in memory-impaired epsilon 4- adults. These effects were stronger for niernory-impaired epsilon 4- subjects than for memory-impaired epsilon 4+ subjects and normal adults. Unexpectedly, memory-impaired epsilon 4+ subjects showed poorer recall following insulin administration on one test of memory. These findings suggest that intranasal insulin administration may have therapeutic benefit without the risk of peripheral hypoglycemia and provide further evidence for apolipoprotein E (APOE) related differences in insulin metabolism. (c) 2005 Elsevier Inc. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Reg Hosp, Alzheimers Res Ctr, St Paul, MN 55101 USA. Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. RP Craft, S (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way,S182-GRECC, Seattle, WA 98108 USA. EM scraft@u.washington.edu OI Frey II, William/0000-0002-6373-0794 FU NIA NIH HHS [P50 AG 05136] NR 70 TC 270 Z9 283 U1 3 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2006 VL 27 IS 3 BP 451 EP 458 DI 10.1016/j.neurobiolaging.2005.03.016 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 018HQ UT WOS:000235755400010 PM 15964100 ER PT J AU Dracheva, S Davis, KL Chin, B Woo, DA Schmeidler, J Haroutunian, V AF Dracheva, S Davis, KL Chin, B Woo, DA Schmeidler, J Haroutunian, V TI Myelin-associated mRNA and protein expression deficits in the anterior cingulate cortex and hippocampus in elderly schizophrenia patients SO NEUROBIOLOGY OF DISEASE LA English DT Article DE oligodendrocytes; myelin; gene expression; PCR; schizophrenia; postmortem; anterior cingulate cortex; hippocampus ID 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; CENTRAL-NERVOUS-SYSTEM; DEMENTED OLD PEOPLE; PREFRONTAL CORTEX; OLIGODENDROCYTE DYSFUNCTION; TEMPORAL CORTEX; HUMAN BRAIN; IN-VIVO; ABNORMALITIES; RECEPTOR AB Microarray and other studies have reported oligodendrocyte and myelin-related (OMR) deficits in schizophrenia. Here, we employed a quantitative approach to determine the magnitude of OMR gene expression deficits and their brain-region specificity. In addition, we examined how expression levels among the studied OMR genes are interrelated. mRNA of MAG, CNP, SOX10, CLDN11, and PMP22, but not MBP and MOBP, was reduced in the hippocampus and anterior cingulate cortex but not in the putamen of patients with schizophrenia. Expression of the only protein examined (CNP) was decreased in the hippocampus but not in the putamen. Correlation and factor analyses revealed that mRNA levels for genes that did exhibit differential expression in schizophrenia (MAG, CNP, SOX10, CLDN11, and PMP2), as opposed to those that did not (MOBP and MBP), loaded on separate factors. Thus, OMR gene and protein expression deficits in schizophrenia are brain-region specific, and the affected components may share regulatory elements. (C) 2005 Elsevier Inc. All rights reserved. C1 Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Haroutunian, V (reprint author), Bronx Vet Adm Med Ctr, 3F-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Vahram.Haroutunian@mssm.edu FU NCRR NIH HHS [M01-RR-00071]; NIMH NIH HHS [MH064673, MH45212] NR 49 TC 110 Z9 117 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAR PY 2006 VL 21 IS 3 BP 531 EP 540 DI 10.1016/j.nbd.2005.08.012 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 020HJ UT WOS:000235899100009 PM 16213148 ER PT J AU Diamond, SG Huppert, TJ Kolehmainen, V Franceschini, MA Kaipio, JP Arridge, SR Boas, DA AF Diamond, SG Huppert, TJ Kolehmainen, V Franceschini, MA Kaipio, JP Arridge, SR Boas, DA TI Dynamic physiological modeling for functional diffuse optical tomography SO NEUROIMAGE LA English DT Review DE physiological modeling; state-space model; near-infrared spectroscopy; diffuse optical tomography; Kalman filter; time-series analysis ID NEAR-INFRARED SPECTROSCOPY; CEREBRAL BLOOD-VOLUME; EVENT-RELATED FMRI; STATE-SPACE MODEL; OXYGENATION CHANGES; MONTE-CARLO; HEMODYNAMIC-RESPONSE; TIME-SERIES; LIGHT-PROPAGATION; BRAIN ACTIVATION AB Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. The diffuse nature of near-infrared photon migration in tissue and the multitude of physiological systems that affect hemodynamics motivate the use of anatomical and physiological models to improve estimates of the functional hemodynamic response. In this paper, we present a linear state-space model for DOT analysis that models the physiological fluctuations present in the data with either static or dynamic estimation. We demonstrate the approach by using auxiliary measurements of blood pressure variability and heart rate variability as inputs to model the background physiology in DOT data. We evaluate the improvements accorded by modeling this physiology on ten human subjects with simulated functional hemodynamic responses added to the baseline physiology. Adding physiological modeling with a static estimator significantly improved estimates of the simulated functional response, and further significant improvements were achieved with a dynamic Kalman filter estimator (paired t tests, it = 10, P < 0.05). These results suggest that physiological modeling can improve DOT analysis. The further improvement with the Kalman filter encourages continued research into dynamic linear modeling of the physiology present in DOT. Cardiovascular dynamics also affect the blood-oxygen-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This state-space approach to DOT analysis could be extended to BOLD fMRI analysis, multimodal studies and real-time analysis. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Univ Kuopio, Dept Appl Phys, FIN-70211 Kuopio, Finland. UCL, Dept Comp Sci, London WC1E 6BT, England. RP Diamond, SG (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM sdiamond@nmr.mgh.harvard.edu RI Kolehmainen, Ville/K-1963-2012; OI Kolehmainen, Ville/0000-0002-5621-795X; Diamond, Solomon/0000-0002-7589-2942; Kaipio, Jari/0000-0002-7392-5149 FU NCI NIH HHS [T32 CA009502, T32 CA009502-19]; NCRR NIH HHS [P41 RR014075, P41 RR014075-07, P41 RR014075-075756, P41 RR014075-086770, P41 RR014075-098606, P41 RR014075-106000]; NIBIB NIH HHS [R01 EB002482, R01 EB001954, R01 EB001954-04A2, R01 EB001954-05, R01 EB002482-02, R01 EB002482-03] NR 102 TC 65 Z9 65 U1 1 U2 13 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 MAR PY 2006 VL 30 IS 1 BP 88 EP 101 DI 10.1016/j.neuroimage.2005.09.016 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 017LY UT WOS:000235696300008 PM 16242967 ER PT J AU Seidman, LJ Biederman, J Valera, EM Monuteaux, MC Doyle, AE Faraone, SV AF Seidman, LJ Biederman, J Valera, EM Monuteaux, MC Doyle, AE Faraone, SV TI Neuropsychological functioning in girls with attention-deficit/hyperactivity disorder with and without learning disabilities SO NEUROPSYCHOLOGY LA English DT Article DE ADHD; executive functions; learning disabilities; girls ID DEFICIT-HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION DEFICITS; CLINICALLY REFERRED SAMPLE; OSTERRIETH COMPLEX FIGURE; READING-DISABILITY; SUSTAINED ATTENTION; DISRUPTIVE BEHAVIOR; COGNITIVE DEFICITS; GENDER-DIFFERENCES; CHILDREN AB The authors' goal was to assess neuropsychological performance in girls with attention-deficit/hyperactivity disorder (ADHD) and evaluate the role of comorbid learning disabilities (LDs). Participants were 140 girls with ADHD and 122 girls without ADHD, ages 6-17 years. Neuropsychological performance was measured in a standardized manner, blind to clinical status. LD was defined by a combined regression-based and low-achievement classification. ADHD was associated with modest, but significant., neuropsychological impairment. as measured with an aggregate measure of performance and with the Stroop Color-Word Test, independent of age, social class, IQ, and psychiatric comorbidity. Neuropsychological deficits were most pronounced in girls with both ADHD and an LD and in those without medications. These results extend to females the previously documented association of LDs with neuropsychological functioning in males with ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, Pediat Psychopharmacol Program, Boston, MA 02114 USA. RP Seidman, LJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, Pediat Psychopharmacol Program, ACC 725,15 Parkman St, Boston, MA 02114 USA. EM lseidman@bidmc.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01MH/HD 62152]; NIMH NIH HHS [R01MH-41314, R01MH-50657] NR 90 TC 31 Z9 35 U1 4 U2 8 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAR PY 2006 VL 20 IS 2 BP 166 EP 177 DI 10.1037/0894-4105.20.2.166 PG 12 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 031IW UT WOS:000236699000004 PM 16594777 ER PT J AU Magee, T Lee, SM Giuliano, KK Munro, B AF Magee, T Lee, SM Giuliano, KK Munro, B TI Generating new knowledge from existing data - The use of large data sets for nursing research SO NURSING RESEARCH LA English DT Article; Proceedings Paper CT Conference on Translational Research for Quality Outcomes CY APR 07-09, 2005 CL New York, NY SP E Nursing Res Soc, Columbia Univ Sch Nursing DE databases; nursing methodology research; nursing theory ID SECONDARY ANALYSIS; FAMILIES; ISSUES AB Background: An unprecedented amount of data from a variety of disciplines containing variables of interest to nursing are available to nurse researchers. In response, the use of large data sets is emerging as a legitimate method that can help facilitate the translation of knowledge to practice. Objective: To explore the spectrum of methodological issues and practical applications encountered by three nurse researchers using secondary data analysis of three existing large data sets as a means to ask new questions and generate new nursing knowledge. Methods: Three research studies using the analysis of three existing large data sets were described. The following are discussed: developing a theoretical framework, selecting an appropriate data set, operationalizing and measuring variables, preparing data for analysis, and identifying threats to validity and reliability. Results: Although the use of existing data may shorten the time from question to answer, the research process remains the same. The three research studies were used to illustrate conceptual congruence, threats to internal and external validity, and threats to reliability and generalizability. Discussion: Data obtained from a variety of disciplines and for a variety of reasons can and should be used to answer nursing practice and research questions. Using existing large data sets offers nurse researchers a unique opportunity to ask and answer questions that can affect how nurses care for patients in a time-effective and cost-efficient manner. Exploring the spectrum of methodological issues and practical applications involved in this work will help guide nurse researchers through the process. C1 Univ Illinois, Dept Maternal Child Nursing, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Knight Nursing Ctr Clin & Profess Dev, Boston, MA 02114 USA. Philips Med Syst, Andover, MA USA. Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. RP Magee, T (reprint author), Univ Illinois, Dept Maternal Child Nursing, Chicago, IL 60637 USA. EM tramagee@uic.edu NR 29 TC 19 Z9 19 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2006 VL 55 IS 2 SU S BP S50 EP S56 DI 10.1097/00006199-200603001-00009 PG 7 WC Nursing SC Nursing GA 034CQ UT WOS:000236902800010 PM 16601635 ER PT J AU Higuchi, M Kudo, T Suzuki, S Evans, TT Sasaki, R Wada, Y Shirakawa, T Sawyer, JR Gotoh, A AF Higuchi, M Kudo, T Suzuki, S Evans, TT Sasaki, R Wada, Y Shirakawa, T Sawyer, JR Gotoh, A TI Mitochondrial DNA determines androgen dependence in prostate cancer cell lines SO ONCOGENE LA English DT Article DE mitochondrial DNA; prostate cancer; hormone dependence ID FACTOR-KAPPA-B; NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY; SACCHAROMYCES-CEREVISIAE; MULTIPLE DELETIONS; MUTATOR PHENOTYPE; POINT MUTATIONS; MTDNA; ACTIVATION; EXPRESSION; CARCINOMA AB Prostate cancer progresses from an androgen-dependent to androgen-independent stage after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic large-deletion mitochondrial DNA is very common in prostate cancer. To investigate the role of mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted mitochondrial DNA in accordance with the progression of prostate cancer. We demonstrated that the androgen-independent cell line C4-2, established by inoculation of the androgen-dependent LNCaP cell line into castrated mice, has a greatly reduced amount of normal mitochondrial DNA and an accumulation of large-deletion DNA. Strikingly, the depletion of mitochondrial DNA from androgen-dependent LNCaP resulted in a loss of androgen dependence. Reconstitution of normal mitochondrial DNA to the mitochondrial DNA-depleted clone restored androgen dependence. These results indicate that mitochondrial DNA determines androgen dependence of prostate cancer cell lines. Further, mitochondrial DNA-deficient cells formed tumors in castrated athymic mice, whereas LNCaP did not. The accumulation of large deletion and depletion of mitochondrial DNA may thus play a role in the development of androgen independence, leading to progression of prostate cancers. C1 Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. VA Med Ctr, Houston, TX USA. Dept Neurol, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Kobe Univ, Sch Med, Dept Radiol, Chuo Ku, Kobe, Hyogo 657, Japan. Kobe Univ, Sch Med, Dept Clin Genet, Chuo Ku, Kobe, Hyogo 657, Japan. Kobe Univ, Sch Med, Dept Urol, Chuo Ku, Kobe, Hyogo 657, Japan. Kobe Univ, Sch Med, Int Ctr Med Res, Chuo Ku, Kobe, Hyogo 657, Japan. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. RP Higuchi, M (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, 4301 W Markham Slot 516, Little Rock, AR 72205 USA. EM mhiguchi@uams.edu RI Suzuki, Seigo/G-5378-2012 FU NCI NIH HHS [R01 CA100846, CA100846, R01 CA100846-01A1, R01 CA100846-02, R01 CA100846-03, R01 CA100846-04, R01 CA100846-05, R01 CA100846-06] NR 44 TC 52 Z9 52 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 2006 VL 25 IS 10 BP 1437 EP 1445 DI 10.1038/sj.onc.1209190 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 020EE UT WOS:000235890400001 PM 16278679 ER PT J AU Howlin, J McBryan, J Napoletano, S Lambe, T McArdle, E Shioda, T Martin, F AF Howlin, J McBryan, J Napoletano, S Lambe, T McArdle, E Shioda, T Martin, F TI CITED1 homozygous null mice display aberrant pubertal mammary ductal morphogenesis SO ONCOGENE LA English DT Article DE mammary gland; development; ductal morphogenesis; puberty; CITED1; amphiregulin ID GROWTH-FACTOR-BETA; ESTROGEN-RECEPTOR-ALPHA; BREAST-CANCER CELLS; EPITHELIAL-CELLS; GLAND DEVELOPMENT; TRANSFORMING GROWTH-FACTOR-BETA-1; NUCLEAR-PROTEIN; MELANOMA-CELLS; EXPRESSION; GENES AB Expression microarray analysis identified CITED1 among a group of genes specifically upregulated in the pubertal mouse mammary gland. At puberty, CITED1 localizes to the luminal epithelial cell population of the mammary ducts and the body cells of the terminal end buds. Generation of CITED1 gene knockout mice showed that homozygous null mutants exhibit retarded mammary ductal growth at puberty and, in addition, dilated ductal structures with a lack of spatial restriction of the subtending branches. Analysis of CITED1 homozygous null and heterozygous null mammary gland gene expression using microarrays suggested that the mammary specific phenotype seen in the homozygous null females is due to a disturbance in the transcription of a number of key mediators of pubertal ductal morphogenesis. These include estrogen and TGF beta responsive genes, such as the EGFR/ErbB2 ligand, amphiregulin, whose transcription we suggest is directly or indirectly regulated by CITED1. C1 Univ Coll Dublin, Conway Inst, Dublin 4, Ireland. Univ Coll Dublin, Sch Biomol & Biomed Sci, Dublin 4, Ireland. Massachusetts Gen Hosp, Ctr Canc, Lab Tumour Biol, Charlestown, MA USA. RP Martin, F (reprint author), Univ Coll Dublin, Conway Inst, Dublin 4, Ireland. EM finian.martin@ucd.ie RI Howlin, Jill /G-9665-2011; Lambe, Teresa/E-5733-2016; OI Howlin, Jill /0000-0002-2766-3002; Lambe, Teresa/0000-0001-7711-897X; McBryan, Jean/0000-0002-7568-2208 FU NCI NIH HHS [CA082230] NR 48 TC 27 Z9 28 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 2006 VL 25 IS 10 BP 1532 EP 1542 DI 10.1038/sj.onc.1209183 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 020EE UT WOS:000235890400010 PM 16278680 ER PT J AU Engle, LJ Simpson, CL Landers, JE AF Engle, LJ Simpson, CL Landers, JE TI Using high-throughput SNP technologies to study cancer SO ONCOGENE LA English DT Review DE SNP; polymorphisms; cancer; genotyping ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENOME-WIDE ASSOCIATION; PROSTATE-CANCER; METHYLENETETRAHYDROFOLATE REDUCTASE; BREAST-CANCER; COLORECTAL-CANCER; COMPLEX DISEASE; GASTRIC-CANCER; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE AB Identifying genes involved in the development of cancer is crucial to fully understanding cancer biology, for developing novel therapeutics for cancer treatment and for providing methods for cancer prevention and early diagnosis. The use of polymorphic markers, in particular single nucleotide polymorphisms ( SNPs), promises to provide a comprehensive tool for analysing the human genome and identifying those genes and genomic regions contributing to the cancer phenotype. This review summarizes the various analytical methodologies in which SNPs are used and presents examples of how each of these methodologies have been used to locate genes and genomic regions of interest for various cancer types. Additionally many of the current SNP-analysing technologies will be reviewed with particular attention paid to the advantages and disadvantages of each and how each technology can be applied to the analysis of the genome for identifying cancer-related genes. C1 Cetek Corp, Marlborough, MA USA. Univ London Kings Coll, Inst Psychiat, London WC2R 2LS, England. Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Charlestown, MA USA. RP Landers, JE (reprint author), 13th St,CNY149-3-3310, Charlestown, MA 02129 USA. EM jelanders@partners.org NR 91 TC 69 Z9 73 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 2006 VL 25 IS 11 BP 1594 EP 1601 DI 10.1038/sj.onc.1209368 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 020JL UT WOS:000235904700001 PM 16550159 ER PT J AU Ohtsuka, T Liu, XF Koga, Y Kitajima, Y Nakafusa, Y Ha, CW Lee, SW Miyazaki, K AF Ohtsuka, T Liu, XF Koga, Y Kitajima, Y Nakafusa, Y Ha, CW Lee, SW Miyazaki, K TI Methylation-induced silencing of ASC and the effect of expressed ASC on p53-mediated chemosensitivity in colorectal cancer SO ONCOGENE LA English DT Article DE ASC; p53; methylation; chemosensitivity; colorectal cancer ID RECRUITMENT DOMAIN PROTEIN; APOPTOTIC RESPONSE; HUMAN BREAST; P53; GENE; CELLS; BAX; ACTIVATION; MUTATIONS; ASC/TMS1 AB Tumor suppressor p53 is known to play a crucial role in chemosensitivity in colorectal cancer. We previously demonstrated that an apoptosis-associated speck-like protein, ASC, is a p53-target gene which regulates p53-Bax mitochondrial apoptotic pathway. ASC is also known to be a target of methylation-induced gene silencing. An inactivation of ASC might thus cause resistance to chemotherapy, and if this is the case, then the expression of ASC would restore the chemosensitivity. The aim of this study was to clarify this hypothesis. ASC was methylated in 25% of all resected specimens in patients with colorectal cancer; however, ASC methylation did not always correspond to a lack of ASC protein. When expressed in colon cancer cells, in which ASC is absent due to methylation, ASC was found to enhance the chemosensitivity in a p53-dependent manner. In p53-null cells, ASC increased the p53-mediated cell death induced by p53-expressing adenovirus infection. Our data suggest that the methylation-induced silencing of ASC might cause resistance to p53-mediated chemosensitivity in colorectal cancer. The gene introduction of ASC may thus restore such chemosensitivity, and this modality may therefore be a useful new treatment strategy for colorectal cancer. C1 Saga Univ, Fac Med, Dept Surg, Saga 8498501, Japan. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Orthoped Surg, Seoul, South Korea. Massachusetts Gen Hosp, Cutaneuos Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Ohtsuka, T (reprint author), Saga Univ, Fac Med, Dept Surg, Saga 8498501, Japan. EM ootsuka4@cc.saga-u.ac.jp OI HA, Chul-Won/0000-0001-5123-6513 FU NCI NIH HHS [CA80058-06, CA078356-05] NR 21 TC 14 Z9 19 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 2006 VL 25 IS 12 BP 1807 EP 1811 DI 10.1038/sj.onc.1209204 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 021VJ UT WOS:000236013700012 PM 16331272 ER PT J AU Ji, H Houghton, AM Mariani, TJ Perera, S Kim, CB Padera, R Tonon, G McNamara, K Marconcini, LA Hezel, A El-Bardeesy, N Bronson, RT Sugarbaker, D Maser, RS Shapiro, SD Wong, KK AF Ji, H Houghton, AM Mariani, TJ Perera, S Kim, CB Padera, R Tonon, G McNamara, K Marconcini, LA Hezel, A El-Bardeesy, N Bronson, RT Sugarbaker, D Maser, RS Shapiro, SD Wong, KK TI K-ras activation generates an inflammatory response in lung tumors SO ONCOGENE LA English DT Article DE K-ras; inflammation; lung cancer; macrophages; neutrophils ID PEPTIDE ENA-78; CANCER; INTERLEUKIN-8; CELLS; ANGIOGENESIS; EXPRESSION; CARCINOGENESIS; IDENTIFICATION; TUMORIGENESIS; INDUCTION AB Activating mutations in K-ras are one of the most common genetic alterations in human lung cancer. To dissect the role of K-ras activation in bronchial epithelial cells during lung tumorigenesis, we created a model of lung adenocarcinoma by generating a conditional mutant mouse with both Clara cell secretory protein (CC10)-Cre recombinase and the Lox-Stop-Lox K-ras(G12D) alleles. The activation of K-ras mutant allele in CC10 positive cells resulted in a progressive phenotype characterized by cellular atypia, adenoma and ultimately adenocarcinoma. Surprisingly, K-ras activation in the bronchiolar epithelium is associated with a robust inflammatory response characterized by an abundant infiltration of alveolar macrophages and neutrophils. These mice displayed early mortality in the setting of this pulmonary inflammatory response with a median survival of 8 weeks. Bronchoalveolar lavage fluid from these mutant mice contained the MIP-2, KC, MCP-1 and LIX chemokines that increased significantly with age. Cell lines derived from these tumors directly produced MIP-2, LIX and KC. This model demonstrates that K-ras activation in the lung induces the elaboration of inflammatory chemokines and provides an excellent means to further study the complex interactions between inflammatory cells, chemokines and tumor progression. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St,M413, Boston, MA 02115 USA. EM kwong1@partners.org RI Maser, Richard/B-2970-2012 FU NHLBI NIH HHS [R01 HL70321]; NIA NIH HHS [K08AG 2400401] NR 34 TC 123 Z9 125 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 2006 VL 25 IS 14 BP 2105 EP 2112 DI 10.1038/sj.onc.1209237 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 026RL UT WOS:000236359700013 PM 16288213 ER PT J AU Desanto-Madeya, S Bauer-Wu, S Gross, A AF Desanto-Madeya, S Bauer-Wu, S Gross, A TI Activities of daily living for women with advanced breast cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Univ Massachusetts, Boston, MA 02125 USA. Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 19 BP 399 EP 399 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600041 ER PT J AU Cooley, ME Blood, E Hoskinson, R Garvey, A AF Cooley, ME Blood, E Hoskinson, R Garvey, A TI Gender differences in smoking relapse. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 26 BP 401 EP 402 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600048 ER PT J AU Bauer-Wu, S Fulton, M Winer, E Partridge, A AF Bauer-Wu, S Fulton, M Winer, E Partridge, A TI Oncology nurses' attitudes and practices about informing clinical trials participants of study results. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 59 BP 411 EP 411 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600081 ER PT J AU Mazeika, T Guglia, J AF Mazeika, T Guglia, J TI Development of an oncology specific clinical research center. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, OCN, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 61 BP 411 EP 411 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600083 ER PT J AU Bartholomay, M Finn, S Rounds, A Bigelow, R Barrett, E Coakley, A Bolton, R Cashavelly, B AF Bartholomay, M Finn, S Rounds, A Bigelow, R Barrett, E Coakley, A Bolton, R Cashavelly, B TI Uncovering practice differences related to the care of indwelling and external tunneled catheters across practice settings in a large academic medical center. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, AOCN, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 89 BP 419 EP 420 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600111 ER PT J AU Walsh, S Broks, L Gribbin, N AF Walsh, S Broks, L Gribbin, N TI Implementing triage and resource nursing roles in an ambulatory infusion unit. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, OCN, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 97 BP 422 EP 422 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600119 ER PT J AU Lipshires, K AF Lipshires, K TI Helping nurses utilize computer-based applications. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 130 BP 431 EP 431 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600152 ER PT J AU Roper, K Santacroce, SJ AF Roper, K Santacroce, SJ TI Web-based interventions in oncology: Maintaining treatment fidelity. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Yale Univ, Sch Nursing, New Haven, CT 06536 USA. Dana Farber Canc Inst, OCN, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 135 BP 433 EP 433 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600157 ER PT J AU Radwin, L Wilkes, G Curtin, L Saba, C Tracey, L Garvey, J Whitehouse, J Sanabria, C Schrantz, A Teixeira, L Hackel, M Willis, K AF Radwin, L Wilkes, G Curtin, L Saba, C Tracey, L Garvey, J Whitehouse, J Sanabria, C Schrantz, A Teixeira, L Hackel, M Willis, K TI Enhancing patients' trust in oncology nursing care: A challenge for nursing leaders. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Univ Massachusetts, Boston, MA 02125 USA. Boston Med Ctr, AOCN, Boston, MA USA. Brockton Hosp, Brockton, MA USA. Cape Cod Hosp, Falmouth, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 179 BP 445 EP 445 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600201 ER PT J AU DeCristofaro, S AF DeCristofaro, S TI Creating a mobile resource center van program for cancer prevention, education and screening in the community. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, OCN, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 195 BP 449 EP 450 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600217 ER PT J AU Pellerin, L Perryman, S Hanley, D Thompson, L Tracey, E AF Pellerin, L Perryman, S Hanley, D Thompson, L Tracey, E TI Recruitment of minority nurses to oncology. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, OCN, Boston, MA 02115 USA. Dana Farber Canc Inst, AOCN, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 208 BP 453 EP 453 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600230 ER PT J AU Bauer-Wu, S Norris, R Liu, Q AF Bauer-Wu, S Norris, R Liu, Q TI Self-care and coping activities of metastatic breast cancer patients: Description and factors associated with use. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 238 BP 462 EP 462 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600260 ER PT J AU Bauer-Wu, S Gross, A Liu, D AF Bauer-Wu, S Gross, A Liu, D TI Prevalence and predictors of complementary and alternative therapies use by women with advanced breast cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 267 BP 470 EP 471 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600289 ER PT J AU Verrier, D Toomey-Mathews, E Lipshires, K AF Verrier, D Toomey-Mathews, E Lipshires, K TI Computerized order entry: A dynamic initiative for nursing with patients on a clinical trial. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 271 BP 471 EP 472 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600293 ER PT J AU Fitzgerald, EM Finn, SM Empoliti, J AF Fitzgerald, EM Finn, SM Empoliti, J TI Chemotherapy administration on non oncology units: Promoting quality and safety. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 273 BP 472 EP 472 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600295 ER PT J AU Gross, A Bauer-Wu, S Mills, J O'Rourke, J Ott, MJ Hanley, D AF Gross, A Bauer-Wu, S Mills, J O'Rourke, J Ott, MJ Hanley, D TI Developing and implementing a support and renewal program for nursing and patient care services staff. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 297 BP 478 EP 479 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600319 ER PT J AU Thompson, L Dalton, J Hanley, D Ponte, PR AF Thompson, L Dalton, J Hanley, D Ponte, PR TI Developing a community health rotation at a comprehensive cancer center. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, OCN, Boston, MA 02115 USA. Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 296 BP 478 EP 478 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600318 ER PT J AU Cashavelly, B Binda, K Alterman, E AF Cashavelly, B Binda, K Alterman, E TI Support for the oncology support staff: Recognizing difficulties that face non-licensed staff in an oncology setting. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, AOCN, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 299 BP 479 EP 479 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600321 ER PT J AU Macmillan, L AF Macmillan, L TI Patient memorial services to assist oncology staff bereavement. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 307 BP 481 EP 481 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600329 ER PT J AU Laccetti, M Lee, C Marangi, J Tierno, K Solari, F Lynch, C AF Laccetti, M Lee, C Marangi, J Tierno, K Solari, F Lynch, C TI Caring for the patient after pelvic exenteration. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Coll, Wm F Connell Sch Nursing, AOCN, Chestnut Hill, MA 02167 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2006 VL 33 IS 2 MA 308 BP 482 EP 482 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 031II UT WOS:000236697600330 ER PT J AU Barabino, S Rolando, M AF Barabino, S Rolando, M TI In vivo confocal microscopy of ocular cicatricial pemphigoid SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Lab Immunol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Cornea Serv, Boston, MA USA. Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. RP Barabino, S (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Lab Immunol, 20 Staniford St, Boston, MA 02114 USA. EM barabino@vision.eri.harvard.edu NR 4 TC 5 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1082-3069 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD MAR-APR PY 2006 VL 37 IS 2 BP 175 EP 176 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 024XB UT WOS:000236228600017 PM 16583645 ER PT J AU Hart, ES Albright, MB Rebello, GN Grottkau, BE AF Hart, ES Albright, MB Rebello, GN Grottkau, BE TI Developmental dysplasia of the hip - Nursing implications and anticipatory guidance for parents SO ORTHOPAEDIC NURSING LA English DT Article ID CONGENITAL DISLOCATION; ULTRASOUND; RELIABILITY; DIAGNOSIS AB Developmental dysplasia of the hip (DDH) is a comprehensive term used to describe an abnormal relationship between the femoral head and the acetabulum. Developmental dysplasia of the hip includes a very wide spectrum of abnormality from a frank dislocation (very unstable) to a stable hip with a slightly shallow acetabulum. As many of these findings may not be present at birth, the term developmental more accurately reflects the biologic features than does the term congenital. Despite the recent increased awareness of DDH and the importance of thorough screening programs, hip dysplasia continues to be a frequently missed diagnosis in pediatrics. Earlier detection and diagnosis of DDH is associated with a much more successful and less invasive outcome. C1 Massachusetts Gen Hosp Children, Dept Orthopaed Surg, Yawkey Ctr Outpatient Care, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat Orthopaed, Boston, MA 02114 USA. RP Hart, ES (reprint author), Massachusetts Gen Hosp Children, Dept Orthopaed Surg, Yawkey Ctr Outpatient Care, Boston, MA USA. NR 39 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0744-6020 J9 ORTHOP NURS JI Orthop. Nurs. PD MAR-APR PY 2006 VL 25 IS 2 BP 100 EP 109 PG 10 WC Nursing; Orthopedics SC Nursing; Orthopedics GA 036PL UT WOS:000237086900003 PM 16572026 ER PT J AU Gallagher, RM AF Gallagher, RM TI Health system studies of pain in older adults: Can we save the "golden years"? 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 2 TC 1 Z9 1 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 MAR-APR PY 2006 VL 7 IS 2 BP 101 EP 102 DI 10.1111/j.1526-4637.2006.00136.x PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 024UE UT WOS:000236220900001 PM 16634721 ER PT J AU Everett, LL Van Rooyen, IF Warner, MH Shurtleff, HA Saneto, RP Ojemann, JG AF Everett, LL Van Rooyen, IF Warner, MH Shurtleff, HA Saneto, RP Ojemann, JG TI Use of dexmedetomidine in awake craniotomy in adolescents: report of two cases SO PEDIATRIC ANESTHESIA LA English DT Article DE dexmedetomidine; craniotomy; awake; anesthesia ID STIMULATION; LOCALIZATION; PROPOFOL; CHILDREN AB Awake craniotomy is a key tool in resection of lesions near critical functional regions, particularly the speech area. Craniotomy with an awake portion for mapping may be performed in carefully selected adolescents and preteenaged children. A number of different regimens may be used for sedation and anesthesia in these cases. We describe two adolescent patients in whom awake craniotomy was performed using an intravenous anesthesia technique with dexmedetomidine and without need for airway instrumentation. C1 Univ Washington, Dept Pediat Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. RP Everett, LL (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol, 55 Fruit St,Clin 322, Boston, MA 02114 USA. EM leverett@partners.org OI Ojemann, Jeffrey/0000-0001-7580-8934 NR 14 TC 24 Z9 25 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD MAR PY 2006 VL 16 IS 3 BP 338 EP 342 DI 10.1111/j.1460-9592.2005.01697.x PG 5 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 012WJ UT WOS:000235371300019 PM 16490103 ER PT J AU Turner, EH Loftis, JM Blackwell, AD AF Turner, EH Loftis, JM Blackwell, AD TI Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE serotonin; antidepressants; 5-HTP; tryptophan; depression; selective serotonin re-uptake inhibitor ID TRYPTOPHAN-HYDROXYLASE ISOFORM; POSITRON-EMISSION-TOMOGRAPHY; SEASONAL AFFECTIVE-DISORDER; ALPHA-INDUCED CHANGES; RAT-LIVER CELLS; INTERFERON-ALPHA; MAJOR DEPRESSION; INDOLEAMINE 2,3-DIOXYGENASE; ANTIDEPRESSANT ACTION; SLEEP-DEPRIVATION AB This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. In the absence of supplementation with exogenous 5-HTP, the amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase, indoleamine 2,3-dioxygenase, and tryptophan 2,3-dioxygenase (TDO). Factors affecting each of these are reviewed. The amount of 5-HTP reaching the central nervous system (CNS) is affected by the extent to which 5-HTP is converted to serotonin in the periphery. This conversion is controlled by the enzyme amino acid decarboxylase, which, in the periphery, can be blocked by peripheral decarboxylase inhibitors (PDIs) such as carbidopa. Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials. Safety issues with 5-HTP are also reviewed, with emphasis on eosinophilia myalgia syndrome (EMS) and serotonin syndrome. Published by Elsevier Inc. C1 Portland VA Med Ctr, Mood Disorders Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. Univ Oregon, Dept Anthropol, Eugene, OR 97403 USA. RP Turner, EH (reprint author), Portland VA Med Ctr, Mood Disorders Ctr, P3MHDC,3710 SW Us Vet Hosp Rd, Portland, OR 97239 USA. EM Erick.turner@med.va.gov RI Blackwell, Aaron/B-5258-2008; Turner, Erick/A-4848-2008 OI Blackwell, Aaron/0000-0002-5871-9865; Turner, Erick/0000-0002-3522-3357 NR 121 TC 83 Z9 87 U1 8 U2 40 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAR PY 2006 VL 109 IS 3 BP 325 EP 338 DI 10.1016/j.pharmthera.2005.06.004 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 013KW UT WOS:000235409200002 PM 16023217 ER PT J AU DeMonaco, HJ Ali, A von Hippel, E AF DeMonaco, HJ Ali, A von Hippel, E TI The major role of clinicians in the discovery of off-label drug therapies SO PHARMACOTHERAPY LA English DT Article DE off-label drug use; prescription drugs; new molecular entities; lead users ID INNOVATION; USERS; FIELD AB Objective. To determine the role of clinicians in the discovery of off-label use of prescription drugs approved by the United States Food and Drug Administration (FDA). Data Sources. Micromedex Healthcare Series was used to identify new uses of new molecular entities approved by the FDA in 1998, literature from January 1999-December 2003 was accessed through MEDLINE, and relevant patents were identified through the U.S. Patent and Trademark Office. Data Synthesis and Main Finding. A survey of new therapeutic uses for new molecular entity drugs approved in 1998 was conducted for the subsequent 5 years of commercial availability. During that period, 143 new applications were identified in a computerized search of the literature for the 29 new drugs considered and approved in 1998. Literature and patent searches were conducted to identify the first report of each new application. Authors of the seminal articles were contacted through an electronic survey to determine whether they were in fact the originators of the new applications. if they were, examination of article content and author surveys were used to explore if each new application was discovered through clinical practice that was independent of pharmaceutical company or university research (field discovery) or if the discovery was made by or with the involvement of pharmaceutical company or university researchers (central discovery). Eighty-two (57%) of the 143 drug therapy innovations in our sample were discovered by practicing clinicians through field discovery. Conclusion. To our knowledge, the major role of clinicians in the discovery of new, off-label drug therapies has not been previously documented or explored. We propose that this finding has important regulatory and health policy implications. C1 Massachusetts Gen Hosp, Decis Support & Qual Management Unit, Boston, MA 02114 USA. MIT, Alfred P Sloan Sch Management, Cambridge, MA 02139 USA. Harvard Univ, Program Hlth Policy, Boston, MA 02115 USA. RP DeMonaco, HJ (reprint author), Massachusetts Gen Hosp, Decis Support & Qual Management Unit, 55 Fruit St, Boston, MA 02114 USA. EM hdemonaco@partners.org NR 29 TC 44 Z9 46 U1 2 U2 8 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAR PY 2006 VL 26 IS 3 BP 323 EP 332 DI 10.1592/phco.26.3.323 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 018SX UT WOS:000235786200003 PM 16503712 ER PT J AU Kosaka, S Kawana, S Zouboulis, CC Hasan, T Ortel, B AF Kosaka, S Kawana, S Zouboulis, CC Hasan, T Ortel, B TI Targeting of sebocytes by aminolevulinic acid-dependent photosensitization SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INDUCED PROTOPORPHYRIN-IX; PHOTODYNAMIC THERAPY; 5-AMINOLEVULINIC ACID; ACNE-VULGARIS; DIFFERENTIATION; CELLS; ALA; DERMATOLOGY; MECHANISM AB Photodynamic therapy using 5-aminolevulinic acid-induced protoporphyrin IX has been developed as a very useful therapeutic modality. Recently, several authors have reported on the efficacy of this procedure for acne. This approach is based on the fact that 5-aminolevulinic acid-induced protoporphyrin IX has strong selectivity for sebaceous glands. We used the immortalized human sebaceous gland cell line SZ95 to investigate cellular mechanisms of photodynamic therapy using 5-aminolevulinic acid-induced protoporphyrin IX. Quantification of induced protoporphyrin IX production showed dependence on the applied 5-aminolevulinic acid dose. When SZ95 sebocytes were differentiated by arachidonic acid treatment, there was no difference between them and the control cells with respect to both the amount of 5-aminolevulinic acid-induced protoporphyrin IX and the phototoxic effects. We altered protoporphyrin IX formation rates by growing cells scattered as single cells in the culture dishes. Single cells produced significantly lower protoporphyrin IX levels than those grown with intercellular contacts. Intracellular localization of protoporphyrin IX was imaged using confocal laser scanning microscopy. The differentiation-specific lipid droplets were virtually excluded from protoporphyrin IX fluorescence. In addition to weak mitochondrial and strong membrane fluorescence, distinctive spots with strong fluorescence were observed. These did not colocalize with fluorescent probes for mitochondria, lysosomes or the Golgi apparati. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. Nippon Med Coll, Dept Dermatol, Tokyo 113, Japan. Charite Univ Med Berlin, Dept Dermatol, Berlin, Germany. RP Kosaka, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. EM skosaka@partners.org RI Dr. Zouboulis, Christos/I-4493-2013 OI Dr. Zouboulis, Christos/0000-0003-1646-2608 FU NCI NIH HHS [1PO1 CA84203-01] NR 26 TC 14 Z9 14 U1 0 U2 2 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 MAR-APR PY 2006 VL 82 IS 2 BP 453 EP 457 DI 10.1562/2005-08-08-RA-643 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 036CK UT WOS:000237048300017 PM 16613498 ER PT J AU Shalizi, CR Haslinger, R Rouquier, JB Klinkner, KL Moore, C AF Shalizi, CR Haslinger, R Rouquier, JB Klinkner, KL Moore, C TI Automatic filters for the detection of coherent structure in spatiotemporal systems SO PHYSICAL REVIEW E LA English DT Article ID KARHUNEN-LOEVE DECOMPOSITION; CELLULAR-AUTOMATA; LYAPUNOV EXPONENTS; COMPUTATIONAL MECHANICS; CHAOS; COMPLEXITY; PATTERNS; PREDICTION; DIFFUSION; DYNAMICS AB Most current methods for identifying coherent structures in spatially extended systems rely on prior information about the form which those structures take. Here we present two approaches to automatically filter the changing configurations of spatial dynamical systems and extract coherent structures. One, local sensitivity filtering, is a modification of the local Lyapunov exponent approach suitable to cellular automata and other discrete spatial systems. The other, local statistical complexity filtering, calculates the amount of information needed for optimal prediction of the system's behavior in the vicinity of a given point. By examining the changing spatiotemporal distributions of these quantities, we can find the coherent structures in a variety of pattern-forming cellular automata, without needing to guess or postulate the form of that structure. We apply both filters to elementary and cyclical cellular automata (ECA and CCA) and find that they readily identify particles, domains, and other more complicated structures. We compare the results from ECA with earlier ones based upon the theory of formal languages and the results from CCA with a more traditional approach based on an order parameter and free energy. While sensitivity and statistical complexity are equally adept at uncovering structure, they are based on different system properties (dynamical and probabilistic, respectively) and provide complementary information. C1 Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Ecole Normale Super Lyon, Lab Informat Parallelisme, F-69364 Lyon, France. Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. Univ New Mexico, Dept Comp Sci, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Shalizi, CR (reprint author), Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. EM cshalizi@cmu.edu; robhh@nmr.mgh.harvard.edu; jean-baptiste.rouquier@ens-lyon.fr; klinkner@cmu.edu; moore@santafe.edu FU NIDA NIH HHS [R01 DA 015644]; NIMH NIH HHS [R01 MH 59733] NR 64 TC 29 Z9 29 U1 0 U2 4 PU AMERICAN 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 MAR PY 2006 VL 73 IS 3 AR 036104 DI 10.1103/PhysRevE.73.036104 PN 2 PG 16 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 028DS UT WOS:000236467700013 PM 16605595 ER PT J AU Vazquez, A Oliveira, JG Dezso, Z Goh, KI Kondor, I Barabasi, AL AF Vazquez, A Oliveira, JG Dezso, Z Goh, KI Kondor, I Barabasi, AL TI Modeling bursts and heavy tails in human dynamics SO PHYSICAL REVIEW E LA English DT Article ID EVOLUTION; NETWORKS; BEHAVIOR; PATTERNS AB The dynamics of many social, technological and economic phenomena are driven by individual human actions, turning the quantitative understanding of human behavior into a central question of modern science. Current models of human dynamics, used from risk assessment to communications, assume that human actions are randomly distributed in time and thus well approximated by Poisson processes. Here we provide direct evidence that for five human activity patterns, such as email and letter based communications, web browsing, library visits and stock trading, the timing of individual human actions follow non-Poisson statistics, characterized by bursts of rapidly occurring events separated by long periods of inactivity. We show that the bursty nature of human behavior is a consequence of a decision based queuing process: when individuals execute tasks based on some perceived priority, the timing of the tasks will be heavy tailed, most tasks being rapidly executed, while a few experiencing very long waiting times. In contrast, priority blind execution is well approximated by uniform interevent statistics. We discuss two queuing models that capture human activity. The first model assumes that there are no limitations on the number of tasks an individual can hadle at any time, predicting that the waiting time of the individual tasks follow a heavy tailed distribution P(tau(w))similar to tau(-alpha)(w) with alpha=3/2. The second model imposes limitations on the queue length, resulting in a heavy tailed waiting time distribution characterized by alpha=1. We provide empirical evidence supporting the relevance of these two models to human activity patterns, showing that while emails, web browsing and library visitation display alpha=1, the surface mail based communication belongs to the alpha=3/2 universality class. Finally, we discuss possible extension of the proposed queuing models and outline some future challenges in exploring the statistical mechanics of human dynamics. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. Univ Notre Dame, Ctr Complex Networks Res, Notre Dame, IN 46556 USA. Univ Aveiro, Dept Fis, P-3810193 Aveiro, Portugal. Collegium Budapest, H-1014 Budapest, Hungary. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. RI Oliveira, Joao/H-3256-2012; Universidade Aveiro, Departamento Fisica/E-4128-2013 OI Oliveira, Joao/0000-0002-1199-4667; NR 77 TC 275 Z9 306 U1 6 U2 43 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD MAR PY 2006 VL 73 IS 3 AR 036127 DI 10.1103/PhysRevE.73.036127 PN 2 PG 19 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 028DS UT WOS:000236467700036 PM 16605618 ER PT J AU Hsieh, MH Goodman, HM AF Hsieh, MH Goodman, HM TI Functional evidence for the involvement of Arabidopsis IspF homolog in the nonmevalonate pathway of plastid isoprenoid biosynthesis SO PLANTA LA English DT Article DE albino; Arabidopsis; chloroplast; isoprenoids; IspF; nonmevalonate pathway ID 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE; RIPENING TOMATO FRUIT; ESCHERICHIA-COLI; 2,4-CYCLODIPHOSPHATE SYNTHASE; 2C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE; 2-C-METHYL-D-ERYTHRITOL 4-PHOSPHATE; ISOPENTENYL DIPHOSPHATE; CATHARANTHUS-ROSEUS; MOLECULAR ANALYSIS; PHOSPHATE-PATHWAY AB There are two independent pathways, the cytosolic mevalonate (MVA) pathway and the plastid nonmevalonate (nonMVA) pathway, to synthesize isopentenyl diphosphate and dimethylallyl diphosphate in plants. Carotenoids and the phytyl side chain of chlorophylls are isoprenoids derived from the plastid nonMVA pathway. All enzymes involved in the nonMVA pathway have been identified in Escherichia coli. The E. coli IspF protein catalyzes a unique cyclization reaction to convert 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate into 2-C-methyl-D-erythritol 2,4-cyclodiphosphate in the nonMVA pathway. We have characterized an Arabidopsis T-DNA insertion mutant, ispF-1, which has a null mutation in the IspF gene. Homozygous ispF-1 mutants are albino lethal and the IspF transcripts are undetectable in these plants. Moreover, the ispF-1 mutant chloroplasts are filled with vesicles instead of thylakoids. Amino acid sequence alignment reveals that the IspF proteins are highly conserved between plants and bacteria. Interestingly, expression of the Arabidopsis IspF protein can rescue the lethal phenotype of an E. coli ispF Mutant. These results indicate that the Arabidopsis IspF may share similar enzymatic mechanisms with the E. coli protein. C1 Acad Sinica, Inst Plant & Microbial Biol, Taipei 11529, Taiwan. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Hsieh, MH (reprint author), Acad Sinica, Inst Plant & Microbial Biol, Taipei 11529, Taiwan. EM ming@gate.sinica.edu.tw NR 41 TC 29 Z9 30 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0032-0935 J9 PLANTA JI Planta PD MAR PY 2006 VL 223 IS 4 BP 779 EP 784 DI 10.1007/s00425-005-0140-9 PG 6 WC Plant Sciences SC Plant Sciences GA 034YA UT WOS:000236965600015 PM 16231155 ER PT J AU Chun, YS Pribaz, JJ AF Chun, YS Pribaz, JJ TI A cadaver study in preparation for facial allograft transplantation in humans: Part II. Mock facial transplantation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID HAND TRANSPLANTATION C1 Brigham & Womens Hosp, Div Plast & Reconstruct Surg, Boston, MA 02115 USA. RP Pribaz, JJ (reprint author), Brigham & Womens Hosp, Div Plast & Reconstruct Surg, 75 Francis St, Boston, MA 02115 USA. EM jpribaz@partners.org NR 8 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2006 VL 117 IS 3 BP 886 EP 888 DI 10.1097/01.prs.0000204895.86228.24 PG 3 WC Surgery SC Surgery GA 020WA UT WOS:000235942500025 ER PT J AU Hammad, SM Taha, TA Nareika, A Johnson, KR Lopes-Virella, MF Obeid, LM AF Hammad, SM Taha, TA Nareika, A Johnson, KR Lopes-Virella, MF Obeid, LM TI Oxidized LDL immune complexes induce release of sphingosine kinase in human U937 monocytic cells SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Article DE sphingosine kinase; sphingosine 1 phosphate; LDL immune complex; oxidized LDL; macrophage ID LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE-CELLS; INFLAMMATORY CELLS; INDUCED APOPTOSIS; PLASMA-MEMBRANE; ACTIVATION; MACROPHAGES; 1-PHOSPHATE; ANTIBODIES; RECEPTOR AB The transformation of rnacrophages into foam cells is a critical event in the development of atherosclerosis. The most studied aspect of this process is the uptake of modified LDL through the scavenger receptors. Another salient aspect is the effect of modified LDL immune complexes on macrophages activation and foam cell formation. Macrophages internalize oxidized LDL immune complexes (oxLDL-IC) via the Fc-gamma receptor and transform into activated foam cells. In this study we examined the effect of oxLDL-IC on sphingosine kinase 1 (SK1), an enzyme implicated in mediating pro-survival and inflammatory responses through the generation of the signaling molecule sphingosine-1-phosphate (S1P). Intriguingly, oxLDL-IC, but not oxLDL alone, induced an immediate translocation and release of SK1 into the conditioned medium as evidenced by fluorescence confocal microscopy. Immunoblot analysis of cell lysates and conditioned medium revealed a decrease in intracellular SK1 protein levels accompanied by a concomitant increase in extracellular SK1 levels. Furthermore, measurement of S1P formation showed that the activity of cell-associated SK decreased in response to oxLDL-IC compared to oxLDL alone, whereas the activity of SK increased extracellularly. Blocking oxLDL-IC binding to Fc-gamma receptors resulted in decreased levels of extracellular S1P. The data also show that cell survival of human U937 cells exposed to oxLDL-IC increased compared to oxLDL alone. Exogenously added S1P further increased cell survival induced by oxLDL-IC. Taken together, these findings indicate that S1P may be generated extracellularly in response to modified LDL immune complexes and may therefore promote cell survival and prolong cytokine release by activated macrophages. (C) 2006 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Dept Vet Affairs, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Hammad, SM (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, 114 Doughty St,630B,POB 250776, Charleston, SC 29425 USA. EM hammadsm@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NHLBI NIH HHS [HL55782]; NIGMS NIH HHS [GM62887] NR 53 TC 28 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD MAR PY 2006 VL 79 IS 1-2 BP 126 EP 140 DI 10.1016/j.prostaglandins.2005.12.004 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 027NS UT WOS:000236422900010 PM 16516816 ER PT J AU Van Leyen, K Kim, HY Lee, SR Wang, XY Lo, EH AF Van Leyen, K Kim, HY Lee, SR Wang, XY Lo, EH TI 12/15-Lipoxygenase contributions to brain damage following stroke SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Meeting Abstract CT 9th International Conference Eicosanoids CY SEP 11-14, 2005 CL San Francisco, CA C1 Massachusetts Gen Hosp East, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. RI van Leyen, Klaus/C-9126-2013 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 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD MAR PY 2006 VL 79 IS 1-2 BP 158 EP 158 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 027NS UT WOS:000236422900066 ER PT J AU Kaelin, WG AF Kaelin, WG TI The von Hippel-Lindau tumor suppressor protein: Prolyl hydroxylation, oxygen sensing, and cancer SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Meeting Abstract CT 9th International Conference Eicosanoids CY SEP 11-14, 2005 CL San Francisco, CA C1 Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, 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 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD MAR PY 2006 VL 79 IS 1-2 BP 167 EP 167 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 027NS UT WOS:000236422900098 ER PT J AU Tomisawa, Y Ogasawara, YS Maesawa, C Masuda, T Kurebayashi, J Hershman, NJM Ohta, K Wakabayashi, G AF Tomisawa, Y Ogasawara, YS Maesawa, C Masuda, T Kurebayashi, J Hershman, NJM Ohta, K Wakabayashi, G TI Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in human papillary cell carcinoma cell line SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Meeting Abstract CT 9th International Conference Eicosanoids CY SEP 11-14, 2005 CL San Francisco, CA C1 Iwate Med Univ, Sch Med, Dept Surg 1, Morioka, Iwate 0208505, Japan. Iwate Med Univ, Sch Med, Dept Pathol 2, Morioka, Iwate 0208505, Japan. Kawasaki Med Univ, Dept Breast & Thyroid Surg, Okayama 7010192, Japan. Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Yamanashi Med Univ, Dept Internal Med 3, Yamanashi 4093898, Japan. 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 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD MAR PY 2006 VL 79 IS 1-2 BP 185 EP 186 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 027NS UT WOS:000236422900172 ER PT J AU Traum, AZ Wells, MP Aivado, M Libermann, TA Ramoni, MF Schachter, AD AF Traum, AZ Wells, MP Aivado, M Libermann, TA Ramoni, MF Schachter, AD TI SELDI-TOF MS of quadruplicate urine and serum samples to evaluate changes related to storage conditions SO PROTEOMICS LA English DT Article DE repeatability; reproducibility; SELDI; serum; urine ID FLIGHT MASS-SPECTROMETRY; RENAL-ALLOGRAFT REJECTION; CANCER; PROTEOME AB Proteomic profiling with SELDI-TOF MS has facilitated the discovery of disease-specific protein profiles. However, multicenter studies are often hindered by the logistics required for prompt deep-freezing of samples in liquid nitrogen or dry ice within the clinic setting prior to shipping. We report high concordance between MS profiles within sets of quadruplicate split urine and serum samples deep-frozen at 0, 2, 6, and 24 h after sample collection. Gage R&R results confirm that deep-freezing times are not a statistically significant source of SELDI-TOF MS variability for either blood or urine. C1 Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. BIDMC Genom Ctr, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dana Farber Harvard Canc Ctr Proteom Core, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard MIT Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA USA. RP Schachter, AD (reprint author), Div Nephrol, 300 Longwood Ave, Boston, MA USA. EM asher.schachter@childrens.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179 FU NCRR NIH HHS [K23 RR016080, K23 RR016080-05, K32 RR16080]; NIDDK NIH HHS [T32 DK007726, T32 DK 007726] NR 13 TC 33 Z9 40 U1 0 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAR PY 2006 VL 6 IS 5 BP 1676 EP 1680 DI 10.1002/pmic.200500174 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022TS UT WOS:000236079400027 PM 16447157 ER PT J AU Huckans, MS Blackwell, AD Harms, TA Hauser, P AF Huckans, MS Blackwell, AD Harms, TA Hauser, P TI Management of hepatitis C disease among VA patients with schizophrenia and substance use disorders SO PSYCHIATRIC SERVICES LA English DT Article ID DEPRESSION AB Objective: Rates of hepatitis C (HCV) infection, testing, and treatment were compared among patients with schizophrenia, a substance use disorder, or co-occurring schizophrenia or schizoaffective disorder and a substance use disorder and a control group. Methods: Information about 293,445 patients of the Northwest Veterans Healthcare Administration was obtained. Results: The substance use disorder group constituted 13.6 percent of the sample; the schizophrenia group, 1.6 percent; and the co-occurring-disorders group, 1.4 percent. Respectively, these groups were approximately four, two, and six times as likely as the control group to receive HCV testing and about seven, two, and eight times as likely to be infected. The rate of interferon (IFN) therapy was significantly lower for the substance use group and the group with co-occurring disorders. However, the magnitude of the differences was not substantial, suggesting that these high-risk groups were not excluded from IFN therapy. C1 Portland VA Med Ctr, Behav Hlth & Neurosci Div, NW Hepatitis C Resource Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Univ Oregon, Dept Anthropol, Eugene, OR 97403 USA. RP Huckans, MS (reprint author), Portland VA Med Ctr, Behav Hlth & Neurosci Div, NW Hepatitis C Resource Ctr, 3710 SW US Vet Hosp Rd,P3MHDC, Portland, OR 97239 USA. EM marilyn.huckans@med.va.gov RI Blackwell, Aaron/B-5258-2008 OI Blackwell, Aaron/0000-0002-5871-9865 NR 10 TC 18 Z9 19 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2006 VL 57 IS 3 BP 403 EP 406 DI 10.1176/appi.ps.57.3.403 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 019TE UT WOS:000235858800018 PM 16525001 ER PT J AU Grubaugh, AL Frueh, BC Elhai, JD Monnier, J Knapp, RG Magruder, KM AF Grubaugh, AL Frueh, BC Elhai, JD Monnier, J Knapp, RG Magruder, KM TI Racial differences in psychiatric symptom patterns and service use in VA primary care clinics SO PSYCHIATRIC SERVICES LA English DT Article ID VETERANS; HEALTH; PTSD AB The purpose of this study was to assess racial differences in psychopathology and service use in a sample of African-American and Caucasian veterans. Methods: African-American (N=253) and Caucasian (N=460) veterans from primary care clinics at four Department of Veterans Affairs (VA) medical centers were compared on rates of trauma, posttraumatic stress disorder (PTSD), other psychiatric diagnoses, functional status, and use of VA services and benefits. A cross-sectional, epidemiologic design incorporating self-report measures, structured interviews, and chart reviews was used. Results: With the exception of substance abuse or dependence diagnoses and use of substance abuse treatment and urgent care services, few racial differences emerged. Conclusion: Overall, the findings suggest that African-American and Caucasian veterans, including those with PTSD, do not differ significantly in psychopathology or in their use of VA benefits and services. C1 Med Univ S Carolina, Div Publ Psychiat, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs, Med Ctr, Charleston, SC 29425 USA. Univ S Dakota, Disaster Mental Hlth Inst, Vermillion, SD 57069 USA. Med Univ S Carolina, Dept Bioinformat & Epidemiol, Charleston, SC 29425 USA. RP Grubaugh, AL (reprint author), Med Univ S Carolina, Div Publ Psychiat, Dept Psychiat & Behav Sci, 67 President St,POB 250861, Charleston, SC 29425 USA. EM grubaugh@musc.edu NR 10 TC 12 Z9 12 U1 2 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2006 VL 57 IS 3 BP 410 EP 413 DI 10.1176/appi.ps.57.3.410 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 019TE UT WOS:000235858800020 PM 16525003 ER PT J AU Recklitis, CJ Parsons, SK Shih, MC Mertens, A Robison, LL Zeltzer, L AF Recklitis, CJ Parsons, SK Shih, MC Mertens, A Robison, LL Zeltzer, L TI Factor structure of the Brief Symptom Inventory-18 in adult survivors of childhood cancer: Results from the childhood cancer survivor study SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE cancer survivors; pediatric oncology; psychological distress; factor analysis; BSI-18 ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; COVARIANCE STRUCTURE-ANALYSIS; HODGKINS-DISEASE; TEST STATISTICS; PSYCHIATRIC-DISORDERS; SCREENING INSTRUMENT; LEUKEMIA SURVIVORS; ADOLESCENT CANCER; EQUATION MODELS AB The factor structure of the Brief Symptom Inventory-18 (BSI-18; L. R. Derogatis, 2000) was investigated in a sample of adult survivors of childhood cancer enrolled in the Childhood Cancer Survivor Study (CCSS; N = 8,945). An exploratory factor analysis with a randomly chosen subsample supported a 3-factor structure closely corresponding to the 3 BSI-18 subscales: Depression, Anxiety, and Somatization. Confirmatory factor analysis with structural equation modeling validated this 3-dimensional structure in a separate subsample, though an alternative 4-factor model also fit the data. Analysis of the 3-factor model showed consistent,fit in male and female participants. Compared with available community-based norms, survivors reported fewer symptoms of psychological distress. Together, results support the hypothesized 3-dimensional structure of the BSI-18 and indicate the measure may be useful in assessing psychological distress in this growing population of cancer survivors. C1 Dana Farber Canc Inst, Perini Family Survivors Ctr, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Tufts Univ, New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Medford, MA 02155 USA. Tufts Univ, Sch Med, Dept Pediat, Medford, MA 02155 USA. Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Univ Calif Los Angeles, Patients & Survivors Program, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Biobehav Sci, Los Angeles, CA USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, Dept Pediat Oncol, 44 Binney St,SW320B, Boston, MA 02115 USA. EM christopher_recklitis@dfci.harvard.edu OI Zeltzer, Lonnie/0000-0001-9306-9450 FU NCI NIH HHS [U24-CA-55727] NR 72 TC 85 Z9 85 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD MAR PY 2006 VL 18 IS 1 BP 22 EP 32 DI 10.1037/1040-3590.18.1.22 PG 11 WC Psychology, Clinical SC Psychology GA 032LO UT WOS:000236776100003 PM 16594809 ER PT J AU Greer, J Halgin, R AF Greer, J Halgin, R TI Predictors of physician-patient agreement on symptom etiology in primary care SO PSYCHOSOMATIC MEDICINE LA English DT Article DE primary care; physician-patient agreement or concordance; psychological distress ID PRACTITIONER AGREEMENT; MENTAL-DISORDERS; GENERAL-PRACTICE; RECOGNITION; DEPRESSION; COMMUNICATION; ATTRIBUTION; ANXIETY; CONCORDANCE; DIAGNOSIS AB Objective: Primary care patients often report medically unexplained symptoms and may disagree with their physicians about the nature of their presenting complaints. The goals of this study were to explore the level of physician-patient agreement on symptom etiology and to identify predictors of disagreement. Methods: Primary care patients (n = 175) and their physicians rated the extent to which patients' presenting symptoms represented a medical versus a psychological problem. Patients also completed surveys regarding their demographic characteristics, level of psychological distress, health status, recent stress, history of mental health treatment, and reason for office visit. Results: Physicians and patients agreed on the etiology of symptoms in approximately 59% of the cases. Patient sex, history of mental health treatment, and reason for office visit significantly predicted agreement on symptom etiology. Physicians perceived patients with whom they disagreed about symptom etiology as less cooperative. Conclusion: Physician-patient agreement on symptom etiology is low and relates to several patient psychosocial and demographic factors. Identifying the variables associated with disagreement may help to improve communication and patient outcomes in primary care. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. RP Greer, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM jgreer2@partners.org NR 28 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAR-APR PY 2006 VL 68 IS 2 BP 277 EP 282 DI 10.1097/01.psy.0000203239.74461.db PG 6 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 029VB UT WOS:000236591400015 PM 16554394 ER PT J AU Gnanasekaran, SK Finkelstein, JA Hohman, K O'Brien, M Kruskal, B Lieu, TA AF Gnanasekaran, SK Finkelstein, JA Hohman, K O'Brien, M Kruskal, B Lieu, TA TI Parental perspectives on influenza vaccination among children with asthma SO PUBLIC HEALTH REPORTS LA English DT Article ID CHRONIC MEDICAL CONDITIONS; YOUNG-CHILDREN; IMMUNIZATION; RATES; DISEASE; BURDEN AB Objectives. The objectives of this study were to: (1) identify modifiable factors influencing receipt of influenza vaccination among children with asthma, and (2) to evaluate the effect of heightened media attention on vaccination rates. Methods. During November and December 2003, we interviewed parents of children with asthma about their experiences with and beliefs about influenza vaccination. We randomly selected 500 children from a study population of 2,140 children identified with asthma in a managed care organization in Massachusetts. We obtained data on influenza vaccination status from computerized medical records and determined significant factors influencing receipt of influenza vaccination. Results. Children were more likely to be vaccinated if their parent recalled a physician recommendation (odds ratio [OR] 2.6; 95% confidence interval [CI] 1.5, 4.5), believed the vaccine worked well (OR 2.0; 95% CI 1.4, 2.8), or expressed little worry about vaccine adverse effects (OR 1.3; 95% CI 1.0, 1.6), or if the child was younger (OR 1.1 per year of age; 95% CI 1.0, 1.2). During the study period, there was heightened media attention about influenza illness and the vaccine. The influenza vaccination rate for children with asthma was 43% in 2003-04 compared with 27% in 2002-03. Comparison of weekly influenza vaccination rates in 2003-04 and 2002-03 suggested that the media attention was associated with the increase in vaccination rates. Conclusions. Physician recommendations and parental education about influenza vaccine availability, effectiveness, and adverse effects are potentially important influences on influenza vaccination. Our findings suggest that media coverage of the risks of influenza was associated with a significant increase in vaccination rates. C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02214 USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Ctr Child Hlth Care Studies, Brookline, MA 02146 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Univ Hartford, Sch Med, Dept Pediat, Hartford, CT 06117 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Gnanasekaran, SK (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Ste 901, Boston, MA 02214 USA. EM srilakshmi.gnanasekaran@partners.org FU PHS HHS [T32 HP 10018] NR 30 TC 42 Z9 47 U1 1 U2 4 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 2006 VL 121 IS 2 BP 181 EP 188 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 020IA UT WOS:000235900900013 PM 16528952 ER PT J AU Propert, KJ Litwin, MS Wang, Y Alexander, RB Calhoun, E Nickel, JC O'Leary, MP Pontari, M McNaughton-Collins, M AF Propert, KJ Litwin, MS Wang, Y Alexander, RB Calhoun, E Nickel, JC O'Leary, MP Pontari, M McNaughton-Collins, M CA Chronic Prostatitis Collaborat TI Responsiveness of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) SO QUALITY OF LIFE RESEARCH LA English DT Article DE chronic prostatitis; chronic pelvic pain syndrome; symptom index ID PELVIC PAIN SYNDROME; DOUBLE-BLIND; TRIAL; MEN; PREVALENCE AB Objectives: The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) was developed to assess symptoms and quality of life in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We assessed the responsiveness of the NIH-CPSI to change over time and defined thresholds for changes perceptible to patients. Methods: We studied 174 men with CP/CPPS who participated in a placebo-controlled randomized clinical trial. Changes from baseline to six weeks in the NIH-CPSI total score and pain, urinary, and quality of life subscores were compared to a global response assessment (GRA). Effect sizes and Guyatt statistics were calculated to evaluate responsiveness; 95% confidence intervals were produced using bootstrapping. Results: All scores decreased over time with the largest decrease in subjects who reported on the GRA that they were markedly improved. The NIH-CPSI total, pain, and quality of life scores were highly responsive in the improved groups; the urinary score showed minimal responsiveness. There was no evidence of responsiveness among those subjects who worsened on the trial. ROC curves identified a 6-point decline in the NIH-CPSI total score as the optimal threshold to predict treatment response. Conclusions: The NIH-CPSI total score and pain and quality of life subscores are responsive to change over time. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Hlth Serv, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Maryland, Sch Med, Div Urol, Baltimore, MD USA. Northwestern Univ, Sch Med, Inst Hlth Serv Res & Hlth Policy Studies, Chicago, IL USA. Northwestern Univ, Sch Med, Dept Urol, Chicago, IL USA. Queens Univ, Dept Urol, Kingston, ON, Canada. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19122 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. RP Propert, KJ (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Blockley Hall,Room 614,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kpropert@cceb.upenn.edu FU NIDDK NIH HHS [U01 DK53730, U01 DK53732, U01 DK53734, U01 DK53736, U01 DK53738, U01 DK53746, U01 DK53752] NR 15 TC 51 Z9 53 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD MAR PY 2006 VL 15 IS 2 BP 299 EP 305 DI 10.1007/s11136-005-1317-1 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 011EM UT WOS:000235250800009 PM 16468084 ER PT J AU Hayter, RG Rhea, JT Small, A Tafazoli, FS Novelline, RA AF Hayter, RG Rhea, JT Small, A Tafazoli, FS Novelline, RA TI Suspected aortic dissection and other aortic disorders: Multi-detector row CT in 373 cases in the emergency setting SO RADIOLOGY LA English DT Article ID DESCENDING THORACIC AORTA; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; INTRAMURAL HEMATOMA; NATURAL-HISTORY; HELICAL CT; PROGNOSTIC PROFILES; CLINICAL-FEATURES; DIAGNOSIS; HEMORRHAGE; ANEURYSM AB Purpose: To retrospectively review the authors' experience, with multi-detector row computed tomography (CT) for detection of aortic dissection in the emergency setting. Materials and Methods: The investigation was institutional review board approved, did not, require informed patient consent. and was HIPAA compliant. In 373 clinical evaluations hi the emergency setting, 365 patients suspected of having aortic dissection and/or other aortic disorders underwent multidetector CT. Criteria for acute aortic disorder were confirmed by using surgical and pathologic diagnoses or findings at clinical follow-Up and any subsequent imaging as the reference standard. Positive cases were characterized according to type of disorder interpreted. Resulting sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were Calculated by, using two-way contingency table. All Cases found to be negative for acute aortic disorders were grouped according to alternative CT findings. Results: Sixty-seven (18.0%) of the 373 cases were interpreted as positive for acute aortic disorder. One hundred twelve acute aortic disorders were identified in these 67 cases: 23 acute aortic dissections, 14 acute aortic intramural hematomas, 20 acute penetrating aortic ulcers, 44 new or enlarging aortic aneurysms, and 11 acute aortic ruptures. Three hundred five (81.8%) cases were interpreted as negative for acute aortic disorder. In 48 negative cases, multidetector CT depicted alternative findings that. accounted for the clinical presentation. Of these, three included both acute aortic disorders and alternative findings, and 45 included only alternative findings. One (0.3%) case was indeterminate for acute aortic disorder. Overall, 112 findings were interpreted as positive for acute aortic disorder. an alternative finding, or both at. CT. No interpretations were false-posirive, one was false-negative. 67 were true-positive, and 304 were true-negative. Sensitivity. specificity, PPV, NPV, and accuracy were 99% (67 of 68). 100% (304 of 304) 10096 (67 of 67). 99.7% (304 of 305), and 99.5% (371 of 373), respectively. Conclusion: The positivity rate for acute aortic dissection or other acute aortic disorder in 373 cases examined at multi-detector row CT was 18,0%. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hayter, RG (reprint author), Massachusetts Gen Hosp, Dept Radiol, 107 Ave Louis Pasteur,Room 185, Boston, MA 02115 USA. EM robert_hayter@student.hms.harvard.edu NR 45 TC 77 Z9 94 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2006 VL 238 IS 3 BP 841 EP 852 DI 10.1148/radiol.2383041528 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 014YW UT WOS:000235520100010 PM 16452396 ER PT J AU Sahani, DV Saokar, A Hahn, PF Brugge, WR Fernandez-del Castillo, C AF Sahani, DV Saokar, A Hahn, PF Brugge, WR Fernandez-del Castillo, C TI Pancreatic cysts 3 cm or smaller: How aggressive should treatment be? SO RADIOLOGY LA English DT Article ID NEOPLASMS; CYSTADENOMAS; TUMORS AB Purpose: To retrospectively determine the frequency of malignancy in small (<= 3 cm) pancreatic cysts, to evaluate whether cyst morphologic features can help predict the presence of malignancy, and to determine the natural history of small pancreatic Cysts at follow-up imaging. Materials and Methods: Institutional review board approval was obtained; informed patient consent was not required. By means of a computerized search, 510 patients with pancreatic cysts that had been detected at computed tomography (CT) or magnetic resonance (MR) imaging were identified. Cysts that were 3 cm or smaller at surgery or endoscopic ultrasonography (US)-guided cyst fluid aspiration mid biopsy were included. Eighty-six patients-31 men and 55, women aged 24-89 years-fulfilled the criteria. Patients underwent surgery or were monitored with endoscopic, US-guided cyst fluid analysis, cytologic analysis, and follow-up imaging. Imaging findings were compared with surgical and pathology records and with endoscopic US features. Positive predictive values (PPVs) for benignity and malignancyv were calculated on the basis of cyst size and absence or presence of septa in the cysts. Results: Forty-eight patients underwent surgery, and 38 were treated nonsurgically. Seventy-five patients had benign cysts: eight, borderline (malignant) neoplasms; and three, carcinoma in situ lesions. The PPV of small pancreatic cysts for prediction of benignity was 870,6 (75 of 86 patients). Thirty-six patients had unilocular cysts (35 with benign lesions, one with borderline neoplasm). The PPV of urilocular cysts for prediction of benignity was 97% (35 of 36 patients). Fifty patients bad septated cysts; seven of these patients had borderline neoplasms, and three had carcinoma in situ lesions. For prediction of malignancy in small cysts, the PPV of septa was 20% (10 of 50 patients) I which was significantly higher than the 3% (one of 36 patients) PPV of unilocular cysts (P = .042). No significant changes in cyst morphologic features were seen in patients who were followed up with imaging for a mean period of 21.8 months. Conclusion: The majority (n = 75) of small pancreatic cysts were benign. Thirty-six cysts were unilocular, and virtually all of these (n = 35) were benign. The presence of septa was associated with borderline or in situ malignancy in 20% (10 of 50) of cases. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 17 TC 98 Z9 105 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2006 VL 238 IS 3 BP 912 EP 919 DI 10.1148/radiol.2382041806 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 014YW UT WOS:000235520100018 PM 16439566 ER PT J AU Blake, MA Slattery, JMA Kalra, MK Halpern, EF Fischman, AJ Mueller, PR Boland, GW AF Blake, MA Slattery, JMA Kalra, MK Halpern, EF Fischman, AJ Mueller, PR Boland, GW TI Adrenal lesions: Characterization with fused PET/CT image in patients with proved or suspected malignancy - initial experience SO RADIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; DELAYED ENHANCED CT; MASSES; BENIGN; ADENOMAS; TUMORS; INCIDENTALOMAS; F-18-FDG AB Purpose: To retrospectively evaluate the accuracy of the fused positron emission tomograpliie (PET)/computed tomographic (CT) image for characterization of adrenal lesions in patients who have proved malignancy or are suspected of having malignancy. Materials and Methods: Institutional review board approval was received for this retrospective HIPAA-compliant study, and informed consent was waived. Forty-one adrenal lesions in 38 patients (21 men, 17 women; mean age, 66 years; range, 37-86 years) were evaluated with PET/CT. Of the 41 lesions, nine were assumed to be malignant with documentation of enlargement (n = 8) or reduction in size in response to treatment (n = 1), and 32 were assumed to be benign with documentation of stability for 6 months (n = 31) or with confirmation with biopsy results (n = 1). The PET examination findings were positive when adrenal lesion maximum standardized uptake values (SUVs) exceeded hepatic maximum SUVs. CT contrast medium washout analysis was used to further characterize two lesions with PET findings positive for malignancy. The t test was used to assess significant (P < .05) differences between fluorine 18 fluorodeoxyglucose (FDG) uptake of benign lesions and that of malignant lesions. Results: At PET/CT, findings for all malignant lesions were positive (mean adrenal lesion-liver activity ratio, 4.04; range, 1.53-17.08). Of the 32 benign lesions, most (30 of 32) had activity less than that of the liver (mean ratio, 0.66; range, 0.22-6.94). PET/CT demonstrated sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 93.8%, 81.8%, 100%, and. 95.1%, respectively. Incorporating contrast material-enhanced CT with delayed imaging increased specificity to 100% because two lesions with PET findings positive for malignancy were characterized as benign. There was a significant difference between maximum SUV (P < .05) and the ratio of adrenal lesion-liver FDG activity (P < .001) in benign versus malignant adrenal lesions. Conclusion: PET/CT provides a powerful combination of functional and attenuation. information for adrenal lesion characterization. All malignant lesions were detected at PET/CT, with no false-negative results. (c) RSNIA, 2006. C1 Massachusetts Gen Hosp, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. Inst Technol Assessment, Boston, MA USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Div Abdominal & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 100 Z9 108 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2006 VL 238 IS 3 BP 970 EP 977 DI 10.1148/radio.2383042164 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 014YW UT WOS:000235520100025 PM 16505394 ER PT J AU Benacerraf, BR Shipp, TD Bromley, B AF Benacerraf, BR Shipp, TD Bromley, B TI Three-dimensional US of the fetus: Volume imaging SO RADIOLOGY LA English DT Article ID ULTRASOUND; FUTURE; FACE AB Purpose: To retrospectively compare the rapidity, efficiency, and accuracy of three-dimensional (3D) and two-dimensional (2D) ultrasonography (US) for complete anatomic survey in fetuses at 17-21 weeks of gestation. Materials and Methods: Institutional review board approval was obtained, in formed consent was waived, and the study was HIPAA compliant. Fifty consecutive women undergoing fetal anatomic survey at 17-21 weeks of gestation formed the study cohort. After standard 2D US was performed by one of eight sonographers, the same sonographer also obtained five 3D volumes to encompass the entire fetal anatomy. Three physicians interpreting the scans independently evaluated the completeness of the examination and time needed to read the scans, comparing the standard 2D method with the 3D volume reconstruction technique. The paired t test was used to compare biparietal diameter (BPD), femur length, and performance times between the 3D measurements and the 2D measurement. The t test was used to compare fetal anatomy according to volume angle. Differences were significant when P <.05. Results: Mean time to perform 2D US was 19.6 minutes per examination, whereas mean time to perform complete 3D volume acquisition was 1.8 minutes. Mean times needed to interpret 3D images and measure the BPD and femur were 5.53, 4.79, and 5.34 minutes for the three interpreting physicians. Compared with complete fetal surveys performed with 2D US, individual fetal anatomic landmarks (except for fetal arms and cavum septum pellucidum) were identified more than 94% of the tinie by using 3D US. Grouping anatomic views by region, the heart, head, extremities, and abdominal views were completely seen in 88%, 90%, 90%, and 95% of patients, respectively. No Insignificant difference was seen between the three physcians regarding completeness of the 3D examinations (P = .7). One fetus had multiple anomalies, with 3D volumes identified as abnormal by all three physicians. Overall, 74% of 3D BPD measurements were within 1 mm of the 2D measurements, and 64% of 3D femur measurements were within I mm of the 2D measurements. Conclusion: The standard fetal anatomic survey can be performed in less than 2 minutes with 3D volume US, and the volumes can be interpreted in 6-7 minutes, compared with a mean of 19.6 minutes to perform standard 2D US. (c) RSNA, 2006. C1 Brigham & Womens Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Assoc, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. EM bbsono@aol.com NR 10 TC 64 Z9 68 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2006 VL 238 IS 3 BP 988 EP 996 DI 10.1148/radiol.2383050636 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 014YW UT WOS:000235520100027 PM 16424249 ER PT J AU Bortfeld, T Trofimov, A Chan, T Martin, B AF Bortfeld, T Trofimov, A Chan, T Martin, B TI Can IMRT reduce margins? SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 3rd International Conference on Translational Research and Pre-Clinical Strategies in Radiation Oncology CY MAR 12-15, 2006 CL Lugano, SWITZERLAND SP European Sch Oncol, European Soc Radiotherapeut Radiol & Oncol, European Org Res & Treatment Canc, Amer Med Assoc, EACCME C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAR PY 2006 VL 78 SU 1 MA 5 BP S2 EP S2 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 043KD UT WOS:000237599000006 ER PT J AU Delaney, TF AF Delaney, TF TI Advanced-technology radiation therapy in the management of bone and soft tissue sarcomas SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 3rd International Conference on Translational Research and Pre-Clinical Strategies in Radiation Oncology CY MAR 12-15, 2006 CL Lugano, SWITZERLAND SP European Sch Oncol, European Soc Radiotherapeut Radiol & Oncol, European Org Res & Treatment Canc, Amer Med Assoc, EACCME C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAR PY 2006 VL 78 SU 1 MA 59 BP S21 EP S21 DI 10.1016/S0167-8140(06)80553-0 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 043KD UT WOS:000237599000058 ER PT J AU Kachnic, LA Willers, H Li, L Luo, CM Powell, SN AF Kachnic, LA Willers, H Li, L Luo, CM Powell, SN TI Exploiting the Fanconi anemia pathway in cancer therapy: Molecular targeting of upstream vs. downstream genes SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 3rd International Conference on Translational Research and Pre-Clinical Strategies in Radiation Oncology CY MAR 12-15, 2006 CL Lugano, SWITZERLAND SP European Sch Oncol, European Soc Radiotherapeut Radiol & Oncol, European Org Res & Treatment Canc, Amer Med Assoc, EACCME C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAR PY 2006 VL 78 SU 1 MA 214 BP S75 EP S75 DI 10.1016/S0167-8140(06)80691-2 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 043KD UT WOS:000237599000195 ER PT J AU Powell, SN Luo, CM Willers, H Kachnic, LA Taghian, AG AF Powell, SN Luo, CM Willers, H Kachnic, LA Taghian, AG TI Defining a BRCA1/BRCA2 dependent pathway of DNA repair in human breast cancer SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 3rd International Conference on Translational Research and Pre-Clinical Strategies in Radiation Oncology CY MAR 12-15, 2006 CL Lugano, SWITZERLAND SP European Sch Oncol, European Soc Radiotherapeut Radiol & Oncol, European Org Res & Treatment Canc, Amer Med Assoc, EACCME C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAR PY 2006 VL 78 SU 1 MA 32 BP S12 EP S12 DI 10.1016/S0167-8140(06)80526-8 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 043KD UT WOS:000237599000032 ER PT J AU Stelzner, M Chen, DC AF Stelzner, M Chen, DC TI To make a new intestinal mucosa SO REJUVENATION RESEARCH LA English DT Article; Proceedings Paper CT 2nd Conference on Strategies for Engineered Negligible Senescence (SENS) CY SEP, 2005 CL Cambridge, ENGLAND ID ENGINEERED SMALL-INTESTINE; EPITHELIAL ORGANOID UNITS; STEM-CELL TRANSPLANTATION; SMALL-BOWEL; TISSUE; NEOINTESTINE; NEOMUCOSA; SCAFFOLDS; MODEL AB A number of clinical conditions are caused by disorders affecting the mucosal lining of the gastrointestinal tract. Some patients suffer from a loss of mucosal surface area due to congenital defects or due to surgical resections ("short bowel syndrome"). Other patients have inborn or acquired defects of certain mucosal functions (e.g., glucose-galactose malabsorption, bile acid malabsorption). Many patients with these mucosal disorders could be more effectively treated if healthy mucosa were available in larger quantities as a replacement or functional supplement. We therefore developed methods to transplant mucosal stem cells from one part of the intestine to another and to make bioengineered intestinal mucosa. We generated an animal model of bile acid malabsorption using rats that underwent resection of the distal 25% of their small intestine (ileum). This resulted in significant losses of bile acids with the fecal excretions in these animals. We subsequently harvested ileal stem cell clusters from neonatal donors, removed the mucosa from a segment of proximal intestine (jejunum), and implanted the stem cell clusters into the debrided segment of jejunum. After four weeks, the animals had developed a functional "neomucosa." We inserted the "neo-ileal" segment into continuity as a substitute ileum. Postoperative measurements of fecal bile acid excretion showed that we were able to reverse the malabsorption syndrome in this model. This was the first reported neo-mucosa-based treatment of a malabsorption syndrome in vivo. We subsequently studied different biodegradable PGA and PLLA scaffoldings to generate bioengineered intestinal mucosa. We implanted these materials into omentum of rats and were able to identify a PGA/PLLA hybrid material on which engraftment rates of 36% of the available surface area could be achieved. Most recently, we developed a novel technique that permits direct observation of cell-biomaterial interactions after implantation into omentum or intestine in vivo. This method will help to optimize engraftment conditions for stem cell clusters on biomaterials. C1 Vet Adm Greater Los Angeles, Surg Serv 10H2, Los Angeles, CA 90073 USA. RP Stelzner, M (reprint author), Vet Adm Greater Los Angeles, Surg Serv 10H2, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Matthias.Stelzner@va.gov NR 16 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD SPR PY 2006 VL 9 IS 1 BP 20 EP 25 DI 10.1089/rej.2006.9.20 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 035OJ UT WOS:000237010600004 PM 16608391 ER PT J AU Tsai, AG Christie, JD Gaughan, CA Palma, WR Margolis, ML AF Tsai, AG Christie, JD Gaughan, CA Palma, WR Margolis, ML TI Change in forced expiratory time and spirometric performance during a single pulmonary function testing session SO RESPIRATORY CARE LA English DT Article DE pulmonary function test; forced expiratory time ID AIR-FLOW OBSTRUCTION; AIRWAYS OBSTRUCTION; BRONCHODILATOR; DISEASE; REVERSIBILITY; PARAMETERS; SELECTION; THERAPY; ASTHMA AB BACKGROUND: Among patients with obstructive lung disease, the correlation between clinical improvement and bronchodilator response is poor. Forced expiratory time (FET) may explain some discrepancy, but FET has received little attention. METHODS: We analyzed change in FET during the 3 initial satisfactory flow-volume loops in 102 consecutive patients, 37 with normal spirometry and 65 with airflow obstruction referred to a Veterans Administration pulmonary function testing (PFT) laboratory over 5 months. Patients included both PFT-naive and PFT-experienced individuals. We also evaluated the relationship between FET and spirometric performance (sum of forced expiratory volume in the first second and forced vital capacity) and the effect of inhaled bronchodilator on FET among patients with airflow obstruction. RESULTS: Normals and patients with airflow obstruction showed significant increments in FET and in spirometric performance during the 3 initial successive pre-bronchodilator attempts (p < 0.001 for both groups). This was true for PFT-naive and PFT-experienced individuals. There were significant associations between increments in FET and improvements in spirometric performance in all subgroups. After inhaled bronchodilator there was a further FET increment among patients with airflow obstruction (p = 0.009), but there was no significant difference between bronchodilator responders and nonresponders. CONCLUSIONS: Patients with normal pulmonary function and those with obstruction develop longer FET during the initial phases of spirometric testing, regardless of previous PFT experience. Longer FET is associated with better spirometric performance. Bronchodilator administration is associated with modest prolongation of FET, but change in FET did not help identify bronchodilator responders. C1 Hosp Univ Penn, Div Gen Internal Med, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Div Pulm, Philadelphia, PA 19104 USA. Hosp Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Pulm Funct Lab, Philadelphia, PA USA. RP Margolis, ML (reprint author), Philadelphia Vet Affairs Med Ctr, Div Pulm, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM mitchell.margolis@med.va.gov FU PHS HHS [2-T32-HP-010026] NR 24 TC 5 Z9 6 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD MAR PY 2006 VL 51 IS 3 BP 246 EP 251 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 020JT UT WOS:000235905600001 PM 16533413 ER PT J AU Lin, SKV Kuna, ST Bogen, DK AF Lin, SKV Kuna, ST Bogen, DK TI A novel device for measuring long-term oxygen therapy adherence: A preliminary validation SO RESPIRATORY CARE LA English DT Article DE adherence; compliance; monitor; long-term oxygen therapy ID SLEEP APNEA/HYPOPNEA SYNDROME; NASAL CPAP; CONCENTRATOR AB INTRODUCTION: Current methods for measuring patient adherence to long-term oxygen therapy fail to measure the actual amount of time the patient is inhaling oxygen and the pattern of oxygen use within the day. We have developed a novel oxygen-adherence monitor to address these limitations, and this report introduces the monitor and provides preliminary data validating its use. METHODS: This battery-powered monitor attaches to the oxygen source And detects respiratory-related pressure fluctuations transmitted through the nasal cannula. The monitor takes a measurement over a 25-second period, at 4-min intervals. It detects And stores data on 4 different states that describe,the patient's actual use of the oxygen source and nasal cannula: source-off/cannula-off, source-off/cannula-on, source-on/cannula-off, and source-on/cannula-on. We studied the monitor's performance with 10 patients with chronic obstructive pulmonary disease, during A directly-observed sequence of using and not using supplemental oxygen via nasal cannula, while sitting and walking. RESULTS: The monitor correctly detected 122 out of 129 measurements Among all participants, yielding a 95% detection accuracy. CONCLUSIONS A monitor that objectively measures oxygen inhalation, rather than. oxygen expenditure, may help improve the management of patients on long-term oxygen therapy. C1 Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Philadelphia, PA USA. Univ Penn, Ctr Sleep & Resp Neurobiol, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Lin, SKV (reprint author), Univ Penn, Dept Bioengn, 120 Hayden Hall,3320 Smith Walk, Philadelphia, PA 19104 USA. EM sunkai.lin@gmail.com NR 19 TC 1 Z9 2 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD MAR PY 2006 VL 51 IS 3 BP 266 EP 271 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 020JT UT WOS:000235905600004 PM 16533416 ER PT J AU Caplan, B Schutt, RK Turner, WM Goldfinger, SM Seidman, LJ AF Caplan, B Schutt, RK Turner, WM Goldfinger, SM Seidman, LJ TI Change in neurocognition by housing type and substance abuse among formerly homeless seriously mentally ill persons SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; cognition; executive function; homeless; housing; environment ID CARD SORTING TEST; CONTINUOUS PERFORMANCE-TEST; SCHIZOPHRENIC-PATIENTS; COGNITIVE FUNCTION; ILLNESS; INTERVENTIONS; INDIVIDUALS; DYSFUNCTION; DEMENTIA; DEFICITS AB Objective: To test the effect of living in group housing rather than independent apartments on executive functioning, verbal memory and sustained attention among formerly homeless persons with serious mental illness and to determine whether substance abuse modifies this effect. Method: In metropolitan Boston, 112 persons in Department of Mental Health shelters were randomly assigned to group homes ("Evolving Consumer Households", with project facilitator, group meetings, resident decision-making) or independent apartments. All were case managed. A neuropsychological test battery was administered at baseline, at 18 months (Time 2), with an 81% follow-up rate, and at 48 months (Time 3), with a 59% follow-up rate. Hierarchical Linear Modeling was applied to executive functioning-assessed with the Wisconsin Card Sorting Test (Perseverations)-Logical Memory story recall, and an auditory Continuous Performance Test (CPT) for sustained attention. Subject characteristics were controlled. Results: When moved to group homes, subjects without a lifetime substance abuse history improved on Perseverations, while those who moved to independent apartments deteriorated on Perseverations. Across the two housing conditions, subjects showed no change in Perseverations, but improved oil Logical Memory story recall and the CPT. Conclusions: Type of housing placement can influence cognitive functioning; notably, socially isolating housing is associated with weakened executive functioning. Substance abuse significantly diminishes environmental effects. These are important factors to consider in housing placement and subsequent treatment. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Commonwealth Res Ctr,Sch Med,De, Boston, MA 02130 USA. Univ Massachusetts, Dept Sociol, Boston, MA 02125 USA. Univ Maine, Sch Social Work, Orono, ME USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Caplan, B (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div,Commonwealth Res Ctr,Sch Med,De, 170 Morton St, Boston, MA 02130 USA. EM BCaplan@bidmc.harvard.edu FU NIMH NIH HHS [R18MH4808001] NR 41 TC 17 Z9 17 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 2006 VL 83 IS 1 BP 77 EP 86 DI 10.1016/j.schres.2005.11.013 PG 10 WC Psychiatry SC Psychiatry GA 032QI UT WOS:000236789000008 PM 16504484 ER PT J AU Vidal, M AF Vidal, M TI Time for a human interactome project? SO SCIENTIST LA English DT Article ID PROTEIN INTERACTION NETWORK AB With only about 1% of the human interactome mapped, and perhaps 10% for model organisms,a Human Interactome Mapping Project modeled on the Human Genome Project has been proposed. The mapping project could cost anywhere between $100 million to$1 billion, depending on the desired level of quality. C1 Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Vidal, M (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM mvidal@the-scientist.com NR 6 TC 1 Z9 2 U1 0 U2 1 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD MAR PY 2006 VL 20 IS 3 BP 46 EP + PG 4 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 016QE UT WOS:000235634200028 ER PT J AU Palevsky, PM AF Palevsky, PM TI Dialysis modality and dosing strategy in acute renal failure SO SEMINARS IN DIALYSIS LA English DT Article ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; CONTINUOUS ARTERIOVENOUS HEMODIAFILTRATION; CONTINUOUS VENOVENOUS HEMOFILTRATION; REPLACEMENT THERAPY; PROPHYLACTIC DIALYSIS; REQUIRING DIALYSIS; RANDOMIZED-TRIAL; INTERMITTENT; HEMODIALYSIS AB Many fundamental aspects of the management of renal replacement therapy (RRT) in acute renal failure (ARF) remain unresolved. While data from multiple studies support the initiation of RRT, in the absence of other indications, when the BUN has reached a level of approximately 90-100 mg/dl, there are conflicting data regarding the benefit of earlier initiation of renal support. The relative efficacy of the various RRT modalities is uncertain. Despite growing utilization, a survival benefit or greater recovery of renal function has not been demonstrated for continuous renal replacement therapy (CRRT) as compared to conventional intermittent hemodialysis (IHD). Optimal dosing strategies are also poorly defined. While there is increasing evidence that more intensive renal support is associated with better outcomes in ARF, an optimal Kt/V-urea and treatment frequency for IHD remain to be established. Similarly, although data suggest that continuous venovenous hemofiltration (CVVH) should be dosed at no less than 35 ml/kg/hr (postdilution), confirmation of this dosing strategy and validation for other modalities of CRRT are required. C1 VA Pittsburgh Healthcare Syst, Univ Dr Div, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr Div, Renal Sect, Room 7E123 111F-U, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 55 TC 20 Z9 22 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR-APR PY 2006 VL 19 IS 2 BP 165 EP 170 DI 10.1111/j.1525-139X.2006.00144.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 017ME UT WOS:000235696900014 PM 16551296 ER PT J AU Cambria, RP AF Cambria, Richard P. TI Endovascular stent graft repair in the thoracic aorta - Overview SO SEMINARS IN VASCULAR SURGERY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0895-7967 J9 SEMIN VASC SURG JI Semin. Vasc. Surg. PD MAR PY 2006 VL 19 IS 1 BP 1 EP 2 DI 10.1053/j.semvascsurg.2005.11.009 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 108KY UT WOS:000242239900001 ER PT J AU Black, JH Cambria, RP AF Black, James H., II Cambria, Richard P. TI Contemporary results of open surgical repair of descending thoracic aortic aneurysms SO SEMINARS IN VASCULAR SURGERY LA English DT Article ID CEREBROSPINAL-FLUID DRAINAGE; SPINAL-CORD PROTECTION; NATURAL-HISTORY; PARAPLEGIA; EXPERIENCE; SURGERY; RISK; OPERATIONS; MORTALITY; TRIAL AB Considerable progress has been made in the refinement of operative strategies to repair,descending thoracic aortic aneurysms (TAN. While no single strategy has totally eliminated the postoperative morbidities of renovisceral and spinal cord ischemic complications, contemporary reports from centers of excellence detail admirable rates of overall risk in the 5-10% range. Balancing these risks represents a clinical dilemma for the aortic surgeon and a thoughtful, logical risk analysis of the individual patient presentation is clearly warranted before TAA repair. In this article, we review surgical approaches to TAA and adjunctive methods, examine the reports from centers of excellence, and elucidate the challenges yet to be overcome in the management of patients with aneurysms of the descending thoracic aorta. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, WACC 458 15 Parkman St, Boston, MA 02114 USA. NR 34 TC 11 Z9 12 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 0895-7967 J9 SEMIN VASC SURG JI Semin. Vasc. Surg. PD MAR PY 2006 VL 19 IS 1 BP 11 EP 17 DI 10.1053/j.semvascsurg.2005.11.005 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 108KY UT WOS:000242239900003 PM 16533687 ER PT J AU Kwolek, CJ Fairman, R AF Kwolek, Christopher J. Fairman, Ronald TI Update on thoracic aortic endovascular grafting using the Medtronic Talent device SO SEMINARS IN VASCULAR SURGERY LA English DT Article ID ANEURYSM REPAIR; STENT-GRAFTS; FOLLOW-UP; EXPERIENCE; MANAGEMENT; DISSECTION; PLACEMENT; ARCH AB This article provides a brief update on the current status of the treatment of thoracic aortic pathology using the Medtronic Talent device. Preoperative evaluation and selection criterion along with study design are described for the recently completed Phase II VALOR Trial (Evaluation of the Medtronic AVE Talent Thoracic Stent Graft System for the Treatment of Thoracic Aneurysms). In addition, the results of several recent series for the treatment of degenerative aneurysm and more complex aortic pathology such as transection, rupture and acute and chronic dissection are reviewed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. RP Kwolek, CJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc & Endovasc Surg, WAC-458,15 Parkman St, Boston, MA 02114 USA. EM ckwolek@partners.org NR 22 TC 13 Z9 14 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 0895-7967 J9 SEMIN VASC SURG JI Semin. Vasc. Surg. PD MAR PY 2006 VL 19 IS 1 BP 25 EP 31 DI 10.1053/j.semvascsurg.2005.11.002 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 108KY UT WOS:000242239900005 PM 16533689 ER PT J AU Kushida, CA Littner, MR Hirshkowitz, M Morgenthaler, TI Alessi, CA Bailey, D Boehlecke, B Brown, TM Coleman, J Friedman, L Kapen, S Kapur, VK Kramer, M Lee-Chiong, T Owens, J Pancer, JP Swick, TJ Wise, MS AF Kushida, Clete A. Littner, Michael R. Hirshkowitz, Max Morgenthaler, Timothy I. Alessi, Cathy A. Bailey, Dennis Boehlecke, Brian Brown, Terry M. Coleman, Jack, Jr. Friedman, Leah Kapen, Sheldon Kapur, Vishesh K. Kramer, Milton Lee-Chiong, Teofilo Owens, Judith Pancer, Jeffrey P. Swick, Todd J. Wise, Merrill S. TI Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders SO SLEEP LA English DT Article DE sleep related breathing disorder; obstructive sleep apnea; continuous positive airway pressure; CPAP; sleep-disordered breathing; bilevel positive airway pressure; BPAP ID LONG-TERM COMPLIANCE; PLACEBO-CONTROLLED TRIAL; APNEA-HYPOPNEA SYNDROME; NOCTURNAL NASAL VENTILATION; SPLIT-NIGHT POLYSOMNOGRAPHY; PROSPECTIVE PARALLEL TRIAL; AMBULATORY BLOOD-PRESSURE; APNEA/HYPOPNEA SYNDROME; CPAP THERAPY; APNOEA/HYPOPNOEA SYNDROME AB Positive airway pressure (PAP) devices are used to treat patients with sleep related breathing disorders (SRBD) including obstructive sleep apnea (OSA). Currently, PAP devices come in three forms: (1) continuous positive airway pressure (CPAP), (2) bilevel positive airway pressure (BPAP), and (3) automatic self-adjusting positive airway pressure (APAP). After a patient is diagnosed with OSA, the current standard of practice involves performing full, attended polysomnography during which positive pressure is adjusted to determine optimal pressure for maintaining airway patency. This titration is used to find a fixed single pressure for subsequent nightly usage. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Standards of Practice Committee developed these practice parameters as a guideline for using CPAP and BPAP appropriately (an earlier review and practice parameters for APAP was published in 2002). Major conclusions and current recommendations are as follows: 1) A diagnosis of OSA must be established by an acceptable method. 2) CPAP is effective for treating OSA. 3) Full-night, attended studies performed in the laboratory are the preferred approach for titration to determine optimal pressure; however, split-night, diagnostic-titration studies are usually adequate. 4) CPAP usage should be monitored objectively to help assure utilization. 5) Initial CPAP follow-up is recommended during the first few weeks to establish utilization pattern and provide remediation if needed. 6) Longer-term follow-up is recommended yearly or as needed to address mask, machine, or usage problems. 7) Heated humidification and a systematic educational program are recommended to improve CPAP utilization.8) Some functional outcomes such as subjective sleepiness improve with positive pressure treatment in patients with OSA. 9) CPAP and BPAP therapy are safe; side effects and adverse events are mainly minor and reversible. 10) BPAP may be useful in treating some forms of restrictive lung disease or hypoventilation syndromes associated with hypercapnia. C1 Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Sepulveda, CA USA. Baylor Coll Med, Houston, TX USA. VA Med Ctr, Houston, TX USA. Mayo Clin, Mayo Sleep Disorders Ctr, Rochester, MN USA. Univ Calif Los Angeles, Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ N Carolina, Chapel Hill, NC USA. St Joseph Mem Hosp, Murphysboro, IL USA. Middle Tennessee ENT, Murfreesboro, TN USA. Stanford Univ, Sch Med, Stanford, CA USA. VA Med Ctr, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Univ Washington, Sleep Disorder Ctr, Seattle, WA USA. Maimoides Med Ctr, Psychiat Dept, Brooklyn, NY USA. NYU, Sch Med, New York, NY USA. Sleep Clin, Natl Jewish Med & Res Ctr, Denver, CO USA. Rhode Isl Hosp, Dept Pediat, Providence, RI USA. RP Kushida, CA (reprint author), Stanford Sleep Disorders Clin, 401 Quarry Rd,Suite 3301, Stanford, CA 94305 USA. EM clete@stanford.edu RI Kapur, Vishesh/K-1054-2014; OI Kapur, Vishesh/0000-0002-5417-1097; Morgenthaler, Timothy/0000-0002-2614-3793 NR 94 TC 266 Z9 273 U1 2 U2 9 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAR 1 PY 2006 VL 29 IS 3 BP 375 EP 380 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 078SL UT WOS:000240123600014 PM 16553024 ER PT J AU Lewis, MA McBride, CM Pollak, KI Puleo, E Butterfield, RM Emmons, KM AF Lewis, MA McBride, CM Pollak, KI Puleo, E Butterfield, RM Emmons, KM TI Understanding health behavior change among couples: An interdependence and communal coping approach SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE couple health behavior change; communal coping; interdependence theory ID MARITAL-STATUS; SOCIAL-CONTROL; RISK-FACTOR; QUALITY; PERSPECTIVE; MORTALITY; MARRIAGE; PATIENT; SURVIVAL; SMOKING AB Marriage is a ubiquitous social status that consistently is linked to health. Despite this, there has been very little theory development or related research on the extent to which couple members are jointly motivated to and actively engage in health-enhancing behaviors. In this paper we propose an integrative model, based on interdependence theory and communal coping perspectives, that explicitly considers dyadic processes as determinants of couple behavior. Our integrated model applies these constructs to consider how couple dynamics might influence adoption of risk-reducing health habits. Accordingly, we suggest that the couple's interdependence can transform motivation from doing what is in the best interest of the self (person-centered), to doing even selfless actions that are best for the continuation of the relationship (relationship-centered). In turn, this transformation can lead to enhanced motivation for the couple to cope communally or act cooperatively in adopting health-enhancing behavior change. Implications for research related to couples and health behavior change are also highlighted. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ N Carolina, Chapel Hill, NC 27599 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ Massachusetts, Amherst, MA 01003 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Lewis, MA (reprint author), Univ N Carolina, Chapel Hill, NC 27599 USA. EM megan.lewis@unc.edu; cmcbride@mail.nih.gov; polla007@mc.duke.edu; epuleo@schoolph.umass.edu; rita828@earthlink.net; karen_m_emmons@dfci.harvard.edu FU NCI NIH HHS [R01CA76945, R01CA74000] NR 68 TC 147 Z9 147 U1 3 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAR PY 2006 VL 62 IS 6 BP 1369 EP 1380 DI 10.1016/j.socscimed.2005.08.006 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 028NA UT WOS:000236493400007 PM 16146666 ER PT J AU Hung, KE Chung, DC AF Hung, Kenneth E. Chung, Daniel C. TI Colorectal cancer screening: Today and tomorrow SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE colorectal cancer; screening; colonoscopy ID FECAL-OCCULT-BLOOD; CONTRAST BARIUM ENEMA; ASYMPTOMATIC ADULTS; SURVEILLANCE COLONOSCOPY; NEGATIVE COLONOSCOPY; ADENOMATOUS POLYPS; PROTEOMIC PATTERNS; RISK; SIGMOIDOSCOPY; POPULATION AB Colorectal cancer remains a disease with significant morbidity and mortality. However, the prognosis can be greatly improved with early detection. Here, we review the current screening modalities and guidelines for patients at average, moderate, and high risk for colorectal cancer. New experimental modalities are also introduced. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. RP Hung, KE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. EM chung.daniel@mgh.harvard.edu NR 50 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD MAR PY 2006 VL 99 IS 3 BP 240 EP 248 DI 10.1097/01.smj.0000203817.89741.29 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 095NQ UT WOS:000241315000014 PM 16553098 ER PT J AU Miyake, N Brun, ACM Magnusson, M Miyake, K Scadden, DT Karlsson, S AF Miyake, Noriko Brun, Ann C. M. Magnusson, Mattias Miyake, Koichi Scadden, David T. Karlsson, Stefan TI HOXB4-induced self-renewal of hematopoietic stem cells is significantly enhanced by p21 deficiency SO STEM CELLS LA English DT Article DE hematopoiesis; HOXB4 p21; stem cell expansion ID NOD/SCID-REPOPULATING CELLS; BONE-MARROW-CELLS; VECTOR-MEDIATED EXPRESSION; BLOOD CD34(+) CELLS; EX-VIVO EXPANSION; IN-VIVO; GENE-THERAPY; QUANTITATIVE ASSAY; TRANSDUCED CELL; HOMEOBOX GENES AB Enforced expression of the HOXB4 transcription factor and downregulation of p21(Cip1/Waf) (p21) can each independently increase proliferation of murine hematopoietic stem cells (HSCs). We asked whether the increase in HSC self-renewal generated by overexpression of HOXB4 is enhanced in p21-deficient HSCs. HOXB4 was overexpressed in hematopoietic cells from wild-type (wt) and p21(-/-) mice. Bone marrow (BM) cells were transduced with a retroviral vector expressing HOXB4 together with GFP (MIGB4), or a control vector containing GFP alone (MIG) and maintained in liquid culture for up to 11 days. At day 11 of the expansion culture, the number of primary CFU-GM (colony-forming unit granulocyte-macrophage) colonies and the repopulating ability were significantly increased in MIGB4 p21(-/-) BM (p21B4) cells compared with MIGB4-transduced wt BM (wtB4) cells. To test proliferation of HSCs in vivo, we performed competitive repopulation experiments and obtained significantly higher long-term engraftment of expanded p21B4 cells compared with wtB4 cells. The 5-day expansion of p21B4 HSCs generated 100-fold higher numbers of competitive repopulating units compared with wtMIG and threefold higher numbers compared with wtB4. The findings demonstrate that increased expression of HOXB4, in combination with suppression of p21 expression, could be a useful strategy for effective and robust expansion of HSCs. C1 Univ Lund Hosp, Lund Strateg Ctr Stem Cell Biol & Cell Therapy, S-22184 Lund, Sweden. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol,AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02115 USA. RP Brun, ACM (reprint author), Univ Lund Hosp, Lund Strateg Ctr Stem Cell Biol & Cell Therapy, BMC A12, S-22184 Lund, Sweden. EM ann.brun@med.lu.se NR 53 TC 25 Z9 35 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAR PY 2006 VL 24 IS 3 BP 653 EP 661 DI 10.1634/stemcells.2005-0328 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085WX UT WOS:000240636200020 PM 16210402 ER PT J AU Randolph, GW Kamani, D AF Randolph, GW Kamani, D TI The importance of preoperative laryngoscopy in patients undergoing thyroidectomy: Voice, vocal cord function, and the preoperative detection of invasive thyroid malignancy SO SURGERY LA English DT Article ID RECURRENT LARYNGEAL NERVE; CARCINOMA; CANCER; MANAGEMENT; PARALYSIS; AIRWAY AB Background. Vocal cord paralysis is associated with extrathyroidal invasive malignancy. This study was performed to analyze the presentation of Patients with invasive thyroid malignancy and to determine the preoperative symptomatic and radiographic correlates of vocal cord paralysis. Methods. In a group of 365 consecutive patients undergoing thyroidectomy, the group of 21 patients with invasive thyroid malignancy was compared with the 344 patients who had benign thyroid disease or noninvasive cancers. Results. Preoperative recurrent laryngeal nerve paralysis was a robust marker for invasive thyroid malignancy, being present in 70 % of patients with invasive disease and only 0.3 % of patients with noninvasive disease. Vocal cord paralysis was associated with voice change in only one third of Patients. Preoperative computed tomography was read as positive for vocal cord paralysis in only 25 % of patients. Conclusions. Laryngoscopic examination is essential for the detection Of vocal cord paralysis preoperatively. Symptomatic voice assessment and radiographic evaluation are insufficient. Preoperative vocal cord paralysis tracts with invasive disease and facilitates Preoperative recognition, of disease extent, allowing for appropriate operative planning and central neck clearance at first operation. Because of the prevalence (approximately 6 % in our study) of invasive thyroid disease, the importance of Preoperative diagnosis of invasive disease in operative planning and patient counseling, and the importance of vocal cord functional analysis in recurrent laryngeal nerve management algorithms for nerves found infiltrated at operation, and laryngoscopic examination is recommended for all patients undergoing thyroid operation. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Surg Oncol, Endocrine Surg Serv, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu NR 24 TC 71 Z9 74 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2006 VL 139 IS 3 BP 357 EP 362 DI 10.1016/j.surg.2005.08.009 PG 6 WC Surgery SC Surgery GA 028MB UT WOS:000236490500012 PM 16546500 ER PT J AU Lin, T Alam, HB Chen, HZ Britten-Webb, J Rhee, P Kirkpatrick, J Koustova, E AF Lin, T Alam, HB Chen, HZ Britten-Webb, J Rhee, P Kirkpatrick, J Koustova, E TI Cardiac histones are substrates of histone deacetylase activity in hemorrhagic shock and resuscitation SO SURGERY LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-12, 2005 CL Nashville, TN SP Soc Univ Surg ID GENE-EXPRESSION; ACETYLATION; INHIBITORS; CHROMATIN; TRANSCRIPTION; TRAUMA; CANCER AB Background. DIVA transcription is regulated, in Part, by acetylation of nuclear histomes that are, controlled by 2 groups of enzymes: histone deacetylases (HDAC) and histone acetyl transferases (HAT). Whether an imbalance in HDAC/HAT system plays a role in hemorrhage/resuscitation is unknown. The goals of this study were to determine whether hemorrhage results in deacetylation of cardiac histones and whether this can be corrected through the application of different resuscitation strategies or specific HDAC inhibitors. Methods. In the first experiment, rats (n = 6 per group) were subjected to volume-controlled hemorrhage and resuscitated with racemic lactated Ringer's solution, L-lactated Ringer's solution, 7.5 % hypertonic saline solution, ketone Ringer's solution, and pyruvate Ringer's solution. Control groups included no hemorrhage (sham) and hemorrhage with no resuscitation. In the second experiment (n = 5 Per group), 3 HDAC inhibitors (valproic acid, trichostatin A. and suberoylanilide hydroxamic acid) were added to saline solution resuscitation. Heart tissue was collected at the end of resuscitation. Isolated subcellular protein fractions were used in Western, blotting to analyze the patterns of total protein acetylation and histone acetylation specifically. HDAC and HAT activity was measured in tissue extracts. Results. Hemorrhage led to partial histone deacetylazion. Resuscitation resulted in protein hyper-acetylation in nuclear fractions only. A detailed analysis of histones (on 10 acelylation sites) revealed that ketone Ringers solution hyperacetylated histones H2B, H3, and H4. The addition of suberoylanilide hydroxamic acid hyperacetylated histones more effectively than other resuscitation strategies, presumably by direct inhibition of HDAC activity. Conclusion. Hemorrhage/resuscitation is associated with HDAC/HAT activity misbalance, and the acetylation status of cardiac histones is influenced by the choice of resuscitation strategy. Shock-induced changes can be reversed through the infusion, of pharmacologic HDAC inhibitor, even when it is administered after the insult for a limited period of time. C1 Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. RP Alam, HB (reprint author), Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, Sch Med, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 27 TC 37 Z9 40 U1 0 U2 6 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2006 VL 139 IS 3 BP 365 EP 376 DI 10.1016/j.surg.2005.08.022 PG 12 WC Surgery SC Surgery GA 028MB UT WOS:000236490500014 PM 16546502 ER PT J AU Kim, CY O'Rourke, RW Chang, EY Jobe, BA AF Kim, Charles Y. O'Rourke, Robert W. Chang, Eugene Y. Jobe, Blair A. TI Unsedated small-caliber upper endoscopy: An emerging diagnostic and therapeutic technology SO SURGICAL INNOVATION LA English DT Article DE small-caliber endoscopy; transnasal evaluation; diagnostic upper endoscopy ID ESOPHAGOGASTRODUODENOSCOPY EGD; CONVENTIONAL EGD; TRANSNASAL ESOPHAGOGASTRODUODENOSCOPY; GASTROINTESTINAL ENDOSCOPY; RANDOMIZED-TRIAL; ESOPHAGOSCOPY; PLACEMENT; TOLERANCE; SEDATION; RATES AB Although conventional esophagogastroduodenoscopy has become widespread in its applications and availability, it is constrained by the requirement for patient sedation. This requirement contributes to morbidity, time lost from work, and additional resource utilization in personnel and facilities. Small-caliber endoscopy is an emerging technology that enables transnasal evaluation of the upper gastrointestinal tract in a unsedated patient. This procedure can be performed in a wider range of settings, including the clinic setting where a dedicated conscious sedation suite is not available and can be incorporated into the office visit. The applications of small-caliber endoscopy include general diagnostic upper endoscopy, screening and surveillance of Barrett esophagus, and intraoperative diagnostics or postoperative evaluation of the upper gastrointestinal tract. Therapeutic applications include the placement of nasoduodenal feeding tubes, esophageal pH catheters, and impedance catheters. When used in the sedated patient, small-caliber endoscopy can also facilitate esophageal stricture dilation and transnasal placement of a percutaneous endoscopic gastrostomy tube. This review discusses the techniques, equipment, and applications of small-caliber endoscopy of the upper gastrointestinal tract. C1 Portland VA Med Ctr, Surg Serv P3GS, Dept Surg, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. RP Jobe, BA (reprint author), Portland VA Med Ctr, Surg Serv P3GS, Dept Surg, POB 1034, Portland, OR 97207 USA. EM jobeb@ohsu.edu FU NCI NIH HHS [R03 CA105959-01]; NIDDK NIH HHS [K23 DK066165-01] NR 22 TC 11 Z9 12 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1553-3506 J9 SURG INNOV JI Surg. Innov. PD MAR PY 2006 VL 13 IS 1 BP 31 EP 39 DI 10.1177/155335060601300106 PG 9 WC Surgery SC Surgery GA 148ZH UT WOS:000245115400006 PM 16708153 ER PT J AU Tarui, T Akakura, N Majumdar, M Andronicos, N Takagi, J Mazar, AP Bdeir, K Kuo, A Yarovoi, SV Cines, DB Takada, Y AF Tarui, T Akakura, N Majumdar, M Andronicos, N Takagi, J Mazar, AP Bdeir, K Kuo, A Yarovoi, SV Cines, DB Takada, Y TI Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE adhesion receptors/integrins; adhesion molecules; cell migration; angiogenesis and inhibitors; plasminogen activators ID PLATELET GLYCOPROTEIN-IIB/IIIA; MURINE MONOCLONAL-ANTIBODY; CELL-ADHESION; DIFFERENTIAL REGULATION; ENDOTHELIAL-CELLS; IN-VITRO; RECEPTOR; MIGRATION; BINDING; GROWTH AB It has been questioned whether there are receptors for urokinase-type plasminogen activator (uPA) that facilitate plasminogen activation other than the high affinity uPA receptor (uPAR/CD87) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation. uPA also promotes cell adhesion, chemotaxis, and proliferation besides plasminogen activation. These uPA-induced signaling events are not mediated by uPAR, but mediated by unidentified, lower-affinity receptors for the uPA kringle. We found that uPA binds specifically to integrin alpha v beta 3 on CHO cells depleted of uPAR. The binding of uPA to alpha v beta 3 required the uPA kringle domain. The isolated uPA kringle domain binds specifically to purified, recombinant soluble, and cell surface alpha v beta 3, and other integrins (alpha 4 beta 1 and alpha 9 beta 1), and induced migration of CHO cells in an alpha v beta 3-dependent manner. The binding of the uPA kringle to alpha v beta 3 and uPA kringle-induced alpha v beta 3-dependent cell migration were blocked by homologous plasminogen kringles 1-3 or 1-4 (angiostatin), a known integrin antagonist. We studied whether the binding of uPA to integrin alpha v beta 3 through the kringle domain plays a role in plasminogen activation. On CHO cell depleted of uPAR, uPA enhanced plasminogen activation in a kringle and alpha v beta 3-depenclent manner. Endothelial cells bound to and migrated on uPA and uPA kringle in an alpha v beta 3-dependent manner. These results suggest that uPA binding to integrins through the kringle domain plays an important role in both plasminogen activation and uPA-induced intracellular signaling. The uPA kringle-integrin interaction may represent a novel therapeutic target for cancer, inflammation, and vascular remodeling. C1 Univ Calif Davis, Med Ctr, Dept Dermatol, Sacramento, CA 95817 USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Attenuon LLC, San Diego, CA USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Dept Lab Med, Philadelphia, PA 19104 USA. RP Takada, Y (reprint author), Univ Calif Davis, Med Ctr, Dept Dermatol, Res 3,Suite 3300,4645 2nd Ave, Sacramento, CA 95817 USA. EM ytakada@ucdavis.edu OI takada, yoshikazu/0000-0001-5481-9589 FU NHLBI NIH HHS [HL60169]; NIGMS NIH HHS [GM47157] NR 50 TC 51 Z9 54 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAR PY 2006 VL 95 IS 3 BP 524 EP 534 DI 10.1160/TH05-06-0457 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 023QR UT WOS:000236141800019 PM 16525582 ER PT J AU Sugimachi, K Roach, KL Rhoads, DB Tompkins, RG Toner, M AF Sugimachi, K Roach, KL Rhoads, DB Tompkins, RG Toner, M TI Nonmetabolizable glucose compounds impart cryotolerance to primary rat hepatocytes SO TISSUE ENGINEERING LA English DT Article ID FREEZE-TOLERANT FROG; SANDWICH CONFIGURATION; LIVER REPOPULATION; MAMMALIAN-CELLS; TREHALOSE; EXPRESSION; METABOLISM; CRYOPRESERVATION; TRANSPORTER; GLUT1 AB We herein report a novel method for the cryopreservation of hepatocytes using a non-metabolizable glucose derivative in an attempt to mimic the natural cryoprotective adaptations observed in freeze-tolerant frogs. Primary rat hepatocytes were loaded with 3-O-methyl glucose (3OMG) through endogenous glucose transporters without evident toxicity. The 3OMG-loaded hepatocytes were then frozen in a controlled rate freezer down to -80 degrees C and stored in liquid nitrogen at -196 degrees C. Hepatocytes cryopreserved with a relatively small amount of intracellular 3OMG ( < 0.2 M) showed high post-thaw viability and maintained long-term hepatospecific functions, including synthesis, metabolism, and detoxification. Metabolite uptake and secretion rates were also largely preserved in the cryopreserved hepatocytes. This is the first study to demonstrate the use of the non-metabolizable glucose derivative 3OMG in hepatocyte cryopreservation. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Engn Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Endocrine Unit, Boston, MA USA. RP Toner, M (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@sbi.org FU NIDDK NIH HHS [DK46270] NR 41 TC 14 Z9 15 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD MAR PY 2006 VL 12 IS 3 BP 579 EP 588 DI 10.1089/ten.2006.12.579 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 027GB UT WOS:000236401300016 PM 16579691 ER PT J AU Valeri, CR Dennis, RC Ragno, G MacGregor, H Menzoian, JO Khuri, SF AF Valeri, CR Dennis, RC Ragno, G MacGregor, H Menzoian, JO Khuri, SF TI Limitations of the hematocrit level to assess the need for red blood cell transfusion in hypovolemic anemic patients SO TRANSFUSION LA English DT Article ID VOLUME; BIOTIN; ERYTHROCYTES; OPERATIONS; MEDICINE; BABOON; PLASMA AB BACKGROUND: The transfusion trigger that physicians use to determine whether a patient requires a red blood cell (RBC) transfusion is the peripheral venous hematocrit (Hct) value. Although this measurement is an indicator of the concentration of RBCs in the blood, it does not reveal the RBC volume, plasma volume, or total blood volume, nor does it give any indication of whether the patient is hypovolemic, normovolemic, or hypervolemic. STUDY DESIGN AND METHODS: Two patient populations were studied: 41 consecutive patients subjected to elective vascular surgery and 20 consecutive patients subjected to cardiopulmonary bypass surgery. The RBC volume was measured with Cr-51- or Tc-99m-labeled autologous fresh RBCs, and the plasma volume and total blood volume were estimated from the measured RBC volume and the total body Hct level. Measurements made 1 to 2 and 24 hours after surgery were compared to the preoperative values for these two groups of patients. RESULTS: During the 24-hour postoperative period, the RBC, plasma, and total blood volumes were reduced compared to the preoperative volumes. These patients were hypovolemic and anemic, and their Hct values during the 24-hour postoperative period were increased by a mean of 4 to 5 volume-percent compared to values that would be expected if they were normvolemic and anemic. CONCLUSIONS: The Hct values in hypovolemic anemic patients are elevated because the plasma volume does not increase to achieve the normovolemic anemic state. C1 Naval Blood Res Lab, Plymouth, MA 02360 USA. Boston VA Healthcare Syst, W Roxbury Div, Dept Surg, Boston, MA USA. Boston Med Ctr, Dept Vasc Surg, Boston, MA USA. RP Valeri, CR (reprint author), Naval Blood Res Lab, 195 Bournehurst Dr, Plymouth, MA 02360 USA. EM navblood@nbrl.org NR 19 TC 29 Z9 31 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2006 VL 46 IS 3 BP 365 EP 371 DI 10.1111/j.15.7-2995.2006.00730.x PG 7 WC Hematology SC Hematology GA 016ZA UT WOS:000235662500010 PM 16533277 ER PT J AU Mertz, KD Tchinda, J Kufer, R Moller, P Rubin, MA Moch, H Perner, S AF Mertz, KD Tchinda, J Kufer, R Moller, P Rubin, MA Moch, H Perner, S TI Cytogenetic alterations in renal tumors. Applications for comparative genomic hybridization and fluorescence in situ hybridization SO UROLOGE LA German DT Article DE comparative genomic hybridization (CGH); fluorescence in situ hybridization (FISH); renal cell carcinoma; cytogenetics; chromosome ID CELL CARCINOMA; TRANSLOCATION; CHROMOSOME-17; GENE; ONCOCYTOMAS; IMBALANCES; CANCER; FUSES AB The WHO classification of renal cell carcinomas (RCC) takes into account chromosomal alterations. New cytogenetic techniques such as comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) offer alternative methods to the classic cytogenetic banding technique. Clear cell (classic) RCC frequently show the loss of 3p. Papillary RCC are characterized by trisomies and tetrasomies as well as loss of the Y chromosome. CGH analysis demonstrates that DNA copy increase is more common in type I papillary RCC compared to type II. Chromophobe RCC are characterized by losses in chromosomes 1, 2,6,10,13,17, and 21. Oncocytomas can be divided into cases with rearrangements in the 11 q 13 region and those with loss of chromosome 1 and the sex chromosomes. Translocations involving chromosome 3, such as t(3;8)(p14;q24.13) and t(2;3)(q35;q21) have been described in familial clear cell RCC. The most recent class of RCC, seen only in men, is referred to as translocation tumors. These tumors demonstrate a tubulopapillary growth pattern and have a t(X;1)(p11.2;q21.2) translocation. Although not required for most clinical diagnoses, CGH and FISH complement the standard histologic diagnosis of RCC and may provide a definitive diagnosis in a small number of challenging cases. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Ulm Klinikum, Urol Abt, Ulm, Germany. Univ Ulm Klinikum, Inst Pathol, Ulm, Germany. Univ Spital Zurich, Inst Klin Pathol, Zurich, Switzerland. RP Perner, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 221 Longwood Ave,EBRC 420, Boston, MA 02115 USA. EM sperner@partners.org NR 29 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1433-0563 J9 UROLOGE JI Urologe PD MAR PY 2006 VL 45 IS 3 BP 316 EP 322 DI 10.1007/s00120-006-1004-z PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 034VU UT WOS:000236959500005 PM 16465524 ER PT J AU Ramanathan, V Nguyen, PT Nguyen, PV Khan, A Musher, D AF Ramanathan, V Nguyen, PT Nguyen, PV Khan, A Musher, D TI Successful medical management of recurrent emphysematous pyelonephritis SO UROLOGY LA English DT Article ID NONNEUROGENIC NEUROGENIC BLADDER; RENAL-FAILURE; KIDNEY AB Emphysematous pyelonephritis is characterized by infection and gas formation in the renal parenchyma. This rare disorder tends to occur more frequently in patients with diabetes mellitus and urinary tract obstruction. In this case report, we describe a nondiabetic patient with Hinman syndrome who developed recurrent emphysematous pyelonephritis that was successfully treated with antibiotics on both occasions. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. RP Ramanathan, V (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, 2002 Holcombe Blvd,111-J, Houston, TX 77030 USA. EM ramanath@bcm.edu NR 16 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 0090-4295 J9 UROLOGY JI Urology PD MAR PY 2006 VL 67 IS 3 DI 10.1016/j.urology.2005.09.059 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 027PV UT WOS:000236428400054 ER PT J AU Andersen, OM Schmidt, V Spoelgen, R Gliemann, J Behlke, J Galatis, D McKinstry, WJ Parker, MW Masters, CL Hyman, BT Cappai, R Willnow, TE AF Andersen, OM Schmidt, V Spoelgen, R Gliemann, J Behlke, J Galatis, D McKinstry, WJ Parker, MW Masters, CL Hyman, BT Cappai, R Willnow, TE TI Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11 SO BIOCHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; APOLIPOPROTEIN-E RECEPTOR; X-RAY-STRUCTURE; ALZHEIMERS-DISEASE; FAMILY-MEMBER; GROWTH-FACTOR; MOSAIC RECEPTOR; CELL-SURFACE; BETA PEPTIDE; GENE FAMILY AB SorLA/LR11 is a sorting receptor that regulates the intracellular transport and processing of the amyloid precursor protein (APP) in neurons. SorLA/LR11-mediated binding results in sequestration of APP in the Golgi and in protection from processing into the amyloid-beta peptide (A beta), the principal component of senile plaques in Alzheimer's disease (AD). To gain insight into the molecular mechanisms governing sorLA and APP interaction, we have dissected the respective protein interacting domains. Using a fluorescence resonance energy transfer (FRET) based assay of protein proximity, we identified binding sites in the extracellular regions of both proteins. Fine mapping by surface plasmon resonance analysis and analytical ultracentrifugation of recombinant APP and sorLA fragments further narrowed down the binding domains to the cluster of complement-type repeats in sorLA that forms a 1:1 stoichiometric complex with the carbohydrated inked domain of APP. These data shed new light on the molecular determinants of neuronal APP trafficking and processing and on possible targets for intervention with senile plaque formation in patients with AD. C1 Max Delbrueck Ctr Mol Med, D-13125 Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Univ Aarhus, Dept Med Biochem, DK-8000 Aarhus, Denmark. Univ Melbourne, Ctr Neurosci, Melbourne, Vic 3010, Australia. Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. St Vincents Inst Med Res, Biota Struct Biol Lab, Fitzroy, Vic 3065, Australia. RP Andersen, OM (reprint author), Max Delbrueck Ctr Mol Med, D-13125 Berlin, Germany. EM o.andersen@mdc-berlin.de RI Cappai, Roberto/B-3347-2010; Parker, Michael/F-9069-2013; OI Cappai, Roberto/0000-0002-9505-8496; Parker, Michael/0000-0002-3101-1138; McKinstry, William/0000-0001-9668-9364 NR 52 TC 99 Z9 103 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 28 PY 2006 VL 45 IS 8 BP 2618 EP 2628 DI 10.1021/bi052120v PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 018VG UT WOS:000235792300018 PM 16489755 ER PT J AU Armstrong, EJ Morrow, DA Sabatine, MS AF Armstrong, EJ Morrow, DA Sabatine, MS TI Inflammatory biomarkers in acute coronary syndromes - Part III: Biomarkers of oxidative stress and angiogenic growth factors SO CIRCULATION LA English DT Editorial Material ID LOW-DENSITY-LIPOPROTEIN; PHOSPHOLIPASE A(2); PROGNOSTIC VALUE; SECRETORY PHOSPHOLIPASE-A2; UNSTABLE ANGINA; ARTERY-DISEASE; PLASMA-LEVELS; SERUM-LEVELS; CHEST-PAIN; ATHEROSCLEROSIS C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org NR 23 TC 25 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 BP E289 EP E292 DI 10.1161/CIRCULATIONAHA.105.595546 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100019 PM 16505179 ER PT J AU Bibbins-Domingo, K Ali, S Wu, AH Whooley, MA AF Bibbins-Domingo, K Ali, S Wu, AH Whooley, MA TI NT-proBNP: An independent predictor of heart failure SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P111 BP E333 EP E333 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100172 ER PT J AU Bibbins-Domingo, K Ali, S Wu, AHB Schiller, NB Whooley, MA AF Bibbins-Domingo, K Ali, S Wu, AHB Schiller, NB Whooley, MA TI NT-proBNP: An independent predictor of cardiovascular events SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P110 BP E333 EP E333 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100171 ER PT J AU Chae, CU Lloyd-Jones, DM Dec, GW Stevenson, LW Ridker, PM Januzzi, JL AF Chae, CU Lloyd-Jones, DM Dec, GW Stevenson, LW Ridker, PM Januzzi, JL TI C-reactive protein predicts mortality in patients with acute heart failure SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Chicago, IL 60611 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P123 BP E336 EP E336 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100184 ER PT J AU Dublin, S French, B Glazer, NL Wiggins, KL Lumley, TS Psaty, BM Smith, NL Heckbert, SR AF Dublin, S French, B Glazer, NL Wiggins, KL Lumley, TS Psaty, BM Smith, NL Heckbert, SR TI Obesity is associated with increased risk of new-onset atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P193 BP E349 EP E350 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100249 ER PT J AU Fang, MC Go, AS Chang, YC Henault, LE Jensvold, NJ Singer, DE AF Fang, MC Go, AS Chang, YC Henault, LE Jensvold, NJ Singer, DE TI Utility of current stroke risk schemes in patients with atrial fibrillation: The AnTicoagulation and risk factors in atrial fibrillation (ATRIA) study SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 UCSF, San Francisco, CA USA. Kaiser Permanente No Calif, Oakland, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA 3 BP E302 EP E302 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100028 ER PT J AU Fox, CS Massaro, JM Hoffmann, U Maurovich-Horvat, P Vasan, RS Meigs, JB O'Donnell, CJ AF Fox, CS Massaro, JM Hoffmann, U Maurovich-Horvat, P Vasan, RS Meigs, JB O'Donnell, CJ TI Subcutaneous and visceral adipose tissue compartments and association with metabolic risk factors: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 NHLBI Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA 21 BP E306 EP E306 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100046 ER PT J AU Fried, LF Shlipak, MG Sarnak, M Katz, R Cushman, M Kuller, LH Newman, AB AF Fried, LF Shlipak, MG Sarnak, M Katz, R Cushman, M Kuller, LH Newman, AB TI Longitudinal change in inflammatory markers and change in kidney function in an elderly cohort SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Tufts New England Med Ctr, Boston, MA USA. Univ Washington, Seattle, WA 98195 USA. Univ Vermont, Burlington, VT USA. Univ Pittsburgh, Pittsburgh, PA USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P134 BP E338 EP E338 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100195 ER PT J AU Gelber, RP Gaziano, JM Sesso, HD AF Gelber, RP Gaziano, JM Sesso, HD TI A prospective study of body mass index and risk of developing hypertension in men SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Harvard Univ, Sch Med, MAVERIC, VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P21 BP E315 EP E315 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100083 ER PT J AU Glazer, NL Dublin, S Smith, NL French, B Jackson, LA Siscovick, DS Psaty, BM Heckbert, SR AF Glazer, NL Dublin, S Smith, NL French, B Jackson, LA Siscovick, DS Psaty, BM Heckbert, SR TI Newly detected atrial fibrillation and compliance with antithrombotic guidelines SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P9 BP E313 EP E313 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100073 ER PT J AU Halanych, JH Safford, MM Lewis, CE Kiefe, CI AF Halanych, JH Safford, MM Lewis, CE Kiefe, CI TI The association between socioeconomic position and perceived racial discrimination: The CARDIA study SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P342 BP E380 EP E380 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100393 ER PT J AU Ix, JH Shlipak, MG Brandenburg, VM Ali, S Ketteler, M Whooley, MA AF Ix, JH Shlipak, MG Brandenburg, VM Ali, S Ketteler, M Whooley, MA TI Association between human fetuin-A and the metabolic syndrome: Data from the Heart and Soul Study SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Rhein Westfal TH Aachen, Univ Hosp, D-5100 Aachen, Germany. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P167 BP E344 EP E344 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100224 ER PT J AU Ix, JH Shlipak, MG Chertow, GM Ali, S Schiller, NB Whooley, MA AF Ix, JH Shlipak, MG Chertow, GM Ali, S Schiller, NB Whooley, MA TI Cystatin C, left ventricular hypertrophy, and diastolic dysfunction: Data from the Heart and Soul Study SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P127 BP E337 EP E337 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100188 ER PT J AU Lovasi, GS Lemaitre, RN Siscovick, DS Lumley, TS Bis, JC Dublin, S Smith, NL Heckbert, SR Psaty, BM AF Lovasi, GS Lemaitre, RN Siscovick, DS Lumley, TS Bis, JC Dublin, S Smith, NL Heckbert, SR Psaty, BM TI Amount of leisure-time physical activity and risk of nonfatal myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P261 BP E363 EP E364 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100315 ER PT J AU Meigs, JB Rutter, M Sullivan, L Fox, CS D'Agostino, RB Wilson, PW AF Meigs, JB Rutter, M Sullivan, L Fox, CS D'Agostino, RB Wilson, PW TI Insulin resistance substantially increases risk for type 2 diabetes or cardiovascular disease in individuals with ATP3 or IDF metabolic syndrome SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Manchester, Manchester, Lancs, England. Boston Univ, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA 11 BP E304 EP E304 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100036 ER PT J AU O'Donnell, CJ Liu, CY Larson, M Fox, CS Masarro, JM Hwang, SJ Manders, E Hoffmann, U Cupples, A AF O'Donnell, CJ Liu, CY Larson, M Fox, CS Masarro, JM Hwang, SJ Manders, E Hoffmann, U Cupples, A TI Evidence for heritability and genetic linkage for vascular calcification in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 NHLBIs Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA 28 BP E308 EP E308 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100053 ER PT J AU Parikh, NI Hwang, SJ Larson, MG Meigs, JB Levy, D Fox, CS AF Parikh, NI Hwang, SJ Larson, MG Meigs, JB Levy, D Fox, CS TI Cardiovascular disease risk factors in chronic kidney disease: Overall burden and rates of treatment and control SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P83 BP E328 EP E328 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100145 ER PT J AU Safford, MM Halanych, JH Allison, JJ Kirk, K Kiefe, CI AF Safford, MM Halanych, JH Allison, JJ Kirk, K Kiefe, CI TI Uncontrolled hypertension: Are African Americans getting better care? SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P329 BP E377 EP E377 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100380 ER PT J AU Safford, MM Halanych, JI Lewis, CE Levine, D Houser, S Howard, G AF Safford, MM Halanych, JI Lewis, CE Levine, D Houser, S Howard, G TI Racial differences in intensity of hypertension treatment: The reasons for geographic and racial disparities in stroke study SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA 35 BP E309 EP E309 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100060 ER PT J AU Shlipak, MG Sarnak, M Fried, L Newman, A Katz, R Siscovick, D Psaty, B Kestenbaum, B Stehman-Breen, C AF Shlipak, MG Sarnak, M Fried, L Newman, A Katz, R Siscovick, D Psaty, B Kestenbaum, B Stehman-Breen, C TI The burden of preclinical kidney disease in the elderly SO CIRCULATION LA English DT Meeting Abstract CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst C1 Tufts Univ, Boston, MA 02111 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Washington, Seattle, WA 98195 USA. Amgen Corp, Thousand Oaks, CA 91320 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 28 PY 2006 VL 113 IS 8 MA P115 BP E334 EP E334 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 016KW UT WOS:000235620100176 ER PT J AU McMurtray, AM Chen, AK Shapira, JS Chow, TW Mishkin, F Miller, BL Mendez, MF AF McMurtray, AM Chen, AK Shapira, JS Chow, TW Mishkin, F Miller, BL Mendez, MF TI Variations in regional SPECT hypoperfusion and clinical features in frontotemporal dementia SO NEUROLOGY LA English DT Article ID FRONTAL-LOBE DEGENERATION; ALZHEIMERS-DISEASE; PICKS-DISEASE; DIAGNOSTIC-CRITERIA; TEMPORAL VARIANTS; SOCIAL-BEHAVIOR; CONSENSUS; DISORDERS; SYMPTOMS AB Objective: To characterize the presenting clinical features for frontotemporal dementia (FTD) and contrast them with the degree of frontal and temporal hypoperfusion on SPECT imaging. Methods: The authors evaluated 74 patients who eventually met Consensus Criteria for the FTD form of frontotemporal lobar degeneration (excluding primary progressive aphasia and semantic dementia) on 2-year follow-up. On first presentation, these patients had undergone both an FTD Inventory for 12 features based on core and supportive Consensus Criteria and SPECT imaging. The initial clinical diagnostic features were contrasted with variations in regional SPECT hypoperfusion. Results: The patients with FTD had more hypoperfusion in the right frontal lobe than in other regions; the subgroup of 25 patients who met Consensus Criteria from the first presentation had the most right frontal hypoperfusion. Frontal lobe involvement was associated with significant apathy, whereas temporal lobe involvement was associated with hypomania-like behavior. Right frontal lobe hypoperfusion further predicted loss of insight, environmental dependency, and stereotyped behaviors. Other associations included left frontal hypoperfusion with a decline in personal hygiene and left temporal hypoperfusion with compulsions and mental rigidity. Conclusions: On first presentation, frontotemporal dementia (FTD) is disproportionately a right frontal disease evident on behavioral measures and on SPECT. Nonetheless, patients with FTD can initially present with further regional differences in clinical diagnostic features, such as apathy with bifrontal hypoperfusion and hypomania-like behaviors with anterior temporal involvement. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Toronto, Toronto, ON, Canada. Harbor UCLA Med Ctr, Los Angeles, CA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit, 691-1163AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU NIA NIH HHS [P01 AG019724, AG19724-01] NR 43 TC 56 Z9 57 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 28 PY 2006 VL 66 IS 4 BP 517 EP 522 DI 10.1212/01.wnl.0000197983.39436.e7 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 016UF UT WOS:000235645200016 PM 16505304 ER PT J AU Guichard, A Park, JM Cruz-Moreno, B Karin, M Bier, E AF Guichard, A Park, JM Cruz-Moreno, B Karin, M Bier, E TI Anthrax lethal factor and edema factor act on conserved targets in Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitogen-activated protein kinase kinase; c-Jun terminal kinase; downstream of raf1; development; cAMP-dependent PKA ID PROTEIN-KINASE-A; HEDGEHOG SIGNAL-TRANSDUCTION; AMINO-TERMINAL KINASE; CELL SHEET MOVEMENT; BACILLUS-ANTHRACIS; MACROPHAGE APOPTOSIS; TOXIN COMPONENTS; WING DEVELOPMENT; GENE-EXPRESSION; MORPHOGENESIS AB Many bacterial toxins act on conserved components of essential host-signaling pathways. One consequence of this conservation is that genetic model organisms such as Drosophila melanogaster can be used for analyzing the mechanism of toxin action. In this study, we characterize the activities of two anthrax virulence factors, lethal factor (LF) and edema factor, in transgenic Drosophila. LF is a zinc metalloprotease that cleaves and inactivates most human mitogen-activated protein kinase (MAPK) kinases (MAPKKs). We found that LF similarly cleaves the Drosophila MAPK kinases Hemipterous (Hep) and Licorne in vitro. Consistent with these observations, expression of LF in Drosophila inhibited the Hep/c-Jun N-terminal kinase pathway during embryonic dorsal closure and the related process of adult thoracic closure. Epistasis experiments confirmed that LF acts at the level of Hep. We also found that LF inhibits Ras/MAPK signaling during wing development and that LF acts upstream of MAPK and downstream of Raf, consistent with LF acting at the level of Dsor. in addition, we found that edema factor, a potent adenylate cyclase, inhibits the hh pathway during wing development, consistent with the known role of cAMP-dependent PKA in suppressing the Hedgehog response. These results demonstrate that anthrax toxins function in Drosophila as they do in mammalian cells and open the way to using Drosophila as a multicellular host system for studying the in vivo function of diverse toxins and virulence factors. C1 Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Karin, M (reprint author), Univ Calif San Diego, Sect Cell & Dev Biol, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM karin_office@som-bsb.ucsd.edu; bier@biomail.ucsd.edu FU NIAID NIH HHS [R21 AI60976, R21 AI060976, R01 AI0G1712] NR 58 TC 25 Z9 25 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 2006 VL 103 IS 9 BP 3244 EP 3249 DI 10.1073/pnas.0510748103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 018QU UT WOS:000235780700045 PM 16455799 ER PT J AU Luckey, CJ Bhattacharya, D Goldrath, AW Weissman, IL Benoist, C Mathis, D AF Luckey, CJ Bhattacharya, D Goldrath, AW Weissman, IL Benoist, C Mathis, D TI Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OLIGONUCLEOTIDE ARRAY DATA; PROTEASE INHIBITOR 2A; BONE-MARROW; HOMEOSTATIC PROLIFERATION; BLAST-CRISIS; DIFFERENTIATION; EXPRESSION; BMI-1; SURVIVAL; IDENTIFICATION AB The only cells of the hematopoietic system that undergo self-renewal for the lifetime of the organism are long-term hematopoietic stem cells and memory T and B cells. To determine whether there is a shared transcriptional program among these self-renewing populations, we first compared the gene-expression profiles of naive, effector and memory CD8(+) T cells with those of long-term hematopoietic stem cells, short-term hematopoietic stem cells, and lineage-committed progenitors. Transcripts augmented in memory CD8(+) T cells relative to naive and effector T cells were selectively enriched in long-term hematopoietic stem cells and were progressively lost in their short-term and lineage-committed counterparts. Furthermore, transcripts selectively decreased in memory CD8(+) T cells were selectively down-regulated in long-term hematopoietic stem cells and progressively increased with differentiation. To confirm that this pattern was a general property of immunologic memory, we turned to independently generated gene expression profiles of memory, naive, germinal center, and plasma B cells. Once again, memory-enriched and -depleted transcripts were also appropriately augmented and diminished in long-term hematopoietic stem cells, and their expression correlated with progressive loss of self-renewal function. Thus, there appears to be a common signature of both up- and down-regulated transcripts shared between memory T cells, memory B cells, and long-term hematopoietic stem cells. This signature was not consistently enriched in neural or embryonic stem cell populations and, therefore, appears to be restricted to the hematopoeitic system. These observations provide evidence that the shared phenotype of self-renewal in the hematopoietic system is linked at the molecular level. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Dept Pathol, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NHLBI NIH HHS [R01 HL058770, R01HL058770, T32 HL0762-18]; NIAID NIH HHS [AI51530-01, K08 AI063386, R01 AI047457, R01 AI051530, R01AI047457, R37 AI051530]; NIDDK NIH HHS [P30 DK036836, 2 P30 DK36836-17, 5 T32 DK007260-24, P01 DK053074, P01DK053074, T32 DK007260] NR 60 TC 119 Z9 123 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 2006 VL 103 IS 9 BP 3304 EP 3309 DI 10.1073/pnas.0511137103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 018QU UT WOS:000235780700055 PM 16492737 ER PT J AU Morales, JC Franco, S Murphy, MM Bassing, CH Mills, KD Adams, MM Walsh, NC Manis, JP Rassidakis, GZ Alt, FW Carpenter, PB AF Morales, JC Franco, S Murphy, MM Bassing, CH Mills, KD Adams, MM Walsh, NC Manis, JP Rassidakis, GZ Alt, FW Carpenter, PB TI 53BP1 and p53 synergize to suppress genomic instability and lymphomagenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE thymic lymphoma; aneuploidy; translocations ID CLASS-SWITCH RECOMBINATION; DNA-DAMAGE CHECKPOINT; HISTONE H2AX; PROTEIN 53BP1; FUNCTIONAL INTERACTION; TUMOR SUPPRESSION; MICE; STABILITY; ATM; RESPONSES AB p53-binding protein 1 (53BP1) participates in the cellular response to DNA double-stranded breaks where it associates with various DNA repair/cell cycle factors including the H2AX histone variant. Mice deficient for 53BP1 (53BP1(-/-)) are sensitive to ionizing radiation and immunodeficient because of impaired Ig heavy chain class switch recombination. Here we show that, as compared with p53(-/-) mice, 53BP1(-/-)/p53(-/-) animals more rapidly develop tumors, including T cell lymphomas and, at lower frequency, B lineage lymphomas, sarcomas, and teratomas. In addition, T cells from animals deficient for both 53BP1 and p53 (53BP1(-/-)/1p53(-/-)) display elevated levels of genomic instability relative to T cells deficient for either 53BP1 or p53 alone. In contrast to p53(-/-) T cell lymphomas, which routinely display aneuploidy but not translocations, 53BP1(-/-)1p53(-/-) thymic lymphomas fall into two distinct cytogenetic categories, with many harboring clonal translocations (40%) and the remainder showing aneuploidy (60%). We propose that 53BP1, in the context of p53 deficiency, suppresses T cell lymphomagenesis through its roles in both cell-cycle checkpoints and double-stranded break repair. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Joint Program Transfus Med, Childrens Hosp,Dept Lab Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. RP Carpenter, PB (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu; phillip.b.carpenter@uth.tmc.edu FU NCI NIH HHS [CA109901, CA92625, P01 CA092625, P01 CA109901]; NIGMS NIH HHS [GM65812, R01 GM065812, R56 GM065812] NR 36 TC 43 Z9 48 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 2006 VL 103 IS 9 BP 3310 EP 3315 DI 10.1073/pnas.0511259103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 018QU UT WOS:000235780700056 PM 16492765 ER PT J AU Bourquin, JP Subramanian, A Langebrake, C Reinhardte, D Bernard, O Ballerini, P Baruchel, A Cave, H Dastugue, N Hasle, H Kaspers, GL Lessard, M Michaux, L Vyas, P van Wering, E Zwaan, CM Golub, TR Orkin, SH AF Bourquin, JP Subramanian, A Langebrake, C Reinhardte, D Bernard, O Ballerini, P Baruchel, A Cave, H Dastugue, N Hasle, H Kaspers, GL Lessard, M Michaux, L Vyas, P van Wering, E Zwaan, CM Golub, TR Orkin, SH TI Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Down syndrome; GATA1 ID ACUTE MYELOGENOUS LEUKEMIA; TRANSCRIPTION FACTOR GATA-1; DOWN-SYNDROME; MEGAKARYOCYTIC LEUKEMIA; HEMATOPOIESIS; MATURATION; CHILDHOOD; DISCOVERY; FUSION; CANCER AB Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Cambridge, MA 02141 USA. Hannover Med Sch, D-30625 Hannover, Germany. Hop Necker Enfants Malad, INSERM, F-75015 Paris, France. Hop Trousseau, Serv Hematol Biol, F-75012 Paris, France. Hop St Louis, Cent Hematol Lab, Serv Hematol Pediat & Adulte, F-75010 Paris, France. Hop Robert Debre, Lab Biochim Genet, F-75019 Paris, France. Hop Purpan, Hematol Lab, F-31059 Toulouse, France. Aarhus Univ, Skejby Hosp, DK-8200 Aarhus N, Denmark. Vrije Univ Amsterdam, Med Ctr, Dept Pediat Hematol Oncol, NL-1007 MB Amsterdam, Netherlands. Hop Univ Strasbourg, Hop Hautepierre, Hematol Lab, F-67098 Strasbourg, France. Clin Univ St Luc, B-1200 Brussels, Belgium. Dutch Childhood Oncol Grp, The Hague, Netherlands. Oxford Radcliffe Hosp, Dept Haematol, Oxford OX3 9DU, England. Erasmus Med Ctr, Dept Pediat Oncol, NL-3000 CB Rotterdam, Netherlands. Univ Zurich, Kinderklin, Dept Pediat Oncol, CH-8032 Zurich, Switzerland. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu RI Reinhardt, Dirk/D-3939-2011; Bernard, Olivier/E-5721-2016; OI Reinhardt, Dirk/0000-0003-4313-9056; Hasle, Henrik/0000-0003-3976-9231; Vyas, Paresh/0000-0003-3931-0914 NR 29 TC 116 Z9 119 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 2006 VL 103 IS 9 BP 3339 EP 3344 DI 10.1073/pnas.0511150103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 018QU UT WOS:000235780700061 PM 16492768 ER PT J AU Steele, AD Emsley, JG Ozdinler, PH Lindquist, S Macklis, JD AF Steele, AD Emsley, JG Ozdinler, PH Lindquist, S Macklis, JD TI Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neural development; neural precursor; subventricular zone; dentate gyrus ID STEM-CELLS; HIPPOCAMPAL-NEURONS; CELLULAR PRION; NERVOUS-SYSTEM; IN-VITRO; MICE; DIFFERENTIATION; SCRAPIE; DISEASE; GENE AB The misfolding of the prion protein (PrPc) is a central event in prion diseases, yet the normal function of PrPc remains unknown. PrPc has putative roles in many cellular processes including signaling, survival, adhesion, and differentiation. Given the abundance of PrPc in the developing and mature mammalian CNS, we investigated the role of PrPc in neural development and in adult neurogenesis, which occurs constitutively in the dentate gyrus (DG) of the hippocampus and in the olfactory bulb from precursors in the subventricular zone (SVZ)/rostral migratory stream. In vivo, we find that PrPc is expressed immediately adjacent to the proliferative region of the SVZ but not in mitotic cells. In vivo and in vitro studies further find that PrPc is expressed in multipotent neural precursors and mature neurons but is not detectable in glia. Loss- and gain-of-function experiments demonstrate that PrPc levels correlate with differentiation of multipotent neural precursors into mature neurons in vitro and that PrPc levels positively influence neuronal differentiation in a dose-dependent manner. PrPc also increases cellular proliferation in vivo; in the SVZ, PrPc overexpresser (OE) mice have more proliferating cells compared with wild-type (WT) or knockout (KO) mice; in the DG, PrPc OE and WT mice have more proliferating cells compared with KO mice. Our results demonstrate that PrPc plays an important role in neurogenesis and differentiation. Because the final number of neurons produced in the DG is unchanged by PrPc expression, other factors must control the ultimate fate of new neurons. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurosurg,Program Ne, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurol,Program Neuro, Boston, MA 02114 USA. Harvard Univ, Sch Med, Stem Cell Inst, Boston, MA 02114 USA. RP Lindquist, S (reprint author), MIT, Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM lindquist_admin@wi.mit.edu; jeffrey_macklis@hms.harvard.edu FU NINDS NIH HHS [NS49553, NS41590, NS45523, R01 NS041590, R01 NS045523, R01 NS049553, R37 NS041590] NR 26 TC 158 Z9 167 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 2006 VL 103 IS 9 BP 3416 EP 3421 DI 10.1073/pnas.0511290103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 018QU UT WOS:000235780700074 PM 16492732 ER PT J AU Hurt, KJ Sezen, SF Champion, HC Crone, JK Palese, MA Huang, PL Sawa, A Luo, XJ Musicki, B Snyder, SH Burnett, AL AF Hurt, KJ Sezen, SF Champion, HC Crone, JK Palese, MA Huang, PL Sawa, A Luo, XJ Musicki, B Snyder, SH Burnett, AL TI Alternatively spliced neuronal nitric oxide synthase mediates penile erection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE penis; cavernous nerve; NADPH diaphorase ID MICE LACKING; GENE-TRANSFER; RAT; EXPRESSION; TISSUE AB A key role for nitric oxide (NO) in penile erection is well established, but the relative roles of the neuronal NO synthase (nNOS) versus endothelial forms of NOS are not clear. nNOS- and endothelial NOS-deficient mice maintain erectile function and reproductive capacity, questioning the importance of NO. Alternatively, residual NO produced by shorter transcripts in the nNOS(-/-) animals might suffice for normal physiologic function. We show that the beta splice variant of nNOS elicits normal erection despite a decrease in stimulus-response characteristics and a 5-fold increased sensitivity to the NOS inhibitor, L-NAME. Residual nNOS beta generates only 10% of the normal NO level in vitro but produces citrulline and diaphorase staining reflecting in vivo NOS activity in pelvic ganglion nerves that is comparable to WT animals. Thus, alternatively spliced forms of nNOS are major mediators of penile erection and so may be targets for therapeutic intervention. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Internal Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Cellular & Mol Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Snyder, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. EM ssnyder@jhmi.edu; aburnett@jhmi.edu OI hurt, kenneth/0000-0001-6906-350X FU NHLBI NIH HHS [R01 HL057818, R01 HL057818-09]; NIDA NIH HHS [DA 00074, DA00266, K05 DA000074, P50 DA000266]; NIDDK NIH HHS [R01 DK064679, DK64679, DK67223, R01 DK067223]; NIMH NIH HHS [MH-069853, R01 MH069853]; NINDS NIH HHS [P50 NS010828, P50 NS010828-320037, R01 NS033335, R01 NS033335-13, R01 NS048426, R01 NS048426-04] NR 23 TC 39 Z9 41 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 2006 VL 103 IS 9 BP 3440 EP 3443 DI 10.1073/pnas.0511326103 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 018QU UT WOS:000235780700078 PM 16488973 ER PT J AU Alpert, JE Biggs, MM Davis, L Shores-Wilson, K Harlan, WR Schneider, GW Ford, AL Farabaugh, A Stegman, D Ritz, AL Husain, MM Macleod, L Wisniewski, SR Rush, AJ AF Alpert, JE Biggs, MM Davis, L Shores-Wilson, K Harlan, WR Schneider, GW Ford, AL Farabaugh, A Stegman, D Ritz, AL Husain, MM Macleod, L Wisniewski, SR Rush, AJ CA STAR D investigators TI Enrolling research subjects from clinical practice: Ethical and procedural issues in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial SO PSYCHIATRY RESEARCH LA English DT Article DE recruitment; randomized clinical trial; major depressive disorder ID THERAPEUTIC MISCONCEPTION; CONSENT; PARTICIPANTS AB The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial is a multi-site effectiveness study funded by the National Institute of Mental Health (NIMH) with the aim of identifying successful, acceptable and cost-effective treatment strategies for outpatients with unremitted depression. With enrollment of 4041 adults with major depressive disorder (MDD), it is the largest controlled psychiatric treatment study ever undertaken. In the course of developing procedures to ensure that ambitious enrollment goals were met, a number of ethical and practical issues became apparent that underscore the conflicts between effectiveness research and human subject protections. These are delineated as they relate to study design; eligibility criteria; incentives to subjects; investigators and clinical sites; the complementary roles of clinical research coordinators (CRCs) and study clinicians; and recruitment and consent procedures. The STAR*D trial exemplifies the interplay and tension between those strategies that integrate research and clinical aims and roles in the service of enhancing external validity, site participation, and recruitment and retention versus those strategies that differentiate research and clinical treatment in the service of research integrity and human subject protections. We hope that a discussion of these key challenges and dilemmas and how they have been addressed will help inform future discussions concerning design and conduct of ethical effectiveness trials designed to optimize care in real world clinical settings. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Vet Adm Med Ctr, Dept Res, Tuscaloosa, AL 35404 USA. Univ Alabama, Birmingham, AL 35233 USA. NIMH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. Univ Pittsburgh, Epidemiol Data Coordinating Ctr, Pittsburgh, PA 15261 USA. RP Alpert, JE (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,4th Floor, Boston, MA 02114 USA. EM jalpert@partners.org RI Biggs, Dr. Melanie/C-1468-2010; OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 26 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB 28 PY 2006 VL 141 IS 2 BP 193 EP 200 DI 10.1016/j.psychres.2005.04.007 PG 8 WC Psychiatry SC Psychiatry GA 033BB UT WOS:000236820000008 PM 16457894 ER PT J AU Holt, DJ Kunkel, L Weiss, AP Goff, DC Wright, CI Shin, LM Rauch, SL Hootnick, J Heckers, S AF Holt, DJ Kunkel, L Weiss, AP Goff, DC Wright, CI Shin, LM Rauch, SL Hootnick, J Heckers, S TI Increased medial temporal lobe activation during the passive viewing of emotional and neutral facial expressions in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; functional magnetic resonance imaging; amygdala; hippocampus; emotion; face ID PREFRONTAL CORTEX RESPONSES; AFFECT RECOGNITION; HUMAN AMYGDALA; NEURAL RESPONSES; VOLUME REDUCTION; SEX-DIFFERENCES; FEARFUL FACES; MEMORY; FMRI; HIPPOCAMPUS AB Introduction: Patients with schizophrenia show deficits in facial affect and facial identity recognition and exhibit structural and neurophysiological abnormalities in brain regions known to mediate these processes. Functional neuroimaging studies of neural responses to emotional facial expressions in schizophrenia have reported both increases and decreases in medial temporal lobe (MTL) activity in schizophrenia. Some of this variability may be related to the tasks performed and the baseline conditions used. Here we tested whether MTL responses to human faces in schizophrenia are abnormal when unconstrained by a cognitive task and measured relative to a low-level baseline (fixation) condition. Methods: 15 patients with schizophrenia and 16 healthy control subjects underwent functional magnetic resonance imaging (fMRI) while passively viewing human faces displaying fearful, happy, and neutral emotional expressions. Results: Relative to control subjects, the patients demonstrated (1) significantly greater activation of the left hippocampus while viewing all three facial expressions and (2) increased right amygdala, activation during the initial presentation of fearful and neutral facial expressions. Conclusions: In schizophrenia, hippocampal and amygdala activity is elevated during the passive viewing of human faces. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Brigham Behav Neurol Grp, Dept Neurol, Boston, MA 02115 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. McLean Hosp, Belmont, MA 02472 USA. RP Holt, DJ (reprint author), Massachusetts Gen Hosp East, CNY-2,Bldg 149,13th St, Charlestown, MA 02129 USA. EM dholt@partners.org RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIMH NIH HHS [R01MH070560] NR 73 TC 134 Z9 138 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB 28 PY 2006 VL 82 IS 2-3 BP 153 EP 162 DI 10.1016/j.schres.2005.09.021 PG 10 WC Psychiatry SC Psychiatry GA 028MT UT WOS:000236492500005 PM 16377154 ER PT J AU Polli, FE Barton, JJS Vangel, M Goff, DC Iguchi, L Manoach, DS AF Polli, FE Barton, JJS Vangel, M Goff, DC Iguchi, L Manoach, DS TI Schizophrenia patients show intact immediate error-related performance adjustments on an antisaccade task SO SCHIZOPHRENIA RESEARCH LA English DT Article DE error processing; performance monitoring; inhibition; post-error slowing; self-monitoring; antisaccade task ID BIOLOGICAL RELATIVES; CORRECTING BEHAVIOR; CINGULATE CORTEX; BRAIN POTENTIALS; SMOOTH-PURSUIT; DYSFUNCTION; INHIBITION; SCALE AB Objective: Schizophrenia patients consistently show impairments on tasks requiring inhibition such as the antisaccade task. Deficits in performance monitoring including the detection of errors and subsequent adjustments to performance may contribute to such impairments. We examined whether immediate error-related performance adjustments during the antisaccade task were intact in schizophrenia. Method: We compared 21 schizophrenia patients and 14 healthy control subjects on the following measures: 1) error-related, trial-by-trial adjustments in reaction time (pre-error speeding, faster errors and post-error slowing); 2) the speed-accuracy trade-off (SATO) function; and 3) the frequency and type of error self-correction. Results: Although antisaccade performance in schizophrenia was characterized by increased errors and latency of correct responses, measures of immediate error-related performance adjustments were intact. Conclusion: Schizophrenia is characterized by intact immediate error-related performance adjustments, even in the context of impaired antisaccade performance. It is possible that deficiencies in other aspects of error processing, indexed by electrophysiological and hemodynamic markers, contribute to antisaccade and other cognitive deficits in schizophrenia. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ British Columbia, Dept Neurol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada. Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Polli, FE (reprint author), Massachusetts Gen Hosp East, CNY-149,Room 2608,13th St, Charlestown, MA 02129 USA. EM fpolli@nmr.mgh.harvard.edu RI Barton, Jason/A-6362-2012 FU NIMH NIH HHS [F31 MH72120, K23 MH01829]; NINDS NIH HHS [K08 NS01920] NR 37 TC 25 Z9 25 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB 28 PY 2006 VL 82 IS 2-3 BP 191 EP 201 DI 10.1016/j.schres.2005.10.003 PG 11 WC Psychiatry SC Psychiatry GA 028MT UT WOS:000236492500009 PM 16448804 ER PT J AU Kim, TW Kertesz, SG Horton, NJ Tibbetts, N Samet, JH AF Kim, TW Kertesz, SG Horton, NJ Tibbetts, N Samet, JH TI Episodic homelessness and health care utilization in a prospective cohort of HIV-infected persons with alcohol problems SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEDICAL-CARE; SUBSTANCE-ABUSE; ANTIRETROVIRAL THERAPY; SHELTER UTILIZATION; SERVICE UTILIZATION; CASE-MANAGEMENT; URBAN HOMELESS; HOUSING STATUS; SAN-FRANCISCO AB Background: Because individuals with HIV/AIDS often have complex medical and social needs, the impact of housing status on medical service utilization is difficult to isolate from the impact of conditions that may worsen during periods of homelessness such as depression and substance abuse. We examine whether episodes of homelessness are independently associated with suboptimal medical utilization even when accounting for concurrent addiction severity and depression. Methods: We used data from a 30-month cohort of patients with HIV/AIDS and alcohol problems. Housing status, utilization ( ambulatory visits, emergency department (ED) visits, and hospitalizations) and other features were assessed with standardized research interviews at 6-month intervals. Multivariable longitudinal regression models calculated incidence rate ratios (IRR) comparing utilization rates during 6-month intervals ( homeless versus housed). Additional models assessed whether addiction severity and depressive symptoms could account for utilization differences. Results: Of the 349 subjects, 139 (39%) reported homelessness at least once during the study period; among these subjects, the median number of nights homeless per 6-month interview period was 30. Homelessness was associated with higher ED utilization ( IRR = 2.17; 95% CI = 1.72 - 2.74) and hospitalizations ( IRR = 2.30; 1.70 - 3.12), despite no difference in ambulatory care utilization ( IRR = 1.09; 0.89 - 1.33). These associations were attenuated but remained significant when adjusting for addiction severity and depressive symptoms. Conclusion: In patients with HIV/AIDS and alcohol problems, efforts to improve housing stability may help to mitigate intensive medical utilization patterns. C1 Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med,Clin Addict Res & Educ Unit, Boston, MA 02118 USA. Univ Alabama, Sch Med, Dept Med, Div Prevent Med, Birmingham, AL USA. Deep S Ctr Effectiveness, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Smith Coll, Dept Math, Northampton, MA 01063 USA. DM STAT Inc, Medford, MA USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. RP Kim, TW (reprint author), Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med,Clin Addict Res & Educ Unit, Boston, MA 02118 USA. EM theresa.kim@bmc.org; skertesz@mail.dopm.uab.edu; nhorton@felix.smith.edu; nicole.campagnoni@dmstat.com; jsamet@bu.edu RI Horton, Nicholas/A-2493-2008; OI Samet, Jeffrey/0000-0002-0897-3400; Horton, Nicholas/0000-0003-3332-4311; Kim, Theresa/0000-0001-6043-0721 FU NCRR NIH HHS [M01 RR000533, M01-RR00533]; NIAAA NIH HHS [R01-AA11785, R01 AA010870, R01-AA10870, R01-AA13766]; NIDA NIH HHS [K23 DA015487, K23-DA15487, R25 DA013582, R25-DA 13582] NR 49 TC 26 Z9 26 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD FEB 27 PY 2006 VL 6 AR 19 DI 10.1186/1472-6963-6-19 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 029QY UT WOS:000236580700001 PM 16504167 ER PT J AU Yamamoto, S Teranishi, K Kamano, C Samelson-Jones, E Arakawa, H Nobori, S Okumi, M Houser, S Shimizu, A Sachs, DH Yamada, K AF Yamamoto, S Teranishi, K Kamano, C Samelson-Jones, E Arakawa, H Nobori, S Okumi, M Houser, S Shimizu, A Sachs, DH Yamada, K TI Role of the thymus in transplantation tolerance in miniature swine: V. Deficiency of the graft-to-thymus pathway of tolerance induction in recipients of cardiac transplants SO TRANSPLANTATION LA English DT Article DE thymectomy; tolerance; heart; miniature swine ID MISMATCHED RENAL-ALLOGRAFTS; MAJOR HISTOCOMPATIBILITY COMPLEX; ACQUIRED SYSTEMIC TOLERANCE; CLASS-I; INTRATHYMIC INOCULATION; LOBE TRANSPLANTATION; STABLE INDUCTION; CELLS; HEART; THYMOPOIESIS AB Background. We have previously shown that both thymic immigrants (graft to thymus pathway) and thymic emigrants (thymus to graft pathway) are involved in tolerance to renal allografts in miniature swine treated with a short course of calcineurin inhibitors. This study investigates the role of these pathways in cardiac transplant survival in recipients treated with a short course of tacrolimus. Methods. Eleven animals received two-haplotype fully MHC-mismatched cardiac grafts with a 12-day course of tacrolimus. Recipients were thymectomized on day -21 (n=5) or day 0 (n=3), or were left euthymic (n=3). Two of the day -21 thymectomized animals received a day 0 host-MHC matched thymocyte infusion. Results. Euthymic recipients of cardiac grafts treated with an immunosuppressive regimen identical to that previously shown to induce tolerance in euthymic recipients of renal allografts all rejected their grafts. Although no animal became tolerant, animals that were euthymic or thymectomized on clay 0, as well as recipients of day 0 host-type thymocyte infusions following thymectomy on day -21, developed donor-specific hyporesponsiveness and maintained their cardiac grafts for markedly prolonged periods. In contrast, all animals thymectomized on day -21 that did not receive thymocyte infusions developed strong antidonor CTL responses and rejected their grafts by day 35. Conclusions. The graft-to-thymus pathway that plays an important role in tolerance induction to renal allografts appears to be relatively deficient in recipients of cardiac grafts. Strategies to increase donor antigen migration to the host thymus might therefore assist in tolerance induction to cardiac allografts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,IMGH E, Boston, MA 02129 USA. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,IMGH E, 13th St,CNY-149,9019, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu NR 28 TC 9 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 27 PY 2006 VL 81 IS 4 BP 607 EP 613 DI 10.1097/01.tp.0000198735.17555.f1 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 019KB UT WOS:000235832900020 PM 16495810 ER PT J AU Song, G Lazar, GA Kortemme, T Shimaoka, M Desjarlais, JR Baker, D Springer, TA AF Song, G Lazar, GA Kortemme, T Shimaoka, M Desjarlais, JR Baker, D Springer, TA TI Rational design of intercellular adhesion molecule-1 (ICAM-1) variants for antagonizing integrin lymphocyte function-associated antigen-1-dependent adhesion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-PROTEIN COMPLEXES; HIGH-LEVEL EXPRESSION; I-LIKE DOMAIN; CONFORMATIONAL REGULATION; COMPUTATIONAL DESIGN; BINDING-ENERGY; HIGH-AFFINITY; SUBUNIT; RECOGNITION; PREDICTION AB The interaction between integrin lymphocyte function-associated antigen-1 ( LFA-1) and its ligand intercellular adhesion molecule-1 ( ICAM-1) is critical in immunological and inflammatory reactions but, like other adhesive interactions, is of low affinity. Here, multiple rational design methods were used to engineer ICAM-1 mutants with enhanced affinity for LFA-1. Five amino acid substitutions 1) enhance the hydrophobicity and packing of residues surrounding Glu-34 of ICAM-1, which coordinates to a Mg2+ in the LFA-1 I domain, and 2) alter associations at the edges of the binding interface. The affinity of the most improved ICAM-1 mutant for intermediate-and high-affinity LFA-1 I domains was increased by 19-fold and 22-fold, respectively, relative to wild type. Moreover, potency was similarly enhanced for inhibition of LFA-1-dependent ligand binding and cell adhesion. Thus, rational design can be used to engineer novel adhesion molecules with high monomeric affinity; furthermore, the ICAM-1 mutant holds promise for targeting LFA-1-ICAM-1 interaction for biological studies and therapeutic purposes. C1 Harvard Univ, Sch Med, CBR Inst Biochem Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Xencor, Monrovia, CA 91016 USA. Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biochem Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Baker, David/K-8941-2012 OI Baker, David/0000-0001-7896-6217 FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798] NR 47 TC 38 Z9 38 U1 2 U2 5 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 FEB 24 PY 2006 VL 281 IS 8 BP 5042 EP 5049 DI 10.1074/jbc.M51045200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 013RF UT WOS:000235426200058 PM 16354667 ER PT J AU Xu, N Tsai, CL Lee, JT AF Xu, N Tsai, CL Lee, JT TI Transient homologous chromosome pairing marks the onset of X inactivation SO SCIENCE LA English DT Article ID XIST GENE; TSIX; MICE; CHOICE; XITE AB Mammalian X inactivation turns off one female X chromosome to enact dosage compensation between XX and XY individuals. X inactivation is known to be regulated in cis by Xite, Tsix, and Xist, but in principle the two Xs must also be regulated in trans to ensure mutually exclusive silencing. Here, we demonstrate that interchromosomal pairing mediates this communication. Pairing occurs transiently at the onset of X inactivation and is specific to the X-inactivation center. Deleting Xite and Tsix perturbs pairing and counting/choice, whereas their autosomal insertion induces de novo X-autosome pairing. Ectopic X-autosome interactions inhibit endogenous X-X pairing and block the initiation of X-chromosome inactivation. Thus, Tsix and Xite function both in cis and in trans. We propose that Tsix and Xite regulate counting and mutually exclusive choice through X-X pairing. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu NR 21 TC 257 Z9 267 U1 1 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 24 PY 2006 VL 311 IS 5764 BP 1149 EP 1152 DI 10.1126/science.1122984 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 017IU UT WOS:000235688100048 PM 16424298 ER PT J AU Chien, KR AF Chien, KR TI Docus on research: Herceptin and the heart - A molecular modifier of cardiac failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 2 TC 114 Z9 120 U1 0 U2 0 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 FEB 23 PY 2006 VL 354 IS 8 BP 789 EP 790 DI 10.1056/NEJMp058315 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 014CL UT WOS:000235456200002 PM 16495390 ER PT J AU Ryan, PD Harisinghani, M Lerwill, MF Kaufman, DS McDougal, WS AF Ryan, PD Harisinghani, M Lerwill, MF Kaufman, DS McDougal, WS TI A 71-year-old woman with urinary incontinence and a mass in the bladder - Infiltrating lobular carcinoma of the breast, metastatic to the urinary bladder and ovaries. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID URETERAL OBSTRUCTION; CANCER; IMMUNOHISTOCHEMISTRY; SECONDARY; THERAPY; BRCA2 C1 Massachusetts Gen Hosp, Dept Med 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, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ryan, PD (reprint author), Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. NR 19 TC 6 Z9 6 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 FEB 23 PY 2006 VL 354 IS 8 BP 850 EP 856 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 014CL UT WOS:000235456200011 PM 16495398 ER PT J AU Kanani, RS Drachman, DE AF Kanani, RS Drachman, DE TI Malignant obstruction of the superior vena cava SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kanani, RS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 FEB 23 PY 2006 VL 354 IS 8 BP E7 EP E7 DI 10.1056/NEJMicm050661 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 014CL UT WOS:000235456200010 PM 16495388 ER PT J AU Brownstein, BH Logvinenko, T Lederer, JA Cobb, JP Hubbard, WJ Chaudry, IH Remick, DG Baker, HV Xiao, WZ Mannick, JA AF Brownstein, BH Logvinenko, T Lederer, JA Cobb, JP Hubbard, WJ Chaudry, IH Remick, DG Baker, HV Xiao, WZ Mannick, JA CA LS Collaborative Res Program TI Commonality and differences in leukocyte gene expression patterns among three models of inflammation and injury SO PHYSIOLOGICAL GENOMICS LA English DT Article ID OLIGONUCLEOTIDE ARRAYS; TRAUMA-HEMORRHAGE; MURINE MODEL; SEPSIS AB The aim of this study was to compare gene expression profiles of leukocytes from blood (white blood cells; WBCs) and spleen harvested at an early time point after injury or sham injury in mice subjected to trauma/hemorrhage, burn injury, or lipopolysaccharide (LPS) infusion at three experimental sites. Groups of injured or LPS-infused animals and sham controls were killed at 2 h after injury and resuscitation, blood and spleen were harvested, and leukocyte populations were recovered after erythrocyte lysis. RNA was extracted from postlysis leukocyte populations. Complementary RNA was synthesized from each RNA sample and hybridized to microarrays. A large number (500-1,400) of genes were differentially expressed at the 2-h time point in injured or LPS-infused vs. sham animals. Thirteen of the differentially expressed genes in blood, and 46 in the spleen, were upregulated or downregulated in common among all three animal models and may represent a common, early transcriptional response to systemic inflammation from a variety of causes. The majority of these genes could be assigned to pathways involved in the immune response and cell death. The up- or downregulation of a cohort of 23 of these genes was validated by RT-PCR. This large-scale microarray analysis shows that, at the 2-h (1)time point, there is marked alteration in leukocyte gene expression in three animal models of injury and inflammation. Although there is some commonality among the models, the majority of the differentially expressed genes appear to be uniquely associated with the type of injury and/or the inflammatory stimulus. C1 Brigham & Womens Hosp, Dept Surg Immunol, Boston, MA 02115 USA. Washington Univ, Dept Genet, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Univ Alabama Birmingham, Sch Med, Dept Surg, Birmingham, AL 35294 USA. Univ Michigan, Dept Med Sci, Ann Arbor, MI 48109 USA. Univ Florida, Dept Mol Genet, Gainesville, FL USA. Univ Florida, Dept Microbiol, Gainesville, FL USA. Univ Florida, Dept Surg, Gainesville, FL USA. Stanford Genome Technol Ctr, Palo Alto, CA USA. RP Lederer, JA (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM jlederer@rics.bwh.harvard.edu OI xiao, wenzhong/0000-0003-4944-6380; Remick, Daniel/0000-0002-2615-3713; Baker, Henry/0000-0002-8273-5320 FU NIGMS NIH HHS [1U54-GM-62119-03, U54 GM062119] NR 19 TC 22 Z9 24 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 EI 1531-2267 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD FEB 23 PY 2006 VL 24 IS 3 BP 298 EP 309 DI 10.1152/physiolgenomics.00213.2005 PG 12 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 031RV UT WOS:000236722600012 PM 16478828 ER PT J AU Bent, S Padula, A Avins, AL AF Bent, S Padula, A Avins, AL TI Brief communication: Better ways to question patients about adverse medical events - A randomized, controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CONSORT STATEMENT; CLINICAL-TRIAL AB Background: There is no standard method of identifying adverse events in clinical trials. Objective: To determine whether 3 different methods of questioning patients about adverse events in a clinical trial affect the frequency of reported events. Design: Randomized, single-blind, controlled trial. Setting: A Veterans Administration medical center, San Francisco, California. Participants: Men 50 years of age or older who had benign prostatic hyperplasia. Measurement: Frequency of self-reported medical problems. Intervention: The authors randomly assigned 214 men who were undergoing a 1-month, single-blind, placebo run-in period during an existing clinical trial to 3 groups to test different self-administered methods of assessing medical problems at the end of the run-in period. The first group was asked an open-ended question; the second group was asked an open-ended, defined question; and the third group was given a checklist of 53 common side effects. Results: All 214 patients completed the study. Patients assigned to the checklist group reported a total of 238 adverse events; in comparison, patients who were asked an open-ended question or an open-ended, defined question reported 11 and 14 adverse events, respectively (P < 0.001). The percentage of patients reporting any adverse event was also much higher in the group assigned to the checklist (77%) than in the first group (14%) or second group (13%) (P< 0.001). Limitations: The study included only relatively healthy, well-educated, middle-aged men and assessed only self-reported medical problems after the participants had taken placebo for 1 month. All personnel overseeing the study were aware of the group assignments. Conclusions: Different methods of collecting patient data regarding adverse events lead to large differences in the reported rates of adverse events in clinical trials, potentially reducing the validity of comparisons between the side effect profiles of drugs and other interventions. C1 San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bent, S (reprint author), San Francisco Vet Adm Med Ctr, 111-A1,4150 Clermont St, San Francisco, CA 94121 USA. EM bent@itsa.ucsf.edu FU NIDDK NIH HHS [1 R01 DK56199-01, R01 DK056199]; PHS HHS [1 K08 ATO1338-01] NR 13 TC 86 Z9 88 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 21 PY 2006 VL 144 IS 4 BP 257 EP 261 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 015HS UT WOS:000235543100004 PM 16490911 ER PT J AU Kathiresan, S Gona, P Larson, MG Vita, JA Mitchell, GF Tofler, GH Levy, D Newton-Cheh, C Wang, TJ Benjamin, EJ Vasan, RS AF Kathiresan, S Gona, P Larson, MG Vita, JA Mitchell, GF Tofler, GH Levy, D Newton-Cheh, C Wang, TJ Benjamin, EJ Vasan, RS TI Cross-sectional relations of multiple biomarkers from distinct biological pathways to brachial artery endothelial function SO CIRCULATION LA English DT Article DE atrial natriuretic factor; endothelium; inflammation; natriuretic peptides; renin ID FLOW-MEDIATED VASODILATION; BRAIN NATRIURETIC PEPTIDE; PLASMINOGEN-ACTIVATOR INHIBITOR; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; URINARY ALBUMIN EXCRETION; NITRIC-OXIDE; ESSENTIAL-HYPERTENSION; CARDIOVASCULAR EVENTS; HEALTHY-SUBJECTS AB Background - Endothelial dysfunction is a critical intermediate phenotype in the pathogenesis of cardiovascular disease. We evaluated the relative contributions of distinct biological pathways to interindividual variation in endothelial function by relating prototype biomarkers ( representing these pathways) to brachial artery vasodilator function. Methods and Results - We investigated the cross-sectional relations of a panel of 7 biomarkers measured at a routine examination to brachial artery vasodilator function (flow-mediated dilation [FMD] and reactive hyperemia) assessed at a subsequent examination (mean interval, 2.9 years) in 2113 Framingham Heart Study participants (mean age, 61 years; 54% women). We selected biomarkers from 4 biological domains: neurohormonal (N-terminal pro-atrial natriuretic peptide [N-ANP], B-type natriuretic peptide [BNP], renin, aldosterone), hemostatic factors (plasminogen activator inhibitor-1 [PAI-1]), inflammation (C-reactive protein [CRP]), and target organ damage (urine albumin-creatinine ratio). In age- and sex-adjusted models, several biomarkers were related to baseline brachial artery diameter (PAI-1, CRP, urine albumin-creatinine ratio), baseline mean flow (N-ANP, BNP, PAI-1, CRP, aldosterone), FMD (N-ANP, PAI-1, CRP, renin), and reactive hyperemia (BNP, PAI-1, CRP, renin, urine albumin-creatinine ratio). In multivariable analyses relating the 7 biomarkers conjointly to each vascular function measure (adjusting for known risk factors), N-ANP and renin were positively related to FMD (P = 0.001 and P = 0.04, respectively), and N-ANP was inversely related to baseline mean flow velocity (P = 0.01). None of the other biomarkers was significantly related to the vascular function measures studied. Conclusions - In our large community-based sample, a conservative strategy relating several biomarkers to vascular endothelial function identified plasma N-ANP as a key correlate of mean flow under basal conditions and of FMD in response to forearm cuff occlusion. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Evans Dept Med, Boston, MA 02215 USA. Boston Univ, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Cardiovasc Engn Inc, Holliston, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL70100, HL60040, HL67288, K23-HL-074077, K24-HL04334, N01-HC-25195] NR 49 TC 63 Z9 64 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 21 PY 2006 VL 113 IS 7 BP 938 EP 945 DI 10.1161/CIRCULATIONAHA.105.580233 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 013IV UT WOS:000235403900007 PM 16476848 ER PT J AU Armstrong, EJ Morrow, DA Sabatine, MS AF Armstrong, EJ Morrow, DA Sabatine, MS TI Inflammatory biomarkers in acute coronary syndromes - Part II: Acute-phase reactants and biomarkers of endothelial cell activation SO CIRCULATION LA English DT Editorial Material ID C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; INTERCELLULAR-ADHESION MOLECULE-1; LONG-TERM MORTALITY; UNSTABLE ANGINA; RISK STRATIFICATION; PROGNOSTIC VALUE; ELEVATED LEVELS; ARTERY-DISEASE; COLOCALIZES C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org NR 32 TC 46 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 21 PY 2006 VL 113 IS 7 BP E152 EP E155 DI 10.1161/CIRCULATIONAHA.105.595538 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 013IV UT WOS:000235403900019 PM 16490825 ER PT J AU Mansour, MC Singh, J Singh, R Qureishi, A Sokka, S Manzke, R Rasche, V Picard, MH Ruskin, JN AF Mansour, MC Singh, J Singh, R Qureishi, A Sokka, S Manzke, R Rasche, V Picard, MH Ruskin, JN TI Integration of three-dimensional coronary venous angiography with three-dimensional echocardiography for biventricular device implantation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Philips Med Syst, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 21A EP 21A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400089 ER PT J AU Stern, JD Murray, L Chung, J Picard, MH Semigran, MJ Ruskin, JN Singh, JP AF Stern, JD Murray, L Chung, J Picard, MH Semigran, MJ Ruskin, JN Singh, JP TI Impact of pulmonary hypertension on left ventricular reverse remodeling and long-term outcome in patients with cardiac resynchronization therapy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 33A EP 33A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400144 ER PT J AU Wykrzykowska, JJ Fifer, MA Ho, KKL Palacios, I Donnell-Fink, L Yoerger, DM Carrozza, JP Picard, MH Lowry, PA Josephson, ME Vlahakes, GJ Laham, RJ AF Wykrzykowska, JJ Fifer, MA Ho, KKL Palacios, I Donnell-Fink, L Yoerger, DM Carrozza, JP Picard, MH Lowry, PA Josephson, ME Vlahakes, GJ Laham, RJ TI Alcohol septal ablation is safe and effective in patients with left ventricular hypertrophy and outflow tract obstruction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 42A EP 43A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400184 ER PT J AU Wang, TJ Shahzad, K Glasofer, S Handschumacher, MD Bloch, KD Fan, D Picard, MH Semigran, MJ AF Wang, TJ Shahzad, K Glasofer, S Handschumacher, MD Bloch, KD Fan, D Picard, MH Semigran, MJ TI Nesiritide improves left ventricular compliance in diastolic heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 46A EP 46A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400200 ER PT J AU Jaff, M Hadley, G Hermiller, JB Simonton, C Hinohara, T Cannon, L Reisman, M Braden, G Fletcher, DR Zapien, M Chou, TM AF Jaff, M Hadley, G Hermiller, JB Simonton, C Hinohara, T Cannon, L Reisman, M Braden, G Fletcher, DR Zapien, M Chou, TM TI The safety and efficacy of the Starclose (TM) Vascular Closure System: The ultrasound substudy of the clip study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT i2 Summit 2006 CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol, Soc Cardiovascular Angiography Interventions C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Abbott Vasc, Redwood City, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU B BP 47B EP 47B PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CW UT WOS:000235530500201 ER PT J AU Januzzi, JL Chae, CU Baggish, AL Lee-Lewandrowski, E Sluss, P Lewandrowski, KB Lloyd-Jones, DM AF Januzzi, JL Chae, CU Baggish, AL Lee-Lewandrowski, E Sluss, P Lewandrowski, KB Lloyd-Jones, DM TI C-reactive protein concentrations at emergency department presentation strongly predict one year mortality in dyspneic patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Chicago, IL 60611 USA. RI Lloyd-Jones, Donald/C-5899-2009 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 67A EP 67A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400290 ER PT J AU van Kimmenade, RR Pinto, YM Lainchbury, JG Bayes-Genis, A Richards, MA Januzzi, JL AF van Kimmenade, RR Pinto, YM Lainchbury, JG Bayes-Genis, A Richards, MA Januzzi, JL TI There is nothing grey about it: Dyspnea with intermediate aminoterminal pro-B type natriuretic peptide concentrations SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Univ Hosp Maastricht, Maastricht, Netherlands. Massachusetts Gen Hosp, Boston, MA USA. RI Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Bayes-Genis, Antoni/0000-0002-3044-197X; NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 67A EP 68A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400292 ER PT J AU Dhaliwal, AS Deswal, A Pritchett, AM Bozkur, B AF Dhaliwal, AS Deswal, A Pritchett, AM Bozkur, B TI How much reduction is needed in BNP levels to reduce future clinical events with treatment during hospitalization for heart failure? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 72A EP 73A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400313 ER PT J AU Mariani, JA Smolic, AT Marshall, T Preovolos, AC Haijar, RJ Bilney, A Chien, KR Power, JM Kaye, DM AF Mariani, JA Smolic, AT Marshall, T Preovolos, AC Haijar, RJ Bilney, A Chien, KR Power, JM Kaye, DM TI Beneficial impact of cardiac-isolated recirculating delivery of AAV-SERCA2a gene therapy in a large animal model of heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Baker Heart Res Inst, Melbourne, Vic, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 73A EP 73A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400316 ER PT J AU Sakhuja, R Sluss, P Lee-Lewandrowski, E Lewandrowski, KB Januzzi, JL AF Sakhuja, R Sluss, P Lee-Lewandrowski, E Lewandrowski, KB Januzzi, JL TI Beta adrenergic blockers reduce the risk of mortality associated with elevated troponin T in patients with acutely decompensated congestive heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 85A EP 86A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400370 ER PT J AU Baggish, AL van Kimmenade, R Bayes-Genis, A Davis, M Lainchbury, JG Frampton, C Pinto, Y Richards, AM Januzzi, JL AF Baggish, AL van Kimmenade, R Bayes-Genis, A Davis, M Lainchbury, JG Frampton, C Pinto, Y Richards, AM Januzzi, JL TI Hemoglobin and n-terminal pro-brain natriuretic peptide: Independent and synergistic predictors of mortality in patients with acute heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Bayes-Genis, Antoni/0000-0002-3044-197X; NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 89A EP 89A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400386 ER PT J AU Dhaliwal, AS Zhang, QE Deswal, A Pritchett, AM Mann, DL Bozkurt, B AF Dhaliwal, AS Zhang, QE Deswal, A Pritchett, AM Mann, DL Bozkurt, B TI A simple multi-biomarker model does not predict outcomes better than single biomarkers in heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 89A EP 89A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400384 ER PT J AU Fatima, U Maurovich-Horvat, P Mauravich-Horvat, P Cury, R Witzke, C Hoffmann, U Abbara, S Brady, TJ Palacios, IF Holmvang, G AF Fatima, U Maurovich-Horvat, P Mauravich-Horvat, P Cury, R Witzke, C Hoffmann, U Abbara, S Brady, TJ Palacios, IF Holmvang, G TI MRI for diagnosis of myocarditis by global and delayed enhancement techniques: Added value to diagnose unsuspected coronary disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 90A EP 90A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400392 ER PT J AU Chen, AA Wood, MJ Baggish, AL Krauser, DG Tung, R Anwaruddin, S Picard, MH Januzzi, JL AF Chen, AA Wood, MJ Baggish, AL Krauser, DG Tung, R Anwaruddin, S Picard, MH Januzzi, JL TI Obesity has no effect on the sensitivity of NT-ProBNP for detection of systolic and diastolic dysfunction: Results from the ProBNP investigation of dyspnea in the emergency department (PRIDE) echocardiography substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 94A EP 94A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400404 ER PT J AU Neilan, TG Ton-Nu, TT Jassal, DS Marshall, JE Lawlor, D Yoerger, DM Picard, MH Wood, MJ AF Neilan, TG Ton-Nu, TT Jassal, DS Marshall, JE Lawlor, D Yoerger, DM Picard, MH Wood, MJ TI Tissue Doppler and 2-D-derived measurements of peak endocardial systolic velocity, strain and strain rate in senior athletes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 98A EP 99A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400424 ER PT J AU Ristow, B Ali, S Whooley, MA Schiller, NB AF Ristow, B Ali, S Whooley, MA Schiller, NB TI End diastolic pulmonary regurgitation gradient predicts adverse cardiovascular outcomes: Data from the heart and soul study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 FEB 21 PY 2006 VL 47 IS 4 SU A BP 98A EP 98A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400420 ER PT J AU Neilan, TG Ton-Nu, TT Jassal, DS Popovic, ZB Douglas, PS Marshall, JE Lawlor, D Thomas, JD Picard, MH Yoerger, DM Wood, MJ AF Neilan, TG Ton-Nu, TT Jassal, DS Popovic, ZB Douglas, PS Marshall, JE Lawlor, D Thomas, JD Picard, MH Yoerger, DM Wood, MJ TI Myocardial adaptation to short-term high-intensity exercise SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 101A EP 102A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400437 ER PT J AU Akutsu, Y Gewirtz, H Kardan, A Gregory, SA Zervos, GD Thomas, GS Yasuda, T AF Akutsu, Y Gewirtz, H Kardan, A Gregory, SA Zervos, GD Thomas, GS Yasuda, T TI Delayed heart rate recovery after adenosine stress testing with supplemental exercise predicts mortality SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Mission Internal Med Grp, Mission Viejo, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 107A EP 107A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400461 ER PT J AU Neilan, TG Pradhan, AD Weyman, AE AF Neilan, TG Pradhan, AD Weyman, AE TI Does standard normalization for body size variables actually work? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 110A EP 111A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400475 ER PT J AU Ferencik, M Gregory, SA Achenbach, S Yeh, RW Hoffmann, U Inglessis, I Cury, RC Nieman, K Raffel, OC McNulty, IA Brady, TJ Semigran, MJ Jang, IK AF Ferencik, M Gregory, SA Achenbach, S Yeh, RW Hoffmann, U Inglessis, I Cury, RC Nieman, K Raffel, OC McNulty, IA Brady, TJ Semigran, MJ Jang, IK TI Image quality of 64-slice multi-detector computed tomography coronary angiography in heart transplant recipients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Erlangen Nurnberg, Erlangen, Germany. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 130A EP 130A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400560 ER PT J AU Neilan, TG Ton-Nu, TT Jassal, DS Marshall, JE Lawlor, D Lee-Lenvandrowski, E Lewandrowski, KB Yoerger, DM Picard, MH Januzzi, JL Wood, MJ AF Neilan, TG Ton-Nu, TT Jassal, DS Marshall, JE Lawlor, D Lee-Lenvandrowski, E Lewandrowski, KB Yoerger, DM Picard, MH Januzzi, JL Wood, MJ TI Right ventricular injury and dysfunction during endurance sports SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 157A EP 157A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530400675 ER PT J AU Ahmed, S Sabatine, MS Cannon, CP Murphy, SA Braunwald, E Gibson, CM AF Ahmed, S Sabatine, MS Cannon, CP Murphy, SA Braunwald, E Gibson, CM TI Impact of reduced glomerular filtration rate on outcomes in patients with ST-Segment elevation myocardial infarction undergoing fibrinolysis in CLARITY-TIMI 28 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 159A EP 159A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401005 ER PT J AU Ahmed, S Antman, EM Murphy, SA Giugliano, RP Cannon, CP White, H Morrow, DA Braunwald, E AF Ahmed, S Antman, EM Murphy, SA Giugliano, RP Cannon, CP White, H Morrow, DA Braunwald, E TI Impact of age on the outcome of fibrinolytic therapy for ST-segment elevation myocardial infarction: A meta-analysis of a decade of trials SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 159A EP 160A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401006 ER PT J AU Morrow, DA Sabatine, MS Cannon, CP Murphy, SA Brennan, ML Hazen, SL Braunwald, E AF Morrow, DA Sabatine, MS Cannon, CP Murphy, SA Brennan, ML Hazen, SL Braunwald, E TI Concurrent evaluation of novel cardiac biomarkers in ACS: Myelopyroxidase, sCD40L, C-reactive protein and risk of death or recurrent ischemia in TACTICS-TIMI 18 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 196A EP 196A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401163 ER PT J AU Prunier, F Pfister, O del Monte, F Hajjar, R AF Prunier, F Pfister, O del Monte, F Hajjar, R TI Chronic therapy with erythropoietin, even administrated late after reperfusion, induces endothelial progenitor cells mobilization and myocardial salvage in post-mi rats SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 206A EP 206A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401206 ER PT J AU Ahmed, S Cannon, CP Giugliano, RP Shui, A Murphy, SA Morrow, DA Antman, EM Braunwald, E Gibson, CM AF Ahmed, S Cannon, CP Giugliano, RP Shui, A Murphy, SA Morrow, DA Antman, EM Braunwald, E Gibson, CM CA TIMI Study Grp TI The independent and combined risks of diabetes and non-endstage renal impairment in non ST-segment elevation acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 207A EP 207A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401209 ER PT J AU Saleh, JR Ebrahimi, R Shah, AP Wadhani, N Toggart, EJ AF Saleh, JR Ebrahimi, R Shah, AP Wadhani, N Toggart, EJ TI Statins in acute coronary syndrome: A meta-analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Univ Calif Los Angeles, W Los Angeles VA, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 212A EP 212A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401230 ER PT J AU Morrow, DA Wiviott, SD Sabatine, MS Giugliano, RR McCabe, CH Antman, EM Braunwald, E AF Morrow, DA Wiviott, SD Sabatine, MS Giugliano, RR McCabe, CH Antman, EM Braunwald, E CA TIMI Study Grp TI Evaluation of the TIMI Risk Index in a multi-continental population of 19,103 patients with STEMI in the ExTRACT-TIMI 25 trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, TIMI Study Grp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 223A EP 223A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401279 ER PT J AU Yeh, RW Wiviott, SD Giugliano, RP Morrow, DA Bradner, JE Jang, IK Gibson, CM Antman, EM AF Yeh, RW Wiviott, SD Giugliano, RP Morrow, DA Bradner, JE Jang, IK Gibson, CM Antman, EM TI Thrombocytopenia is associated with adverse outcomes following treatment with either enoxaparin or unfractionated heparin in patients presenting with acute coronary syndromes: A TIMI 11B substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 223A EP 223A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401282 ER PT J AU Neilan, TG Pradhan, AD Weyman, AE AF Neilan, TG Pradhan, AD Weyman, AE TI Does normalization for body size variables actually work in a pediatric population? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 243A EP 243A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401365 ER PT J AU Ho, PM Rumsfeld, JS Masoudi, FA McClure, DL Plomondon, ME Steiner, JF Magid, DJ AF Ho, PM Rumsfeld, JS Masoudi, FA McClure, DL Plomondon, ME Steiner, JF Magid, DJ TI The impact of medication non-adherence on hospitalization and mortality among patients with diabetes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Denver VA Med Ctr, Denver, CO USA. Kaiser Permanente, Denver, CO 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 264A EP 264A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530401449 ER PT J AU Schweige, MJ Giugliano, GR Lotfi, A Murphy, SA Cannon, CP AF Schweige, MJ Giugliano, GR Lotfi, A Murphy, SA Cannon, CP TI High dose atorvastatin does not impact the efficacy of clopiclogrel - A PROVE IT TIMI-22 analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol C1 Baystate Med Ctr, TIMI Study Grp, Springfield, MA USA. Brigham & Womens Hosp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 SU A BP 380A EP 380A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015CV UT WOS:000235530402451 ER PT J AU Heidenreich, PA Spertus, JA Jones, PG Weintraub, WS Rumsfeld, JS Rathore, SS Peterson, ED Masoudi, FA Krumholz, HM Havranek, EP Conard, MW Williams, RE AF Heidenreich, PA Spertus, JA Jones, PG Weintraub, WS Rumsfeld, JS Rathore, SS Peterson, ED Masoudi, FA Krumholz, HM Havranek, EP Conard, MW Williams, RE CA Cardiovascular Outcomes Res Cons TI Health status identifies heart failure outpatients at risk for hospitalization or death SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID QUALITY-OF-LIFE; READMISSION; PREDICTOR AB OBJECTIVES We tested the hypothesis that one health status measure, the Kansas City Cardiomyopathy Questionnaire (KCCQ), provides prognostic information independent of other clinical data in outpatients with heart failure (HF). BACKGROUND Health status measures are used to describe a patient's clinical condition and have been shown to predict mortality in Some Populations. Their prognostic value may be particularly useful among patients with HF for identifying candidates for disease management in whom increased care may reduce hospitalizations and prevent death. METHODS We evaluated 505 HF patients from 13 outpatient clinics who had all ejection fraction < 40% using the KCCQ summary score. Proportional hazards regression was used to evaluate the association between the KCCQ summary score (range, 0 to 100; higher scores indicate better health status) and the primary outcome of death or HF admission, adjusting for baseline patient characteristics, 6-min walk distance, and B-type natriuretic peptide (BNP). RESULTS The mean age was 61 years, 76% of patients were male, 51% had an ischemic HF etiology, and 5% were New York Heart Association functional class IV. At 12 months, among the 9% of patients with a KCCQ-score < 25, 37% had been admitted for HF and 20% had died, compared with 7% (HF admissions) and 5% (death) of those with a KCCQ-score = >= 75 (33% of patients, p < 0.0001 for both comparisons). In sequential multivariable models adjusting for clinical variables, 6-min walk, and BNP levels, the KCCQ score remained significantly associated with survival free of HF hospitalization. CONCLUSIONS A low KCCQ score is an independent predictor of poor prognosis in outpatients with HF. C1 Palo Alto VA Hlth Care Syst, Palo Alto, CA 94304 USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Emory Univ, Atlanta, GA 30322 USA. Denver VA Med Ctr, Denver, CO USA. Yale Univ, New Haven, CT USA. Duke Univ, Med Ctr, Durham, NC USA. Denver Hlth Med Ctr, Denver, CO USA. Northwestern Univ, Evanston, IL USA. RP Heidenreich, PA (reprint author), Palo Alto VA Hlth Care Syst, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM heiden@stanford.edu OI Heidenreich, Paul/0000-0001-7730-8490 FU NIGMS NIH HHS [GM07205] NR 14 TC 123 Z9 124 U1 0 U2 4 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 FEB 21 PY 2006 VL 47 IS 4 BP 752 EP 756 DI 10.1016/j.jacc.2005.11.021 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 013QB UT WOS:000235422900011 PM 16487840 ER PT J AU Vyas, AK Guo, HS Moss, AJ Olshansky, B McNitt, SA Hall, J Zareba, W Steinberg, JS Fischer, A Ruskin, J Andrews, ML AF Vyas, AK Guo, HS Moss, AJ Olshansky, B McNitt, SA Hall, J Zareba, W Steinberg, JS Fischer, A Ruskin, J Andrews, ML CA MADIT-II Res Grp TI Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; LIPID-LOWERING DRUGS; CHOLESTEROL LEVELS; FATTY-ACIDS; EVENTS; ARRHYTHMIAS; PREVENTION; SURVIVAL; THERAPY; RISK AB OBJECTIVES We evaluated whether statins have anti-arrhythmic effects by exploring the association of statin use with appropriate implantable cardioverter-defibrillator (TCD) therapy for ventricular tachycardia/ventricular fibrillation (VT/VF) in the Multicenter Automatic Defibrillator fin plantation Trial (MADIT)-II. BACKGROUND A few studies have suggested that lipid-lowering drugs may have anti-arrhythmic effects in patients with coronary artery disease. METHODS Patients receiving an ICD (n = 654; U.S. centers only) in the MADIT-II study were categorized by the percentage of days each patient received statins during follow-up (90% to 100%, n = 386; 11% to 89%, n = 116; and 0% to 10%, n = 152). The Kaplan-Meier method with significance testing by the log-rank statistic and time-dependent proportional hazards regression analysis were used to evaluate the effect of statin use on the probability of ICD therapy for the combined end point VT/VF or cardiac death and for the end point VT/VF. RESULTS The cumulative rate of ICD therapy for VT/VF or cardiac death, whichever occurred first, was significantly reduced in those with >= 90% statin usage compared to those with lower statin usage (p = 0.01.). The time-dependent statin:no statin therapy hazard ratio was 0.65 (p < 0.01) for the end point of VT/VF or cardiac death and 0.72 (p = 0.046) for VT/VF after adjusting for relevant covariates. CONCLUSIONS Statin use in patients, with an ICD was associated with it reduction in the risk of cardiac death or VT/VF, whichever occurred first, and was associated with it reduction in VT/VF episodes. These findings Suggest that statins have anti-arrhythmic properties. C1 Univ Rochester, Med Ctr, Heart Res Follow Up Program, Cardiol Unit,Dept Med, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. Pk Nicollet Clin, Cardiac Electrophysiol Div, St Louis Pk, MN USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. St Lukes Roosevelt Hosp, Div Cardiol, Dept Med, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. RP Vyas, AK (reprint author), Univ Rochester, Med Ctr, Heart Res Follow Up Program, Cardiol Unit,Dept Med, 601 Elmwood Ave,Box 653, Rochester, NY 14642 USA. EM anantvyas@hotmail.com NR 16 TC 98 Z9 104 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 FEB 21 PY 2006 VL 47 IS 4 BP 769 EP 773 DI 10.1016/j.jacc.2005.09.053 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 013QB UT WOS:000235422900014 PM 16487843 ER PT J AU Garcia, DA Regan, S Crowther, M Hylek, EM AF Garcia, DA Regan, S Crowther, M Hylek, EM TI The risk of hemorrhage among patients with warfarin-associated coagulopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ORAL VITAMIN-K; EXCESSIVE ANTICOAGULATION; CONTROLLED-TRIAL; ATRIAL-FIBRILLATION; THERAPY; MANAGEMENT; OUTPATIENTS; INTENSITIES AB OBJECTIVES Among warfarin-treated patients with international normalized ratio (INR) > 5, we sought to determine the risk of major bleeding within 30 days. BACKGROUND For warfarin-treated patients, the risk of bleeding increases as the INR rises, particularly if the INR exceeds 4. The 30-day risk of hemorrhage among outpatients with excessively prolonged INR value,; is unknown. METHODS To assess anticoagulation care in the U.S., a cohort of 6,761 patients taking warfarin was prospectively assembled from 101 participating sites (43% were community-based cardiology practices). From this cohort, 1,104 patients were identified with a first episode of INR > 5. RESULTS A total of 979 met eligibility criteria; complete follow-up information was available for 976 (99.7%). Ninety-six percent (n = 937) of patients had an INR value between 5 and 9; 80% of INR values were < 7. Thirteen patients (1.3%) experienced major hemorrhage during the 30-day follow-up period; among patients whose INR was > 5 and < 9, 0.96% experienced major hemorrhage. None of the bleeding events was fatal. Intervention with vitamin K was uncommon (8.7%). Warfarin doses were withheld for the majority of patients. Fifty percent of patients who were managed conservatively and retested on day 4 or 5 had an INR of 2.0 or less. CONCLUSIONS For warfarin- treated outpatients presenting with an INR > 5 and < 9, the 30-day risk of major bleeding is low (0.96%). Intervention with vitamin K among asymptomatic patients presenting with an INR < 9 is not routine practice in the U.S. C1 Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. McMaster Univ, Dept Med, Hamilton, ON, Canada. Boston Univ, Sch Med, Dept Med, Gen Internal Med Res Unit,Boston Med Ctr, Boston, MA 02118 USA. RP Garcia, DA (reprint author), 2211 Lomas NE,MSC10 5550, Albuquerque, NM 87131 USA. EM davgarcia@salud.unm.edu OI Regan, Susan/0000-0003-0940-2017 NR 24 TC 43 Z9 44 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 FEB 21 PY 2006 VL 47 IS 4 BP 804 EP 808 DI 10.1016/j.jacc.2005.09.058 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 013QB UT WOS:000235422900020 PM 16487849 ER PT J AU Weyman, AE AF Weyman, AE TI The year in echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; CARDIAC RESYNCHRONIZATION THERAPY; ISCHEMIC MITRAL REGURGITATION; INCREMENTAL PROGNOSTIC VALUE; LONG-TERM SURVIVAL; LEFT ATRIAL VOLUME; HEART-FAILURE; CORONARY STENOSIS; VALIDATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weyman, AE (reprint author), Cardiac Ultrasound Lab, 55 Fruit St,YAW 5, Boston, MA 02114 USA. NR 38 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 21 PY 2006 VL 47 IS 4 BP 856 EP 863 DI 10.1016/j.jacc.2005.12.042 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 013QB UT WOS:000235422900027 PM 16487856 ER PT J AU Jiang, SB Sharp, GC Neicu, T Berbeco, RI Flampouri, S Bortfeld, T AF Jiang, SB Sharp, GC Neicu, T Berbeco, RI Flampouri, S Bortfeld, T TI On dose distribution comparison SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MODULATED RADIATION-THERAPY; IMRT VERIFICATION; QUALITY-ASSURANCE; QUANTITATIVE-EVALUATION; FILM DOSIMETRY; RADIOGRAPHIC FILM; GAMMA-EVALUATION; DIODE-ARRAY; KODAK EDR2; DELIVERY AB In radiotherapy practice, one often needs to compare two dose distributions. Especially with the wide clinical implementation of intensity-modulated radiation therapy, software tools for quantitative dose (or fluence) distribution comparison are required for patient-specific quality assurance. Dose distribution comparison is not a trivial task since it has to be performed in both dose and spatial domains in order to be clinically relevant. Each of the existing comparison methods has its own strengths and weaknesses and there is room for improvement. In this work, we developed a general framework for comparing dose distributions. Using a new concept called maximum allowed dose difference (MADD), the comparison in both dose and spatial domains can be performed entirely in the dose domain. Formulae for calculating MADD Values for various comparison methods, such as composite analysis and gamma index, have been derived. For convenience in clinical practice, a new measure called normalized dose difference (NDD) has also been proposed, which is the dose difference at a point scaled by the ratio of MADD to the predetermined dose acceptance tolerance. Unlike the simple dose difference test, NDD works in both low and high dose gradient regions because it considers both dose and spatial acceptance tolerances through MADD. The new method has been applied to a test case and a clinical example. It was found that the new method combines the merits of the existing methods (accurate, simple, clinically intuitive and insensitive to dose grid size) and can easily be implemented into any dose/intensity comparison tool. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jiang, SB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jiang.steve@mgh.hazvard.edu NR 31 TC 34 Z9 36 U1 0 U2 3 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 FEB 21 PY 2006 VL 51 IS 4 BP 759 EP 776 DI 10.1088/0031-9155/51/4/001 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 020VN UT WOS:000235941100001 PM 16467577 ER PT J AU Khademhosseini, A Langer, R Borenstein, J Vacanti, JP AF Khademhosseini, A Langer, R Borenstein, J Vacanti, JP TI Microscale technologies for tissue engineering and biology SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Review DE microfabrication; review; soft lithography; stem cells; microfluiclics ID EMBRYONIC STEM-CELLS; SOFT LITHOGRAPHY; PDMS POLYDIMETHYLSILOXANE; BIODEGRADABLE ELASTOMER; MICROFLUIDIC CHANNELS; CONTACT GUIDANCE; SURFACE-FEATURES; HYALURONIC-ACID; SMALL MOLECULES; LAMINAR FLOWS AB Microscale technologies are emerging as powerful tools for tissue engineering and biological studies. In this review, we present an overview of these technologies in various tissue engineering applications, such as for fabricating 3D microfabricated scaffolds, as templates for cell aggregate formation, or for fabricating materials in a spatially regulated manner. In addition, we give examples of the use of microscale technologies for controlling the cellular microenvironment in vitro and for performing high-throughput assays. The use of microfluidics, surface patterning, and patterned cocultures in regulating various aspects of cellular microenvironment is discussed, as well as the application of these technologies in directing cell fate and elucidating the underlying biology. Throughout this review, we will use specific examples where available and will provide trends and future directions in the field. C1 MIT, Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), MIT, Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM jvacanti@partners.org RI Khademhosseini, Ali/A-9435-2010; Sano, Michael/E-1715-2011; OI Khademhosseini, Ali/0000-0002-2692-1524; Khademhosseini, Ali/0000-0001-6322-8852 FU NHLBI NIH HHS [HL060435, R01 HL060435]; NIDCR NIH HHS [DE013023, DE16516, R01 DE013023, R01 DE016516] NR 110 TC 915 Z9 939 U1 33 U2 443 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 21 PY 2006 VL 103 IS 8 BP 2480 EP 2487 DI 10.1073/pnas.0507681102 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 015MG UT WOS:000235554900004 PM 16477028 ER PT J AU Liberati, NT Urbach, JM Miyata, S Lee, DG Drenkard, E Wu, G Villanueva, J Wei, T Ausubel, FM AF Liberati, NT Urbach, JM Miyata, S Lee, DG Drenkard, E Wu, G Villanueva, J Wei, T Ausubel, FM TI An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genomics; mariner; transposon mutagenesis; Himar1 ID BIOFILM FORMATION; CAENORHABDITIS-ELEGANS; TWITCHING MOTILITY; VIRULENCE FACTORS; SCALE ANALYSIS; III SECRETION; GENOME; GENES; MUTAGENESIS; MODEL AB Random transposon insertion libraries have proven invaluable in studying bacterial genomes. Libraries that approach saturation must be large, with multiple insertions per gene, making comprehensive genome-wide scanning difficult. To facilitate genomescale study of the opportunistic human pathogen Pseudomonas aeruginosa strain PA14, we constructed a nonredundant library of PA14 transposon mutants (the PA14NR Set) in which nonessential PA14 genes are represented by a single transposon insertion chosen from a comprehensive library of insertion mutants. The parental library of PA14 transposon insertion mutants was generated by using MAR2xT7, a transposon compatible with transposonsite hybridization and based on mariner. The transposon-site hybridization genetic footprinting feature broadens the utility of the library by allowing pooled MAR2xT7 mutants to be individually tracked under different experimental conditions. A public, internet-accessible database (the PA14 Transposon Insertion Mutant Database, http://ausubellab.mgh.harvard.edu/cgi-bin/pa14/ home.cgi) was developed to facilitate construction, distribution, and use of the PA14NR Set. The usefulness of the PA14NR Set in genome-wide scanning for phenotypic mutants was validated in a screen for attachment to abiotic surfaces. Comparison of the genes disrupted in the PA14 transposon insertion library with an independently constructed insertion library in A aeruginosa strain PAO1 provides an estimate of the number of P. aeruginosa essential genes. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU NHLBI NIH HHS [U01 HL066678, U01 HL66678]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-10] NR 39 TC 433 Z9 1743 U1 3 U2 48 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 21 PY 2006 VL 103 IS 8 BP 2833 EP 2838 DI 10.1073/pnas.0511100103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 015MG UT WOS:000235554900064 PM 16477005 ER PT J AU Kulesekara, H Lee, V Brencic, A Liberati, N Urbach, J Miyata, S Lee, DG Neely, AN Hyodo, M Hayakawa, Y Ausubel, FM Lory, S AF Kulesekara, H Lee, V Brencic, A Liberati, N Urbach, J Miyata, S Lee, DG Neely, AN Hyodo, M Hayakawa, Y Ausubel, FM Lory, S TI Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3 '-5 ')-cyclic-GMP in virulence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytotoxicity; biofilm ID CYCLIC DI-GMP; BIOFILM FORMATION; VIBRIO-CHOLERAE; SIGNAL-TRANSDUCTION; CELLULOSE BIOSYNTHESIS; ACETOBACTER-XYLINUM; III SECRETION; EAL DOMAINS; SYSTEM; BACTERIA AB The opportunistic pathogen Pseudomonas aeruginosa is responsible for systemic infections in immunocompromised individuals and chronic respiratory disease in patients with cystic fibrosis. Cyclic nucleotides are known to play a variety of roles in the regulation of virulence-related factors in pathogenic bacteria. A set of P. aeruginosa genes, encoding proteins that contain putative domains characteristic of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) that are responsible for the maintenance of cellular levels of the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) was identified in the annotated genomes of P. aeruginosa strains PAO1 and PA14. Although the majority of these genes are components of the A aeruginosa core genome, several are located on presumptive horizontally acquired genomic islands. A comprehensive analysis of P. aeruginosa genes encoding the enzymes of c-di-GMP metabolism (DGC- and PDE-encoding genes) was carried out to analyze the function of c-di-GMP in two disease-related phenomena, cytotoxicity and biofilm formation. Analysis of the phenotypes of DGC and PDE mutants and overexpressing clones revealed that certain virulence-associated traits are controlled by multiple DGCs and PDEs through alterations in c-di-GMP levels. A set of mutants in selected DGC- and PDE-encoding genes exhibited attenuated virulence in a mouse infection model. Given that insertions in different DGC and PDE genes result in distinct phenotypes, it seems likely that the formation or degradation of c-di-GMP by these enzymes is in highly localized and intimately linked to particular targets of c-di-GMP action. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Shriners Hosp Children, Cincinnati, OH 45229 USA. Nagoya Univ, Grad Sch Informat Sci Human Informat, Nagoya, Aichi 4648601, Japan. Nagoya Univ, Core Res Evolut Sci & Technol, Japan Sci & Technol Agcy, Nagoya, Aichi 4648601, Japan. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. EM ausubel@molbio.mgh.harvard.edu; stephen_lory@hms.harvard.edu RI Hyodo, Mamoru/D-5496-2012; OI Hyodo, Mamoru/0000-0002-1766-3949; Lee, Vincent T./0000-0002-3593-0318 NR 37 TC 63 Z9 68 U1 2 U2 23 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 21 PY 2006 VL 103 IS 8 BP 2839 EP 2844 DI 10.1073/pnas.0511090103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 015MG UT WOS:000235554900065 ER PT J AU Podar, K Anderson, KC AF Podar, K Anderson, KC TI Caveolin-1 as a potential new therapeutic target in multiple myeloma SO CANCER LETTERS LA English DT Review DE caveolin-1; multiple myeloma; IL-6; IGF-1; VEGF ID PLASMA-MEMBRANE DOMAINS; PROSTATE-CANCER; PROTEIN-COMPONENT; FREE-CHOLESTEROL; UP-REGULATION; CELLS; GROWTH; EXPRESSION; PHOSPHORYLATION; IDENTIFICATION AB Caveolae are specialized flask-shaped lipid rafts enriched in cholesterol, sphingolipids, and structural marker proteins termed caveolins. Caveolins are highly conserved hairpin loop-shaped, oligomeric proteins of 22-24 kDa. Besides the plasma cell membrane, caveolins are also present in mitochondria, the endoplasmatic reticulum, the Gotgi/trans-Golgi network, and secretory vesicles. They play a critical role in normal vesicular transport, cholesterol homeostasis, and signal transduction. Conversely, dysregulation of caveolin-1 has been associated with several human diseases including multiple myeloma, an incurable malignancy characterized by excess monoclonal plasma cells within the bone marrow. In this mini-review, we characterize the functional role of caveolin-1 in multiple myeloma, and present the preclinical rationale for novel potential therapeutic approaches targeting caveolin-1 in multiple myeloma. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Podar, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [IP50 CA100707, R0-1 CA 50945]; PHS HHS [P0-1 78378] NR 39 TC 15 Z9 16 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 20 PY 2006 VL 233 IS 1 BP 10 EP 15 DI 10.1016/j.canlet.2005.02.035 PG 6 WC Oncology SC Oncology GA 019QH UT WOS:000235851300002 PM 16473666 ER PT J AU Earle, CC Ayanian, JZ AF Earle, CC Ayanian, JZ TI Looking back from death: The value of retrospective studies of end-of-life care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CANCER CARE C1 Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA91753, U01 CA93324, U01 CA93332] NR 18 TC 61 Z9 62 U1 2 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 FEB 20 PY 2006 VL 24 IS 6 BP 838 EP 840 DI 10.1200/JCO.2005.03.9388 PG 3 WC Oncology SC Oncology GA 014HF UT WOS:000235469700002 PM 16484691 ER PT J AU Chen, SN Iversen, ES Friebel, T Finkelstein, D Weber, BL Eisen, A Peterson, LE Schildkraut, JM Isaacs, C Peshkin, BN Corio, C Leondaridis, L Tomlinson, G Dutsm, D Kerber, R Amos, CI Strong, LC Berry, DA Euthus, DM Parmigiani, G AF Chen, SN Iversen, ES Friebel, T Finkelstein, D Weber, BL Eisen, A Peterson, LE Schildkraut, JM Isaacs, C Peshkin, BN Corio, C Leondaridis, L Tomlinson, G Dutsm, D Kerber, R Amos, CI Strong, LC Berry, DA Euthus, DM Parmigiani, G TI Characterization of BRCA1 and BRCA2 mutations in a large United States sample SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER-SUSCEPTIBILITY; ASHKENAZI JEWISH CARRIERS; OVARIAN-CANCER; PROPHYLACTIC OOPHORECTOMY; GENETIC-HETEROGENEITY; FAMILIAL BREAST; FOLLOW-UP; RISK; PENETRANCE; SERIES AB Purpose F An accurate evaluation of the penetrance of BRCA1 and BRCA2 mutations is essential to the identification and clinical management of families at high risk of breast and ovarian cancer. Existing studies have focused on Ashkenazi Jews (AJ) or on families from outside the United States. In this article, we consider the US population using the largest US-based cohort to date of both AJ and non-AJ families. Methods We collected 676 AJ families and 1,272 families of other ethnicities through the Cancer Genetics Network. Two hundred eighty-two AJ families were population based, whereas the remainder was collected through counseling clinics. We used a retrospective likelihood approach to correct for bias induced by oversampling of participants with a positive family history. Our approach takes full advantage of detailed family history information and the Mendelian transmission of mutated alleles in the family. Results In the US population, the estimated cumulative breast cancer risk at age 70 years was 0.46 (95% CI, 0.39 to 0.54) in BRCA1 carriers and 0.43 (95% CI, 0.36 to 0.51) in BRCA2 carriers, whereas ovarian cancer risk was 0.39 (95% CI, 0.30 to 0.50) in BRCA1 carriers and 0.22 (95% CI, 0.14 to 0.32) in BRCA2 carriers. We also reported the prospective risks of developing cancer for cancer-free carriers in 10-yearage intervals. We noted a rapid decrease in the relative risk of breast cancer with age and derived its implication for genetic counseling. Conclusion The penetrance of BRCA mutations in the United States is largely consistent with previous studies on Western populations given the large Cls on existing estimates. However, the absolute cumulative risks are on the lower end of the spectrum. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD USA. Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. Duke Univ, Dept Community & Family Med, Durham, NC USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. GlaxoSmithKline Inc, Translat Med & Genet, W Chester, PA USA. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Univ Texas SW, Dept Pediat, Dallas, TX USA. Univ Texas SW, Dept Surg, Dallas, TX USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. Univ Utah, Huntsman Canc Ctr, Salt Lake City, UT USA. RP Chen, SN (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, 615 N Wolfe St,W7041, Baltimore, MD 21205 USA. EM sichen@jhsph.edu RI Kerber, Richard/B-8038-2009; OI Peterson, Leif/0000-0002-1187-0883 FU NCI NIH HHS [R01 CA105090-04, 5P30 CA06973-39, CA78146-01, P30 CA006973, P30 CA051008, P30-CA-51008, P50 CA062924, P50 CA088843, P50CA62924-05, P50CA88843, R01 CA105090, R01 CA105090-01A1, R01 CA105090-02, R01 CA105090-03, R01CA105090, U01 CA078284, U24 CA078146]; NHLBI NIH HHS [HL 99-024] NR 46 TC 162 Z9 166 U1 0 U2 0 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 FEB 20 PY 2006 VL 24 IS 6 BP 863 EP 871 DI 10.1200/JCO.2005.03.6772 PG 9 WC Oncology SC Oncology GA 014HF UT WOS:000235469700008 PM 16484695 ER PT J AU Redston, M Compton, CC Miedema, BW Niedziviecki, D Dowell, JM Jewell, SD Fleshman, JM Bem, J Mayer, RJ Bertagnolli, MM AF Redston, M Compton, CC Miedema, BW Niedziviecki, D Dowell, JM Jewell, SD Fleshman, JM Bem, J Mayer, RJ Bertagnolli, MM TI Analysis of micrometastatic disease in sentinel lymph nodes from resectable colon cancer: Results of Cancer and Leukemia Group B trial 80001 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID ISOLATED TUMOR-CELLS; COLORECTAL-CANCER; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; METASTASES; CARCINOMA; LYMPHADENECTOMY; ADENOCARCINOMA; MULTICENTER; VALIDATION AB Purpose To determine whether sentinel lymph node (LN) sampling (SLNS) could reduce the number of nodes required to characterize micrometastatic disease (MMD) in patients with potentially curable colon cancer. Patients and Methods Cancer and Leukemia Group B 80001 was a study to determine whether SLNS could identify a subset of LNs that predicted the status of the nodal basin for resectable colon cancer and, therefore, could be extensively evaluated for the presence of micrometastases. Patients enrolled onto this study underwent SLNS after injection of 1 % isosulfan blue, and both sentinel nodes (SNs) and non-SNs obtained during primary tumor resection were sectioned at multiple levels and stained using anti-carcinoembryonic antigen and anticytokeratin antibodies. Results Using standard histopathology, SNs failed to predict the presence of nodal disease in 13 (54%) of 24 node-positive patients. Immunostains were performed for patients whose LNs were negative by standard histopathology. Depending on the immunohistochemical criteria used to assign LN positivity, SN examination resulted in either an unacceptably high false-positive rate (20%) or a low sensitivity for detection of MMD (40%). Conclusion By examining both SNs and non-SNs, this multi-institutional study showed that SNs did not accurately predict the presence of either conventionally defined nodal metastases or MMD. As a result, SLNS is not a useful technique for the study of MMD in patients with colon cancer. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. Washington Univ, Med Ctr, St Louis, MO USA. Duke Univ, Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Ohio State Univ, Columbus, OH 43210 USA. SUNY Upstate Med Univ, Syracuse, NY USA. Vet Adm Med Ctr, Syracuse, NY 13210 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org FU NCI NIH HHS [CA59594, CA31946] NR 28 TC 50 Z9 50 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2006 VL 24 IS 6 BP 878 EP 883 DI 10.1200/JCO.2005.03.6038 PG 6 WC Oncology SC Oncology GA 014HF UT WOS:000235469700010 PM 16418493 ER PT J AU Gordon, HS Street, RL Sharf, BF Kelly, PA Souchek, J AF Gordon, HS Street, RL Sharf, BF Kelly, PA Souchek, J TI Racial differences in trust and lung cancer patients' perceptions of physician communication SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc General Internal Med ID PRIMARY-CARE PHYSICIANS; ETHNIC DISPARITIES; AFRICAN-AMERICANS; HEALTH-CARE; OUTCOMES; STYLE; CONSULTATIONS; CHEMOTHERAPY; SATISFACTION; RELIABILITY AB Purpose Black patients report lower trust in physicians than white patients, but this difference is poorly studied. We examined whether racial differences in patient trust are associated with physician-patient communication about lung cancer treatment. Patients and Methods Data were obtained for 103 patients (22% black and 78% white) visiting thoracic surgery or oncology clinics in a large Southern Veterans Affairs hospital for initial treatment recommendation for suspicious pulmonary nodules or lung cancer. Questionnaires were used to determine patients' perceptions of the quality of the physicians' communication and were used to assess patients' previsit and postvisit trust in physician and trust in health care system. Patients responded on a 10-point scale. Results Previsit trust in physician was statistically similar in black and white patients (mean score, 8.2 v 8.3, respectively; P = .80), but black patients had lower postvisit trust in physician than white patients (8.0 v 9.3, respectively; P = .02). Black patients, compared with white patients, judged the physicians' communication as less informative (7.3 v 8.5, respectively; P = .03), less supportive (8.1 v 9.3, respectively; P = .03), and less partnering (6.4 v 8.2, respectively; P = .001). In mixed linear regression analysis, controlling for clustering of patients by physician, patients' perceptions of physicians' communication were statistically significant (P < .005) predictors of postvisit trust, although patient race, previsit trust, and patient and visit characteristics were not significant (P > .05) predictors. Conclusion Perceptions that physician communication was less supportive, less partnering, and less informative accounted for black patients' lower trust in physicians. Our findings raise concern that black patients may have lower trust in their physicians in part because of poorer physician-patient communication. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Dept Internal Med, Houston, TX 77030 USA. Texas A&M Univ, Dept Commun, College Stn, TX 77843 USA. RP Gordon, HS (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM hgordon@bcm.tmc.edu RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 FU AHRQ HHS [P01 HS10876] NR 46 TC 151 Z9 152 U1 2 U2 10 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 FEB 20 PY 2006 VL 24 IS 6 BP 904 EP 909 DI 10.1200/JCO.2005.03.1955 PG 6 WC Oncology SC Oncology GA 014HF UT WOS:000235469700014 PM 16484700 ER PT J AU Barlogie, B Kyle, RA Anderson, KC Greipp, PR Lazarus, HM Hurd, DD McCoy, J Dakhil, SR Lanier, KS Chapman, RA Cromer, JN Salmon, SE Durie, B Crowley, JC AF Barlogie, B Kyle, RA Anderson, KC Greipp, PR Lazarus, HM Hurd, DD McCoy, J Dakhil, SR Lanier, KS Chapman, RA Cromer, JN Salmon, SE Durie, B Crowley, JC TI Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: Final results of phase III US intergroup trial S9321 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; RANDOMIZED-TRIAL; ALLOGENEIC TRANSPLANTATION; AUTOLOGOUS TRANSPLANTATION; MARROW TRANSPLANTATION; MAINTENANCE TREATMENT; PROGNOSTIC-FACTORS; STAGING SYSTEM; BONE-MARROW; THERAPY AB Purpose Results of a prospective randomized trial conducted by the Intergroupe Francais du Myelome (IFM 90) indicated that autologous hematopoietic cell-supported high-dose therapy (HDT) effected higher complete response rates and extended progression-free survial (PFS) and overall survival (OS) compared with standard-dose therapies (SDT) for patients with multiple myeloma (MM). Patients and Methods In 1993, three North American cooperative groups launched a prospective randomized trial (S9321) comparing HDT (melphalan [MEL] 140 mg/m(2) plus total-body irradiation 12 Gy) with SDT using the vincristine, carmustine, MEL, cyclophosphamide, and prednisone regimen. Responders on both arms (>= 75%) were randomly assigned to interferon (IFN) or no maintenance treatment. Results With a median follow-up time of 76 months, no differences were observed in response rates between the two study arms (HDT, n = 261 patients; SDT, In = 255 patients). Similarly, PFS and OS durations did not differ between the HDT and SDT arms, with 7-year estimates of PFS of 17% and 16%, respectively, and OS of 37% and 42%, respectively. Of 242 patients achieving at least 75% tumor reduction, no difference was observed in PFS or OS among the 121 patients randomly assigned to IFN and the 121 patients randomly assigned to no maintenance therapy. Among 157 patients relapsing on SDT, 87 received a salvage autotransplantation; their median survival time of 30 months was only slightly better than the survival time of the remaining patients who were managed with further SDT (23 months; P = .13). Conclusion The HDT and SDT regimens used in S9321 yielded comparable response rates and PFS and OS durations. IFN maintenance therapy did not benefit patients who achieved >= 75% tumor reduction on either arm. C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Wichita Community Clin Oncol Program, Wichita, KS USA. Columbia River Community Clin Oncol Program, Portland, OR USA. Henry Ford Hosp, Detroit, MI 48202 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Univ Arizona, Ctr Canc, Tucson, AZ 85721 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Barlogie, B (reprint author), SW Oncol Grp, Operat Off, SWOG-9321,14980 Omicron Dr, San Antonio, TX 78245 USA. FU NCI NIH HHS [CA16385, CA03927, CA04919, CA04920, CA12644, CA13612, CA13650, CA14028, CA14548, CA20319, CA22433, CA27057, CA31946, CA32102, CA32291, CA35090, CA35117, CA35119, CA35192, CA35261, CA35431, CA37981, CA38926, CA42777, CA45377, CA45450, CA45560, CA46113, CA46282, CA46368, CA46441, CA52654, CA58415, CA58416, CA58658, CA58686, CA58861, CA63844, CA63845, CA67575, CA68183, CA74647, CA76132, CA76429, CA76447, CA76462] NR 36 TC 283 Z9 305 U1 0 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 FEB 20 PY 2006 VL 24 IS 6 BP 929 EP 936 DI 10.1200/JCO.2005.04.5807 PG 8 WC Oncology SC Oncology GA 014HF UT WOS:000235469700018 PM 16432076 ER PT J AU Pasqualucci, L Compagno, M Houldsworth, J Monti, S Grunn, A Nandula, SV Aster, JC Murty, VV Shipp, MA Dalla-Favera, R AF Pasqualucci, L Compagno, M Houldsworth, J Monti, S Grunn, A Nandula, SV Aster, JC Murty, VV Shipp, MA Dalla-Favera, R TI Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NON-HODGKINS-LYMPHOMA; BLIMP-1 EXPRESSION; DIFFERENTIATION; LYMPHOCYTES; TRANSCRIPTION; MATURATION; REPRESSION; SUBGROUPS; PRDI-BF1; BIOLOGY AB PR domain containing 1 with zinc finger domain (PRDM1)/B lymphocyte-induced maturation protein 1 (BLIMP1) is a transcriptional repressor expressed in a subset of germinal center (GC) B cells and in all plasma cells, and required for terminal B cell differentiation. The BLIMP1 locus lies on chromosome 6q21-q22.1, a region frequently deleted in B cell lymphomas, suggesting that it may harbor a tumor suppressor gene. We report here that the BLIMP1 gene is inactivated by structural alterations in 24% (8 out of 34) activated B cell-like diffuse large cell lymphoma (ABC-DLBCL), but not in GC B cell-like (n = 0/37) or unclassified (n = 0/21) DLBCL. BLIMP1 alterations included gene truncations, nonsense mutations, frameshift deletions, and splice site mutations that generate aberrant transcripts encoding truncated BLIMP1 proteins. In all cases studied, both BLIMP1 alleles were inactivated by deletions or mutations. Furthermore, most non-GC type DLBCL cases (n = 20/26, 77%) lack BLIMP1 protein expression, despite the presence of BLIMP1 mRNA. These results indicate that a sizable fraction of ABC-DLBCL carry an inactive BLIMP1 gene, and suggest that the same gene is inactivated by epigenetic mechanisms in an additional large number of cases. These findings point to a role for BLIMP1 as a tumor suppressor gene, whose inactivation may contribute to lymphomagenesis by blocking post-GC differentiation of B cells toward plasma cells. C1 Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. Mem Sloan Kettering Canc Ctr, Canc Genet Lab, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dalla-Favera, R (reprint author), Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. EM rd10@columbia.edu OI Monti, Stefano/0000-0002-9376-0660 FU NCI NIH HHS [P01 CA092625, CA-092625] NR 27 TC 196 Z9 205 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 20 PY 2006 VL 203 IS 2 BP 311 EP 317 DI 10.1084/jem.20052204 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 017QI UT WOS:000235707700010 PM 16492805 ER PT J AU Blutt, SE Warfield, KL O'Neal, CM Estes, MK Conner, ME AF Blutt, SE Warfield, KL O'Neal, CM Estes, MK Conner, ME TI Host, viral, and vaccine factors that determine protective efficacy induced by rotavirus and virus-like particles (VLPs) SO VACCINE LA English DT Article DE virus-like particles; rotavirus; protective immunity ID SECRETING CELL RESPONSES; CHIMERIC VP6 PROTEIN; INTRANASAL IMMUNIZATION; IMMUNE-RESPONSES; GNOTOBIOTIC PIGS; 2/6-ROTAVIRUS-LIKE PARTICLES; INDEPENDENT PROTECTION; ANTIBODY-RESPONSES; CAPSID PROTEINS; MICE AB Critical factors that are important in protection from rotavirus infection have remained elusive. We demonstrate here that inbred mice (C57BL/6 and BALB/c) exhibit differences in: (1) susceptibility to and (2) VLP-induced protection from rotavirus infection. Comparing protection induced by 2/4/6/7-VLPs with inactivated and live rotavirus, intranasally induced protection was dependent on dsRNA or minor structural proteins and correlated with intestinal antibody, while orally induced protection required immunization with replicating virus. Combination oral/intranasal vaccination did not improve VLP protective efficacy. These studies indicate that host, viral, and vaccine factors determine the level of protective efficacy induced by VLPs. (c) 2005 Elsevier Ltd. All rights reserved. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Michael E Debakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Conner, ME (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mconner@bcm.tmc.edu FU NIAID NIH HHS [AI24998, AI10604]; NIDDK NIH HHS [DK56338] NR 48 TC 30 Z9 31 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 20 PY 2006 VL 24 IS 8 BP 1170 EP 1179 DI 10.1016/j.vaccine.2005.08.090 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 016VD UT WOS:000235647900015 PM 16191453 ER PT J AU Wang, C Hayes, B Vestling, MM Takayama, K AF Wang, C Hayes, B Vestling, MM Takayama, K TI Transposome mutagenesis of an integral membrane transporter in Corynebacterium matruchotii SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE trehalose corynomycolates; Corynomycolic acid; ATP-binding cassette transporter; Tn5 mutagenesis; MALDI mass spectrometry; Mycobacterium tuberculosis ID MYCOBACTERIUM-TUBERCULOSIS; MYCOLIC ACIDS; CELL-WALL; BIOSYNTHESIS; TREHALOSE AB A transposon-5 insertion library of Corynebacterium matruchotii ATCC14266 was generated and screened for mutants with altered corynomycolic acid content. One of these designated 319 mutants showed an interruption of a gene encoding an integral membrane protein. MALDI mass spectra of trehalose monocorynomycolate (TMCM), trehalose dicorynomycolate, and methyl corynomycolates derived from cell wall arabinogalactan-corynomycolate showed that these lipids from the mutant contained a lower amount of shortchain (C-24 to C-34) and much greater amount of long-chain (primarily C-36:2) corynomycolic acids than the wild type. An analysis of mRNA demonstrated that the integral membrane protein and ATP-binding cassette transporter are transcriptionally coupled. These results suggested that the proteins/enzymes encoded by the membrane transporter gene locus preferably move short-chain corynomycolic acids from the cytoplasm across the membrane bilayer to the periplasmic space where the synthesis of TMCM is thought to occur. This is the first evidence linking corynomycolic acid to a transporter gene locus. published by Elsevier Inc. C1 William S Middleton Mem Vet Adm Med Ctr, Mycobacteriol Res Lab, Madison, WI 53705 USA. Univ Wisconsin, Dept Chem, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. RP Takayama, K (reprint author), William S Middleton Mem Vet Adm Med Ctr, Mycobacteriol Res Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. EM Kuni.Takayama@med.va.gov NR 16 TC 10 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 17 PY 2006 VL 340 IS 3 BP 953 EP 960 DI 10.1016/j.bbrc.2005.12.097 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 009DR UT WOS:000235092000030 PM 16403458 ER PT J AU Benassi, B Fanciulli, M Fiorentino, F Porrello, A Chiorino, G Loda, M Zupi, G Biroccio, A AF Benassi, B Fanciulli, M Fiorentino, F Porrello, A Chiorino, G Loda, M Zupi, G Biroccio, A TI c-Myc phosphorylation is required for cellular response to oxidative stress SO MOLECULAR CELL LA English DT Article ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; NAPHTHOFLAVONE-INDUCED EXPRESSION; REGULATORY SUBUNIT GENE; HUMAN-MELANOMA CELLS; INDUCED APOPTOSIS; GENOMIC TARGETS; UP-REGULATION; GLUTATHIONE; PROTEINS; PATHWAYS AB Aside from the well-established roles of c-Myc in the regulation of cell cycle, differentiation, and apoptosis, a recent picture is beginning to emerge linking c-Myc to the regulation of metabolic pathways. Here, we define a further function for c-Myc in determining cellular redox balance, identifying glutathione (GSH) as the leading molecule mediating this process. The link between c-Myc and GSH is gamma-glutamyl-cysteine synthetase (gamma-GCS), the rate-limiting enzyme catalyzing GSH biosynthesis. Indeed, c-Myc transcriptionally regulates gamma-GCS by binding and activating the promoters of both gamma-GCS heavy and light subunits. Exposure to H2O2 enhances c-Myc recruitment to gamma-GCS regulatory regions through ERK-dependent phosphorylation. Phosphorylation at Ser-62 is required for c-Myc recruitment to gamma-GCS promoters and determines the cellular response to oxidative stress induced by different stimuli. Thus, the c-Myc phosphorylation-dependent activation of the GSH-directed survival pathway can contribute to oxidative stress resistance in tumor cells, which generally exhibit deregulated c-Myc expression. C1 Duke Univ, Expt Chemotherapy Lab, Durham, NC 27708 USA. Duke Univ, Lab B, Expt Res Ctr, Regina Elena Canc Inst, Durham, NC 27708 USA. Genoma Mol Genet Lab, Rome, Italy. Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. Regina Elena Inst Canc Res, Expt Res Ctr, Mol Oncogenesis Lab, Rome, Italy. Canc Genom Lab, Biella, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Biroccio, A (reprint author), Duke Univ, Expt Chemotherapy Lab, Durham, NC 27708 USA. EM biroccio@ifo.it RI Chiorino, Giovanna/K-5037-2016; OI Chiorino, Giovanna/0000-0002-9502-6400; Biroccio, Annamaria/0000-0003-3198-3532 NR 40 TC 93 Z9 98 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD FEB 17 PY 2006 VL 21 IS 4 BP 509 EP 519 DI 10.1016/j.molcel.2006.01.009 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 016EC UT WOS:000235602500009 PM 16483932 ER PT J AU Vasudevan, A Breakefield, XO Bhide, PG AF Vasudevan, A Breakefield, XO Bhide, PG TI Developmental patterns of torsinA and torsinB expression SO BRAIN RESEARCH LA English DT Article DE torsion dystonia; brain development ID VISUAL-CORTEX; POSTNATAL-DEVELOPMENT; NEURONAL MIGRATION; RAT NEOSTRIATUM; DYT1 DYSTONIA; DENTATE GYRUS; CELLS; CONNECTIONS; PROTEIN; BRAIN AB Early onset torsion dystonia is characterized by involuntary movements and distorted postures and is usually caused by a 3-bp (GAG) deletion in the DYT1 (TOR1A) gene. DYT1 codes for torsinA, a member of the AAA(+) family of proteins, implicated in membrane recycling and chaperone functions. A close relative, torsinB may be involved in similar cellular functions. We investigated torsinA and torsinB message and protein levels in the developing mouse brain. TorsinA expression was highest during prenatal and early postnatal development (until postnatal day 14; P14), whereas torsinB expression was highest during late postnatal periods (from P14 onwards) and in the adult. In addition, significant regional variation in the expression of the two torsins was seen within the developing brain. Thus, torsinA expression was highest in the cerebral cortex from embryonic day 15 (E15)-E17 and in the striatum from E17-P7, while torsinB was highest in the cerebral cortex between P7-P14 and in the striatum from P7-P30. TorsinA was also highly expressed in the thalamus from P0-P7 and in the cerebellum from P7-P14. Although functional significance of the patterns of torsinA and B expression in the developing brain remains to be established, our findings provide a basis for investigating the role of torsins in specific processes such as neurogenesis, neuronal migration, axon/dendrite development, and synaptogenesis. Published by Elsevier B.V. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02129 USA. RP Vasudevan, A (reprint author), Massachusetts Gen Hosp, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. EM avasudevan@bics.bwh.harvard.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU NINDS NIH HHS [P01 NS37409, P01 NS037409] NR 51 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 16 PY 2006 VL 1073 BP 139 EP 145 DI 10.1016/j.brainres.2005.12.087 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 030VE UT WOS:000236662400016 PM 16458269 ER PT J AU Christakis, NA Allison, PD AF Christakis, NA Allison, PD TI Mortality after the hospitalization of a spouse SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MEDICARE CLAIMS; OLDER PERSONS; HEALTH-CARE; DEATH; CAREGIVERS; INFORMATION; DEMENTIA; DISEASES; DECLINE; BURDEN AB BACKGROUND: The illness of a spouse can affect the health of a caregiving partner. We examined the association between the hospitalization of a spouse and a partner's risk of death among elderly people. METHODS: We studied 518,240 couples who were enrolled in Medicare in 1993. We used Cox regression analysis and fixed-effects (case-time-control) methods to assess hospitalizations and deaths during nine years of follow-up. RESULTS: Overall, 383,480 husbands (74 percent) and 347,269 wives (67 percent) were hospitalized at least once, and 252,557 husbands (49 percent) and 156,004 wives (30 percent) died. Mortality after the hospitalization of a spouse varied according to the spouse's diagnosis. Among men, 6.4 percent died within a year after a spouse's hospitalization for colon cancer, 6.9 percent after a spouse's hospitalization for stroke, 7.5 percent after a spouse's hospitalization for psychiatric disease, and 8.6 percent after a spouse's hospitalization for dementia. Among women, 3.0 percent died within a year after a spouse's hospitalization for colon cancer, 3.7 percent after a spouse's hospitalization for stroke, 5.7 percent after a spouse's hospitalization for psychiatric disease, and 5.0 percent after a spouse's hospitalization for dementia. After adjustment for measured covariates, the risk of death for men was not significantly higher after a spouse's hospitalization for colon cancer (hazard ratio, 1.02; 95 percent confidence interval, 0.95 to 1.09) but was higher after hospitalization for stroke (hazard ratio, 1.06; 95 percent confidence interval, 1.03 to 1.09), congestive heart failure (hazard ratio, 1.12; 95 percent confidence interval, 1.07 to 1.16), hip fracture (hazard ratio, 1.15; 95 percent confidence interval, 1.11 to 1.18), psychiatric disease (hazard ratio, 1.19; 95 percent confidence interval, 1.12 to 1.26), or dementia (hazard ratio, 1.22; 95 percent confidence interval, 1.12 to 1.32). For women, the various risks of death after a spouse's hospitalization were similar. Overall, for men, the risk of death associated with a spouse's hospitalization was 22 percent of that associated with a spouse's death (95 percent confidence interval, 17 to 27 percent); for women, the risk was 16 percent of that associated with death (95 percent confidence interval, 8 to 24 percent). CONCLUSIONS: Among elderly people hospitalization of a spouse is associated with an increased risk of death, and the effect of the illness of a spouse varies among diagnoses. Such interpersonal health effects have clinical and policy implications for the care of patients and their families. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Palliat Care Serv, Boston, MA 02114 USA. Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA. Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. RP Christakis, NA (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM christakis@hcp.med.harvard.edu RI Allison, Paul/A-1345-2007; Christakis, Nicholas/B-6690-2008; Christakis, Nicholas/C-3205-2009 OI Allison, Paul/0000-0002-0646-5242; FU NIA NIH HHS [R-01 AG17548-01] NR 37 TC 202 Z9 209 U1 3 U2 22 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 FEB 16 PY 2006 VL 354 IS 7 BP 719 EP 730 DI 10.1056/NEJMsa050196 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 012CP UT WOS:000235316100008 PM 16481639 ER PT J AU Walton, DS Mukai, S Grabowski, EF Munzenrider, JE Dryja, TP Wiegand, T Mukai, S Harris, NL AF Walton, DS Mukai, S Grabowski, EF Munzenrider, JE Dryja, TP Wiegand, T Mukai, S Harris, NL TI An 11-year-old girl with loss of vision in the right eye - Retinoblastoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DIFFUSE INFILTRATING RETINOBLASTOMA; PROTON-RADIATION-THERAPY; CANCER; SKULL; BASE; RISK; DIAGNOSIS; CHILDREN; TUMORS C1 Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Walton, DS (reprint author), Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. NR 30 TC 5 Z9 5 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 FEB 16 PY 2006 VL 354 IS 7 BP 741 EP 748 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 012CP UT WOS:000235316100012 PM 16481642 ER PT J AU Finkelstein, JS AF Finkelstein, JS TI Calcium plus vitamin D for postmenopausal women - Bone appetit? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; D SUPPLEMENTATION; PREVENTION; FRACTURES; METAANALYSIS; DENSITY; OSTEOPOROSIS; PROGESTIN C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [K24 DK02759] NR 13 TC 21 Z9 24 U1 0 U2 0 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 FEB 16 PY 2006 VL 354 IS 7 BP 750 EP 752 DI 10.1056/NEJMe068007 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 012CP UT WOS:000235316100013 PM 16481643 ER PT J AU Mehta, SS Silver, RJ Aaronson, A Abraharnson, M Goldfine, AB AF Mehta, SS Silver, RJ Aaronson, A Abraharnson, M Goldfine, AB TI Comparison of aspirin resistance in type 1 versus type 2 diabetes mellitus SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; FUNCTION ASSAY-ASA; LOW-DOSE ASPIRIN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PRIMARY PREVENTION; PLATELET; STROKE; PREVALENCE; EVENTS AB This study sought to determine the frequency of aspirin resistance in an ambulatory population of patients with type 1 diabetes mellitus (T1D) or type 2 diabetes mellitus (T2D). Platelet aggregation was assessed during the routine clinical evaluation of 203 ambulatory patients with diabetes (T1D, n = 92; T2D, n = 111) who were recommended aspirin for primary or secondary cardiovascular. protection. Consecutively received laboratory samples were evaluated using the Ultegra Rapid Platelet Function Assay-ASA. Resistance to aspirin was detected in 18.7% of diabetic aspirin users, with similar rates in T1D, (21.7%, p = 0.5) and T2D (16.2%, p = 0.6). Aspirin resistance was not related to age, glycohemoglobin, total cholesterol, or a history of cardiovascular disease. Female gender was a strong independent predictor of aspirin resistance in patients with T1D (p = 0.001). Platelet aggregation was correlated with high-density lipoprotein (HDL) cholesterol in the entire cohort (r = 0.21, p = 0.005) and in patients with T1D (r = 0.32, p = 0.04) or T2D (r = 0.21, p = 0.04), such that patients with low HDL cholesterol levels were more likely to be aspirin sensitive. The results suggest that aspirin can inhibit platelet aggregation in most patients with diabetes and is a reasonable first-line antiplatelet agent in patients with diabetes. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Goldfine, AB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM allison.goldfine@joslin.harvard.edu FU NIDDK NIH HHS [K23-DK02795] NR 20 TC 32 Z9 33 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 15 PY 2006 VL 97 IS 4 BP 567 EP 570 DI 10.1016/j.amjcard.2005.09.093 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 014KP UT WOS:000235479200026 PM 16461058 ER PT J AU Jick, SS Lieberman, ES Rahman, MU Choi, HK AF Jick, SS Lieberman, ES Rahman, MU Choi, HK TI Glucocorticoid use, other associated factors, and the risk of tuberculosis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE glucocorticoid; adiposity; smoking; tuberculosis; bronchitis; emphysema ID RHEUMATOID-ARTHRITIS; MYCOBACTERIUM-TUBERCULOSIS; THERAPY; POPULATION; INFLIXIMAB; INFECTION; DISEASES; SMOKING AB Objective. To evaluate the association of glucocorticoids and other purported risk factors with the development of tuberculosis. Methods. We conducted a case-control study of tuberculosis cases identified during 1990-2001 using the General Practice Research Database in the United Kingdom. Cases were patients with a first time diagnosis of tuberculosis accompanied by at least 6 months of treatment with at least 3 different tuberculosis medications. Up to 4 controls were matched to each case on age, sex, the practice attended by the case, index date, and amount of prior computerized records. Results. The study encompassed 497 new cases of tuberculosis and 1,966 controls derived from 16,629,041 person-years at risk (n = 2,757,084 persons). The adjusted odds ratio (OR) of tuberculosis for current use of a glucocorticoid compared with no use was 4.9 (95% confidence interval [95% CI] 2.9-8.3). The adjusted ORs for use of < 15 mg and >= 15 mg of prednisone or its equivalent daily dose were 2.8 (95% CI 1.0-7.9) and 7.7 (95% CI 2.8-21.4), respectively. Adjusted ORs of tuberculosis were 2.8 for patients with a body mass index (BMI) < 20 compared with normal BMI; 1.6 for current smokers compared with nonsmokers; and 3.8, 3.2, 2.0, and 1.4 for those with history of diabetes, emphysema, bronchitis, and asthma, respectively, compared with those without such history (all P values < 0.05). Conclusion. These results indicate that patients treated with glucocorticoids have an increased risk of developing tuberculosis, independent of other risk factors. Low adiposity, diabetes, current smoking, and obstructive pulmonary disorders are also important independent risk factors for tuberculosis. C1 Boston Univ, Sch Med, Boston Collaborat Drug Surveillance Program, Lexington, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Summit Med Grp, Summit, NJ USA. Centocor Inc, Malvern, PA 19355 USA. RP Choi, HK (reprint author), Univ British Columbia, Dept Med, Div Rheumatol, Arthrit Res Ctr Canada, 895 W 10th Ave, Vancouver, BC V5Z 1L7, Canada. EM hchoi@partners.org RI Research Datalink, Clinical Practice/H-2477-2013; CPRD, CPRD/B-9594-2017; OI Jick, Susan/0000-0002-2215-1067 NR 22 TC 148 Z9 151 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD FEB 15 PY 2006 VL 55 IS 1 BP 19 EP 26 DI 10.1002/art.21705 PG 8 WC Rheumatology SC Rheumatology GA 032UI UT WOS:000236800400007 PM 16463407 ER PT J AU Becton, D Dahl, GV Ravindranath, Y Chang, MN Behm, FG Raimondi, SC Head, DR Stine, KC Lacayo, NJ Sikic, BI Arceci, RJ Weinstein, H AF Becton, D Dahl, GV Ravindranath, Y Chang, MN Behm, FG Raimondi, SC Head, DR Stine, KC Lacayo, NJ Sikic, BI Arceci, RJ Weinstein, H TI Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421 SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CYTARABINE; CANCER RESISTANCE PROTEIN; MULTIDRUG-RESISTANCE; CONSOLIDATION CHEMOTHERAPY; CLINICAL-SIGNIFICANCE; COOPERATIVE GROUP; EXPRESSION; MITOXANTRONE AB Relapse is a major obstacle in the cure of acute myeloid leukemia (AML). The Pediatric Oncology Group AML Study 9421 tested 2 different strategies to improve event-free survival (EFS) and overall survival (OS). Patients were randomized to receive standard-dose DAT (daunorubicin, cytarabine, and thioguanine) or high-dose DAT during induction. To interfere with P-glycoprotein (P-g p)-dependent drug efflux, the second randomization tested the benefit of cyclosporine (CsA) added to consolidation chemotherapy. Of the 282 children randomly assigned to receive standard DAT induction, 248 (87.9%) achieved remission compared to 253 (91%) of the 278 receiving high-dose DAT (P = ns). Children with HLA-identical sibling donors who achieved a complete remission received an allogeneic bone marrow transplant as consolidation. For the 83 patients receiving a matched related donor bone marrow transplantation (BMT), the 3-year disease-free survival (DFS) is 67%. Of the 418 children who achieved remission and went on to consolidation with and without CsA, the DFS was 40.6% and 33.9%, respectively (P = .24). Overexpression of P-gp was infrequent (14%) in this pediatric population. In this study, intensifying induction with high-dose DAT and the addition of CsA to consolidation chemotherapy did not prolong the durations of remission or improve overall survival for children with AML. C1 Stanford Univ, Sch Med, Div Pediat Hematol Oncol, Palo Alto, CA 94304 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Ctr Data, Childrens Oncol Grp, Gainesville, FL USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Vanderbilt Childrens Hosp, Nashville, TN USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Oncol Grp, Arcadia, CA USA. RP Stanford Univ, Sch Med, Dept Pediat, Div Hematol Oncol, BMT,1000 Welch Rd,Suite 300, Palo Alto, CA 94304 USA. EM gary.dahl@stanford.edu FU NCI NIH HHS [R01 CA90916] NR 40 TC 52 Z9 53 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD FEB 15 PY 2006 VL 107 IS 4 BP 1315 EP 1324 DI 10.1128/blood-2004-08-3218 PG 10 WC Hematology SC Hematology GA 011VH UT WOS:000235296100018 PM 16254147 ER PT J AU Hirano, N Butler, MO Xia, Z Ansen, S von Bergwelt-Baildon, MS Neuberg, D Freeman, GJ Nadler, LM AF Hirano, N Butler, MO Xia, Z Ansen, S von Bergwelt-Baildon, MS Neuberg, D Freeman, GJ Nadler, LM TI Engagement of CD83 ligand induces prolonged expansion of CD8(+) T cells and preferential enrichment for antigen specificity SO BLOOD LA English DT Article ID DENDRITIC CELLS; PRESENTING CELLS; LYMPHOCYTE RESPONSES; DROSOPHILA CELLS; IN-VITRO; B-CELLS; IMMUNOTHERAPY; EXPRESSION; INDUCTION; SUPERFAMILY AB Following T-cell receptor and CD28 signaling, CD8(+) T cells express a receptor for CD83, a molecule up-regulated on functionally mature dendritic cells. Although this expression pattern suggests that CD83 is involved in adaptive immunity, little is known about its function in the periphery, and the existence of its ligand on T cells is controversial. We demonstrate that the engagement of the CD83 ligand (CD83L) preferentially enriches and significantly amplifies the number of antigen-specific CD8(+) T cells. Coengagement of the T-cell receptor, CD28, and CD83L supports priming of naive CD8(+) T cells that retain antigen specificity and cytotoxic function for more than 6 months. Therefore, engagement of the CD83L provides a unique signal to activated CD8+ T cells that could be exploited to generate long-lived antigen-specific cytotoxic T cells for the treatment of cancer and infection. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Computat Biol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hirano, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02215 USA. EM naoto_hirano@dfci.harvard.edu FU NCI NIH HHS [CA84500, CA87720, CA92625-04]; NHLBI NIH HHS [HL54785-08]; NIAID NIH HHS [AI56299] NR 37 TC 85 Z9 91 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2006 VL 107 IS 4 BP 1528 EP 1536 DI 10.1182/blood-2005-05-2073 PG 9 WC Hematology SC Hematology GA 011VH UT WOS:000235296100045 PM 16239433 ER PT J AU Ge, YB Dombkowski, AA LaFiura, KM Tatman, D Yedidi, RS Stout, ML Buck, SA Massey, G Becton, DL Weinstein, HJ Ravindranath, Y Matherly, LH Taub, JW AF Ge, YB Dombkowski, AA LaFiura, KM Tatman, D Yedidi, RS Stout, ML Buck, SA Massey, G Becton, DL Weinstein, HJ Ravindranath, Y Matherly, LH Taub, JW TI Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE MEGAKARYOBLASTIC LEUKEMIA; HIGH CURE RATE; MYELODYSPLASTIC SYNDROME; CYTOSINE-ARABINOSIDE; CYTIDINE DEAMINASE; MOLECULAR-CLONING; DIRECT-CONTACT; CELL LINES; CHILDREN AB Children with Down syndrome (DS) with acute megakaryocytic leukemia (AMkL) have very high survival rates compared with non-DS AMkL patients. Somatic mutations identified in the X-linked transcription factor gene, GATA1, in essentially all DS AMkL cases result in the synthesis of a shorter (40 kDa) protein (GATA1s) with altered transactivation activity and may lead to altered expression of GATA1 target genes. Using the Affymetrix U133A microarray chip, we identified 551 differentially expressed genes between DS and non-DS AMkL samples. Transcripts for the bone marrow stromal-cell antigen 2 (BST2) gene, encoding a transmembrane glycoprotein potentially involved in interactions between leukemia cells and bone marrow stromal cells, were 7.3-fold higher (validated by real-time polymerase chain reaction) in the non-DS compared with the DS group. Additional studies confirmed GATA1 protein binding and transactivation of the BST2 promoter; however, stimulation of BST2 promoter activity by GATA1s was substantially reduced compared with the full-length GATA1. CMK sublines, transfected with the BST2 cDNA and incubated with HS-5 bone marrow stromal cells, exhibited up to 1.7-fold reduced cytosine arabinoside (ara-C)-induced apoptosis, compared with mock-transfected cells. Our results demonstrate that genes that account for differences in survival between IDS and non-DS AMkL cases may be identified by microarray analysis and that differential geneexpression may reflect relative trans-activation capacities of the GATA1s and full-length GATA1 proteins. C1 Childrens Hosp, Div Pediat Hematol Oncol, Detroit, MI 48201 USA. Wayne State Univ, Expt & Clin Therapeut Program, Barbara Ann Karmanos Canc Inst, Inst Environm Hlth Sci, Detroit, MI USA. Wayne State Univ, Dept Pediat & Pharmacol, Sch Med, Detroit, MI USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Univ Arkansas, Little Rock, AR 72204 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Taub, JW (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM jtaub@med.wayne.edu OI Yedidi, Ravikiran/0000-0003-2755-1307 FU NCI NIH HHS [R01 CA92308]; NIEHS NIH HHS [P30 ES06639] NR 32 TC 64 Z9 66 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2006 VL 107 IS 4 BP 1570 EP 1581 DI 10.1182/blood-2005-06-2219 PG 12 WC Hematology SC Hematology GA 011VH UT WOS:000235296100050 PM 16249385 ER PT J AU Spencer, BA Babey, SH Etzioni, DA Ponce, NA Brown, ER Yu, HJ Chawla, N Litwin, MS AF Spencer, BA Babey, SH Etzioni, DA Ponce, NA Brown, ER Yu, HJ Chawla, N Litwin, MS TI A population-based survey of prostate-specific antigen testing among California men at higher risk for prostate carcinoma SO CANCER LA English DT Article DE prostate carcinoma; prostate-specific antigen; screening; high risk; African American ID AFRICAN-AMERICAN MEN; CANCER SCREENING PRACTICES; RADICAL PROSTATECTOMY; MORTALITY-RATES; RELATIVE RISK; UNITED-STATES; WHITE MEN; TRENDS; UPDATE; METAANALYSIS AB BACKGROUND. Despite the lack of evidence demonstrating a survival benefit from prostate-specific antigen (PSA) screening, its use has become widespread, organizations have encouraged physicians to discuss early detection of prostate carcinoma, and two higher risk groups have been recognized. In the current study, the authors examined whether African-American men and men who had a family history of prostate carcinoma underwent PSA testing preferentially, and patterns of test use were examined according to age, race, and other factors. METHODS. Data regarding self-reported PSA test use in the past year among men age 50 years and older Without a history of prostate carcinoma (n = 8713 men) were analyzed from the 2001 California Health Interview Survey. RESULTS. The overall rate of PSA use was 43.0%. Older age, higher socioeconomic status, having a usual Source of healthcare, and a family history of prostate carcinoma were the strongest predictors of testing. Higher risk African-American men age 50 years and older were no more likely to be tested than white men. Men at higher risk who had a family history of prostate carcinoma were more likely to have been tested than men who had no such family history. CONCLUSIONS. Rates of PSA use among higher risk men who had a family history of prostate carcinoma were higher compared with the rates among men without such a family history. However, PSA testing rates among higher risk African-American men were no different than the rates among lower risk white men, Suggesting that some risk factors for prostate carcinoma (but not others) are associated with preferential testing. Testing in all groups was associated with access to care variables, highlighting the importance of removing barriers to preventive healthcare services. C1 Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles Ctr Hlth Policy Res, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Hlth Serv, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Spencer, BA (reprint author), Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med, Box 951738, Los Angeles, CA 90095 USA. EM spencerb@ucla.edu OI Ponce, Ninez/0000-0001-5151-6718 FU NCI NIH HHS [N02PC95057] NR 44 TC 34 Z9 34 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 2006 VL 106 IS 4 BP 765 EP 774 DI 10.1002/cncr.21673 PG 10 WC Oncology SC Oncology GA 012FU UT WOS:000235324400006 PM 16419068 ER PT J AU Friedenberg, WR Rue, M Blood, EA Dalton, WS Shustik, C Larson, RA Sonneveld, P Greipp, PR AF Friedenberg, WR Rue, M Blood, EA Dalton, WS Shustik, C Larson, RA Sonneveld, P Greipp, PR TI Phase III study of PSC-833 (Valspodar) in combination with vincristine, doxorubicin, and dexamethasone (Valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95) - A Trial of the Eastern Cooperative Oncology Group SO CANCER LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CA SP Amer Soc Hematol DE refractory multiple myeloma; VAD; valspodar; PSC-833 ID MULTIDRUG-RESISTANCE MDR1; P-GLYCOPROTEIN; DRUG-RESISTANCE; LEUKEMIA; CHEMOTHERAPY; CYCLOSPORINE; EXPRESSION; MODULATION; CANCER; CELLS AB BACKGROUND. Preliminary studies have shown valspodar (PSC-833: Novartis Pharmaceuticals, East Hanover, NJ) to be a potent inhibitor of multidrug resistance (MDR), one cause of resistance to chemotherapy. An international randomized control Study (Phase III) evaluated the use of vincristine, doxorubicin, and dexamethasone (VAD) with (n = 46) and without (n = 48) valspodar in the treatment of patients with recurring or refractory multiple myeloma. METHODS. Patients with documented recurrence or refractory myetoma were stratified based on prior treatment exposure and creatinine and randomized. Because of interaction of valspodar with vincristine and doxorubicin, the doses of these drugs were reduced compared with the VAD-alone arm, and the doxorubicin was further reduced in the last 15 patients when given with valspodar based on pharmacokinetic and toxicity studies. RESULTS. There were no complete or near-complete responses. There were 29% partial responses (PRs) in the VAD-alone arm and 44% with valspodar (P = 0.2). Median progression-free survival was 7 months with VAD alone and 4.9 months with valspodar (P = 0.50). Subjective response was 19% with VAD alone and 17% with valspodar (P = 1.0). Median survival with VAD alone was 18.5 months and 15.3 with the addition of valspodar (P = 0.055). Toxicity of Grade 3 or greater was higher (P < 0.0001) in the valspodar arm (89%) compared with the VAD-alone arm (58%). The reduction of doxorubicin dose reduced toxicity but not significantly (P = 0.11). CONCLUSION. The addition of the MDR-modulating agent valspodar to VAD did not improve treatment outcome. Toxicity was increased in the valspodar-treated group compared with VAD alone. C1 Guthrie Fdn Educ & Res, Dept Hematol Oncol, Milan, PA 18831 USA. Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Dept Hematol Oncol, Tampa, FL 33682 USA. Royal Victoria Hosp, Dept Hematol Oncol, Montreal, PQ H3A 1A1, Canada. Natl Canc Inst, Toronto, ON, Canada. Univ Chicago, Dept Hematol Oncol, Chicago, IL 60637 USA. Canc & Leukemia Grp B, Chicago, IL USA. Erasmus Med Ctr, Dept Hematol Oncol, Rotterdam, Netherlands. European Org Res Treatment Canc, Ctr Data, Brussels, Belgium. Mayo Clin, Dept Hematol Oncol, Rochester, MN USA. RP Friedenberg, WR (reprint author), Guthrie Fdn Educ & Res, Dept Hematol Oncol, RR 1,Box 290 a1, Milan, PA 18831 USA. EM wfriedenberg@direcway.com RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 FU NCI NIH HHS [CA41287, CA13650, CA21115, CA23318, CA31946, CA66636, CA73590] NR 37 TC 66 Z9 70 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 2006 VL 106 IS 4 BP 830 EP 838 DI 10.1002/cncr.21666 PG 9 WC Oncology SC Oncology GA 012FU UT WOS:000235324400014 PM 16419071 ER PT J AU Polite, BN Lamont, EB AF Polite, BN Lamont, EB TI Are venous thromboembolic events associated with subsequent breast and colorectal carcinoma diagnoses in the elderly? A case-control study of medicare beneficiaries SO CANCER LA English DT Article DE venous thrombosis; pulmonary embolism; colorectal neoplasms; breast neoplasms ID DEEP-VEIN THROMBOSIS; PULMONARY-EMBOLISM; OCCULT CANCER; SOCIOECONOMIC DATA; UNITED-STATES; RISK; MALIGNANCY; UPDATE; SURVEILLANCE; GUIDELINES AB BACKGROUND. Multiple epidemiologic studies have reported associations between venous thromboembolic events and Subsequent cancer diagnoses, but the published results have not suggested clear cancer screening approaches. METHODS. Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results-Medicare Program, the authors identified patients who were diagnosed with breast and colorectal carcinoma (n = 7166 patients) and compared them with a noncancer control group (n = 126,668 patients) according to their history of hospitalization for deep vein thrombosis (DVT) or pulmonary embolism (PE) in Medicare claims files over the previous 24 months. Using logistic regression analysis, the authors calculated the odds of receiving a diagnosis of breast carcinoma or colorectal carcinoma in the 24 months after admission for DVT or PE. RESULTS. Patients who were hospitalized for DVT or PE had nearly 3.0 times the odds of being diagnosed with colorectal carcinoma (odds ratio [OR], 2.83; 95% confidence interval [95% CI], 1.92-4.17) and > 1.5 times the odds of being diagnosed with breast carcinoma (OR, 1.78; 95% CI, 1.05-3.02) in the subsequent 24 months. CONCLUSIONS. Because hospitalization for DVT or PE is associated with all increased risk of a breast or colorectal carcinoma diagnosis in the subsequent 2 years, physicians Should be vigilant in assessing the cancer screening status Of patients with new DVT and/or PE to be certain that they are up to date with recommended breast and colorectal screening guidelines. C1 Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Healthcare Policy, Boston, MA 02115 USA. RP Polite, BN (reprint author), Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM bpolite@medicine.bsd.uchicago.edu FU NCI NIH HHS [K07 CA93892, K07 CA093892] NR 35 TC 6 Z9 6 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 2006 VL 106 IS 4 BP 923 EP 930 DI 10.1002/cncr.21672 PG 8 WC Oncology SC Oncology GA 012FU UT WOS:000235324400025 PM 16411227 ER PT J AU Kwak, EL Kim, S Zhang, JM Cardiff, RD Schmidt, EV Haber, DA AF Kwak, EL Kim, S Zhang, JM Cardiff, RD Schmidt, EV Haber, DA TI Mammary tumorigenesis following transgenic expression of a dominant negative CHK2 mutant SO CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER RISK; DNA-DAMAGE RESPONSE; BREAST-CANCER; MICE; BRCA1; CHECKPOINT; MUTATIONS; KINASE; TUMORS; CHEK2-ASTERISK-1100DELC AB A truncating allele of the cell cycle checkpoint kinase CHK2 is present in 1% of the population, conferring a moderate increase in breast cancer risk, and inactivation of chk2 enhances mammary tumorigenesis in mice with targeted inactivation of brca1. We used the mouse mammary tumor virus (MMTV) promoter to target expression of a kinase-dead CHK2 allele (D347A). Mammary tumors, of predominantly micropapillary histology, developed in 40% of MMTV-CHK2-D347A transgenic mice with an average latency of 20 months. Tumors metastasized to lung and spleen; tumor-derived cell lines were frequently aneuploid and showed suppression of irradiation-induced p53 function. Primary hematopoietic malignancies were also observed in the spleen, another site of MMTV expression. The increased rate of tumor formation in MMTV-CHK2-D347A mice, compared with the relatively low incidence in chk2-null mice, provides a model to study modifiers of CHK2-dependent transformation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY-7 Bldg 149,13th St, Charlestown, MA 02129 USA. EM Haber@helix.mgh.harvard.edu FU NCI NIH HHS [CA84066, R01 CA089140, R01 CA063117-10, R01 CA084066, R01 CA069069-10]; NCRR NIH HHS [U42 RR014905] NR 30 TC 16 Z9 16 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2006 VL 66 IS 4 BP 1923 EP 1928 DI 10.1158/0008-5472.CAN-05-1237 PG 6 WC Oncology SC Oncology GA 013CM UT WOS:000235387200010 PM 16488990 ER PT J AU Zhao, R Xiang, N Domann, FE Zhong, WX AF Zhao, R Xiang, N Domann, FE Zhong, WX TI Expression of p53 enhances selenite-induced superoxide production and apoptosis in human prostate cancer cells SO CANCER RESEARCH LA English DT Article ID SE-METHYLSELENOCYSTEINE; ADENOCARCINOMA CELLS; MEDIATED APOPTOSIS; OXIDATIVE STRESS; REDOX MECHANISM; PREVENTION; PROTEIN; GLUTATHIONE; MORTALITY; SELENOMETHIONINE AB Although the anticancer effects of selenium have been shown in clinical, preclinical, and laboratory studies, the underlying mechanism(s) remains unclear. Our previous study showed that sodium selenite induced LNCaP human prostate cancer cell apoptosis in association with production of reactive oxygen species, alteration of cell redox state, and mitochondrial damage. In the present study, we showed that selenite-induced apoptosis was superoxide mediated and p53 dependent via mitochondrial pathways. In addition, we also showed that superoxide production by selenite was p53 dependent. Our study showed that wild-type p53-expressing LNCaP cells were more sensitive to selenite-induced apoptosis than p53-null PC3 cells. Selenite treatment resulted in high levels of superoxide production in LNCaP cells but only low levels in PC3 cells. LNCaP cells also showed sequential increases in levels of phosphorylated p53 (serine 15), total p53, Bax, and p21(Waf1) proteins following selenite treatment. The effects of selenite were suppressed by pretreatment with a synthetic superoxide dismutase mimic or by knockdown of p53 via RNA interference. LNCaP cells treated with selenite also showed p53 translocation to mitochondria, cytochrome c release into the cytosol, and activation of caspase-9. On the other hand, restoration of wild-type p53 expression in PC3 cells increased cellular sensitivity to selenite and resulted in increased superoxide production, caspase-9 activation, and apoptosis following selenite treatment. These results suggest that selenite induces apoptosis by producing superoxide to activate p53 and to induce p53 mitochondrial translocation. Activation of p53 in turn synergistically enhances superoxide production and apoptosis induced by selenite. C1 Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Ctr Clin Sci, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI USA. Univ Iowa, Free Rad & Radiat Biol Program, Iowa City, IA USA. RP Zhong, WX (reprint author), Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Ctr Clin Sci, K4-868,Box 8550,600 Highland Ave, Madison, WI 53792 USA. EM wzhong3@wisc.edu OI Domann, Frederick/0000-0002-0489-2179 FU NCI NIH HHS [CA1114281, R01 CA114281] NR 47 TC 74 Z9 79 U1 0 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2006 VL 66 IS 4 BP 2296 EP 2304 DI 10.1158/0008-5472.CAN-05-2216 PG 9 WC Oncology SC Oncology GA 013CM UT WOS:000235387200054 PM 16489034 ER PT J AU Yan, HJ Frost, P Shi, YJ Hoang, B Sharma, S Fisher, M Gera, J Lichtenstein, A AF Yan, HJ Frost, P Shi, YJ Hoang, B Sharma, S Fisher, M Gera, J Lichtenstein, A TI Mechanism by which mammalian target of rapamycin inhibitors sensitize multiple myeloma cells to dexamethasone-induced apoptosis SO CANCER RESEARCH LA English DT Article ID MESSENGER-RNA TRANSLATION; SITE-MEDIATED TRANSLATION; CYCLIN D1; ENHANCED SENSITIVITY; IMMUNOPHILIN FKBP51; SQUIRREL-MONKEY; AKT ACTIVITY; PROTEIN; RESISTANCE; KINASE AB Mammalian target of rapamycin (mTOR) inhibitors curtail cap-dependent translation. However, they can also induce post-translational modifications of proteins. We assessed both effects to understand the mechanism by which mTOR inhibitors like rapamycin sensitize multiple myeloma cells to dexamethasone-induced apoptosis. Sensitization was achieved in multiple myeloma cells irrespective of their PTEN or p53 status, enhanced by activation of AKT, and associated with stimulation of both intrinsic and extrinsic pathways of apoptosis. The sensitizing effect was not due to post-translational modifications of the RAFTK kinase, Jun kinase, p38 mitogen-activated protein kinase, or BAD. Sensitization was also not associated with a rapamycin-mediated increase in glucocorticoid receptor reporter expression. However, when cap-dependent translation was prevented by transfection with a mutant 4E-BP1 construct, which is resistant to mTOR-induced phosphorylation, cells responded to dexamethasonc with enhanced apoptosis, mirroring the effect of coexposure to rapamycin. Thus, sensitization is mediated by inhibition of cap-dependent translation. A high-throughput screening for translational efficiency identified several antiapoptotic proteins whose translation was inhibited by rapamycin. Immunoblot assay confirmed rapamycin-induced down-regulated expressions of XIAP, CIAP1, HSP-27, and BAG-3, which may play a role in the sensitization to apoptosis. Studies in a xenograft model showed synergistic in vivo antimyeloma effects when dexamethasone was combined with the mTOR inhibitor CCI-779. Synergistic effects were associated with an enhanced multiple myeloma cell apoptosis in vivo. This study supports the strategy of combining dexamethasone with mTOR inhibitors in multiple myeloma and identifies a mechanism by which the synergistic effect is achieved. C1 Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Ctr, Dept Med, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Ctr, Dept Pathol, Sch Med, Los Angeles, CA USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. RP Lichtenstein, A (reprint author), Univ Calif Los Angeles, Med Ctr, W Los Angeles VA, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM alan.lichtenstein@med.va.gov OI Frost, Patrick/0000-0003-3348-5983 FU NCI NIH HHS [CA 111448, CA 96920] NR 47 TC 81 Z9 87 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2006 VL 66 IS 4 BP 2305 EP 2313 DI 10.1158/0008-5472.CAN-05-2447 PG 9 WC Oncology SC Oncology GA 013CM UT WOS:000235387200055 PM 16489035 ER PT J AU Friedman, A Tian, JJP Fulci, G Chiocca, EA Wang, J AF Friedman, A Tian, JJP Fulci, G Chiocca, EA Wang, J TI Glioma virotherapy: Effects of innate immune suppression and increased viral replication capacity SO CANCER RESEARCH LA English DT Article ID HERPES-SIMPLEX-VIRUS; PHASE-I TRIAL; MALIGNANT GLIOMA; ONCOLYTIC VIRUS; TUMOR-CELLS; NECK-CANCER; RECURRENT HEAD; ADENOVIRUS; ONYX-015; MUTANT AB Oncolytic viruses are genetically altered replication-competent viruses that infect, and reproduce in, cancer cells but do not harm normal cells. On lysis of the infected cells, the newly formed viruses burst out and infect other tumor cells. Experiments with injecting mutant herpes simplex virus 1 (hrR3) into glioma implanted in brains of rats show lack of efficacy in eradicating the cancer. This failure is attributed to interference by the immune system. Initial pretreatment with immunosuppressive agent cyclophosphamide reduces the percentage of immune cells. We introduce a mathematical model and use it to determine how different protocols of cyclophosphamide treatment and how increased burst size of the mutated virus will affect the growth of the cancer. One of our conclusions is that the diameter of the cancer will decrease from 4 mm to eventually 1 mm if the burst size of the virus is triple that which is currently available. The effect of repeated cyclophosphamide treatment is to maintain a low density of uninfected cells in the tumor, thus reducing the probability of migration of tumor cells to other locations in the brain. C1 Ohio State Univ, Math Biosci Inst, Columbus, OH 43210 USA. Ohio State Univ, Dardinger Ctr Neurooncol & Neurosci, Dept Neurol Surg, Columbus, OH 43210 USA. Ohio State Univ, Dept Math, Columbus, OH 43210 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Tian, JJP (reprint author), Ohio State Univ, Math Biosci Inst, 18th Ave, Columbus, OH 43210 USA. EM tianjj@mbi.ohio-state.edu NR 30 TC 80 Z9 81 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2006 VL 66 IS 4 BP 2314 EP 2319 DI 10.1158/0008-5472.CAN-05-2661 PG 6 WC Oncology SC Oncology GA 013CM UT WOS:000235387200056 PM 16489036 ER PT J AU Tworoger, SS Sluss, P Hankinson, SE AF Tworoger, SS Sluss, P Hankinson, SE TI Association between plasma prolactin concentrations and risk of breast cancer among predominately premenopausal women SO CANCER RESEARCH LA English DT Article ID SERUM PROLACTIN; RECEPTOR GENE; PROGESTERONE RECEPTORS; TRANSGENIC MICE; HORMONE LEVELS; ESTROGEN; EXPRESSION; GROWTH; CARCINOMA; CELLS AB Recent evidence suggests that prolactin may be positively associated with postmenopausal breast cancer risk; however, little data are available in younger women. Therefore, we conducted a prospective, nested case-control study to examine the relationship between plasma prolactin concentrations and breast cancer risk in predominately premenopausal women from the Nurses' Health Study II. Blood samples were collected from 1996 to 1999. The analysis includes 316 cases of breast cancer diagnosed after blood donation and before June 1, 2003, who had two controls matched on age, fasting status, time of day and month of blood collection, race/ethnicity, and timing of blood draw within the menstrual cycle. Sixty-three percent of participants provided a timed follicular and luteal menstrual phase blood sample; other women provided a single untimed sample. When including all women, we observed a positive association between prolactin and breast cancer risk [relative risk (RR), top quartile versus bottom quartile, 1.5; 95% confidence interval (95% CI), 1.0-2.3; P-trend = 0.03] that was slightly stronger among estrogen receptor-positive/progesterone receptor-positive tumors (comparable RR, 1.9; 95% CI, 1.1-3.3; P-trend = 0.04). Associations were similar among premenopausal women only. However, we did not find an association between prolactin and breast cancer risk among the subset of women who only provided timed samples (comparable RR, average of timed samples, 1.3; 95% CI, 0.8-2.3; P-trend = 0.40). The association seemed stronger among women >= 45 years old and for cases diagnosed within similar to 4 years of blood collection. Our data suggest a modest positive association between prolactin and breast cancer risk among predominately premenopausal women; however, further follow-up is needed to increase power for subgroup analyses. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Reprod Endocrinol Unit Lab, Boston, MA 02114 USA. RP Tworoger, SS (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. EM nhsst@channing.harvard.edu OI Tworoger, Shelley/0000-0002-6986-7046 FU NCI NIH HHS [CA50385, CA67262, T32 CA090001] NR 57 TC 122 Z9 124 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2006 VL 66 IS 4 BP 2476 EP 2482 DI 10.1158/0008-5472.CAN-05-3369 PG 7 WC Oncology SC Oncology GA 013CM UT WOS:000235387200075 PM 16489055 ER PT J AU Valencia, A Kochevar, IE AF Valencia, A Kochevar, IE TI Ultraviolet A induces apoptosis via reactive oxygen species in a model for Smith-Lemli-Opitz syndrome SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE keratinocytes; Smith-Lemli-Opitz; UVA; reactive oxygen species; apoptosis; free radicals ID HUMAN KERATINOCYTES; SINGLET OXYGEN; CHOLESTEROL-BIOSYNTHESIS; UVA RADIATION; ACTIVATION; CELLS; PHOTOSENSITIVITY; EXPRESSION; FIBROBLASTS; IRRADIATION AB Solar ultraviolet A (UVA) radiation induces many responses in skin including oxidative stress, DNA damage, inflammation, and skin cancer. Smith-Lemli-Opitz syndrome (SLO-S) patients show dramatically enhanced immediate (5 min) and extended (24-48 h) skin inflammation in response to low UVA doses compared to normal skin. Mutations in Delta(7)-dehydrocholesterol reductase, which converts 7-dehydrocholesterol to cholesterol, produces high levels of 7-dehydrocholesterol in SLO-S patient's serum. Since 7-dehydrocholesterol is more rapidly oxidized than cholesterol, we hypothesized that 7-dehydrocholesterol enhances UVA-induced oxidative stress leading to keratinocyte death and inflammation. When keratinocytes containing high 7-dehydrocholesterol and low cholesterol were exposed to UVA (10 Rem), eightfold greater reactive oxygen species (ROS) were produced than in normal keratinocytes after 15 min. UVA induced 7-dehydrocholesterol concentration-dependent cell death at 24 h. These responses were inhibited by antioxidants, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (diphenyleneiodonium) and a mitochondria-specific radical quencher. Cell death was characterized by activation of caspases-3, -8, and -9 and by phosphatidylserine translocation. Studies using antioxidants and specific caspase inhibitors indicated that activation of caspase-8, but not caspase-9, mediates ROS-dependent caspase-3 activation and suggested that ROS from NADPH oxidase activate caspase-8. These results support a ROS-mediated apoptotic mechanism for the enhanced UVA-induced inflammation in SLO-S patients. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu FU NIGMS NIH HHS [GM 30955] NR 27 TC 50 Z9 51 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB 15 PY 2006 VL 40 IS 4 BP 641 EP 650 DI 10.1016/j.freeradbiomed.2005.09.036 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 014TM UT WOS:000235503000011 PM 16458195 ER PT J AU Nenci, A Huth, M Funteh, A Schmidt-Supprian, M Bloch, W Metzger, D Chambon, P Rajewsky, K Krieg, T Haase, I Pasparakis, M AF Nenci, A Huth, M Funteh, A Schmidt-Supprian, M Bloch, W Metzger, D Chambon, P Rajewsky, K Krieg, T Haase, I Pasparakis, M TI Skin lesion development in a mouse model of incontinentia pigmenti is triggered by NEMO deficiency in epidermal keratinocytes and requires TNF signaling SO HUMAN MOLECULAR GENETICS LA English DT Article ID NF-KAPPA-B; KINASE COMPLEX; MICE; DISEASE; PROLIFERATION; PROTEINS; REL AB NF-kappa B essential modulator (NEMO), the regulatory subunit of the I kappa B kinase, is essential for NF-kappa B activation. Mutations disrupting the X-linked NEMO gene cause incontinentia pigmenti (IP), a human genetic disease characterized by male embryonic lethality and by a complex pathology affecting primarily the skin in heterozygous females. The cellular and molecular mechanisms leading to skin lesion pathogenesis in IP patients remain elusive. Here we used epidermis-specific deletion of NEMO in mice to investigate the mechanisms causing the skin pathology in IP. NEMO deletion completely inhibited NF-kappa B activation and sensitized keratinocytes to tumor necrosis factor (TNF)-induced death but did not affect epidermal development. Keratinocyte-restricted NEMO deletion, either constitutive or induced in adult skin, caused inflammatory skin lesions, identifying the NEMO-deficient keratinocyte as the initiating cell type that triggers the skin pathology in IP. Furthermore, genetic ablation of tumor necrosis factor receptor 1 (TNFRI) rescued the skin phenotype demonstrating that TNF signaling is essential for skin lesion pathogenesis in IP. These results identify the NEMO-deficient keratinocyte as a potent initiator of skin inflammation and provide novel insights into the mechanism leading to the pathogenesis of IP. C1 European Mol Biol Lab, Mouse Biol Unit, I-00016 Monterotondo, Rome, Italy. Univ Cologne, Ctr Mol Med, Dept Dermatol, D-50924 Cologne, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Deutsch Sporthsch, IG I, Abt Mol & Zellulare Sportmed, D-50933 Cologne, Germany. ULP, INSERM, CNRS, IGBMC, F-67404 Illkirch Graffenstaden, CU De Strasbour, France. ICS, F-67404 Illkirch Graffenstaden, CU De Strasbour, France. RP Pasparakis, M (reprint author), European Mol Biol Lab, Mouse Biol Unit, Via Ramarini 32, I-00016 Monterotondo, Rome, Italy. EM pasparakis@embl-monterotondo.it RI Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Pasparakis, Manolis/0000-0002-9870-0966 NR 35 TC 58 Z9 60 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB 15 PY 2006 VL 15 IS 4 BP 531 EP 542 DI 10.1093/hmg/ddi470 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 011OX UT WOS:000235279000002 PM 16399796 ER PT J AU Oishi, K Gaengel, K Krishnamoorthy, S Kamiya, K Kim, IK Ying, HW Weber, U Perkins, LA Tartaglia, M Mlodzik, M Pick, L Gelb, BD AF Oishi, K Gaengel, K Krishnamoorthy, S Kamiya, K Kim, IK Ying, HW Weber, U Perkins, LA Tartaglia, M Mlodzik, M Pick, L Gelb, BD TI Transgenic Drosophila models of Noonan syndrome causing PTPN11 gain-of-function mutations SO HUMAN MOLECULAR GENETICS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; JUVENILE MYELOMONOCYTIC LEUKEMIA; EPIDERMAL-GROWTH-FACTOR; ACUTE MYELOID-LEUKEMIA; ENDOCARDIAL CUSHION; PATTERN-FORMATION; TURNER-PHENOTYPE; KINASE TORSO; WILD-TYPE; RECEPTOR AB Mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase SHP-2, causes Noonan syndrome (NS), an autosomal dominant disorder with pleomorphic developmental abnormalities. Certain germline and somatic PTPN11 mutations cause leukemias. Mutations have gain-of-function (GOF) effects with the commonest NS allele, N308D, being weaker than the leukemia-causing mutations. To study the effects of disease-associated PTPN11 alleles, we generated transgenic fruitflies with GAL4-inducible expression of wild-type or mutant csw, the Drosophila orthologue of PTPN11. All three transgenic mutant CSWs rescued a hypomorphic csw allele's eye phenotype, documenting activity. Ubiquitous expression of two strong csw mutant alleles were lethal, but did not perturb development from some CSW-dependent receptor tyrosine kinase pathways. Ubiquitous expression of the weaker N308D allele caused ectopic wing veins, identical to the EGFR GOF phenotype. Epistatic analyses established that csw(N308D)'s ectopic wing vein phenotype required intact EGF ligand and receptor, and that this transgene interacted genetically with Notch, DPP and JAK/STAT signaling. Expression of the mutant csw transgenes increased RAS-MAP kinase activation, which was necessary but not sufficient for transducing their phenotypes. The findings from these fly models provided hypotheses testable in mammalian models, in which these signaling cassettes are largely conserved. In addition, these fly models can be used for sensitized screens to identify novel interacting genes as well as for high-throughput screening of therapeutic compounds for NS and PTPN11-related cancers. C1 CUNY Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Brookdale Dept Mol Cell & Dev Biol, New York, NY 10029 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Ist Super Sanita, Lab Metab & Biochim Patol, I-00161 Rome, Italy. Univ Maryland, Dept Entomol, College Pk, MD 20742 USA. RP Gelb, BD (reprint author), CUNY Mt Sinai Sch Med, Dept Pediat, 1 Gustave L Levy Pl,Box 1498, New York, NY 10029 USA. EM bruce.gelb@mssm.edu OI Tartaglia, Marco/0000-0001-7736-9672 FU NEI NIH HHS [R01 EY014597, EY 14597]; NHLBI NIH HHS [HL 71207, R01 HL071207]; NICHD NIH HHS [HD 39942, P01 HD039942]; NIGMS NIH HHS [GM 61707, R01 GM061707]; Telethon [GGP04172] NR 56 TC 30 Z9 32 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB 15 PY 2006 VL 15 IS 4 BP 543 EP 553 DI 10.1093/hmg/ddi471 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 011OX UT WOS:000235279000003 PM 16399795 ER PT J AU Arnaud, P Hata, K Kaneda, M Li, E Sasaki, H Feil, R Kelsey, G AF Arnaud, P Hata, K Kaneda, M Li, E Sasaki, H Feil, R Kelsey, G TI Stochastic imprinting in the progeny of Dnmt3L(-/-) females SO HUMAN MOLECULAR GENETICS LA English DT Article ID H19 METHYLATION IMPRINT; PRIMORDIAL GERM-CELLS; EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; DNA METHYLTRANSFERASES; HYDATIDIFORM MOLE; PARENTAL ALLELES; CONTROL REGION; OOCYTE GROWTH; DNMT3A AB The cis-acting regulatory sequences of imprinted genes are subject to germline-specific epigenetic modifications, the imprints, so that this class of genes is exclusively expressed from either the paternal or maternal allele in offspring. How genes are differentially marked in the germlines remains largely to be elucidated. Although the exact nature of the mark is not fully known, DNA methylation [at differentially methylated regions (DMRs)] appears to be a major, functional component. Recent data in mice indicate that Dnmt3a, an enzyme with de novo DNA methyltransferase activity, and the related protein Dnmt3L are required for methylation of imprinted loci in germ cells. Maternal methylation imprints, in particular, are strictly dependent on the presence of Dnmt3L. Here, we show that, unexpectedly, methylation imprints can be present in some progeny of Dnmt3L(-/-) females. This incomplete penetrance of the effect of Dnmt3L deficiency in oocytes is neither embryo nor locus specific, but stochastic. We establish that, when it occurs, methylation is present in both embryo and extra-embryonic tissues and results in a functional imprint. This suggests that this maternal methylation is inherited, directly or indirectly, from the gamete. Our results indicate that in the absence of Dnmt3L, factors such as Dnmt3a and possibly others can act alone to mark individual DMRs. However, establishment of appropriate maternal imprints at all loci does require a combination of all factors. This observation can provide a basis to understand mechanisms involved in some sporadic cases of imprinting-related diseases and polymorphic imprinting in human. C1 Inst Mol Genet, CNRS, UMR 5535, F-34090 Montpellier, France. Univ Montpellier 2, F-34090 Montpellier, France. Res Org Informat & Syst, Natl Inst Genet, Dept Integrated Genet, Div Human Genet, Mishima, Shizuoka 4118540, Japan. Grad Univ Adv Studies, Sch Life Sci, Dept Genet, Mishima, Shizuoka 4118540, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. Babraham Inst, Lab Dev Genet & Imprinting, Cambridge, England. RP Arnaud, P (reprint author), Inst Mol Genet, CNRS, UMR 5535, 1919 Route Mende, F-34090 Montpellier, France. EM philippe.arnaud@igmm.cnrs.fr RI Feil, Robert/D-2087-2013; Kaneda, Masahiro/E-3117-2010; arnaud, Philippe/O-9507-2015; OI Feil, Robert/0000-0002-5671-5860; Kaneda, Masahiro/0000-0003-0660-7156; arnaud, Philippe/0000-0002-7937-8764; Kelsey, Gavin/0000-0002-9762-5634 NR 58 TC 43 Z9 44 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB 15 PY 2006 VL 15 IS 4 BP 589 EP 598 DI 10.1093/hmg/ddi475 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 011OX UT WOS:000235279000007 PM 16403808 ER PT J AU Lee, SJ Lindquist, K Segal, MR Covinsky, KE AF Lee, SJ Lindquist, K Segal, MR Covinsky, KE TI Development and validation of a prognostic index for 4-year mortality in older adults SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; ADMINISTRATIVE DATA; PREDICTIVE MODEL; UNITED-STATES; COMORBIDITY; COMMUNITY; HEALTH; RISK; HOSPITALIZATION; PREVENTION AB Context Both comorbid conditions and functional measures predict mortality in older adults, but few prognostic indexes combine both classes of predictors. Combining easily obtained measures into an accurate predictive model could be useful to clinicians advising patients, as well as policy makers and epidemiologists interested in risk adjustment. Objective To develop and validate a prognostic index for 4-year mortality using information that can be obtained from patient report. Design, Setting, and Participants Using the 1998 wave of the Health and Retirement Study (HRS), a population-based study of community-dwelling US adults older than 50 years, we developed the prognostic index from 11 701 individuals and validated the index with 8009. Individuals were asked about their demographic characteristics, whether they had specific diseases, and whether they had difficulty with a series of functional measures. We identified variables independently associated with mortality and weighted the variables to create a risk index. Main Outcome Measure Death by December 31, 2002. Results The overall response rate was 81%. During the 4-year follow-up, there were 1361 deaths (12%) in the development cohort and 1072 deaths (13%) in the validation cohort. Twelve independent predictors of mortality were identified: 2 demographic variables (age: 60-64 years, 1 point; 65-69 years, 2 points; 70-74 years, 3 points; 75-79 years, 4 points; 80-84 years, 5 points, >85 years, 7 points and male sex, 2 points), 6 comorbid conditions (diabetes, 1 point; cancer, 2 points; lung disease, 2 points; heart failure, 2 points; current tobacco use, 2 points; and body mass index <25, 1 point), and difficulty with 4 functional variables (bathing, 2 points; walking several blocks, 2 points; managing money, 2 points, and pushing large objects, 1 point. Scores on the risk index were strongly associated with 4-year mortality in the validation cohort, with 0 to 5 points predicting a less than 4% risk, 6 to 9 points predicting a 15% risk, 10 to 13 points predicting a 42% risk, and 14 or more points predicting a 64% risk. The risk index showed excellent discrimination with a c statistic of 0.84 in the development cohort and 0.82 in the validation cohort. Conclusion This prognostic index, incorporating age, sex, self-reported comorbid conditions, and functional measures, accurately stratifies community-dwelling older adults into groups at varying risk of mortality. C1 San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Lee, SJ (reprint author), San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. EM sei.lee@va.gov FU AHRQ HHS [K02-HS00006]; NIA NIH HHS [R01AG023626, U01AG09740] NR 46 TC 315 Z9 320 U1 2 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 FEB 15 PY 2006 VL 295 IS 7 BP 801 EP 808 DI 10.1001/jama.295.7.801 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 011YZ UT WOS:000235306700025 PM 16478903 ER PT J AU Serlin, DM Kuang, PP Subramanian, M O'Regan, A Li, XF Berman, JS Goldstein, RH AF Serlin, DM Kuang, PP Subramanian, M O'Regan, A Li, XF Berman, JS Goldstein, RH TI Interleukin-1 beta induces osteopontin expression in pulmonary fibroblasts SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE osteopontin; interleukin-1 beta; lung; fibroblast ID TRANSFORMING-GROWTH-FACTOR; RAT CARDIAC FIBROBLASTS; GENE-EXPRESSION; CRESCENTIC GLOMERULONEPHRITIS; DEFICIENT MICE; LUNG FIBROSIS; IN-VITRO; BLEOMYCIN; RECEPTOR; KINASE AB Osteopontin is a multifunctional matricellular protein identified as one of the most upregulated genes in pulmonary fibrosis. Experimental animal models have identified early pro-fibrotic cytokines as essential to the pathogenesis of inflammation-induced Pulmonary fibrosis. However, the principal Sources of osteopontin in the fibroproliferative lung, and the factors responsible for its induction, have not been fully defined. We isolated primary rat lung fibroblasts in Culture to examine the expression and regulation Of lung fibroblast-derived osteopontin. Our results demonstrate a potent and dramatic increase in osteopontin expression induced by interleukin-1 beta (IL-1 beta), whereas tumor necrosis factor-a, transforming growth factor-beta, and angiotensin II had minimal effect. Stimulation with IL-1 beta resulted in the secretion of soluble osteopontin protein. We found that osteopontin expression by IL-1 beta was regulated via signaling primarily through the mitogen-activated protein kinase member ERK1/2, partially by p38 MAPK, but not at all by JNK. Finally, the mechanism of IL-1 beta increase in osteopontin mRNA requires de novo transcription and translation. In conclusion, we find that osteopontin is expressed by primary lung fibroblasts and is potently Upregulated by the early inflammatory and pro-fibrotic cytokine IL-1 beta. Activated fibroblasts may be a significant source of osteopontin production during lung fibrogenesis. C1 Boston Univ, Sch Med, Ctr Pulm, Dept Med, Boston, MA 02118 USA. Boston VA Healthcare Syst, Div Pulm Med, Dept Med, Boston, MA USA. Univ Coll Hosp Galway, Galway, Ireland. RP Serlin, DM (reprint author), Boston Univ, Sch Med, Ctr Pulm, Dept Med, 715 Albany St,R304, Boston, MA 02118 USA. EM daserlin@bu.edu FU NHLBI NIH HHS [R01 HL 63339, F32 HL 71388, P01 HL 46902, R01 HL 70182] NR 38 TC 24 Z9 28 U1 0 U2 3 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 FEB 15 PY 2006 VL 97 IS 3 BP 519 EP 529 DI 10.1002/jcb.20661 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 009PJ UT WOS:000235124100009 PM 16211580 ER PT J AU Kujawa, SG Liberman, MC AF Kujawa, SG Liberman, MC TI Acceleration of age-related hearing loss by early noise exposure: Evidence of a misspent youth SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mouse; noise-induced hearing loss; age-related hearing loss; primary neural degeneration; neuropathy; auditory ID PRODUCT OTOACOUSTIC EMISSIONS; HAIR CELL LOSS; PURE-TONE THRESHOLDS; ACOUSTIC TRAUMA; COCHLEAR DEGENERATION; DEVELOPMENTAL-CHANGES; INBRED STRAINS; GRADED SERIES; C57BL/6 MICE; RAT COCHLEAS AB Age-related and noise-induced hearing losses in humans are multifactorial, with contributions from, and potential interactions among, numerous variables that can shape final outcome. A recent retrospective clinical study suggests an age-noise interaction that exacerbates age-related hearing loss in previously noise-damaged ears (Gates et al., 2000). Here, we address the issue in an animal model by comparing noise-induced and age-related hearing loss (NIHL; AHL) in groups of CBA/CaJ mice exposed identically (8-16 kHz noise band at 100 dB sound pressure level for 2 h) but at different ages (4-124 weeks) and held with unexposed cohorts for different postexposure times (2-96 weeks). When evaluated 2 weeks after exposure, maximum threshold shifts in young-exposed animals (4-8 weeks) were 40-50 dB; older-exposed animals (>= 16 weeks) showed essentially no shift at the same postexposure time. However, when held for long postexposure times, animals with previous exposure demonstrated AHL and histopathology fundamentally unlike unexposed, aging animals or old-exposed animals held for 2 weeks only. Specifically, they showed substantial, ongoing deterioration of cochlear neural responses, without additional change in preneural responses, and corresponding histologic evidence of primary neural degeneration throughout the cochlea. This was true particularly for young-exposed animals; however, delayed neuropathy was observed in all noise-exposed animals held 96 weeks after exposure, even those that showed no NIHL 2 weeks after exposure. Data suggest that pathologic but sublethal changes initiated by early noise exposure render the inner ears significantly more vulnerable to aging. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Audiol, Boston, MA 02114 USA. Harvard Univ, Eaton Peabody Lab, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Kujawa, SG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Audiol, 243 Charles St, Boston, MA 02114 USA. EM sharon_kujawa@meei.harvard.edu RI Duncan, Jeremy/K-7230-2013 OI Duncan, Jeremy/0000-0002-5555-3273 FU NIDCD NIH HHS [P30 DC005209, R01 DC 00188, R01 DC000188, R21 DC04983] NR 72 TC 220 Z9 232 U1 5 U2 41 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 15 PY 2006 VL 26 IS 7 BP 2115 EP 2123 DI 10.1523/JNEUROSCI.4985-05.2006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 012LT UT WOS:000235341400027 PM 16481444 ER PT J AU Ma, QL Lim, GP Harris-White, ME Yang, FS Ambegaokar, SS Glabe, CG Teter, B Frautschy, SA Cole, GM AF Ma, QL Lim, GP Harris-White, ME Yang, FS Ambegaokar, SS Glabe, CG Teter, B Frautschy, SA Cole, GM TI Antibodies against beta-amyloid reduce A beta oligomers, glycogen synthase kinase-3 beta activation and tau phosphorylation in vivo and in vitro SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Alzheimer's disease; passive immunization; immunoneutralization; amyloid; neurofibrillary tangles ID LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; TRANSGENIC MICE; MOUSE MODEL; INDUCED NEURODEGENERATION; HIPPOCAMPAL-NEURONS; PRECURSOR PROTEIN; PEPTIDE; PATHOLOGY; LITHIUM AB Although active and passive immunization against the beta-amyloid peptide (A beta) of amyloid plaque-bearing transgenic mice markedly reduces amyloid plaque deposition and improves cognition, the mechanisms of neuroprotection and impact on toxic oligomer species are not understood. We demonstrate that compared to control IgG2b, passive immunization with intracerebroventricular (icv) anti-A beta (1-15) antibody into the AD HuAPPsw (Tg2576) transgenic mouse model reduced specific oligomeric forms of A beta, including the dodecamers; that correlate with cognitive decline. Interestingly, the reduction of soluble A beta oligomers, but not insoluble A beta, significantly correlated with reduced tau phosphorylation by glycogen synthase kinase-3 beta (GSK-3 beta), a major tau kinase implicated previously in mediating A beta toxicity. A conformationally-directed antibody against amyloid oligomers (larger than tetramer) also reduced A beta oligomer-induced activation of GSK3 beta and protected human neuronal SH-SY5Y cells from A beta oligomer-induced neurotoxicity, supporting a role for A beta oligomers in human tau kinase activation. These data suggest that antibodies that are highly specific for toxic oligomer subspecies may reduce toxicity via reduction of GSK-3 beta, which could be an important strategy for Alzheimer's disease (AD) therapeutics. (c) 2005Wiley-Liss, Inc. C1 Greater Los Angeles Vet Affairs Healthcare Syst, VA Med Ctr, Geriatr Res & Clin Ctr, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. RP Cole, GM (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, VA Med Ctr, Geriatr Res & Clin Ctr, Alzheimer Res 151,Bldg 7,Rm A102,16111 Plummer St, Sepulveda, CA 91343 USA. EM gmcole@ucla.edu FU NIA NIH HHS [P50 AG016570, R01 AG010685, R01 AG021975, R01 AG022080, R01 AG10685]; NINDS NIH HHS [R01 NS043946, R01 NS43946] NR 60 TC 93 Z9 101 U1 2 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 15 PY 2006 VL 83 IS 3 BP 374 EP 384 DI 10.1002/jnr.20734 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 015BX UT WOS:000235528000003 PM 16385556 ER PT J AU Greenfield, EA Reddy, J Lees, A Dyer, CA Koul, O Nguyen, K Bell, S Kassam, N Hinojoza, J Eaton, MJ Lees, MB Kuchroo, VK Sobel, RA AF Greenfield, EA Reddy, J Lees, A Dyer, CA Koul, O Nguyen, K Bell, S Kassam, N Hinojoza, J Eaton, MJ Lees, MB Kuchroo, VK Sobel, RA TI Monoclonal antibodies to distinct regions of human myelin proteolipid protein simultaneously recognize central nervous system myelin and neurons of many vertebrate species SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE demyelination; evolution; M6 proteins; multiple sclerosis; rhombex ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; SOMA-RESTRICTED PRODUCTS; MULTIPLE-SCLEROSIS; ANTIMYELIN ANTIBODIES; BASIC-PROTEIN; GENE FAMILY; ENCEPHALITOGENIC EPITOPE; CEREBROSPINAL-FLUID; IMMUNE RECOGNITION; CLONAL EXPANSION AB Myelin proteolipid protein (PLP), the major protein of mammalian CNS myelin, is a member of the proteolipid gene family (pgf). It is an evolutionarily conserved polytopic integral membrane protein and a potential autoantigen in multiple sclerosis (MS). To analyze antibody recognition of PLP epitopes in situ, monoclonal antibodies (mAbs) specific for different regions of human PLP (50-69, 100-123, 139-151, 178-191, 200-219, 264-276) were generated and used to immunostain CNS tissues of representative vertebrates. mAbs to each region recognized whole human PLP on Western blots; the anti-100-123 mAb did not recognize DM-20, the PLP isoform that lacks residues 116-150. All of the mAbs stained fixed, permeabilized oligodendrocytes and mammalian and avian CNS tissue myelin. Most of the mAbs also stained amphibian, teleost, and elasmobranch CNS myelin despite greater diversity of their pgf myelin protein sequences. Myelin staining was observed when there was at least 40% identity of the mAb epitope and known pgf myelin proteins of the same or related species. The pgf myelin proteins of teleosts and elasmobranchs lack 116-150; the anti-100-123 mAb did not stain their myelin. In addition to myelin, the anti-178-191 mAb stained many neurons in all species; other mAbs stained distinct neuron subpopulations in different species. Neuronal staining was observed when there was at least approximately 30% identity of the PLP mAb epitope and known pgf neuronal proteins of the same or related species. Thus, anti-human PLP epitope mAbs simultaneously recognize CNS myelin and neurons even without extensive sequence identity. Widespread anti-PLP mAb recognition of neurons suggests a novel potential pathophysiologic mechanism in MS patients, i.e., that anti-PLP antibodies associated with demyelination might simultaneously recognize pgf epitopes in neurons, thereby affecting their functions. (c) 2006Wiley-Liss, Inc. C1 Vet Affairs Hlth Care Syst, Lab Serv 113, Palo Alto, CA 94304 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Biosynexus Inc, Gaithersburg, MD USA. Childrens Hosp Philadelphia, Abramson Res Ctr, Dept Neurol, Philadelphia, PA USA. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Div Biomed Sci, Waltham, MA USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA USA. RP Sobel, RA (reprint author), Vet Affairs Hlth Care Syst, Lab Serv 113, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM raysobel@stanford.edu RI Reddy, Jay/K-7200-2014 OI Reddy, Jay/0000-0003-4082-9254 FU NINDS NIH HHS [P01 NS38037, NS 046414, NS 30843] NR 72 TC 16 Z9 18 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 15 PY 2006 VL 83 IS 3 BP 415 EP 431 DI 10.1002/jnr.20748 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 015BX UT WOS:000235528000007 PM 16416423 ER PT J AU Demirci, M Saribas, O Uluc, K Cekirge, S Boke, E Ay, H AF Demirci, M Saribas, O Uluc, K Cekirge, S Boke, E Ay, H TI Carotid artery stenting and endarterectomy have different effects on heart rate variability SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE carotid artery; endarterectomy; stenting; baroreceptor; heart rate variability ID BLOOD-PRESSURE; BARORECEPTOR SENSITIVITY; MYOCARDIAL-INFARCTION; FREQUENCY-DOMAIN; BAROREFLEX; SURGERY; SINUS; ANESTHESIA; STENOSIS; TIME AB Objective: Due to their close proximity to the carotid sinus baroreceptor region, carotid endarterectomy (CEA) and carotid angioplasty/stenting (CAS) carry an inherent risk of affecting baroreflex-mediated regulation of the heart rate. Variations in the heart rate can be studied by measuring heart rate variability (HRV), in which distinct frequency bands in the power spectrum represent sympathetic and parasympathetic modulations on sinus node pacemaker activity. We aimed to investigate the influence of CEA and CAS on HRV. Methods: One-hour recordings of R-R intervals on ECG were obtained before and after CEA (10 patients) or CAS (12 patients). The power spectrum of the R-R time series was estimated using the FFT technique. The power in low frequency (LF) and high frequency (HF) bands were computed and normalized to their total power (TP). The LF/HF ratio, an index of sympathovagal balance, was calculated. Results: Compared to preoperative levels, LF/HF exhibited 85%, 96%, and 70% increase on the second, third, and fourth days after CEA, respectively. In contrast, LF/HF decreased by 26%, 32%, and 26% on the respective days following CAS; the difference between groups was significant (p=0.0069). Normalized LF increased after CEA and decreased after CAS, while the opposite was observed for normalized HF (p=0.0217). There was no significant change in TP. Conclusions: CEA and CAS have differential effects on the sympathovagal balance on the heart. The relative increase in sympathetic modulation after CEA and parasympathetic modulation after CAS are likely mediated by alterations in the sensitivity of carotid sinus baroreceptors. Altered cardiac autonomic modulation may play a role in the occurrence of cardiac disturbances following carotid interventions. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, AA Martinos Ctr Biomed Imaging Stroke Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, AA Martinos Ctr Biomed Imaging Stroke Serv, Charlestown, MA 02129 USA. Hacattepe Univ Hosp, Dept Neurol, Ankara, Turkey. Hacattepe Univ Hosp, Dept Radiol, Ankara, Turkey. Hacattepe Univ Hosp, Dept Cardiovasc Surg, Ankara, Turkey. RP Ay, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, AA Martinos Ctr Biomed Imaging Stroke Serv, CNY149-2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Demirci, Mehmet/D-7081-2012 OI Demirci, Mehmet/0000-0002-7316-3877 NR 23 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD FEB 15 PY 2006 VL 241 IS 1-2 BP 45 EP 51 DI 10.1016/j.jns.2005.10.011 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 011CS UT WOS:000235245900008 PM 16325863 ER PT J AU Chua, EF Schacter, DL Rand-Glovannetti, E Sperling, RA AF Chua, EF Schacter, DL Rand-Glovannetti, E Sperling, RA TI Understanding metamemory: Neural correlates of the cognitive process and subjective level of confidence in recognition memory SO NEUROIMAGE LA English DT Article DE memory; hippocampus; metamemory; fMRI; parietal cortex ID RIGHT PREFRONTAL CORTEX; EVENT-RELATED FMRI; ALZHEIMERS-DISEASE; DEFAULT-MODE; FUNCTIONAL MRI; WORKING-MEMORY; AUTOBIOGRAPHICAL MEMORIES; EPISODIC RETRIEVAL; FALSE RECOGNITION; BRAIN ACTIVITY AB An essential feature of human memory is the capacity to assess confidence in one's own memory performance, but the neural mechanisms underlying the process of determining confidence in memory performance have not yet been isolated. Using functional magnetic resonance imaging, we examined both the process of confidence assessment and the subjective level of high or low confidence expressed during this process. The comparison of confidence assessment to recognition showed greater relative activation during confidence assessment in medial and lateral parietal regions, which typically deactivate during cognitive tasks, previously described as part of the "default network". Furthermore, comparisons of high versus low confidence judgments revealed modulation of neural activity in the hippocampus, cingulate and other limbic regions, previously described as the Circuit of Papez. Our findings suggest that activity in two distinct networks of brain regions contribute to the subjective experience of "knowing you know" through memory monitoring processes and signaling subjective confidence level for recognition memory. (c) 2005 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Sperling, RA (reprint author), Memory Disorders Unit, 221 Longwood Ave, Boston, MA 02215 USA. EM reisa@rics.bwh.harvard.edu RI Chua, Elizabeth/B-3770-2010; OI Schacter, Daniel/0000-0002-2460-6061 FU NCRR NIH HHS [P41RR14075]; NIA NIH HHS [P01-AG-04953, R01-AG08441]; NIMH NIH HHS [MH60941]; NINDS NIH HHS [K23-NS02189] NR 63 TC 84 Z9 85 U1 1 U2 13 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 FEB 15 PY 2006 VL 29 IS 4 BP 1150 EP 1160 DI 10.1016/j.neuroimage.2005.09.058 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 015EJ UT WOS:000235534400013 PM 16303318 ER PT J AU Holsehneider, DP Yang, J Sadler, TR Nguyen, PT Givrad, TK Maarek, JMI AF Holsehneider, DP Yang, J Sadler, TR Nguyen, PT Givrad, TK Maarek, JMI TI Mapping cerebral blood flow changes during auditory-cued conditioned fear in the nontethered, nonrestrained rat SO NEUROIMAGE LA English DT Review DE brain mapping; functional neuroimaging; fear conditioning; cerebral blood flow; statistical parametric mapping; medial prefrontal cortex; amygdala; hippocampus; striatum; septum; periaqueductal gray ID MEDIAL PREFRONTAL CORTEX; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; DIFFERENT ANTEROGRADE AMNESIAS; MIDBRAIN PERIAQUEDUCTAL GRAY; FOS-LIKE IMMUNOREACTIVITY; LATERAL AMYGDALA NEURONS; FREELY MOVING RATS; CONTEXTUAL FEAR; DORSAL HIPPOCAMPUS; VENTRAL HIPPOCAMPUS AB Conditioned fear (CF) is one of the most frequently used behavioral paradigms; however, little work has mapped changes in cerebral perfusion during CF in the rat-the species which has dominated CF research. Adult rats carrying an implanted minipump were exposed to a tone (controls, n = 8) or a tone conditioned in association with footshocks (CS group, n = 9). During reexposure to the tone 24 h later, animals were injected intravenously by remote activation with [C-14]-iodoantipyrine using the pump. Significant group differences in regional CBF-related tissue radioactivity (CBF-TR) were determined by region-of-interest analysis of brain autoradiographs, as well as in the reconstructed, three-dimensional brain by statistical parametric mapping (SPM). CS animals demonstrated significantly greater, fear-enhanced increases in CBF-TR in auditory cortex than controls. The lateral amygdala was activated, whereas the basolateral/basomedial and central amygdala were deactivated. In the hippocampus and medial prefrontal cortex, CBF-TR increased significantly ventrally but not dorsally. Significant activations were noted in medial striatum and the thalamic midline and intralaminar nuclei. However, the ventrolateral/dorsolateral striatum and its afferents from motor and somatosensory cortex were deactivated, consistent with the behavioral immobility seen during CF. Significant activations were also noted in the lateral septum, periaqueductal gray, and deep mesencephalic nucleus/tegmental tract. Our results show that auditory stimuli endowed with aversive properties through conditioning result in significant redistribution of cerebral perfusion. SPM is a useful tool in the brain mapping of complex rodent behaviors, in particular the changes in activation patterns in limbic, thalamic, motor, and cortical circuits during CF. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ So Calif, Dept Cell & Neurobiol, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Dept Psychiat & Behav Sci, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Dept Neurol, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Dept Pathol, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biomed Engn, Keck Sch Med, Los Angeles, CA 90089 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. RP Holsehneider, DP (reprint author), Univ So Calif, Dept Cell & Neurobiol, Keck Sch Med, 1333 San Pablo St,BMT 403,MC 9112, Los Angeles, CA 90089 USA. EM holschne@usc.edu FU NCCIH NIH HHS [R24 AT002681, 1R24AT002681]; NIBIB NIH HHS [R01 EB000300, 8R01 EB-00300]; NINDS NIH HHS [1R01 NS050171, R01 NS050171] NR 134 TC 29 Z9 30 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 15 PY 2006 VL 29 IS 4 BP 1344 EP 1358 DI 10.1016/j.neuroimage.2005.08.038 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 015EJ UT WOS:000235534400033 PM 16216535 ER PT J AU Graham, CS Wells, A Liu, T Sherman, KE Peters, M Chung, RT Bhan, AK Andersen, J Koziel, MJ AF Graham, CS Wells, A Liu, T Sherman, KE Peters, M Chung, RT Bhan, AK Andersen, J Koziel, MJ CA ACTG 5071 Study Team TI Relationships between cellular immune responses and treatment outcomes with interferon and ribavirin in HIV/hepatitis C virus co-infection SO AIDS LA English DT Article; Proceedings Paper CT 11th Conference on Retroviruses and Opportunistic Infections CY FEB 08-11, 2004 CL San Francisco, CA DE hepatitis C virus; interferon alpha; cellular immunity; interferon gamma; interleukin 10 ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; HIV-INFECTED PATIENTS; LIVER-DISEASE; T-CELLS; PEGINTERFERON; HCV; ANTIGENS; THERAPY AB Objective: To test the hypothesis that hepatitis C virus (HCV)-specific interferon (IFN)gamma immune responses are correlated with HCV virological response following treatment in subjects with HIV-1 and HCV co-infection. Design: Immune responses were studied in a treatment trial comparing standard interferon alfa (IFN) to pegylated interferon alfa (PEG-IFN), each with ribavirin (R). Methods: Using HCV antigens core, NS3 and NS5, and Candida, enzyme-linked immunosorbent spots on peripheral blood mononuclear cells measured IFN gamma and interleukin (IL)-10 production. Immunologic, virologic and clinical variables were modeled using recursive partitioning (CART) to identify factors associated with HCV virological response at week 24 (VR) and week 72 (SVR) in 108 patients. Results: There were no significant differences in baseline IFN gamma immune responses and higher IL-10 to NS3 in subjects with VR versus non-responders. Subjects who had significant decreases in IL-10 responses at week 24 compared to baseline for NS3, NS5, or summed HCV responses were more likely to be VR. Using baseline immunological responses and clinical data in CART models, patients who were randomized to PEG-IFN/R and had high IL-10 responses to summed HCV proteins were more likely to be VR (73%), whereas those on IFN/R who had low IFN gamma responses to Candida were less likely to be VR (5%). The main correlate of SVR for genotype-1 subjects was maintenance of HCV-specific IFN gamma responses from baseline to week 72. Conclusions: In this cohort of subjects with HIV and HCV, a decrease in HCV-specific IL-10 responses and maintenance of IFN gamma responses during treatment with IFN were associated with week 24 or 72 virological response. (C) 2006 Lippincott Williams & Wilkins. C1 Beth Israel Deaconess Med Ctr, Harvard Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Cincinnati, Cincinnati, OH USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Graham, CS (reprint author), Beth Israel Deaconess Med Ctr, Harvard Inst Med, Room 221,4 Blackfan Circle, Boston, MA 02115 USA. EM cgraham@bidmc.harvard.edu FU NIAID NIH HHS [AI38855, AI 38858, U01 AI038858, U01 AI038855, R01 AI050752]; NIDA NIH HHS [DA14495-01, K08 DA014495] NR 25 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD FEB 14 PY 2006 VL 20 IS 3 BP 345 EP 351 DI 10.1097/01.aids.0000206500.16783.2e PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 015UM UT WOS:000235576600005 PM 16439867 ER PT J AU Ellenbogen, KA Levine, JH Berger, RD Daubert, JP Winters, SL Greenstein, E Shalaby, A Schaechter, A Subacius, H Kadish, A AF Ellenbogen, KA Levine, JH Berger, RD Daubert, JP Winters, SL Greenstein, E Shalaby, A Schaechter, A Subacius, H Kadish, A CA DEFINITE Investigators TI Are implantable cardioverter defibrillator shocks a surrogate for sudden cardiac death in patients with nonischemic cardiomyopathy? SO CIRCULATION LA English DT Article DE sudden death; arrhythmia; heart arrest; syncope; defibrillation ID IDIOPATHIC DILATED CARDIOMYOPATHY; NONSUSTAINED VENTRICULAR-TACHYCARDIA; SYNCOPE; STIMULATION; ISCHEMIA; ORIGIN; RISK AB Background-Ventricular tachyarrhythmias long enough to cause implantable cardioverter defibrillator (ICD) shocks are generally thought to progress to cardiac arrest. In previous ICD trials, shocks have been considered an appropriate surrogate for sudden cardiac death (SCD) because the number of shocks has been thought to be equivalent to the mortality excess in patients without ICDs. The practice of equating ICD shocks with mortality is controversial and has not been validated critically. Methods and Results-The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation ( DEFINITE) trial was a prospective, randomized, multicenter trial of ICD therapy in 458 patients with nonischemic cardiomyopathy. Patients were randomized to receive standard medical therapy (STD) or STD plus an ICD. Shock electrograms were reviewed, and the cause of death was evaluated by a separate blinded events committee. There were 15 SCD or cardiac arrests in the STD group and only 3 in the ICD arm. In contrast, of the 229 patients randomized to an ICD, 33 received 70 appropriate ICD shocks. Patients in the ICD arm were more likely to have an arrhythmic event ( ICD shock plus SCD) than patients in the STD arm ( hazard ratio 2.12, 95% CI 1.153 to 3.893, P=0.013). The number of arrhythmic events when one includes syncope as a potential arrhythmic event was similar in both groups ( hazard ratio 1.20, 95% CI 0.774 to 1.865, P=0.414). Approximately the same number of total events was noted in each arm when we compared syncope plus SCD/cardiac arrest in the STD arm with SCD plus ICD shocks plus syncope in the ICD arm. Conclusions-Appropriate ICD shocks occur more frequently than SCD in patients with nonischemic cardiomyopathy. This suggests that episodes of nonsustained ventricular tachycardia frequently terminate spontaneously in such patients. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Med, Richmond, VA 23298 USA. St Francis Mem Hosp, Roslyn, NY USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ Rochester, Rochester, NY USA. Morristown Mem Hosp, Morristown, NJ USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NW Mem Hosp, Bluhm Cardiovasc Inst, Clin Trials Unit, Chicago, IL 60611 USA. RP Ellenbogen, KA (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Med, POB 980053, Richmond, VA 23298 USA. EM kellenbogen@pol.net OI Subacius, Haris/0000-0003-4061-1220 NR 15 TC 170 Z9 172 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 14 PY 2006 VL 113 IS 6 BP 776 EP 782 DI 10.1161/CIRCULATIONAHA.105.561571 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 012DU UT WOS:000235319200008 PM 16461817 ER PT J AU Magnani, JW Dec, GW AF Magnani, JW Dec, GW TI Myocarditis - Current trends in diagnosis and treatment SO CIRCULATION LA English DT Review DE cardiomyopathy; heart failure; myocarditis; viruses ID LEFT-VENTRICULAR DYSFUNCTION; GIANT-CELL MYOCARDITIS; IDIOPATHIC DILATED CARDIOMYOPATHY; COXSACKIE-B VIRUS; SUBSEQUENT IMMUNOGLOBULIN SUBSTITUTION; CARDIOVASCULAR MAGNETIC-RESONANCE; POLYMERASE-CHAIN-REACTION; CHRONIC HEART-FAILURE; CARDIAC TROPONIN-I; TERM FOLLOW-UP C1 Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Cardiol Div, Bigelow 800,Mailstop 817,55 Fruit St, Boston, MA 02114 USA. EM gdec@partners.org NR 119 TC 216 Z9 241 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 14 PY 2006 VL 113 IS 6 BP 876 EP 890 DI 10.1161/CIRCULATIONAHA.105.584532 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 012DU UT WOS:000235319200021 PM 16476862 ER PT J AU Armstrong, EJ Morrow, DA Sabatine, MS AF Armstrong, EJ Morrow, DA Sabatine, MS TI Inflammatory biomarkers in acute coronary syndromes Part I: Introduction and cytokines SO CIRCULATION LA English DT Editorial Material ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; UNSTABLE ANGINA; ATHEROSCLEROTIC PLAQUES; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; INCREASED RISK; INTERLEUKIN-6; EVENTS; INSTABILITY; EXPRESSION C1 Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org NR 18 TC 69 Z9 75 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 14 PY 2006 VL 113 IS 6 BP E72 EP E75 DI 10.1161/CIRCULATIONAHA.105.595520 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 012DU UT WOS:000235319200024 PM 16476853 ER PT J AU Tyler, KL Pape, J Goody, RJ Corkill, M Kleinschmidt-DeMasters, BK AF Tyler, KL Pape, J Goody, RJ Corkill, M Kleinschmidt-DeMasters, BK TI CSF findings in 250 patients with serologically confirmed West Nile virus meningitis and encephalitis SO NEUROLOGY LA English DT Article ID BACTERIAL-MENINGITIS; UNITED-STATES; NEW-YORK; INFECTION AB Objective: To provide a large, comprehensive evaluation of the CSF findings in patients with serologically confirmed West Nile virus (WNV), CNS disease, and their correlation with outcome. Methods: CSF samples from 334 WNV-infected hospitalized patients were analyzed. Information was available and extracted from the medical records of 250 of these patients, and CSF parameters correlated with clinical and epidemiologic features of disease ( e. g., patient age, sex, outcome). Results: Patients with meningitis had a mean of 226 cells/mm(3), and those with encephalitis had a mean of 227 cells/mm(3). Three percent of meningitis patients and 5% of encephalitis patients had fewer than 5 cells/mm(3), and approximately 8% of both groups had more than 500 cells/mm(3). Patients with meningitis had a mean of 41% neutrophils, and those with encephalitis had 45%. Forty-five percent of meningitis patients and 37% of encephalitis patients had at least 50% neutrophils in their initial CSF specimen. Neither the mean percent neutrophils nor their distribution differed significantly between groups. Forty-seven percent of encephalitis patients and 16% of meningitis patients had CSF protein of 100 mg/dL or greater (p < 0.01). Although specific CSF parameters, including nucleated cell count and protein concentration, correlated significantly with outcome, multivariate analysis suggested that their total predictive value was modest. Age was an additional predictor of outcome independent of CSF variables in all patients. Conclusions: Serologically confirmed West Nile virus meningitis and encephalitis produce similar degrees of CSF pleocytosis and are frequently associated with substantial CSF neutrophilia. Patients with encephalitis have higher CSF protein concentrations and are more likely to have adverse outcomes, including admission to long-term care facilities or even death after their acute illness. CSF findings were only a modest predictor of disease outcome, with patient age adding important independent prognostic information. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurosurg, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. Colorado Dept Publ Hlth & Environm, Denver, CO USA. Exempla Lutheran Hosp, Dept Pathol, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, 4200 E 9th Ave, Denver, CO 80262 USA. EM ken.tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 NR 17 TC 49 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 14 PY 2006 VL 66 IS 3 BP 361 EP 365 DI 10.1212/01.wnl.0000195890.70898.1f PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 012ON UT WOS:000235348600013 PM 16382032 ER PT J AU Shoulson, I Growdon, J Como, P Kamp, C Kieburtz, K LeWitt, P Oakes, D Siderowf, A Blindauer, K Comella, C Janko, K Camicioli, R Morehouse, S Grace, J Friedman, J Lannon, M Hauser, R Gauger, L Waters, C Schuman, S Stacy, M Williamson, K Siemers, E Belden, J Tarsy, D Ryan, P Gordon, MF Winnick, R Blindauer, K Gardiner, I Brocht, A Watts, A Zhang, L Leventhal, C Raubertas, R Tariot, P Broome, S Gautille, T Lloyd, K McClure, D Lieberman, A Schneider, J AF Shoulson, I Growdon, J Como, P Kamp, C Kieburtz, K LeWitt, P Oakes, D Siderowf, A Blindauer, K Comella, C Janko, K Camicioli, R Morehouse, S Grace, J Friedman, J Lannon, M Hauser, R Gauger, L Waters, C Schuman, S Stacy, M Williamson, K Siemers, E Belden, J Tarsy, D Ryan, P Gordon, MF Winnick, R Blindauer, K Gardiner, I Brocht, A Watts, A Zhang, L Leventhal, C Raubertas, R Tariot, P Broome, S Gautille, T Lloyd, K McClure, D Lieberman, A Schneider, J CA Parkinson Study Grp TI Randomized placebo-controlled study of the nicotinic agonist SIB-1508Y in Parkinson disease SO NEUROLOGY LA English DT Article ID ACETYLCHOLINE-RECEPTOR AGONIST; MONKEYS AB This randomized, placebo-controlled, 5-week Phase II trial evaluated the safety and tolerability of SIB-1508Y, a selective alpha 4 beta 2 nicotinic acetylcholine receptor agonist, in 77 individuals with early Parkinson disease. Lightheadedness was a common dosage-related adverse effect at higher dosages, leading to frequent dosage reduction, drug discontinuation, and eventual trial redesign. A maximally tolerated dosage of 10 mg daily was identified. No antiparkinsonian or cognitive-enhancing effects were demonstrated in this trial. C1 Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. Univ Rochester, Med Ctr, Rochester, NY 14627 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Clin Neurosci Ctr, Southfield, MI USA. RP Blindauer, K (reprint author), Med Coll Wisconsin, Dept Neurol, 9200 W Wisconsoin Ave, Milwaukee, WI 53226 USA. EM kblindau@mcw.edu NR 8 TC 28 Z9 28 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB 14 PY 2006 VL 66 IS 3 BP 408 EP 410 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 012ON UT WOS:000235348600021 ER PT J AU Smolen, GA Sordella, R Muir, B Mohapatra, G Barmettler, A Archibald, H Kim, WJ Okimoto, RA Bell, DW Sgroi, DC Christensen, JG Settleman, J Haber, DA AF Smolen, GA Sordella, R Muir, B Mohapatra, G Barmettler, A Archibald, H Kim, WJ Okimoto, RA Bell, DW Sgroi, DC Christensen, JG Settleman, J Haber, DA TI Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene amplification; molecular marker; oncogene addiction; targeted therapy ID CELL LUNG-CANCER; COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; HUMAN-BREAST-CANCER; C-MET; GEFITINIB; MUTATIONS; TRIAL; LINE; COMBINATION AB The success of molecular targeted therapy in cancer may depend on the selection of appropriate tumor types whose survival depends on the drug target, so-called "oncogene addiction." Preclinical approaches to defining drug-responsive subsets are needed if initial clinical trials are to be directed at the most susceptible patient population. Here, we show that gastric cancer cells with high-level stable chromosomal amplification of the growth factor receptor MET are extraordinarily susceptible to the selective inhibitor PHA-665752. Although MET activation has primarily been linked with tumor cell migration and invasiveness, the amplified wild-type MET in these cells is constitutively activated, and its continued signaling is required for cell survival. Treatment with PHA-665752 triggers massive apoptosis in 5 of 5 gastric cancer cell lines with MET amplification but in 0 of 12 without increased gene copy numbers (P = 0.00016). MET amplification may thus identify a subset of epithelial cancers that are uniquely sensitive to disruption of this pathway and define a patient group that is appropriate for clinical trials of targeted therapy using MET inhibitors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Mol Pathol Res Unit, Charlestown, MA 02129 USA. Pfizer Inc, Res Pharmacol, San Diego, CA 92121 USA. RP Haber, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu FU NCI NIH HHS [F32 CA117737]; PHS HHS [P01 95281] NR 30 TC 323 Z9 330 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 14 PY 2006 VL 103 IS 7 BP 2316 EP 2321 DI 10.1073/pnas.0508776103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 013LU UT WOS:000235411600057 PM 16461907 ER PT J AU Januzzi, JL Sakhuja, R O'Donoghue, M Baggish, AL Anwaruddin, S Chae, CU Cameron, R Krauser, DG Tung, R Camargo, AA Lloyd-Jones, DM AF Januzzi, JL Sakhuja, R O'Donoghue, M Baggish, AL Anwaruddin, S Chae, CU Cameron, R Krauser, DG Tung, R Camargo, AA Lloyd-Jones, DM TI Utility of amino-terminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; ACUTE PULMONARY-EMBOLISM; CHRONIC HEART-FAILURE; ST-SEGMENT ELEVATION; RISK STRATIFICATION; MYOCARDIAL-INFARCTION; NT-PROBNP; PROGNOSIS; ADMISSION; SURVIVAL AB Background: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for diagnosis and triage of patients with dyspnea, but its role for predicting outcomes in such patients remains undefined. Methods: A total of 599 breathless patients treated in the emergency department were prospectively enrolled, and a sample of blood was obtained for NT-proBNP measurements. After 1 year, the vital status of each patient was ascertained, and the association between NT-proBNP values at presentation and mortality was assessed. Results: At 1 year, 91 patients (15.2%) had died. Median NT-proBNP concentrations at presentation among decedents were significantly higher than those of survivors (3277 vs 299 pg/mL; P<.001). The optimal NT-proBNP cut point for predicting 1-year mortality was 986 pg/mL. In a multivariable model, an NT-proBNP concentration greater than 986 pg/mL at presentation was the single strongest predictor of death at 1 year (hazard ratio [HR], 2.88; 95% confidence interval, 1.64-5.06; P<.001), independent of a diagnosis of heart failure. Other factors associated with death included age (by decade; HR, 1.20), heart rate (by decile; HR, 1.13), urea nitrogen level (by decile; HR, 1.20), systolic blood pressure less than 100 mm Hg (HR, 1.94), heart murmur (HR, 1.92), and New York Heart Association classification (HR, 1.38 for each increase in class). The NT-proBNP concentration alone had an area under the receiver operating characteristic curve (AUC) of 0.76 for predicting mortality; the other significant covariates combined had an AUC of 0.80. The final model for predicting death, combining NT-proBNP with other covariates associated with mortality, had a superior AUC of 0.82. Conclusion: In addition to assisting in emergency department diagnosis and triage, NT-proBNP concentrations at presentation are strongly predictive of 1-year mortality in dyspneic patients. C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org RI Lloyd-Jones, Donald/C-5899-2009 NR 30 TC 114 Z9 122 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 13 PY 2006 VL 166 IS 3 BP 315 EP 320 DI 10.1001/archinte.166.3.315 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 011SP UT WOS:000235288700007 PM 16476871 ER PT J AU Au, DH Udris, EM Fihn, SD McDonell, MB Curtis, JR AF Au, DH Udris, EM Fihn, SD McDonell, MB Curtis, JR TI Differences in health care utilization at the end of life among patients with chronic obstructive pulmonary disease and patients with lung cancer SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID OF-LIFE; ADVANCE DIRECTIVES; DATABASES; HOSPITALS; PROGNOSIS; COSTS; COPD AB Background: We sought to examine health care resource utilization in the last 6 months of life among patients who died with chronic obstructive pulmonary disease (COPD) compared with those who died with lung cancer and to examine geographic variations in care. Methods: We performed a retrospective cohort study of patients diagnosed as having COPD or lung cancer, who were seen in 1 of 7 Veteran Affairs medical centers primary care clinics and who died during the study period. Our outcome of interest was health care resource utilization in the last 6 months of life. Results: In the last 6 months of life, patients with COPD were more likely to visit their primary care providers but had fewer hospital admissions compared with patients with lung cancer. Patients with COPD had twice the odds of being admitted to an intensive care unit (ICU), 5 times the odds of remaining there 2 weeks or longer, and received fewer opiates and benzodiazepine prescriptions compared with patients with lung cancer. There were geographic variations in the use of ICUs for patients with COPD but not for those with lung cancer. Total health care costs were $4000 higher for patients with COPD because of ICU utilization. Conclusions: In the last 6 months of life, patients with COPD were more likely to have had a primary care visit and been admitted to an ICU but less likely to receive palliative medications compared with patients with lung cancer. We found significant geographic variability in ICU utilization but only for patients with COPD. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. RP Au, DH (reprint author), Hlth Serv Res Dev MS 152, Div Pulm & Crit Care Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM dau@u.washington.edu NR 24 TC 81 Z9 84 U1 4 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 13 PY 2006 VL 166 IS 3 BP 326 EP 331 DI 10.1001/archinte.166.3.326 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 011SP UT WOS:000235288700009 PM 16476873 ER PT J AU Shrank, WH Hoang, TY Ettner, SL Glassman, PA Nair, K DeLapp, D Dirstine, J Avorn, J Asch, SM AF Shrank, WH Hoang, TY Ettner, SL Glassman, PA Nair, K DeLapp, D Dirstine, J Avorn, J Asch, SM TI The implications of choice - Prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INCENTIVE-BASED FORMULARIES; DRUG UTILIZATION; MANAGED CARE; ANTIHYPERTENSIVE THERAPY; PRESCRIPTION DRUGS; INHALED STEROIDS; BENEFIT PLANS; ASTHMA; DISCONTINUATION; PERSISTENCE AB Background: A large proportion of Americans are enrolled in 3-tier pharmacy benefit plans. We studied whether patients enrolled in such plans who receive generic or preferred brand-name agents when initiating chronic therapy were more adherent to treatment than those who received nonpreferred brand-name medications. Methods: We analyzed pharmacy claims filled between October 1, 2001, and October 1, 2003, from a large health plan for 6 classes of chronic medications: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, calcium channel blockers, oral contraceptives, orally inhaled corticosteroids, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors. We measured adherence as the proportion of days covered (PDC) in each drug class during the first year of therapy. We evaluated how the formulary status of the initial prescription (generic, preferred, or nonpreferred) influenced PDC and adequate adherence, defined as PDC greater than 80%, over the subsequent year. Results: A total of 7532 new prescriptions were filled in 1 of the classes evaluated: 1747 (23.2%) for nonpreferred medications, 4376 (58.1%) for preferred drugs, and 1409 (18.7%) for generic drugs. After controlling for patient sociodemographic characteristics and drug class, PDC was 12.6% greater for patients initiated on generic medications vs nonpreferred medications (58.8% vs 52.2%; P<.001). The PDC was 8.8% greater for patients initiated on preferred vs nonpreferred medications (56.8% vs 52.2%; P<.001). Patients initiated on generic and preferred medications had 62% and 30% greater odds, respectively, of achieving adequate adherence compared with those who received nonpreferred medications. Conclusion: In 3-tier pharmacy benefit plans, prescribing generic or preferred medications within a therapeutic class is associated with improvements in adherence to therapy. C1 Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA. Harvard Univ, Sch Med, Boston, MA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. Univ Colorado, Hlth Sci Ctr, Dept Pharm, Denver, CO USA. Anthem Blue Cross & Blue Shield, Denver, CO USA. Anthem Prescript Management, Denver, CO USA. RP Shrank, WH (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM wshrank@partners.org RI Mendoza, Elvia/A-9361-2012 NR 39 TC 188 Z9 192 U1 2 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 13 PY 2006 VL 166 IS 3 BP 332 EP 337 DI 10.1001/archinte.166.3.332 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 011SP UT WOS:000235288700010 PM 16476874 ER PT J AU Lasser, KE Seger, DL Yu, DT Karson, AS Fiskio, JM Seger, AC Shah, NR Gandhi, TK Rothschild, JM Bates, DW AF Lasser, KE Seger, DL Yu, DT Karson, AS Fiskio, JM Seger, AC Shah, NR Gandhi, TK Rothschild, JM Bates, DW TI Adherence to black box warnings for prescription medications in outpatients SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ADVERSE DRUG EVENTS; FREQUENCY; METFORMIN; CARE AB Background: Few data are available regarding the prevalence of potentially dangerous drug-drug, drug-laboratory, and drug-disease interactions among outpatients. Our objectives were to determine how frequently clinicians prescribe drugs in violation of black box warnings for these issues and to determine how frequently such prescribing results in harm. Methods: In an observational study of 51 outpatient practices using an electronic health record, we measured the frequency with which patients received prescriptions in violation of black box warnings for drug-drug, drug laboratory, and/or drug-disease interactions. We performed medical record reviews in a sample of patients to detect adverse drug events. Multivariate analysis was conducted to assess the relationship of prescribing in violation of black box warnings to patient and clinician characteristics, adjusting for potential confounders and clustering. Results: Of 324 548 outpatients who received a medication in 2002, 2354 (0.7%) received a prescription in violation of a black box warning. After adjustment, receipt of medication in violation of a black box warning was more likely when patients were 75 years or older or female. The number of medications taken, the number of medical problems, and the site of care were also associated with violations. Less than 1% of patients who received a drug in violation of a black box warning had an adverse drug event as a result. Conclusions: About 7 in 1000 outpatients received a prescription violating a black box warning. Few incidents resulted in detectable harm. C1 Cambridge Hlth Alliance, Dept Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Partners HealthCare Syst, Wellesley, MA USA. Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. RP Lasser, KE (reprint author), Cambridge Hlth Alliance, Dept Med, 1493 Cambridge St, Cambridge, MA 02139 USA. EM klasser@challiance.org NR 26 TC 51 Z9 51 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 13 PY 2006 VL 166 IS 3 BP 338 EP 344 DI 10.1001/archinte.166.3.338 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 011SP UT WOS:000235288700011 PM 16476875 ER PT J AU Castano, AP Liu, Q Hamblin, MR AF Castano, AP Liu, Q Hamblin, MR TI A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy SO BRITISH JOURNAL OF CANCER LA English DT Article DE photodynamic therapy; green fluorescent protein; antitumour immunity; benzoporphyrin derivative; radiation-induced fibrosarcoma; fluorescence imaging ID CYTOTOXIC T-LYMPHOCYTE; LASER IMMUNOTHERAPY; ANTIBODY-RESPONSES; ANTITUMOR IMMUNITY; METASTATIC TUMORS; DENDRITIC CELLS; MOUSE-TUMORS; IN-VIVO; CANCER; ANTIGEN AB The ideal cancer treatment should both destroy the primary tumour and at the same time educate the immune system to recognise the tumour as foreign so that distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the i.v. administration of photosensitisers followed by illumination of the tumour with red light producing reactive oxygen species that eventually cause vascular shutdown and tumour cell death by apoptosis and necrosis. Anti-tumour immunity is stimulated after PDT due to the acute inflammatory response, generation of tumour-specific antigens, and induction of heat-shock proteins. Green fluorescent protein (GFP) is used as an optical reporter to noninvasively image the progression of mouse tumours, and in addition, may act as a foreign (jellyfish) antigen. We asked whether GFP-expressing tumours could be used to monitor the response of tumour-bearing mice to PDT, and whether the tumour response differed when a nonimmunogenic tumour cell line was transduced with GFP. We injected RIF-1 or RIF-1 EGFP (stably transduced with a retroviral vector) cells in the leg of C3H/HeN mice and both the cells and tumour grew equally well. We used PDT with benzoporphyrin derivative and a short drug-light interval. There were complete cures and 100% mouse survival of RIF-1 EGFP while RIF-1 wild-type tumours all recurred. Cured mice were resistant to rechallenge with RIF-1 EGFP cells and a rechallenge with wild-type RIF-1 cells grew significantly slower. There was also slower RIF-1 EGFP rechallenge growth but no rejection when RIF-1 EGFP tumours were surgically removed. There was a low rate of PDT cure of tumours when RIF-1 cells were transduced with an empty retroviral vector. The presence of antibodies against EGFP in mouse serum suggests EGFP can act as a foreign antigen and PDT can then stimulate a long-term memory immune response. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA083882, R01 CA083882-03]; NIAID NIH HHS [R01-CA/AI838801] NR 36 TC 31 Z9 33 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB 13 PY 2006 VL 94 IS 3 BP 391 EP 397 DI 10.1038/sj.bjc.6602953 PG 7 WC Oncology SC Oncology GA 010JG UT WOS:000235183800007 PM 16421588 ER PT J AU Herl, L Lleo, A Thomas, AV Nyborg, AC Jansen, K Golde, TE Hyman, BT Berezovska, O AF Herl, L Lleo, A Thomas, AV Nyborg, AC Jansen, K Golde, TE Hyman, BT Berezovska, O TI Detection of presenilin-1 homodimer formation in intact cells using fluorescent lifetime imaging microscopy SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE presenilin; gamma-secretase; FLIM; protein-protein interactions; dimerization; Alzheimer's disease ID GAMMA-SECRETASE ACTIVITY; SIGNAL PEPTIDE PEPTIDASE; ALZHEIMERS-DISEASE; DOCKING SITE; BETA-APP; COMPLEX; NICASTRIN; PROTEIN; PEN-2; APH-1 AB Presenilin-1 (PS1) is a multipass transmembrane domain protein, which is believed to he the catalytic complex. The complex is comprised of four major components: PS 1. nicastrin, Aph- 1. and Pen-2. The exact stoichiometric relationship between the four components remains unclear. It has been shown that gamma-secretase exists is high molecular weight complexes. suggesting the possibility of dimer/multimer formation. We combined a biochemical approach with it novel morphological microscopy assay to analyze PS1 dimer formation and subcellular distribution in situ. in intact mammalian cells. Both coimmunoprecipitation and fluorescent lifetime imaging microscopy approaches showed that wildtype PS1 Molecules form dimers. Moreover, PS1 holoproteins containing the D257A mutation also come into close enough proximity to form a dimer, suggesting that cleavage within the tool is not necessary for dimer formation. Taken together these data suggest that PSI dimerization occurs during normal PS1 function, (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, Charlestown, MA 02129 USA. Mayo Clin Jacksonville, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. RP Berezovska, O (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, Charlestown, MA 02129 USA. EM oberezovska@partners.org FU NIA NIH HHS [P01 AG15379-06] NR 37 TC 21 Z9 22 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 10 PY 2006 VL 340 IS 2 BP 668 EP 674 DI 10.1016/j.bbrc.2005.12.063 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 004DI UT WOS:000234731800045 PM 16376853 ER PT J AU Mareninova, OA Sung, KF Hong, P Lugea, A Pandol, SJ Gukovsky, I Gukovskaya, AS AF Mareninova, OA Sung, KF Hong, P Lugea, A Pandol, SJ Gukovsky, I Gukovskaya, AS TI Cell death in pancreatitis - Caspases protect from necrotizing pancreatitis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; RECEPTOR-INTERACTING PROTEIN; ACINAR-CELLS; INDUCED APOPTOSIS; INFLAMMATORY MEDIATORS; SIGNALING COMPLEX; APAF-1 APOPTOSOME; CYTOCHROME-C; KINASE RIP; ACTIVATION AB Mechanisms of cell death in pancreatitis remain unknown. Parenchymal necrosis is a major complication of pancreatitis; also, the severity of experimental pancreatitis correlates directly with necrosis and inversely with apoptosis. Thus, shifting death responses from necrosis to apoptosis may have a therapeutic value. To determine cell death pathways in pancreatitis and the possibility of necrosis/apoptosis switch, we utilized the differences between the rat model of cerulein pancreatitis, with relatively high apoptosis and low necrosis, and the mouse model, with little apoptosis and high necrosis. We found that caspases were greatly activated during cerulein pancreatitis in the rat but not mouse. Endogenous caspase inhibitor X-linked inhibitor of apoptosis protein (XIAP) underwent complete degradation in the rat but remained intact in the mouse model. Furthermore, XIAP inhibition with embelin triggered caspase activation in the mouse model, implicating XIAP in caspase blockade in pancreatitis. Caspase inhibitors decreased apoptosis and markedly stimulated necrosis in the rat model, worsening pancreatitis parameters. Conversely, caspase induction with embelin stimulated apoptosis and decreased necrosis in mouse model. Thus, caspases not only mediate apoptosis but also protect from necrosis in pancreatitis. One protective mechanism is through degradation of receptor-interacting protein (RIP), a key mediator of "programmed" necrosis. We found that RIP was cleaved (i.e. inactivated) in the rat but not the mouse model. Caspase inhibition restored RIP levels; conversely, caspase induction with embelin triggered RIP cleavage. Our results indicate key roles for caspases, XIAP, and RIP in the regulation of cell death in pancreatitis. Manipulating these signals to change the pattern of death responses presents a therapeutic strategy for treatment of pancreatitis. C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Chang Gung Mem Hosp, Dept HepatoGastroenterol, Taipei 333, Taiwan. RP Gukovskaya, AS (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NIDDK NIH HHS [DK59936] NR 78 TC 157 Z9 168 U1 1 U2 7 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 FEB 10 PY 2006 VL 281 IS 6 BP 3370 EP 3381 DI 10.1074/jbc.M511276200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 009QV UT WOS:000235128200045 PM 16339139 ER PT J AU Barbera, AJ Chodaparambil, JV Kelley-Clarke, B Joukov, V Walter, JC Luger, K Kaye, KM AF Barbera, AJ Chodaparambil, JV Kelley-Clarke, B Joukov, V Walter, JC Luger, K Kaye, KM TI The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA SO SCIENCE LA English DT Article ID EPSTEIN-BARR-VIRUS; NUCLEAR ANTIGEN; DNA-SEQUENCES; CORE PARTICLE; PROTEIN INTERACTIONS; MITOTIC CHROMOSOMES; ANGSTROM RESOLUTION; EPISOME-MAINTENANCE; CRYSTAL-STRUCTURE; GENE-EXPRESSION AB Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) mediates viral genome attachment to mitotic chromosomes. We find that N-terminal LANA docks onto chromosomes by binding nucleosomes through the folded region of histones H2A-H2B. The same LANA residues were required for both H2A-H2B binding and chromosome association. Further, LANA did not bind Xenopus sperm chromatin, which is deficient in H2A-H2B; chromatin binding was rescued after assembly of nucleosomes containing H2A-H2B. We also describe the 2.9-angstrom crystal structure of a nucleosome complexed with the first 23 LANA amino acids. The LANA peptide forms a hairpin that interacts exclusively with an acidic H2A-H2B region that is implicated in the formation of higher order chromatin structure. Our findings present a paradigm for how nucleosomes may serve as binding platforms for viral and cellular proteins and reveal a previously unknown mechanism for KSHV latency. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Colorado State Univ, Howard Hughes Med Inst, Ft Collins, CO 80523 USA. Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Kaye, KM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. EM kkaye@rics.bwh.harvard.edu RI Chodaparambil, Jayanth/F-3229-2015 FU NCI NIH HHS [CA82036]; NIGMS NIH HHS [GM067777, GM62267, R01 GM067777] NR 38 TC 237 Z9 244 U1 4 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 10 PY 2006 VL 311 IS 5762 BP 856 EP 861 DI 10.1126/science.1120541 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 012XT UT WOS:000235374900051 PM 16469929 ER PT J AU Barber, DL Wherry, EJ Masopust, D Zhu, BG Allison, JP Sharpe, AH Freeman, GJ Ahmed, R AF Barber, DL Wherry, EJ Masopust, D Zhu, BG Allison, JP Sharpe, AH Freeman, GJ Ahmed, R TI Restoring function in exhausted CD8 T cells during chronic viral infection SO NATURE LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; IN-VIVO; B7 FAMILY; PD-1; PERSISTENCE; TOLERANCE; RESPONSES; MEMORY; MEMBER; IMMUNOTHERAPY AB Functional impairment of antigen-specific T cells is a defining characteristic of many chronic infections, but the underlying mechanisms of T-cell dysfunction are not well understood. To address this question, we analysed genes expressed in functionally impaired virus-specific CD8 T cells present in mice chronically infected with lymphocytic choriomeningitis virus ( LCMV), and compared these with the gene profile of functional memory CD8 T cells. Here we report that PD-1 ( programmed death 1; also known as Pdcd1) was selectively upregulated by the exhausted T cells, and that in vivo administration of antibodies that blocked the interaction of this inhibitory receptor with its ligand, PD-L1 ( also known as B7-H1), enhanced T-cell responses. Notably, we found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the 'helpless' CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load. Blockade of the CTLA-4 ( cytotoxic T-lymphocyte-associated protein 4) inhibitory pathway had no effect on either T-cell function or viral control. These studies identify a specific mechanism of T-cell exhaustion and define a potentially effective immunological strategy for the treatment of chronic viral infections. C1 Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, Dept Med, New York, NY 10021 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ahmed, R (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. EM ra@microbio.emory.edu RI masopust, david/B-5027-2008 NR 30 TC 1707 Z9 1836 U1 32 U2 159 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 9 PY 2006 VL 439 IS 7077 BP 682 EP 687 DI 10.1038/nature04444 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 010KH UT WOS:000235193100035 PM 16382236 ER EF