FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Song, MK Hwang, IK Rosenthal, MJ Harris, DM Yamaguchi, DT Yip, I Go, VLW AF Song, MK Hwang, IK Rosenthal, MJ Harris, DM Yamaguchi, DT Yip, I Go, VLW TI Anti-hyperglycemic activity of zinc plus cyclo (his-pro) in genetically diabetic Goto-Kakizaki and aged rats SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE cyclo (his-pro); zinc; Goto-Kakizaki rats; diabetes mellitus; glucose uptake; aged rats ID THYROTROPIN-RELEASING-HORMONE; HUMAN SKELETAL-MUSCLE; INSULIN-RECEPTOR KINASE; ARACHIDONIC-ACID; CYCLO(HIS-PRO) LEVELS; DEFICIENT MICE; ORAL GLUCOSE; MELLITUS; RESISTANCE; TRANSPORT AB We previously reported that treatment of streptozotocin-induced diabetic rats with zinc plus cyclo (his-pro) (CHP) decreased fed blood glucose levels and water intake. The present study was conducted to examine the dose-dependent, acute, and chronic treatment effects of CHP on oral glucose tolerance (OGT), fed blood glucose levels, water intake, and plasma insulin levels in young and aged Sprague-Dawley (S-D) rats, nondiabetic Wistar rats, and genetically diabetic Goto-Kakizaki (GK) rats. Acute gastric gavage of 10 mg zinc plus 1.0 mg CHP/kg body weight significantly improved OGT in 4- and 13-month-old nondiabetic S-D rats and in 2-month-old diabetic G-K rats. Young S-D and G-K rats returned to pretreatment OGT values 1 week after acute gavage of zinc plus CHP (ZC), but improved OGT values persisted for at least 1 week after gavage in aged S-D rats. OGT values and fed blood glucose decreased to the greatest extent among other treatments when G-K rats were given free access to drinking water containing 1.0 to 1.5 mg CHP/L plus 10 mg zinc/L for 2 weeks. Although food and water intake showed a tendency to decrease, no statistically significant differences were observed in young G-K rats. Plasma insulin levels and blood glucose levels in both normal and diabetic G-K rats decreased with 2-week treatment with ZC. To test the direct effects of ZC on muscle tissue, we observed the effect of various doses of ZC on normal and G-K rat muscle slices. The optimal level of CHP alone for maximal muscle glucose uptake in muscle slices from normal rats was 10 mug/mL and 5.0 mug/mL in G-K rats, and ZC stimulated glucose uptake. However, no statistically significant difference was demonstrated between normal and G-K rat tissues in this study. These results indicate that oral intake of an optimal dose of ZC stimulates blood glucose metabolism, probably by stimulating muscle glucose utilization. C1 Univ Calif Los Angeles, Ctr Human Nutr, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Harris, DM (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, David Geffen Sch Med, 13-145 Warren Hall, Los Angeles, CA 90095 USA. EM dmharris@ucla.edu FU NIDDK NIH HHS [1 R43 DK 56546-01] NR 37 TC 53 Z9 54 U1 0 U2 3 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD DEC PY 2003 VL 228 IS 11 BP 1338 EP 1345 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 833FG UT WOS:000222321300012 PM 14681549 ER PT J AU Hussein, MR Wood, GS AF Hussein, MR Wood, GS TI hMLH1 and hMSH2 gene mutations are present in radial growth-phase cutaneous malignant melanoma cell lines and can be induced further by ultraviolet-B irradiation SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE CMM; cutaneous malignant melanomas; PCR; polymerase chain reaction; MMR; mismatch repair gene ID NONPOLYPOSIS COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; MISMATCH REPAIR; DYSPLASTIC NEVI; DNA DAMAGE; SKIN; METALLOTHIONEIN; REPLICATION; FIBROBLASTS; EXPRESSION AB Microsatellite instability and reduced expression of mismatch repair proteins were reported in melanomas. However, little is known about the mutational changes of the mismatch repair genes in radial growth-phase melanoma especially following UVB irradiation. To investigate these changes, an in vitro system consisting of radial growth-phase Wistar melanoma cell lines (WM35, WM3211 and WM1650) was established. The cells were UVB irradiated (10 mJ/cm(2)), and evaluated for mutational changes of exon regions 13, 16 and 19 (hMLH1) and 6, 7 and 12 (hMSH2) of these genes before and after irradiation. The genomic DNAs were PCR amplified and the products were directly sequenced. Transition (C-->T, G-->A, T-->C) and transversion (G-->T, A-->T) mutations were found in exons 6, 16 and 19. Some were present in both the sham-irradiated and UV-irradiated cells but others were only detected after UVB irradiation. hMLH1 and hMSH2 gene mutations occur early in melanoma tumorigenesis. The ability of UVB irradiation to induce additional mutations in these repair genes suggests its possible role in melanoma pathogenesis. Further investigation will be needed to determine whether mutations such as these contribute to the development of microsatellite instability in melanoma. C1 Univ Wisconsin, Dept Dermatol, Madison, WI 53715 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Dermatol, 1 S Pk,7th Floor, Madison, WI 53715 USA. FU NIAMS NIH HHS [AR02136] NR 21 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD DEC PY 2003 VL 12 IS 6 BP 872 EP 875 DI 10.1111/j.0906-6705.2003.00104.x PG 4 WC Dermatology SC Dermatology GA 753XY UT WOS:000187274700018 PM 14714570 ER PT J AU Natsume, A Wolfe, D Hu, J Huang, SH Puskovic, V Glorioso, JC Fink, DJ Mata, M AF Natsume, A Wolfe, D Hu, J Huang, SH Puskovic, V Glorioso, JC Fink, DJ Mata, M TI Enhanced functional recovery after proximal nerve root injury by vector-mediated gene transfer SO EXPERIMENTAL NEUROLOGY LA English DT Article DE gene therapy; HSV; nerve crush; spinal injuries; apoptosis; Bcl-2; GDNF ID WALKING TRACK ANALYSIS; INDUCED CELL-DEATH; MICE LACKING GDNF; MOTOR-NEURONS; NEUROTROPHIC FACTOR; PERIPHERAL-NERVE; SCIATIC-NERVE; PROTOONCOGENE BCL-2; EXPRESSION; APOPTOSIS AB In order to test the functional implication of herpes simplex virus (HSV) vector-mediated gene transfer after axonal injury, we injected replication-incompetent HSV vectors coding for the anti-apoptotic peptide Bcl-2 and the glial cell-derived neurotrophic factor (GDNF), separately or in combination into ventral spinal cord 30 min after a crush injury to the proximal spinal root that was combined with moderate mechanical traction. HSV-mediated expression of Bcl-2 or GDNF enhanced functional recovery assessed by histologic, electrophysiologic, and behavioral parameters up to 5 months after injury. The most sensitive measure of distal motor function, the sciatic function index, was significantly improved in animals injected with the two vectors together. These results suggest an approach to root trauma that might be used to enhance functional recovery after injury. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15217 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15217 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA 15217 USA. RP Fink, DJ (reprint author), Univ Pittsburgh, Dept Neurol, S-521 ST,200 Lothrop St, Pittsburgh, PA 15217 USA. RI Natsume, Atsushi/I-7364-2014 OI Natsume, Atsushi/0000-0002-9113-0470 NR 40 TC 15 Z9 20 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2003 VL 184 IS 2 BP 878 EP 886 DI 10.1016/S0014-4886(03)00334-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 758KW UT WOS:000187634400034 PM 14769380 ER PT J AU Lugea, A Gukovsky, I Gukovskaya, AS Pandol, SJ AF Lugea, A Gukovsky, I Gukovskaya, AS Pandol, SJ TI Nonoxidative ethanol metabolites alter extracellular matrix protein content in rat pancreas SO GASTROENTEROLOGY LA English Estonian DT Article ID ACID ETHYL-ESTERS; HEPATIC STELLATE CELLS; NECROSIS-FACTOR-ALPHA; FAT-STORING CELLS; PLASMINOGEN-ACTIVATOR; GENE-EXPRESSION; ACINAR-CELLS; LIVER FIBROSIS; IN-VIVO; COLLAGEN AB Background & Aims: The mechanisms involved in ethanol-induced pancreas fibrosis are poorly understood. Here we show that fatty acid ethyl esters (FAEEs), nonoxidative ethanol metabolites, increase extracellular matrix (ECM) protein levels in pancreas. Methods: Rat pancreatic acini were incubated for 1-4 hours with FAEEs or acetaldehyde. In another set of experiments, rats received an intravenous infusion of FAEEs for 6 hours. Collagens were assessed by a hydroxyproline assay. Laminin and fibronectin were analyzed by Western blotting. Gene expression of ECM proteins was measured by conventional and real-time reverse-transcription polymerase chain reaction (RT-PCR). Matrix metalloproteinase (MMP), plasmin, and urokinase-type plasminogen activator (uPA) activities were determined by zymography and fluorogenic assays. Results: FAEEs increased Collagen, laminin, and fibronectin levels in pancreatic acini without affecting messenger RNA (mRNA) expression for these proteins. Actinomycin D, a transcriptional inhibitor, did not block the increase in ECM proteins induced by FAEEs. FAEEs reduced the activity of the serine protease, plasmin, and that of the uPA. Consistent with these results, the serine protease inhibitor aprotinin reproduced the effects of FAEEs and prevented the further increase in ECM proteins induced by FAEEs. In vivo administration of FAEEs reduced plasmin and uPA activities and increased ECM protein levels in pancreas. Acetaldehyde had minor effects on ECM protein levels and did not affect plasmin activity. Conclusions: FAEEs increase ECM protein levels in pancreas. The results suggest that this effect is caused primarily by an inhibition in ECM degradation via serine proteases including the plasminogen system. C1 Univ So Calif, Res Ctr Alcohol Liver & Pancreat Dis, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Lugea, A (reprint author), Univ So Calif, Res Ctr Alcohol Liver & Pancreat Dis, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 258,Room 339,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIAAA NIH HHS [P50-AA11999] NR 68 TC 31 Z9 31 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2003 VL 125 IS 6 BP 1845 EP 1859 DI 10.1053/S0016-5085(03)01508-7 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 752QA UT WOS:000187177600035 PM 14724836 ER PT J AU Croker, BP Gilkeson, G Morel, L AF Croker, BP Gilkeson, G Morel, L TI Genetic interactions between susceptibility loci reveal epistatic pathogenic networks in murine lupus SO GENES AND IMMUNITY LA English DT Article DE lupus; genetics; epistasis; clinical heterogeneity; mice ID CONGENIC MOUSE STRAINS; YAA GENE; B-CELL; SLE PATHOGENESIS; T-CELL; ERYTHEMATOSUS; DISSECTION; MICE; COMPLEX; MODEL AB Interactions between Sle1 and other susceptibility loci were required for disease development in the NZM2410 model of lupus. Sle1 corresponds to at least three subloci, Sle1a, Sle1b, and Sle1c, each of which independently causes loss of tolerance to chromatin, but displays a distinctive immune profile. We have used congenic strains to analyze the interactions between the Sle1 subloci and other lupus susceptibility loci using Y autoimmunity accelerator (Yaa) and Fas(lpr) as sensitizing mutations. Sle1 coexpressed with either one of these single susceptibility alleles resulted in a highly penetrant nephritis, splenomegaly, production of nephrophilic antibodies, and increased expression of B- and T-cell activation markers. Here, we show that only Sle1b interacted with Yaa to produce these phenotypes, suggesting that Sle1b and Yaa belong to the same functional pathway. Interactions between the three Sle1 loci and lpr resulted in lymphocyte activation and lupus nephritis, but a significant mortality was observed only for the Sle1a. lpr combination. This suggests a major role for the FAS pathway in keeping in check the loss of tolerance mediated by the Sle1 loci, especially for Sle1a. Our results illustrate the complexity of interactions between susceptibility loci in polygenic diseases such as lupus and may explain the clinical heterogeneity of the disease. C1 Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. N Florida S George Vet Hlth Syst, Gainesville, FL USA. Ralph H Johnson Vet Affairs Med Coll, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Morel, L (reprint author), Univ Florida, Dept Pathol, Box 100275, Gainesville, FL 32610 USA. FU NIAID NIH HHS [AI-54054] NR 39 TC 35 Z9 35 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD DEC PY 2003 VL 4 IS 8 BP 575 EP 585 DI 10.1038/sj.gene.6364028 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 747HR UT WOS:000186799600007 PM 14647198 ER PT J AU Ostrow, JD Tiribelli, C AF Ostrow, JD Tiribelli, C TI Bilirubin, a curse and a boon SO GUT LA English DT Editorial Material ID SILICIC-ACID CHROMATOGRAPHY; GLUTATHIONE-S-TRANSFERASES; UNCONJUGATED BILIRUBIN; OXIDATIVE STRESS; RAT-LIVER; IN-VITRO; PERMEABILITY TRANSITION; URSODEOXYCHOLIC ACID; MULTIDRUG-RESISTANCE; INDUCED APOPTOSIS AB Unconjugated bilirubin is a curse at high concentrations, producing apoptosis and cell death, but a boon at more physiological levels, protecting cells against oxidant damage. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Res Serv 151L, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, GI Hepatol Div, Seattle, WA 98195 USA. RP Ostrow, JD (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Res Serv 151L, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 55 TC 11 Z9 13 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD DEC 1 PY 2003 VL 52 IS 12 BP 1668 EP 1670 DI 10.1136/gut.52.12.1668 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 746KR UT WOS:000186746000004 PM 14633940 ER PT J AU Sugimoto, K Ikeda, F Stadanlick, J Nunes, FA Alter, H Chang, KM AF Sugimoto, K Ikeda, F Stadanlick, J Nunes, FA Alter, H Chang, KM TI Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; IMMUNE-RESPONSES; PERIPHERAL-BLOOD; DENDRITIC CELLS; CORE PROTEIN; QUANTITATIVE-ANALYSIS; LYMPHOCYTE RESPONSE; ENVELOPE PROTEIN; PLUS RIBAVIRIN; VIRAL LOAD AB Hepatitis C virus (HCV) has a high propensity for persistence. To better define the immunologic determinants of HCV clearance and persistence, we examined the circulating HCV-specific T-cell frequency, repertoire, and cytokine phenotype ex vivo in 24 HCV seropositive subjects (12 chronic, 12 recovered), using 361 overlapping peptides in 36 antigenic pools that span the entire HCV core, NS3-NS5. Consistent with T-cell-mediated control of HCV, the overall HCV-specific type-1 T-cell response was significantly greater in average frequency (0.24% vs. 0.04% circulating lymphocytes, P = .001) and scope (14/36 vs. 4/36 pools, P = .002) among the recovered than the chronic subjects, and the T-cell response correlated inversely with HCV titer among the chronic subjects (R = -0.51, P = .049). Although highly antigenic regions were identified throughout the HCV genome, there was no apparent difference in the overall HCV-specific T-cell repertoire or type-1/type-2 cytokine profile relative to outcome. Notably, HCV persistence was associated with a reversible CD4-mediated suppression of HCV-specific CD8 T cells and with higher frequency of CD4(+)CD25(+) regulatory T cells (7.3% chronic vs. 2.5% recovered, P = .002) that could directly suppress HCV-specific type-1 CD8 T cells ex vivo. In conclusion, we found that HCV persistence is associated with a global quantitative and functional suppression of HCV-specific T cells but not differential antigenic hierarchy or cytokine phenotype relative to HCV clearance. The high frequency of CD4(+)CD25(+) regulatory T cells and their suppression of HCV-specific CD8 T cells ex vivo suggests a novel role for regulatory T cells in HCV persistence. C1 Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Penn Hosp, Philadelphia, PA 19107 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Chang, KM (reprint author), Univ Penn, Dept Med, GI Div, Univ & Woodland Ave, Philadelphia, PA 19104 USA. RI Yang, Chen/G-1379-2010 FU NCRR NIH HHS [M01-RR00040]; NIAAA NIH HHS [AA12849]; NIAID NIH HHS [AI47519] NR 50 TC 266 Z9 292 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2003 VL 38 IS 6 BP 1437 EP 1448 DI 10.1016/j.hep.2003.09.026 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 751BC UT WOS:000187032100015 PM 14647055 ER PT J AU Lathers, DMR Achille, NJ Young, MRI AF Lathers, DMR Achille, NJ Young, MRI TI Incomplete Th2 skewing of cytokines in plasma of patients with squamous cell carcinoma of the head and neck SO HUMAN IMMUNOLOGY LA English DT Article DE cancer; cytokine; HNSCC; Th1; Th2 ID TUMOR-INFILTRATING LYMPHOCYTES; GROWTH-FACTOR BETA-1; COLORECTAL-CANCER; PERIPHERAL-BLOOD; CD34(+) CELLS; T-CELLS; IMMUNOTHERAPY; EXPRESSION; MECHANISMS AB Levels of cytokines, and in particular those that reflect Th1 or Th2 bias, were measured in the plasma of patients with head and neck squamous cell carcinomas (HNSCC). Compared with plasma cytokine levels of age-matched controls, cytokine levels in HNSCC patients suggested a shift to a Th2 bias as levels of the Th2 cytokines interleukin-4 (IL-4), IL-6, and IL-10 were increased, and levels of the Th1 cytokine interferon-gamma (IFN-gamma) were decreased. However, levels of the Th1 cytokines IL-2 and granulocyte macrophage-colony-stimulating factor (GM-CSF) were increased, which is not consistent with full Th2 skewing. Assessment of cytokine levels in patients with malignancies other than HNSCC demonstrated many similarities to HNSCC patients, but HNSCC patients exhibited a more pronounced increase in GM-CSF levels and a decline in IFN-gamma levels. For most cytokines there was no association between the shifts in cytokine levels in HNSCC patients and either the extent of tumor burden or extent of metastasis. However, patients with large HNSCC tended to be the population that demonstrated increased levels of IL-4 and IL-6. These results suggest skewing toward a Th2 bias in HNSCC patients, with the Th2 shift being incomplete and indicative of the presence, rather than the extent, of malignant disease. Human Immunology 64, 1160-1166 (2003). (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Inc. C1 Loyola Univ, Stritch Sch Med, Dept Pathol, Maywood, IL 60153 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Hosp, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [CA 78262, CA 79768, CA 85266] NR 23 TC 41 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD DEC PY 2003 VL 64 IS 12 BP 1160 EP 1166 DI 10.1016/j.humimm.2003.08.024 PG 7 WC Immunology SC Immunology GA 748XH UT WOS:000186885900005 PM 14630398 ER PT J AU Chatzinikolaou, I Hanna, H Graviss, L Chaiban, G Perego, C Arbuckle, R Champlin, R Darouiche, R Samonis, G Raad, I AF Chatzinikolaou, I Hanna, H Graviss, L Chaiban, G Perego, C Arbuckle, R Champlin, R Darouiche, R Samonis, G Raad, I TI Clinical experience with minocycline and rifampin-impregnated central venous catheters in bone marrow transplantation recipients: Efficacy and low risk of developing staphylococcal resistance SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 27-30, 2002 CL SAN DIEGO, CALIFORNIA ID BLOOD-STREAM INFECTIONS; BACTERIAL-RESISTANCE; IN-VITRO; ANTISEPTICS; ANTIBIOTICS; CULTURES AB In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections. C1 Univ Texas, MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Div Internal Med, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Pharm, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Bone Marrow Transplantat, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Infect Dis Sect, Houston, TX USA. Univ Crete, Sch Med, Dept Infect Dis, Div Internal Med, Rethimnon, Crete, Greece. RP Hanna, H (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Div Internal Med, 1515 Holcombe Blvd,Unit 402, Houston, TX 77030 USA. NR 10 TC 33 Z9 35 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 2003 VL 24 IS 12 BP 961 EP 963 DI 10.1086/502167 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 753MX UT WOS:000187236100014 PM 14700414 ER PT J AU Brochard, L Mancebo, J Tobin, M AF Brochard, L Mancebo, J Tobin, M TI Searching for evidence: don't forget the foundations SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS SYNDROME; END-EXPIRATORY PRESSURE; STATUS-ASTHMATICUS; VENTILATION C1 Univ Paris 12, Hop Henri Mondor, Assistance Publ Hop Paris, Med Intens Care Unit, F-94010 Creteil, France. INSERM, U492, F-94010 Creteil, France. Univ Autonoma Barcelona, St Pau Hosp, Intens Care Unit, E-08193 Barcelona, Spain. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ Chicago, Stritch Sch Med, Hines, IL 60141 USA. RP Brochard, L (reprint author), Univ Paris 12, Hop Henri Mondor, Assistance Publ Hop Paris, Med Intens Care Unit, F-94010 Creteil, France. NR 10 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2003 VL 29 IS 12 BP 2109 EP 2111 DI 10.1007/s00134-003-2012-8 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 747VN UT WOS:000186825900001 PM 14566454 ER PT J AU Butters, MA Sweet, RA Mulsant, BH Kamboh, MI Pollock, BG Begley, AE Reynolds, CF DeKosky, ST AF Butters, MA Sweet, RA Mulsant, BH Kamboh, MI Pollock, BG Begley, AE Reynolds, CF DeKosky, ST TI APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE apolipoprotein E; geriatric; late-life; depression; Alzheimer's disease ID APOLIPOPROTEIN E-EPSILON-4 FREQUENCY; MINI-MENTAL-STATE; 2-YEAR FOLLOW-UP; ALZHEIMERS-DISEASE; RISK-FACTORS; GERIATRIC DEPRESSION; REVERSIBLE DEMENTIA; PSEUDODEMENTIA; POLYMORPHISM; REANALYSIS AB Objective There is a recognized but poorly understood relationship between late-life depression (LLD) and progressive dementia. Both cognitive impairment co-occurring with LLD and a late age-of-onset of first lifetime depressive episode appear to be associated with subsequent progressive dementia. A history of major depression, especially when the first onset occurs in late-life, has been identified as a risk factor for Alzheimer's disease (AD). The major genetic risk factor for sporadic AD is carrying one or more apolipoprotein E4 (APOE4) alleles. We hypothesized that the association between LLD and dementia risk would be mediated by APOE4, specifically that APOE4 allele frequency would be associated with cognitive impairment and later age-of-depression-onset. We also predicted that APOE4 allele frequency would be increased among subjects with LLD. Methods We compared the distribution of APOE2, APOE3, and APOE4 alleles in groups of LLD (n = 160), AD (n = 568) and elderly control (EC; n = 156) subjects. Results The allele distribution of the cognitively impaired LLD subgroup was not different from either the cognitively normal subgroup or the EC group but was different from the AD group. However, mean age-of-onset of depression in APOE4 carriers (51.4 +/- 20.7) was significantly lower than non-carriers (58.8 +/- 16.8). The allele distribution in LLD overall was significantly different from the AD but not the EC group. Conclusions The finding that neither LLD, accompanying cognitive impairment, nor late age-of-onset was associated with an increased APOE4 allele frequency suggests that LLD acts as a risk factor for developing AD as well as non-AD dementia through mechanisms independent of APOE4. The unexpected finding that age-of-onset of LLD was significantly reduced in APOE4 carriers is similar to the association between APOE4 and age-of-onset in AD. Replication of the association of APOE4 with earlier age-of-depression-onset is indicated. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Butters, MA (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. OI Kamboh, M. Ilyas/0000-0002-3453-1438 FU NIA NIH HHS [AG05133, AG13672]; NIMH NIH HHS [MH01613, MH01684, MH37869, MH43832, MH52247, MH65416, MH66231] NR 37 TC 30 Z9 32 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD DEC PY 2003 VL 18 IS 12 BP 1075 EP 1081 DI 10.1002/gps.1006 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 757XR UT WOS:000187587200001 PM 14677138 ER PT J AU Gross, RD Atwood, CW Grayhack, JP Shaiman, S AF Gross, RD Atwood, CW Grayhack, JP Shaiman, S TI Lung volume effects on pharyngeal swallowing physiology SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE deglutition; dysphagia; dynamic; subglottic mechanoreceptors; subglottic air pressure ID PASSY-MUIR VALVE; FUNDAMENTAL-FREQUENCY; NECK-CANCER; ASPIRATION; TRACHEOSTOMY; COORDINATION; PRESSURE; DYSPHAGIA; STROKE; RESPIRATION AB The experiment was a prospective, repeated-measures design intended to determine how the variation of lung volume affects specific measures of swallowing physiology. Swallows were recorded in 28 healthy subjects, who ranged in age from 21 to 40 yr (mean age of 29 yr), by using simultaneous videofluoroscopy, bipolar intramuscular electromyography, and respiratory inductance plethysmography. Each subject swallowed three standardized pudding-like consistency boluses at three randomized lung volumes: total lung capacity, functional residual capacity, and residual volume. The results showed that pharyngeal activity duration of deglutition for swallows produced at residual volume was significantly longer than those occurring at total lung capacity or at functional residual capacity. No significant differences were found for bolus transit time or intramuscular electromyography of the superior constrictor. The results of this experiment lend support to the hypothesis that the respiratory system may have a regulatory function related to swallowing and that positive subglottic air pressure may be important for swallowing integrity. Eventually, new treatment paradigms for oropharyngeal dysphagia that are based on respiratory physiology may be developed. C1 Vet Affairs Pittsburgh Healthcare Syst, Dept Speech Pathol & Audiol, Pittsburgh, PA 15240 USA. Vet Affairs Pittsburgh Healthcare Syst, Pulm Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. RP Gross, RD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Dept Speech Pathol & Audiol, Univ Dr C 132A-U, Pittsburgh, PA 15240 USA. NR 49 TC 24 Z9 26 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 2003 VL 95 IS 6 BP 2211 EP 2217 DI 10.1152/japplphysiol.00316.2003 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 750PF UT WOS:000187004400004 PM 12909607 ER PT J AU Epstein, S Inzerillo, AM Caminis, J Zaidi, M AF Epstein, S Inzerillo, AM Caminis, J Zaidi, M TI Disorders associated with acute rapid and severe bone loss SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Review ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; HORMONE REPLACEMENT THERAPY; CORTICOSTEROID-INDUCED OSTEOPOROSIS; OSTEOBLAST-LIKE CELLS; A-INDUCED OSTEOPENIA; ORTHOTOPIC LIVER-TRANSPLANTATION; TREATED RHEUMATOID-ARTHRITIS; RANDOMIZED CONTROLLED-TRIAL; PRIMARY BILIARY-CIRRHOSIS; ESTROGEN PLUS PROGESTIN AB We describe a constellation of bone diseases characterized by the common feature of acute, rapid, and severe bone loss accompanied by dramatic fracture rates. These disorders are poorly recognized, resulting mainly from systemic diseases, frailty, immobilization, and immunosuppressive drugs, such as glucocorticoids and the calcineurin inhibitors. The opportunity to prevent or treat fractures is commonly missed because they are often not detected. Ideally, patients need to be identified early and preventative therapy initiated promptly to avoid the rapid bone loss and fractures. The most effective therapy at present seems to be the bisphosphonates, particularly when bone resorption is predominant. However, more severe forms of bone loss that result from an osteoblastic defect and reduced bone formation may benefit potentially more from newer anabolic agents, such as recombinant human parathyroid hormone (rhPTH). C1 Mt Sinai Bone Program, Mt Sinai Sch Med, Bronx VA Med Ctr, Dept Med, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Dept Med, Sch Med, Div Endocrinol, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Dept Med, Sch Med, Div Endocrinol, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Dept Geriatr, Sch Med, Div Endocrinol, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Dept Physiol, Sch Med, Div Endocrinol, New York, NY 10029 USA. Novartis Pharmaceut Corp, Arthrit Bone Sect, E Hanover, NJ USA. RP Epstein, S (reprint author), Mt Sinai Bone Program, Mt Sinai Sch Med, Bronx VA Med Ctr, Dept Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIA NIH HHS [R01-AG 14197-08] NR 161 TC 35 Z9 41 U1 2 U2 3 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 DEC PY 2003 VL 18 IS 12 BP 2083 EP 2094 DI 10.1359/jbmr.2003.18.12.2083 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 745WB UT WOS:000186712700001 PM 14672343 ER PT J AU Kammerer, CM Schneider, JL Cole, SA Hixson, JE Samollow, PB O'Connell, JR Perez, R Dyer, TD Almasy, L Blangero, J Bauer, RL Mitchell, BD AF Kammerer, CM Schneider, JL Cole, SA Hixson, JE Samollow, PB O'Connell, JR Perez, R Dyer, TD Almasy, L Blangero, J Bauer, RL Mitchell, BD TI Quantitative trait loci on chromosomes 2p, 4p, and 13q influence bone mineral density of the forearm and hip in Mexican Americans SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE genetic; linkage; bone density; forearm; genome scan ID LINKAGE ANALYSIS; GENOME SCREEN; OSTEOPOROSIS; GENE; OSTEOBLASTS; PEDIGREES; FRACTURES; SUGGESTS; CELLS; SCAN AB Introduction: The San Antonio Family Osteoporosis Study (SAFOS) was designed to identify genes and environmental factors that influence bone mineral density (BMD) using data from large Mexican-American families. Materials and Methods: We performed a genome-wide linkage analysis using 416 highly polymorphic microsatellite markers spaced approximately 9.5 cM apart to locate and identify quantitative trait loci (QTL) that affect BMD of the forearm and hip. Multipoint variance components linkage analyses were done using data on all 664 subjects, as well as two subgroups of 259 men and 261 premenopausal women, from 29 families for which genotypic and phenotypic data were available. Results: We obtained significant evidence for a QTL affecting forearm (radius midpoint) BMD in men and women combined on chromosome 4p near D4S2639 (maximum LOD = 4.33, genomic p = 0.006) and suggestive evidence for a QTL on chromosome 12q near locus D12S2070 (maximum conditional LOD = 2.35). We found suggestive evidence for a QTL influencing trochanter BMD on chromosome 6 (maximum LOD = 2.27), but no evidence for QTL affecting the femoral neck in men and women combined. In men, we obtained evidence for QTL affecting neck and trochanter BMD on chromosomes 2p near D2S1780 (maximum LOD = 3.98, genomic p = 0.013) and 13q near D13S788 (maximum LOD = 3.46, genomic p = 0.039), respectively. We found no evidence for QTL affecting forearm or hip BMD in premenopausal women. Conclusion: These results provide strong evidence that a QTL on chromosome 4p affects radius BMD in Mexican-American men and women, as well as evidence that QTL on chromosomes 2p and 13q affect hip BMD in men. Our results are consistent with some reports in humans and mice. C1 Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. Univ Maryland, Sch Med, Div Endocrinol, Baltimore, MD 21201 USA. Audie L Murphy Mem Vet Adm Med Ctr, Dept Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Kammerer, CM (reprint author), Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, 130 DeSoto St,A310 Crabtree Hall, Pittsburgh, PA 15261 USA. OI Mitchell, Braxton/0000-0003-4920-4744 FU NCRR NIH HHS [M01-RR-01346]; NHLBI NIH HHS [P01-HL45522]; NIAMS NIH HHS [R01 AR43351] NR 35 TC 80 Z9 84 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2003 VL 18 IS 12 BP 2245 EP 2252 DI 10.1359/jbmr.2003.18.12.2245 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 745WB UT WOS:000186712700019 PM 14672361 ER PT J AU Nielsen-Preiss, SM Silva, SR Gillette, JM AF Nielsen-Preiss, SM Silva, SR Gillette, JM TI Role of PTEN and Akt in the regulation of growth and apoptosis in human osteoblastic cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE apoptosis; cell cycle; osteosarcoma; kinase; phosphatase inhibitor ID TUMOR-SUPPRESSOR PTEN; LIPID PHOSPHATASE-ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; OSTEOGENIC-SARCOMA; HUMAN OSTEOSARCOMA; LUNG METASTASES; G(1) ARREST; ALLELE LOSS; PROTEIN; KINASE AB Cancer cells are characterized by either an increased ability to proliferate or a diminished capacity to undergo programmed cell death. PTEN is instrumental in regulating the balance between growth and death in several cell types and has been described as a tumor suppressor. The chromosome arm on which PTEN is located is deleted in a subset of human osteosarcoma tumors. Therefore, we predicted that the loss of PTEN expression was contributing to increased Akt activation and the subsequent growth and survival of osteosarcoma tumor cells. Immunoblot analyses of several human osteosarcoma cell lines and normal osteoblasts revealed relatively abundant levels of PTEN. Furthermore, stimulation of cell growth or induction of apoptosis in osteosarcoma cells failed to affect PTEN expression or activity. Therefore, routine regulation of osteosarcoma cell growth and survival appears to be independent of changes in PTEN. Subsequently, the activation of a downstream target of PTEN activity, the survival factor Akt, was analyzed. Inappropriate activation of Akt could bypass the negative regulation by PTEN. Analyses of Akt expression in several osteosarcoma cell lines and normal osteoblasts revealed uniformly low basal levels of phosphorylated Akt. The levels of phosphorylated Akt did not increase following growth stimulation. In addition, osteosarcoma cell growth was unaffected by inhibitors of phosphatidylinositol-3 kinase, an upstream activator of the Akt signaling pathway. These data further suggest that the Akt pathway is not the predominant signaling cascade required for osteoblastic growth. However, inhibition of PTEN activity resulted in increased levels of Akt phosphorylation and enhanced cell proliferation. These data suggest that while abundant levels of PTEN normally maintain Akt in an inactive form in osteoblastic cells, the Akt signaling pathway is intact and functional. (C) 2003 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Orthopaed, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Cellular & Dev Biol, Denver, CO 80262 USA. RP Nielsen-Preiss, SM (reprint author), Denver VA Med Ctr, Dept Endocrinol, 1055 Clermont St,Bldg 1,9C-115,Mailstop 111H, Denver, CO 80220 USA. NR 66 TC 17 Z9 19 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC 1 PY 2003 VL 90 IS 5 BP 964 EP 975 DI 10.1002/jcb.10709 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 747UH UT WOS:000186822900010 PM 14624456 ER PT J AU Shoback, DM Bilezikian, JP Turner, SA McCary, LC Guo, MD Peacock, M AF Shoback, DM Bilezikian, JP Turner, SA McCary, LC Guo, MD Peacock, M TI The calcimimetic cinacalcet normalizes serum calcium in subjects with primary hyperparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EXTRACELLULAR CA2+-SENSING RECEPTOR; POSTMENOPAUSAL WOMEN; PARATHYROID SURGERY; ALENDRONATE; CA2+ AB Calcimimetics increase the sensitivity of the calcium-sensing receptor (CaR) to circulating serum calcium, reducing the secretion of PTH and the serum calcium concentration. We evaluated the calcimimetic cinacalcet, a novel therapy for the management of primary hyperparathyroidism. In this randomized, double-blind, dose-finding study, patients (n = 22) with primary hyperparathyroidism were given cinacalcet ( 30, 40, or 50 mg) or placebo twice daily for 15 d and observed for an additional 7 d. Serum calcium, plasma PTH, and 24-h and fasting urine calcium were measured. Baseline mean serum calcium was 10.6 mg/dl for the combined cinacalcet-treated patients (normal range, 8.4 - 10.3 mg/dl), compared with 10.4 mg/dl for the placebo group. Mean PTH at baseline was 102 pg/ml (normal range, 10 - 65 pg/ml) for the combined cinacalcet-treated patients, compared with 100 pg/ml in the placebo group. Serum calcium normalized after the second dose on d 1 and remained normal through d 15 in all cinacalcet dose groups. Maximum decreases in PTH of over 50% occurred 2 - 4 h after dosing in all cinacalcet-treated groups. The fasting and 24-h urine calcium to creatinine ratios were similar in the cinacalcet and placebo groups. This study demonstrates that cinacalcet safely normalized serum calcium and lowered PTH concentrations without increasing urinary calcium excretion in the study subjects, indicating the potential benefit of cinacalcet as a medical treatment for primary hyperparathyroidism. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Endocrine Unit 111N, Dept Med, San Francisco, CA 94121 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. RP Shoback, DM (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Endocrine Unit 111N, Dept Med, 4150 Clement St, San Francisco, CA 94121 USA. EM Dolores@itsa.ucsf.edu FU NIDDK NIH HHS [R01 DK032333] NR 21 TC 153 Z9 157 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC 1 PY 2003 VL 88 IS 12 BP 5644 EP 5649 DI 10.1210/jc.2002-021597 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 752TZ UT WOS:000187184400010 PM 14671147 ER PT J AU Purnell, JQ Weigle, DS Breen, P Cummings, DE AF Purnell, JQ Weigle, DS Breen, P Cummings, DE TI Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GH-RELEASING HORMONE; PLASMA GHRELIN; FOOD-INTAKE; CIRCULATING GHRELIN; HUMAN OBESITY; WEIGHT-LOSS; STOMACH; SECRETION; GLUCOSE; LIPASE AB The gut peptide, ghrelin, may participate in the control of energy homeostasis and pituitary hormone secretion in humans, stimulating both food intake and, at pharmacological doses, ACTH and cortisol secretion. Meal consumption and weight loss regulate ghrelin levels, but less is known about the relationship of ghrelin to body composition, aging, menopausal status, and lipid metabolism. Therefore, 60 adult men and women of widely varying ages and weights were characterized in terms of body composition and levels of ghrelin, glucose, insulin, lipids, and cortisol. Fasting ghrelin levels correlated positively with age and negatively with BMI and fat cell size, but were not related to fat mass, intraabdominal fat, or lean mass. Fasting ghrelin levels correlated most strongly with insulin levels (r = - 0.39; P = 0.002), insulin resistance as determined by the quantitative insulin sensitivity check index (r = 0.38; P = 0.003), and high-density lipoprotein cholesterol levels (r = 0.33; P = 0.009). Meal-induced ghrelin suppression correlated with the postprandial rise in insulin (r = 0.39; P < 0.05). Ghrelin levels were similar in men and women and did not vary by menopausal status or in association with cortisol levels. Our data are consistent with the hypotheses that insulin may negatively regulate ghrelin and that high-density lipoprotein may be a carrier particle for circulating ghrelin. C1 Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Harborview Med Ctr, Seattle, WA 98108 USA. RP Purnell, JQ (reprint author), Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, L607,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM purnellj@ohsu.edu FU NCRR NIH HHS [M01RR00334, M01RR00037]; NIDDK NIH HHS [R01 DK61516, P30DK17047, R01 DK55460, K23 DK02689, K24 DK02860] NR 30 TC 187 Z9 194 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC 1 PY 2003 VL 88 IS 12 BP 5747 EP 5752 DI 10.1210/jc.2003-030513 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 752TZ UT WOS:000187184400027 PM 14671163 ER PT J AU Kerlikowske, K Miglioretti, DL Ballard-Barbash, R Weaver, DL Buist, DSM Barlow, WE Cutter, G Geller, BM Yankaskas, B Taplin, SH Carney, PA AF Kerlikowske, K Miglioretti, DL Ballard-Barbash, R Weaver, DL Buist, DSM Barlow, WE Cutter, G Geller, BM Yankaskas, B Taplin, SH Carney, PA TI Prognostic characteristics of breast cancer among postmenopausal hormone users in a screened population SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; PLUS PROGESTIN; WOMENS HEALTH; COLLABORATIVE REANALYSIS; TUMOR CHARACTERISTICS; MENOPAUSAL ESTROGEN; FAMILY HISTORY; RISK; MAMMOGRAPHY; DENSITY AB Purpose: We determined the risk of breast cancer and tumor characteristics among current postmenopausal hormone therapy users compared with nonusers, by duration of use. Methods: From January 1996 to December 2000, data were collected prospectively on 374,465 postmenopausal women aged 50 to 79 years who underwent screening mammography. We calculated the relative risk (RR) of breast cancer (invasive or ductal carcinoma-in-situ) and type of breast cancer within 12 months of postmenopausal therapy use among current hormone users with a uterus (proxy for estrogen and progestin use) and without a uterus (proxy for estrogen use), compared with nonusers. Results: Compared with nonusers, women using estrogen and progestin for greater than or equal to 5 years were at increased risk of breast tumors of stage O or I (RR, 1.51; 95% CI, 1.37 to 1.66), stage II or higher (RR, 1.46; 95% CI, 1.30 to 1.63), size less than or equal to 20 mm (RR, 1.59; 95% CI, 1.43 to 1.76), size greater than 20 mm (RR, 1.24; 95% CI, 1.09 to 1.42), grade 1 or 2 (RR, 1.60; 95% CI, 1.44 to 1.77), grade 3 or 4 (RR, 1.54; 95% CI, 1.37 to 1.73), and estrogen receptor-positive (RR, 1.72; 95%a CI, 1.55 to 1.90). Estrogen-only users were slightly more likely to have estrogen receptor-positive breast cancer compared with nonusers (RR, 1.14; 95% CI, 1.06 to 1.23). Conclusion: Use of estrogen and progestin postmenopausal hormone therapy for five years or more increased the likelihood of developing breast cancer, including both tumors with favorable prognostic features and tumors with unfavorable prognostic features. (C) 2003 by American Society of Clinical Oncology. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94143 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. NCI, Appl Res Program, DCCPS, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ Nevada, Sch Med, Appl Res Facil, Ctr Res Design & Stat Methods, Reno, NV 89557 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Dept Community & Family Med, Dartmouth Med Sch, Lebanon, NH 03766 USA. RP Kerlikowske, K (reprint author), San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NCI NIH HHS [U01CA70013, U01CA86082, U01CA63740, U01CA69976, U01CA63736, U01CA63731, U01CA86076, U01CA70040] NR 49 TC 93 Z9 97 U1 0 U2 1 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 DEC 1 PY 2003 VL 21 IS 23 BP 4314 EP 4321 DI 10.1200/JCO.2003.05.151 PG 8 WC Oncology SC Oncology GA 749HB UT WOS:000186912900012 PM 14645420 ER PT J AU Ubel, PA Jepson, C Asch, DA AF Ubel, PA Jepson, C Asch, DA TI Misperceptions about beta-blockers and diuretics - A national survey of primary care physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hypertension treatment; physician survey; pharmaceutical promotion ID SINGLE-DRUG THERAPY; QUALITY-OF-LIFE; COMMERCIAL SOURCES; UNITED-STATES; HYPERTENSION; BEHAVIOR; TRENDS; REPRESENTATIVES; MANAGEMENT; MORBIDITY AB BACKGROUND: Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe beta-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than beta-blockers and diuretics. METHODS: We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS: Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P < .001). They also perceive that beta-blockers are less tolerated than the other 3 classes (P < .001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. CONCLUSIONS: Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and beta-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of beta-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines. C1 Univ Michigan, Program Improving Hlth Care Decis, Ann Arbor, MI 48109 USA. VA Ann Arbor Healthcare Syst, VA Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Ubel, PA (reprint author), Univ Michigan, Program Improving Hlth Care Decis, 300 N Ingalls,Room 7C27, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [R01-CA78052-01] NR 24 TC 34 Z9 34 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2003 VL 18 IS 12 BP 977 EP 983 DI 10.1111/j.1525-1497.2003.20414.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 756DK UT WOS:000187450400002 PM 14687255 ER PT J AU Van Voorhees, BW Cooper, LA Rost, KM Nutting, P Rubenstein, LV Meredith, L Wang, NY Ford, DE AF Van Voorhees, BW Cooper, LA Rost, KM Nutting, P Rubenstein, LV Meredith, L Wang, NY Ford, DE TI Primary care patients with depression are less accepting of treatment than those seen by mental health specialists SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 2002 CL ATLANTA, GEORGIA SP Soc Gen Internal Med DE attitudes; depression; quality improvement ID NATIONAL COMORBIDITY SURVEY; YOUNG-ADULTS; MAJOR DEPRESSION; UNITED-STATES; SEEKING HELP; DISORDERS; SERVICES; QUALITY; RISK; DISTURBANCES AB OBJECTIVE: This study examined whether depressed patients treated exclusively in primary care report less need for care and less acceptability of treatment options than those depressed patients treated in the specialty mental health setting after up to 6 months of treatment. DESIGN: Cross-sectional study. SETTING: Forty-five community primary care practices. PARTICIPANTS: A total of 881 persons with major depression who had received mental health services in the previous 6 months and who enrolled in 3 of the 4 Quality Improvement for Depression Collaboration Studies. MEASUREMENTS AND RESULTS: Patients were categorized into 1 of 2 groups: 1) having received mental health services exclusively from a primary care provider (45%), or 2) having received any services from a mental health specialist (55%) in the previous 6 months. Compared with patients who received care from mental health specialists, patients who received mental health services exclusively from primary care providers had 2.7-fold the odds (95% confidence interval [CI], 1.6 to 4.4) of reporting that no treatment was definitely acceptable and had 2.4-fold the odds (95% CI, 1.5 to 3.9) of reporting that evidence-based treatment options (antidepressant medication) were definitely not acceptable. These results were adjusted for demographic, social/behavioral, depression severity, and economic factors using multiple logistic regression analysis. CONCLUSIONS: Patients with depression treated exclusively by primary care providers have attitudes and beliefs more averse to care than those seen by mental health specialists. These differences in attitudes and beliefs may contribute to lower quality depression care observed in comparisons of primary care and specialty mental health providers. C1 Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA. Univ Colorado, Hlth Sci Ctr, Dept Family Med, Denver, CO USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RAND Corp, Hlth Program, Santa Monica, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. RP Ford, DE (reprint author), Johns Hopkins Univ, Sch Med, Div Gen Internal Med, 2024 E Monument St,Suite 2500, Baltimore, MD 21205 USA. OI Wang, Nae-Yuh/0000-0001-6513-9730 FU BHP HRSA HHS [T32PE10025]; NIMH NIH HHS [5-R01MH5443] NR 55 TC 36 Z9 36 U1 4 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2003 VL 18 IS 12 BP 991 EP 1000 DI 10.1111/j.1525-1497.2003.21060.x PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 756DK UT WOS:000187450400004 PM 14687257 ER PT J AU Adeoye, OM Ferrell, RE Kirshner, MA Mulsant, BH Seligman, K Begley, AE Reynolds, CF Pollock, BG AF Adeoye, OM Ferrell, RE Kirshner, MA Mulsant, BH Seligman, K Begley, AE Reynolds, CF Pollock, BG TI alpha 1-acid glycoprotein in late-life depression: Relationship to medical burden and genetics SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE alpha 1-acid glycoprotein; AAG; late-life depression; CIRS-G ID IMIPRAMINE; BINDING; DISORDERS; ORM1; AGE AB Serum alpha1-acid glycoprotein (AAG) concentrations were examined in relationship to age, medical burden, depression, and mental status in elderly control (n = 19, mean age = 72.1 +/- 6.8 years) and depressed (n = 58, mean age = 71.9 +/- 7.1 years) subjects. DNA was analyzed for allelic variants of the AGP1 (ORM1) gene in both groups. Depressed subjects' AAG serum levels were measured at baseline and after 6 weeks of antidepressant treatment. Before treatment, depressed subjects had significantly higher serum AAG concentrations than nondepressed controls (t(49.2) = -3.48, P =.0011). Pretreatment AAG levels also correlated with degree of medical burden, measured by the Cumulative Illness Rating Scale-Geriatrics (r = 0.28, P =.0303), but not with age, depression severity, or cognitive scores. There was no significant difference between responders and nonresponders on changes in AAG levels from baseline to week 6. Frequency differences in ORM1 allelic variants apparently did not influence increased AAG concentrations in depressed patients. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15213 USA. Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA. VA Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Pollock, BG (reprint author), Univ Pittsburgh, Dept Psychiat, Thomas Detre Hall,3811 O Hara St, Pittsburgh, PA 15213 USA. EM pollockbg@upmc.edu FU NIMH NIH HHS [MH65416, MH01613, MH52247, MH30915, MH59666] NR 16 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2003 VL 16 IS 4 BP 235 EP 239 DI 10.1177/0891988703258321 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 847GK UT WOS:000223380500008 PM 14653433 ER PT J AU Anstead, GM Chandrasekar, B Zhang, Q Melby, PC AF Anstead, GM Chandrasekar, B Zhang, Q Melby, PC TI Multinutrient undernutrition dysregulates the resident macrophage proinflammatory cytokine network, nuclear factor-kappa B activation, and nitric oxide production SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE transcription factor; immunodeficiency; tumor necrosis factor-alpha; interleukin-6; interleukin-10 ID TUMOR-NECROSIS-FACTOR; PROTEIN-CALORIE MALNUTRITION; BLOOD MONONUCLEAR-CELLS; ALPHA MESSENGER-RNA; REGULATORY FACTOR-I; GROWTH-FACTOR-I; INTERFERON-GAMMA; TNF-ALPHA; INTERLEUKIN-6 GENE; HUMAN MONOCYTES AB We have described previously a murine model of multinutrient undernutrition that reproduced the features of moderate human malnutrition and led to increased early dissemination of Leishmania donovani. Peritoneal cells from these malnourished mice produced decreased NO after stimulation with IFN-gamma/LPS. We hypothesized that malnutrition may cause a deficit in NF-kappaB activation, a principal transcription pathway for inducible NO synthase and proinflammatory cytokines. Macrophages from malnourished mice, stimulated with IFN-gamma/LPS, showed increased IL-6 production and decreased IL-10 and TNF-alpha, production. Neutralization of TNF-alpha in macrophage cultures from the control mice mimicked the effect of malnutrition on NO and IL-10 production, whereas supplemental TNF-alpha added to cultures of macrophages from malnourished mice increased NO secretion. NF-kappaB nuclear binding activity in macrophages from the malnourished mice was reduced early after stimulation, but increased to supranormal values by 16- or 24-h poststimulation. Blocking NO production in the macrophages from the control mice reproduced the effect of malnutrition on the late activation of NF-kappaB, whereas supplemental NO decreased the late NF-kappaB activation in the malnourished mice. Thus, in macrophages from the malnourished mice, initial deficits in NF-kappaB activity probably lead to decreased TNF-alpha, which results in decreased NO; however, IL-6 is regulated independently from NF-kappaB and TNF-alpha. The late activation of NF-kappaB in the macrophages from malnourished mice is due to absence of negative feedback from NO. J. Leukoc. Biol. 74: 982-991; 2003. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Med Serv, Dept Vet Affairs Med Ctr, San Antonio, TX USA. RP Anstead, GM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL-68020] NR 69 TC 30 Z9 30 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2003 VL 74 IS 6 BP 982 EP 991 DI 10.1189/jlb.0203064 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755FJ UT WOS:000187392600005 PM 12960263 ER PT J AU Narender, N Shailendra, G Avtar, S Inderjit, S AF Narender, N Shailendra, G Avtar, S Inderjit, S TI Anti-inflammatory effect of lovastatin in multiple sclerosis by inducing Th2 immune responses involving GATA3/STAT6 transcription SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE cytokines; EAE; signal transduction; statin; T-cells C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 98 EP 98 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200342 ER PT J AU Paintlia, AS Gilg, AG Khan, M Singh, AK Barbosa, E Singh, I AF Paintlia, AS Gilg, AG Khan, M Singh, AK Barbosa, E Singh, I TI Correlation of very long chain fatty acids accumulation and inflammatory disease progression in childhood X-ALD SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE human childhood X-ALD brain; inflammatory cytokines and chemokines; super gene array; very long chain fatty acids C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 101 EP 101 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200354 ER PT J AU Khan, M Giri, S Shah, EH Kawada, Y Singh, I Singh, AK AF Khan, M Giri, S Shah, EH Kawada, Y Singh, I Singh, AK TI Galactosylsphingosine (psychosine) inhibits lipid metabolism of peroxisomes in glial cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE antioxidant; glial cells; peroxisomes; plasmalogens; psychosine C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 157 EP 157 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200567 ER PT J AU Dracheva, S Elhakem, SL Marcus, SM Siever, LJ McGurk, SR Haroutunian, V AF Dracheva, S Elhakem, SL Marcus, SM Siever, LJ McGurk, SR Haroutunian, V TI RNA editing and alternative splicing of human serotonin 2C receptor in schizophrenia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE alternative splicing; dorsolateral prefrontal cortex; real-time PCR; RNA editing; schizophrenia; serotonin 2C receptor ID PRE-MESSENGER-RNAS; ADENOSINE-DEAMINASE; 5-HT2C RECEPTOR; MOLECULAR BEACONS; PREFRONTAL CORTEX; MULTIPLEX DETECTION; ELDERLY PATIENTS; GLUR-B; EXPRESSION; CLONING AB Serotonin 2C receptor (5-HT2CR) heterogeneity in the brain occurs mostly from two different sources: (i) 5-HT2CR mRNA undergoes adenosine-to-inosine editing events at five positions, which leads to amino acid substitutions that produce receptor variants with different pharmacological properties; (ii) 5-HT2CR mRNA is alternatively spliced, resulting in a truncated mRNA isoform (5-HT2CR-tr) which encodes a non-functional serotonin receptor. 5-HT2CR mRNA editing efficiencies and the expression of the full-length and the truncated 5-HT2CR mRNA splice isoforms were analyzed in the prefrontal cortex of elderly subjects with schizophrenia vs. matched controls (ns = 15). No significant differences were found, indicating that there are no alterations in editing or alternative splicing of 5-HT(2C)Rs that are associated with schizophrenia in persons treated with antipsychotic medications. Quantitation of 5-HT2CR and 5-HT2CR-tr mRNA variants revealed that the expression of 5-HT2CR-tr was similar to 50% of that observed for the full-length isoform. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. RP Haroutunian, V (reprint author), Bronx Vet Affairs Med Ctr, Dept Psychiat, 30 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 46 TC 52 Z9 54 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 IS 6 BP 1402 EP 1412 DI 10.1046/j.1471-4159.2003.02115.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 749GU UT WOS:000186912100009 PM 14713296 ER PT J AU Mendez, MF Papasian, NC Lim, GTH AF Mendez, MF Papasian, NC Lim, GTH TI Thalamic acalculia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Letter ID NUMBER C1 Univ Calif Los Angeles, Dept Neurol, VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), Univ Calif Los Angeles, Dept Neurol, VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90024 USA. NR 5 TC 3 Z9 3 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 2003 VL 15 IS 1 BP 115 EP 116 DI 10.1176/appi.neuropsych.15.1.115 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 641RH UT WOS:000180759300019 PM 12556583 ER PT J AU Gerard, SK Park, HM AF Gerard, SK Park, HM TI I-131 Dosimetry and thyroid stunning SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter ID CANCER C1 San Francisco VA Med Ctr, San Francisco, CA USA. Indiana Univ, Med Ctr, Wishard Hlth Serv, Indianapolis, IN 46204 USA. RP Gerard, SK (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA. NR 6 TC 1 Z9 5 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2003 VL 44 IS 12 BP 2039 EP 2040 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 753EP UT WOS:000187219400033 PM 14660731 ER PT J AU Shen, KZ Johnson, SW AF Shen, KZ Johnson, SW TI Group II metabotropic glutamate receptor modulation of excitatory transmission in rat subthalamic nucleus SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID PROTEIN-KINASE-C; NEURONS IN-VITRO; SYNAPTIC-TRANSMISSION; BASAL GANGLIA; PARKINSONS-DISEASE; MESSENGER-RNA; PRESYNAPTIC REGULATION; HIPPOCAMPAL SLICES; PERFORANT PATH; CA2+ CHANNELS AB Patch pipettes were used to record currents in whole-cell configuration to study the effects of group II metabotropic glutamate receptor (mGluR) stimulation on synaptic transmission in slices of rat subthalamic nucleus. Evoked glutamatergic excitatory postsynaptic currents (EPSCs) were reversibly reduced by the selective group II mGluR agonist (2'S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) in a concentration-dependent manner, with an IC50 Of 0.19 +/- 0.05 muM. DCG IV (1 mum) had no effect on inhibitory postsynaptic currents mediated by GABA. DCG IV-induced inhibition of EPSCs was reversed by the selective group II mGluR antagonist LY 341495 (100 nM) and mimicked by another selective group II agonist (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-1). Inhibition of EPSC amplitude by DCG IV and L-CCG-1 was associated with an increase in the paired-pulse ratio of EPSCs. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (2 muM) reduced the inhibitory effect of DCG IV on EPSCs. However, the response to DCG IV was not affected by the protein kinase A (PKA) activator forskolin (20 muM), by the adenylyl cyclase inhibitor MDL 12230A (20 muM), or by the phosphodiesterase inhibitor Ro 20-1724 (50 muM). DCG IV-induced inhibition of EPSCs was reduced by the non-selective protein kinase inhibitors H-7 (100 muM), H-8 (50 muM) and HA-1004 (100 muM). These results suggest that group II mGluR stimulation acts presynaptically to inhibit glutamate release by a PKC-dependent mechanism in the subthalamic nucleus. C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Vet Adm Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, R&D 61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. FU NINDS NIH HHS [NS 38175, R01 NS038175] NR 47 TC 9 Z9 9 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 1 PY 2003 VL 553 IS 2 BP 489 EP 496 DI 10.1113/jphysiol.2003.052209 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 754AC UT WOS:000187279700014 PM 14500768 ER PT J AU Hazlett-Stevens, H Craske, MG Mayer, EA Chang, L Naliboff, BD AF Hazlett-Stevens, H Craske, MG Mayer, EA Chang, L Naliboff, BD TI Prevalence of irritable bowel syndrome among university students - The roles of worry, neuroticism, anxiety sensitivity and visceral anxiety SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE anxiety sensitivity; generalized anxiety disorder; irritable bowel syndrome; neuroticism; worry ID FUNCTIONAL GASTROINTESTINAL DISORDERS; REPORT DIAGNOSTIC MEASURE; PANIC DISORDER; QUESTIONNAIRE; DEPRESSION; CARE; VALIDATION; SYMPTOMS; SEEKING AB Objective: Relationships between presence of irritable bowel syndrome (IBS) and generalized anxiety disorder (GAD), chronic worry, neuroticism, anxiety sensitivity and anxiety about visceral sensations were examined among university students. Methods: College student participants were administered self-report diagnostic measures of IBS and GAD, the Penn State Worry Questionnaire (PSWQ), the Neuroticism subscale of the Eysenck Personality Questionnaire, the Anxiety Sensitivity Index (ASI) and five additional items designed to measure visceral anxiety. Results: The prevalence of IBS and its associated characteristics among students were similar to previous community survey studies, with the exception of lower symptom severity in the university sample. IBS was associated with a higher frequency of GAD and greater worry, neuroticism, anxiety sensitivity and visceral anxiety. Logistic regression analyses further showed that the measure of anxiety specific to visceral sensations was the strongest predictor of IBS diagnostic status. Conclusion: While various aspects of anxiety appear related to IBS, specific anxiety about visceral sensations appears to be the most significant factor. Implications of the associations between anxiety-related variables, particularly anxiety about visceral sensations, are discussed. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Nevada, Dept Psychol, Reno, NV 89557 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr, Neuroentric Dis Program, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Sch Med, Dept Physiol, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Hazlett-Stevens, H (reprint author), Univ Nevada, Dept Psychol, Reno, NV 89557 USA. NR 30 TC 79 Z9 81 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD DEC PY 2003 VL 55 IS 6 BP 501 EP 505 DI 10.1016/S0022-3999(03)00019-9 PG 5 WC Psychiatry SC Psychiatry GA 754BG UT WOS:000187282400005 PM 14642979 ER PT J AU Suarez-Almazor, ME Drummond, M AF Suarez-Almazor, ME Drummond, M TI Regulatory issues and economic efficiency SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT International Conference on Health Economics in Rheumatology CY APR 08-09, 2003 CL ROCHESTER, MINNESOTA SP Natl Inst Arthritis, Musculoskeletal & Skin Dis C1 Baylor Coll Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England. RP Suarez-Almazor, ME (reprint author), Baylor Coll Med, Houston, TX 77030 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2003 VL 30 SU 68 BP 5 EP 7 PG 3 WC Rheumatology SC Rheumatology GA 758LM UT WOS:000187635900002 ER PT J AU Chuang, KH Covinsky, KE Sands, LP Fortinsky, RH Palmer, RM Landefeld, CS AF Chuang, KH Covinsky, KE Sands, LP Fortinsky, RH Palmer, RM Landefeld, CS TI Diagnosis-related group-adjusted hospital costs are higher in older medical patients with lower functional status SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 08-12, 2002 CL WASHINGTON, D.C. SP Amer Geriatr Soc DE diagnosis-related groups; functional status; healthcare costs; Medicare; reimbursement methods ID PROSPECTIVE-PAYMENT SYSTEM; MORTALITY; ADULTS; CARE; CONSUMPTION; VALIDATION; SEVERITY; CHARGES; ELDERS; INDEX AB Objectives: To determine whether hospital costs are higher in patients with lower functional status at admission, defined as dependence in one or more activities of daily living (ADLs), after adjustment for Medicare Diagnosis-Related Group (DRG) payments. Design: Prospective study. General medical service at a teaching hospital. Setting: One thousand six hundred twelve patients aged 70 and older. Measurements: The hospital cost of care for each patient was determined using a cost management information system, which allocates all hospital costs to individual patients. Results: Hospital costs were higher in patients dependent in ADLs on admission than in patients independent in ADLs on admission ($5,300 vs $4,060, P<.01). Mean hospital costs remained higher in ADL-dependent patients than in ADL-independent patients in an analysis that adjusted for DRG weight ($5,240 vs $4,140, P<.01), and in multivariate analyses adjusting for age, race, sex, Charlson comorbidity score, acute physiology and chronic health evaluation score, and admission from a nursing home as well as for DRG weight ($5,200 vs $4,220, P<.01). This difference represents a 23% (95% confidence interval=15-32%) higher cost to take care of older dependent patients. Conclusion: Hospital cost is higher in patients with worse ADL function, even after adjusting for DRG payments. If this finding is true in other hospitals, DRG-based payments provide hospitals a financial incentive to avoid patients dependent in ADLs and disadvantage hospitals with more patients dependent in ADLs. C1 San Francisco VA Med Ctr, Div Geriatr, Vet Affairs Natl Qual Scholars Fellowship Program, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Div Geriatr, Farmington, CT USA. Cleveland Clin Fdn, Geriatr Med Sect, Cleveland, OH 44195 USA. RP Chuang, KH (reprint author), San Francisco VA Med Ctr, Div Geriatr, Vet Affairs Natl Qual Scholars Fellowship Program, 4150 Clement St,181G, San Francisco, CA 94121 USA. RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU AHRQ HHS [K02HS00006-01]; NIA NIH HHS [AG00412, AG10418] NR 30 TC 44 Z9 44 U1 5 U2 9 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2003 VL 51 IS 12 BP 1729 EP 1734 DI 10.1046/j.1532-5415.2003.51556.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 743FU UT WOS:000186562400006 PM 14687350 ER PT J AU Yarbrough, WM Mukherjee, R Escobar, GP Sample, JA McLean, JE Dowdy, KB Hendrick, JW Gibson, WC Hardin, AE Mingoia, JT White, PC Stiko, A Armstrong, RC Crawford, FA Spinale, FG AF Yarbrough, WM Mukherjee, R Escobar, GP Sample, JA McLean, JE Dowdy, KB Hendrick, JW Gibson, WC Hardin, AE Mingoia, JT White, PC Stiko, A Armstrong, RC Crawford, FA Spinale, FG TI Pharmacologic inhibition of intracellular caspases after myocardial infarction attenuates left ventricular remodeling: A potentially novel pathway SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 04-07, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Thorac Surg ID ANGIOTENSIN-CONVERTING ENZYME; MYOCYTE CELL-DEATH; ISCHEMIA-REPERFUSION; CARDIAC MYOCYTES; HEART-FAILURE; APOPTOSIS; INJURY; RATS; OVEREXPRESSION; DYSFUNCTION AB Objective: Myocyte death occurs by necrosis and caspase-mediated apoptosis in the setting of myocardial infarction. In vitro studies suggest that caspase activation within myocytes causes contractile protein degradation without inducing cell death. Thus, caspase activation may evoke left ventricular remodeling through 2 independent processes post-myocardial infarction. However, the effects of caspase activation on left ventricular geometry post-myocardial infarction remain unclear. This project applied broad-spectrum caspase inhibition to a chronic porcine model of myocardial infarction. Methods: Coronary snares and sonomicrometry crystals in remote and area-at-risk regions were placed in pigs (n = 22, 34 kg). Geometric measurements at end diastole and end systole, including-left ventricular area by echocardiography and interregional distance by sonomicrometry, were obtained at baseline. Coronary occlusion was instituted for 60 minutes, followed by reperfusion and repeated geometric measurements at 7 days, including left ventriculography. At reperfusion, pigs were randomized to saline (n 12) or caspase inhibition (n = 10, IDN6734, 2 mg/kg intravenously, then 2 mg . kg . h for 24 hours) at a dose that achieved desired plasma concentrations (790 +/- 142 ng/mL) as predicted by prior pharmacokinetic studies. Results: Infarct size and 24-hour troponin-I values were not significantly different between the saline and caspase inhibition groups (51% +/- 8% vs 42% +/- 6% and 189 20 ng/mL vs 152 +/- 26 ng/mL, respectively, P >.10). At 7 days, end-diastole volume was increased in both groups compared with reference control values (47 1 mL, P <.05), but it was decreased with caspase inhibition (72 +/- 4 mL) compared with saline (84 +/- 4 mL, P <.05). Similarly, end-diastole and end-systole areas increased by 32% +/- 3% and 81% +/- 16% in the saline group but were attenuated with caspase inhibition (19% +/- 3% and 31% +/- 10%, respectively, P <.05). End-diastole interregional distance increased by 30% +/- 7% in the saline group but was attenuated with caspase inhibition (12% +/- 5%, P <.05). Conclusion: Despite equivalent degrees of myocardial injury, caspase inhibition reduced post-myocardial infarction left ventricular remodeling as evidenced by multiple, independent assessments of left ventricular dilation. Thus, caspase activation alters left ventricular geometry in the absence of significant effects on myocardial injury. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Assoc Med Ctr, Charleston, SC USA. Idun Pharmaceut Inc, San Diego, CA USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, 770 MUSC Complex,STRB,Suiite 625, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL-07260, HL-97012, HL-45024] NR 28 TC 20 Z9 21 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2003 VL 126 IS 6 BP 1892 EP 1899 DI 10.1016/j.jtcvs.2003.08.012 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 757JZ UT WOS:000187560400033 PM 14688702 ER PT J AU Almaden, Y Felsenfeld, AJ Rodriguez, M Canadillas, S Luque, FQ Bas, A Bravo, J Torregrosa, V Palma, A Ramos, B Sanchez, C Martin-Malo, A Canalejo, A AF Almaden, Y Felsenfeld, AJ Rodriguez, M Canadillas, S Luque, FQ Bas, A Bravo, J Torregrosa, V Palma, A Ramos, B Sanchez, C Martin-Malo, A Canalejo, A TI Proliferation in hyperplastic human and normal rat parathyroid glands: Role of phosphate, calcitriol, and gender SO KIDNEY INTERNATIONAL LA English DT Article DE calcitriol; cell proliferation; gender; hyperplasia; parathyroid gland; phosphate ID CHRONIC-RENAL-FAILURE; HORMONE GENE-EXPRESSION; IN-VITRO; SECONDARY HYPERPARATHYROIDISM; CELL-PROLIFERATION; UREMIC PATIENTS; VITAMIN-D; HEMODIALYSIS-PATIENTS; PTH SECRETION; RISK-FACTORS AB Background. Parathyroid gland hyperplasia develops in azotemic patients. A phosphate excess and calcitriol deficiency play critical roles in its development. Our goals were to determine whether differences in serum phosphate values at parathyroidectomy (PTX) in hemodialysis patients with refractory hyperparathyroidism: (1) correlated with parathyroid cell proliferation; and (2) affected the antiproliferative response to in vitro calcitriol. Studies were also performed to determine whether the phosphate concentration in the medium affected the antiproliferative response to calcitriol, and whether a high phosphate diet and calcitriol treatment affected parathyroid cell proliferation and parathyroid hormone (PTH) levels in normal rats. Methods. Forty-seven parathyroid glands from 19 hemodialysis patients were obtained at PTX. Flow cytometry was used to determine cell proliferation (percent cells in S phase) in excised parathyroid glands. Similarly, cell proliferation was determined in parathyroid tissue incubated for 24 hours in medium with or without 10(-7) mol/L calcitriol and with 1 or 4 mmol/L phosphate. In normal rats, the effect of 3 days of a high phosphate diet (1.2% P) and calcitriol treatment (100 pmol/kg) on PTH values and cell proliferation was evaluated. Results. In cells from freshly removed parathyroid glands obtained at PTX from hemodialysis patients, there were no significant correlations between the percent cells in S phase and age, gender, and serum phosphate, calcium, and PTH. While incubation of parathyroid tissue with 10 7 mol/L calcitriol did reduce cell proliferation (P < 0.001), both the pre-PTX serum phosphate value (P = 0.003) and female gender (P = 0.003) were associated with a decreased response to calcitriol. Incubation of parathyroid tissue in medium containing 4 mmol/L phosphate did not increase cell proliferation. In normal rats, a high phosphate diet for 3 days increased cell proliferation (P < 0.05) and PTH levels (P < 0.05), and calcitriol treatment was without effect. Conclusion. Our findings suggest a high phosphate burden, as well as female gender, favor parathyroid cell proliferation and both may reduce the inhibition of parathyroid function by calcitriol. C1 Univ Huelva, Dept Environm Biol & Publ Hlth, Huelva 21071, Spain. Hosp Univ Reina Sofia, Unit Invest, Cordoba, Spain. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Hosp Univ Reina Sofia, Serv Nephrol, Cordoba, Spain. Hosp Clin, Serv Nephrol, Granada, Spain. Hosp Clin Barcelona, Serv Nephrol, Barcelona, Spain. Hosp Virgen Macarena, Serv Nephrol, Seville, Spain. Hosp Carlos Haya, Serv Nephrol, Malaga, Spain. Hosp Ciudad Jaen, Serv Nephrol, Jaen, Spain. RP Canalejo, A (reprint author), Univ Huelva, Dept Environm Biol & Publ Hlth, Campus Carmen,Avd Fuerzas Armadas S-N, Huelva 21071, Spain. RI Rodriguez, teresa/H-5452-2011; Canalejo, Antonio/L-8407-2014 OI Canalejo, Antonio/0000-0003-2098-8960 NR 42 TC 27 Z9 30 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2003 VL 64 IS 6 BP 2311 EP 2317 DI 10.1046/j.1523-1755.2003.00331.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 740YV UT WOS:000186431600040 PM 14633156 ER PT J AU Washington, DL Bernstein, SJ Kahan, JP Leape, LL Kamberg, CJ Shekelle, PG AF Washington, DL Bernstein, SJ Kahan, JP Leape, LL Kamberg, CJ Shekelle, PG TI Reliability of clinical guideline development using mail-only versus in-person expert panels SO MEDICAL CARE LA English DT Article DE practice guidelines; Delphi technique; reproducibility of results; myocardial revascularization/utilization; hysterectomy/utilization ID NEW-YORK-STATE; CORONARY ANGIOGRAPHY; MEDICAL PROCEDURES; APPROPRIATENESS; CARE; REVASCULARIZATION; EMERGENCY; UNDERUSE AB BACKGROUND. Clinical practice guidelines quickly become outdated. One reason they might not be updated as often as needed is the expense of collecting expert judgment regarding the evidence. The RAND-UCLA Appropriateness Method is one commonly used method for collecting expert opinion. We tested whether a less expensive, mail-only process could substitute for the standard in-person process normally used. METHODS. We performed a 4-way replication of the appropriateness panel process for coronary revascularization and hysterectomy, conducting 3 panels using the conventional in-person method and 1 panel entirely by mail. All indications were classified as inappropriate or not (to evaluate overuse), and coronary revascularization indications were classified as necessary or not (to evaluate underuse). Kappa statistics were calculated for the comparison in ratings from the 2 methods. RESULTS. Agreement beyond chance between the 2 panel methods ranged from moderate to substantial. The kappa statistic to detect overuse was 0.57 for coronary revascularization and 0.70 for hysterectomy. The kappa statistic to detect coronary revascularization underuse was 0.76. There were no cases in which coronary revascularization was considered inappropriate by 1 method, but necessary or appropriate by the other. Three of 636 (0.5%) hysterectomy cases were categorized as inappropriate by 1 method but appropriate by the other. CONCLUSIONS. The reproducibility of the overuse and underuse assessments from the mail-only compared with the conventional in-person conduct of expert panels in this application was similar to the underlying reproducibility of the process. This suggests a potential role for updating guidelines using an expert judgment process conducted entirely through the mail. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. RAND Europe, Leiden, Netherlands. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RAND, Arlington, VA USA. RAND, Santa Monica, CA USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. FU AHRQ HHS [HS07185-02] NR 23 TC 21 Z9 22 U1 0 U2 0 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 DEC PY 2003 VL 41 IS 12 BP 1374 EP 1381 DI 10.1097/01.MLR.0000100583.76137.3E PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 748RE UT WOS:000186874200008 PM 14668670 ER PT J AU Finlayson, CA Chappell, J Leitner, JW Goalstone, ML Garrity, M Nawaz, S Ciaraldi, TP Draznin, B AF Finlayson, CA Chappell, J Leitner, JW Goalstone, ML Garrity, M Nawaz, S Ciaraldi, TP Draznin, B TI Enhanced insulin signaling via Shc in human breast cancer SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID NEGATIVE ALPHA-SUBUNIT; SMOOTH-MUSCLE-CELLS; DIABETES-MELLITUS; GROWTH-FACTOR; RECEPTOR; FARNESYLTRANSFERASE; RESISTANCE; FARNESYL; PATHWAY; PROTEIN AB Insulin is a mild mitogen and has been shown to potentiate mitogenic influence of other growth factors. Because hyperinsulinema and/or overexpression of insulin receptors have been linked to development, progression, and outcome of breast cancer, we attempted to evaluate the mechanism of these associations. We have compared the expression of insulin receptors and the magnitude of insulin signaling in breast tumors and adjacent normal mammary tissue samples obtained from 20 patients. We observed that insulin binding more than doubled in the tumors as compared with the normal tissue (P < .1 by paired t est). Insulin signaling to Shc, judged by the magnitude of its phosphorylation, was also significantly enhanced in the tumors. In contrast, the phosphorylation of the insulin-receptor substrate-1 (IRS-1), Akt, and mitogen -activated protein (MAP) kinase were identical in the tumorous and normal mammary tissues. Finally, tumors displayed significantly increased amounts of farnesylated p21 Ras and geranylgeranylated Rho-A (P < .1), consistent with Shc-dependent activation of farnesyl (FTase) and geranylgeranyl transferases (GGTase) in the tumor tissue. We conclude that the mechanism of the mitogenic influence of insulin in breast cancer may include increased expression of insulin receptors, preferential hyperphosphorylation of Shc, and increased amounts of prenylated p21 Ras and Rho-A in tumor tissue as compared with adjacent normal mammary tissue. (C) 2003 Elsevier Inc. All rights reserved. C1 VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. San Diego VA Med Ctr, Res Serv, La Jolla, CA USA. Denver VA Med Ctr, Pathol Serv, Denver, CO USA. RP Draznin, B (reprint author), VA Med Ctr, 151,1055 Clermont St, Denver, CO 80220 USA. NR 43 TC 23 Z9 27 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2003 VL 52 IS 12 BP 1606 EP 1611 DI 10.1016/S0026-0495(03)00311-1 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754MH UT WOS:000187320600016 PM 14669164 ER PT J AU Samii, A Dahlen, DD Spence, AM Maronian, NC Kraus, EE Lennon, VA AF Samii, A Dahlen, DD Spence, AM Maronian, NC Kraus, EE Lennon, VA TI Paraneoplastic movement disorder in a patient with non-Hodgkin's lymphoma and CRMP-5 autoantibody SO MOVEMENT DISORDERS LA English DT Article DE chorea; dystonia; B-cell lymphoma; autoimmunity; rituximab ID CHOREA; CANCER; ENCEPHALITIS; PARKINSONISM; OPSOCLONUS; CARCINOMA; DYSTONIA AB The paraneoplastic autoantibody, collapsin response-mediator protein (CRMP)-5 immunoglobulin G (IgG), is specific for neuronal cytoplasmic CRMP-5, and is usually associated with small-cell lung carcinoma or thymoma. We report on details of a movement disorder that followed anti-B-cell therapy in a patient with lymphoma, and was accompanied by CRMP-5 IgG. (C) 2003 Movement Disorder Society. C1 Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Mayo Clin, Dept Immunol, Rochester, MN USA. Univ Washington, Sch Med, Dept Otolaryngol, Seattle, WA USA. Univ Washington, Sch Med, Dept Hematol, Seattle, WA USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. RP Samii, A (reprint author), VA Puget Sound Hlth Care Syst, Mailstop 127,1660 S Columbian Way, Seattle, WA 98108 USA. NR 18 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD DEC PY 2003 VL 18 IS 12 BP 1556 EP 1558 DI 10.1002/md.10616 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 756FV UT WOS:000187455900025 PM 14673901 ER PT J AU Scortegagna, M Ding, K Oktay, Y Gaur, A Thurmond, F Yan, LJ Marck, BT Matsumoto, AM Shelton, JM Richardson, JA Bennett, MJ Garcia, JA AF Scortegagna, M Ding, K Oktay, Y Gaur, A Thurmond, F Yan, LJ Marck, BT Matsumoto, AM Shelton, JM Richardson, JA Bennett, MJ Garcia, JA TI Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1(-/-) mice SO NATURE GENETICS LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; HYPOXIA-INDUCIBLE FACTOR-1; SYSTEMIC CARNITINE DEFICIENCY; LUNG EPITHELIAL-CELLS; GENE-EXPRESSION; OXIDATIVE STRESS; MITOCHONDRIAL ABNORMALITIES; DILATED CARDIOMYOPATHY; ENDOTHELIAL-CELLS; KNOCKOUT MICE AB Hypoxia-inducible factor (HIF) transcription factors respond to multiple environmental stressors, including hypoxia and hypoglycemia. We report that mice lacking the HIF family member HIF-2alpha (encoded by Epas1) have a syndrome of multiple-organ pathology, biochemical abnormalities and altered gene expression patterns. Histological and ultrastructural analyses showed retinopathy, hepatic steatosis, cardiac hypertrophy, skeletal myopathy, hypocellular bone marrow, azoospermia and mitochondrial abnormalities in these mice. Serum and urine metabolite studies showed hypoglycemia, lactic acidosis, altered Krebs cycle function and dysregulated fatty acid oxidation. Biochemical assays showed enhanced generation of reactive oxygen species (ROS), whereas molecular analyses indicated reduced expression of genes encoding the primary antioxidant enzymes (AOEs). Transfection analyses showed that HIF-2alpha could efficiently transactivate the promoters of the primary AOEs. Prenatal or postnatal treatment of Epas1(-/-) mice with a superoxide dismutase (SOD) mimetic reversed several aspects of the null phenotype. We propose a rheostat role for HIF-2alpha that allows for the maintenance of ROS as well as mitochondrial homeostasis. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Washington, Sch Med, Dept Med,VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA. Childrens Med Ctr, Dept Pathol, Dallas, TX 75235 USA. RP Garcia, JA (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. RI Oktay, Yavuz/F-2703-2015; Oktay, Yavuz/G-4794-2015 OI Oktay, Yavuz/0000-0002-0158-2693; Yan, Liang-Jun/0000-0002-5815-5430 FU NHLBI NIH HHS [K08 HL067154] NR 50 TC 296 Z9 300 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2003 VL 35 IS 4 BP 331 EP 340 DI 10.1038/ng1266 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 747DY UT WOS:000186791000014 PM 14608355 ER PT J AU Paintlia, AS Gilg, AG Khan, M Singh, AK Barbosa, E Singh, I AF Paintlia, AS Gilg, AG Khan, M Singh, AK Barbosa, E Singh, I TI Correlation of very long chain fatty acid accumulation and inflammatory disease progression in childhood X-ALD: implications for potential therapies SO NEUROBIOLOGY OF DISEASE LA English DT Article DE human childhood X-ALD brain; very long chain fatty acids; inflammatory cytokines and chemokines; super gene array ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MULTIPLE-SCLEROSIS LESIONS; COLONY-STIMULATING FACTOR; BLOOD MONONUCLEAR-CELLS; TUMOR-NECROSIS-FACTOR; LINKED ADRENOLEUKODYSTROPHY AB This study was designed to understand the role of inflammatory mediators involved in the neurobiology of childhood adrenoleukodystrophy (cALD) by comparing the differential expression of the inflammatory mediators with metabolite very long chain fatty acids that accumulate in this disease. Histopathological examinations indicated extensive demyelination and accumulation of infiltrates in perivascular cuffs in plaque area (PA) and inflammatory area (IA) compared to normal looking area (NLA) of the cALD brain and controls. The PA had excessive accumulation of cholesterol ester (25-30-fold), VLC fatty acids (8-12-fold), and exhaustive depletion of cholesterol (60-70%) and sphingomyelin (50-55%) in comparison to controls. The mRNA expression of cytokines (IL-1alpha, IL-2, IL-3, IL-6, TNF-alpha, and GM-CSF), chemokines (CCL2, -4, -7, -11, -16, -21, -22, CXCL1, CX3CL1, and SDF-2) and NOS in IA was significantly increased compared to NLA of the cALD and controls determined by gene array, semiquantitative RT-PCR, and immunohistochemistry. These results indicate that accumulation of VLC fatty acid contents in membrane domains associated with signal transduction pathways may trigger the inflammatory process through activation of resident glial cells (microglia and astrocytes) resulting in loss of myelin and oligodendrocytes. (C) 2003 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 316-CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. OI Paintlia, Ajaib/0000-0003-4525-5333 FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40144] NR 81 TC 68 Z9 69 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2003 VL 14 IS 3 BP 425 EP 439 DI 10.1016/j.nbd.2003.08.012 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 754XJ UT WOS:000187358300012 PM 14678759 ER PT J AU Fu, SS Ma, GX Tu, XM Siu, PT Metlay, JP AF Fu, SS Ma, GX Tu, XM Siu, PT Metlay, JP TI Cigarette smoking among Chinese Americans and the influence of linguistic acculturation SO NICOTINE & TOBACCO RESEARCH LA English DT Article; Proceedings Paper CT SGIM 2001 Annual Meeting CY MAY 02-05, 2001 CL SAN DIEGO, CALIFORNIA SP SGIM ID MEXICAN-AMERICANS; SCALE; HISPANICS; VALIDATION; ADULTS; GENDER AB Less acculturated Chinese Americans experience cultural and language barriers. The present study assessed the relationship between linguistic aspects of acculturation and cigarette smoking among Chinese Americans. A cross-sectional, self-administered survey was administered to a consecutive sample of 541 Chinese American adults (aged 18 years or older) attending four pediatric, medical, or dental practices located in Philadelphia's Chinatown from November 2000 to February 2001. Linguistic acculturation was measured by adapting a reliable and valid acculturation scale developed for Southeast Asians. English and Chinese language proficiency subscales were utilized to analyze the association between language proficiency and current smoking. Whereas 25% of Chinese American men reported current smoking, only 3% of Chinese American women reported current smoking. Chinese American men with lower English proficiency reported significantly higher rates of current smoking compared with Chinese American men with a higher level of English proficiency (33% vs. 18%, p<.01). Less English-proficient Chinese American male smokers were less likely to have received advice from a physician to quit smoking (50% vs. 85%, p=.01). In multivariate analysis, increased English proficiency was associated with decreased odds of current smoking (OR=0.38, 95% CI=0.16-0.89) among Chinese American men after controlling for confounding variables. In conclusion, higher English proficiency was associated with decreased current smoking among Chinese American men. Chinese American men with limited English proficiency should especially be targeted for tobacco control interventions. Further research is needed to assess whether acculturation is associated with smoking among Chinese American women and with use of smoking cessation treatments and services by Chinese American smokers. C1 CCDOR, Gen Internal Med Sect, Dept Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. Temple Univ, Dept Hlth Studies, Philadelphia, PA 19122 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Fu, SS (reprint author), CCDOR, Gen Internal Med Sect, VA Med Ctr 1110, 1 Vet Dr, Minneapolis, MN 55417 USA. EM steven.fu@med.va.gov FU BHP HRSA HHS [T32PE10026] NR 38 TC 30 Z9 30 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2003 VL 5 IS 6 BP 803 EP 811 DI 10.1080/14622200310001614566 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 764ZL UT WOS:000188241000002 PM 14668064 ER PT J AU Burgio, KL Zyczynski, H Locher, JL Richter, HE Redden, DT Wright, KC AF Burgio, KL Zyczynski, H Locher, JL Richter, HE Redden, DT Wright, KC TI Urinary incontinence in the 12-month postpartum period SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BLADDER NECK MOBILITY; STRESS-INCONTINENCE; VAGINAL DELIVERY; FECAL INCONTINENCE; CIGARETTE-SMOKING; CESAREAN-SECTION; PREGNANCY; CHILDBIRTH; WOMEN; BIRTH AB OBJECTIVE: To describe the prevalence and severity of urinary incontinence in die 12-month postpartum period and to relate this incontinence to several potential risk factors including body mass index, smoking, oral contraceptives, breast-feeding, and pelvic floor muscle exercise. METHODS: Participants were 523 women, aged 14 to 42 years, who had obstetrical deliveries. The women were interviewed in their rooms on postpartum day 2 or 3 and by telephone 6 weeks, 3 months, 6 months, and 12 months postpartum. Chart abstraction was conducted to obtain obstetrical data from the index delivery. RESULTS: At 6 weeks postpartum, 11.36% of women reported some degree of urinary incontinence since the index delivery. Although the rate of incontinence did not change significantly over the postpartum year, frequency of accidents decreased over time. In the generalized estimating equation, postpartum incontinence was significantly associated with seven variables: baseline report of smoking (odds ratio [OR] 2.934; P =.002), incontinence during pregnancy (OR 2.002; P =.007), length of breast-feeding (OR 1.169; P =.023), vaginal delivery (OR 2.360; P =.002), use of forceps (OR 1.870; P =.024), and two time-varying covariates: frequency of urination (OR 1.123; P = <.001) and body mass index (OR 1.055; P =.005). Factors not associated with postpartum incontinence included age, race, education, episiotomy, number of vaginal deliveries, attendance at childbirth preparation classes, and performing pelvic floor muscle exercises during the postpartum period. CONCLUSION: Postpartum incontinence is associated with several risk factors, some of which are potentially modifiable and others that can help target at-risk women for early intervention. C1 Dept Vet Affairs Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. Univ Alabama, Sch Med, Ctr Aging, Birmingham, AL USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, GRECC, 11G,700 19th St S, Birmingham, AL 35233 USA. FU NIA NIH HHS [K04 AG00431] NR 44 TC 104 Z9 111 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2003 VL 102 IS 6 BP 1291 EP 1298 DI 10.1016/j.obstetgynecol.2003.09.013 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 747NX UT WOS:000186811800013 PM 14662217 ER PT J AU Turk, DC Dworkin, RH Allen, RR Bellamy, N Brandenburg, N Carr, DB Cleeland, C Dionne, R Farrar, JT Galer, BS Hewitt, DJ Jadad, AR Katz, NP Kramer, LD Manning, DC McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robinson, JP Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Witter, J AF Turk, DC Dworkin, RH Allen, RR Bellamy, N Brandenburg, N Carr, DB Cleeland, C Dionne, R Farrar, JT Galer, BS Hewitt, DJ Jadad, AR Katz, NP Kramer, LD Manning, DC McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robinson, JP Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Witter, J TI Core outcome domains for chronic pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Article DE chronic pain; clinical trials; assessment; outcomes; quality of life; physical functioning; emotional functioning; adverse events; global ratings ID QUALITY-OF-LIFE; LOW-BACK-PAIN; CONSORT STATEMENT; HEALTH-STATUS; IMPACT; RESPONSIVENESS; OSTEOARTHRITIS; MANAGEMENT; DISTRESS; SOCIETY AB Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia. governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Rochester, Rochester, NY USA. AstraZeneca, Wilmington, DE USA. Univ Queensland, St Lucia, Qld 4067, Australia. Pfizer Pharmaceut Grp, New York, NY USA. Tufts Univ, Dept Anesthesiol, Medford, MA 02155 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. Ortho McNeil Pharmaceut Inc, Raritan, NJ USA. Univ Toronto, Toronto, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. Harvard Univ, Cambridge, MA 02138 USA. Purdue Pharma, Stamford, CT USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. NIH, Bethesda, MD 20892 USA. Dalhousie Univ, Dept Psychol, Halifax, NS, Canada. GlaxoSmithKline, Res Triangle Pk, NC USA. US FDA, Rockville, MD 20857 USA. Univ Washington, Dept Phys Med & Rehabil, Seattle, WA 98195 USA. Elan Pharmaceut, San Diego, CA USA. Abbott Labs, Lake Forest, IL USA. Univ Calif San Diego, La Jolla, CA 92093 USA. US Dept Vet Affairs, Washington, DC USA. RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. EM turkdc@u.washington.edu RI Farrar, John/A-1037-2007; Bellamy, Nicholas/G-3631-2010 OI Farrar, John/0000-0001-8656-5157; McGrath, Patrick/0000-0002-9568-2571 NR 48 TC 488 Z9 497 U1 3 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2003 VL 106 IS 3 BP 337 EP 345 DI 10.1016/j.pain.2003.08.001 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 753AR UT WOS:000187209600014 PM 14659516 ER PT J AU Ostrow, JD Pascolo, L Tiribelli, C AF Ostrow, JD Pascolo, L Tiribelli, C TI Letter to the editor SO PEDIATRIC RESEARCH LA English DT Letter ID DEVELOPING RAT-BRAIN; BILIRUBIN INDUCES APOPTOSIS; NEURONS; NEUROTOXICITY; CELLS C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Sch Med, GI Hepatol Div, Seattle, WA 98108 USA. Univ Trieste, Ctr Studio Fegato, AREA Sci Pk, I-34012 Trieste, Italy. Univ Trieste, Dept BBCM, I-34012 Trieste, Italy. RP Ostrow, JD (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. NR 10 TC 16 Z9 16 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD DEC PY 2003 VL 54 IS 6 BP 926 EP 926 DI 10.1203/01.PDR.0000103388.01854.91 PG 1 WC Pediatrics SC Pediatrics GA 747QQ UT WOS:000186816100023 PM 14661625 ER PT J AU Takata, GS Chan, LS Morphew, T Mangione-Smith, R Morton, SC Shekelle, P AF Takata, GS Chan, LS Morphew, T Mangione-Smith, R Morton, SC Shekelle, P TI Evidence assessment of the accuracy of methods of diagnosing middle ear effusion in children with otitis media with effusion SO PEDIATRICS LA English DT Review DE diagnostic methods; otitis media with effusion ID GRADIENT ACOUSTIC REFLECTOMETRY; PNEUMATIC OTOSCOPY; 3-YEAR-OLD CHILDREN; PREDICTIVE VALUE; CLINICAL-TRIALS; GLUE EAR; TYMPANOMETRY; AUDIOMETRY; IDENTIFICATION; MYRINGOTOMY AB Objectives. We report the findings of an evidence assessment on the accuracy of methods of diagnosing middle ear effusion in children with otitis media with effusion ( OME). Methods. We searched Medline ( 1966 - January 2000), the Cochrane Library ( through January 2000), and Embase ( 1980 - January 2000) and identified additional articles from reference lists in proceedings, published articles, reports, and guidelines. Excluded were nonhuman studies; case reports; editorials; letters; reviews; practice guidelines; non - English- language publications; and studies on patients with immunodeficiencies, craniofacial anomalies ( including cleft palate), primary mucosal disorders, or genetic conditions. From each eligible study, we calculated the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and prevalence of OME in the cohort. We determined the number of studies for each comparison of a diagnostic method and a reference standard listed within the scope of our assessment. For comparisons with 3 or more studies, we derived random effects estimates of sensitivity, specificity, and prevalence rate. Using the pooled estimates, we plotted the performance of each diagnostic test in terms of sensitivity and ( 1 - specificity) and identified the best performer among the tests included in the comparison. Results. Among 8 diagnostic methods, pneumatic otoscopy had the best apparent performance with a sensitivity of 94% ( 95% confidence interval: 92% - 96%) and a specificity of 80% ( 95% confidence interval: 75% - 86%). However, examiner qualifications were reported inconsistently, and training was not specified. Conclusions. The finding that pneumatic otoscopy can do as well as or better than tympanometry and acoustic reflectometry has significant practical implications. For the typical clinician, pneumatic otoscopy should be easier to use than other diagnostic methods. The important question may be what degree of training will be needed for the clinician to be as effective with pneumatic otoscopy as were the examiners in the studies reviewed in this report. C1 Childrens Hosp Los Angeles, Div Gen Pediat, Los Angeles, CA 90027 USA. Los Angeles Cty & Univ So Calif, Med Ctr, Div Biostat & Outcomes Assessment, Los Angeles, CA USA. Univ So Calif, Dept Pediat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. RAND Corp, So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. RAND Corp, Stat Grp, Santa Monica, CA USA. GReater Los Angeles Vet Affair Healthcare Syst, Hlth Serv Res & Dev Serv, Los Angeles, CA USA. RP Takata, GS (reprint author), Childrens Hosp Los Angeles, Div Gen Pediat, 4650 Sunset Blvd,MS 76, Los Angeles, CA 90027 USA. NR 68 TC 69 Z9 77 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2003 VL 112 IS 6 BP 1379 EP 1387 DI 10.1542/peds.112.6.1379 PG 9 WC Pediatrics SC Pediatrics GA 749YK UT WOS:000186957500025 PM 14654613 ER PT J AU Grant, NN Anawalt, BD AF Grant, NN Anawalt, BD TI Male hypogonadism in the primary care clinic SO PRIMARY CARE LA English DT Article ID BONE-MINERAL DENSITY; TESTOSTERONE REPLACEMENT THERAPY; CORONARY-HEART-DISEASE; OBSTRUCTIVE SLEEP-APNEA; HEALTHY ADULT MEN; TRANSDERMAL SYSTEM; SERUM TESTOSTERONE; BODY-COMPOSITION; PROSTATE-CANCER; MUSCLE STRENGTH AB Hypogonadism is common in clinical practice but is freqently unrecognized and underdiagnosed. The common causes of male hypogonadism vary with the age of presentation. The overall prevalence of male hypogonadism based upon low serum total testosterone levels is high and increases with age from <5% for men in their twenties and thirties to 12%, 19%, 28%, and 49% for men in their fifties, sixties, seventies, and eighties, respectively [1]. A common cause of hypogonadism in boys and young men is Klinefelter's syndrome, a congenital abnormality occurring in approximately 1:500 men [2,3] that results in a primary testicular disorder associated with small, undeveloped testes and elevated serum gonadotropins. In older men, hypogonadism is often caused by pituitary dysfunction and gonadotropin deficiency due to hyperprolactinemia, corticosteroid excess, hemochromatosis, or pituitary tumors. As men age, serum testosterone levels tend to decline, and some older men develop a clinical syndrome consistent with hypogonadism, a common syndrome of aging called "andropause." There are many pitfalls in making the diagnosis of male hypogonadism. First, male hypogonadism is sometimes difficult to recognize because the signs and symptoms are often nonspecific and overlap with other common syndromes such as depression or are dismissed as the result of normal aging. Second, the biochemical diagnosis of male hypogonadism is not straightforward because it might not be clear which testosterone assay to select from the many that are available. Finally, even after the diagnosis of male hypogonadism is made, the patient and clinician must weigh the potential benefits and risks of androgen replacement therapy. However, new diagnostic tools and therapies are making decisions easier. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Univ Washington, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM bradley.anawalt@med.va.gov NR 75 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-4543 EI 1558-299X J9 PRIMARY CARE JI Primary Care PD DEC PY 2003 VL 30 IS 4 BP 743 EP + DI 10.1016/S0095-4543(03)00091-5 PG 22 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 757GM UT WOS:000187554700007 PM 15024894 ER PT J AU Yao, JK AF Yao, JK TI Special issue: Recent advances of membrane pathology in schizophrenia - Preface SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Editorial Material C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Med Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15206 USA. RP Yao, JK (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Med Ctr, 7180 Highland Dr,Bldg 13, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 365 EP 365 DI 10.1016/j.plefa.2003.08.007 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500001 ER PT J AU Skosnik, PD Yao, JK AF Skosnik, PD Yao, JK TI From membrane phospholipid defects to altered neurotransmission: is arachidonic acid a nexus in the pathophysiology of schizophrenia? SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Review DE schizophrenia; phospholipid metabolism; polyunsaturated fatty acids; arachidonic acid signaling; eicosanoids; endocannabinoids; cytokines; neurotransmission; neurodevelopment; oxidative stress ID ESSENTIAL FATTY-ACIDS; MAGNETIC-RESONANCE-SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; ETHYL-EICOSAPENTAENOIC ACID; POSTMORTEM HUMAN BRAIN; DRUG-FREE PATIENTS; NIACIN SKIN FLUSH; PROTEIN-KINASE-C; RED-BLOOD-CELLS; CANNABINOID RECEPTOR AB Schizophrenia (SZ) is a devastating neuropsychiatric disorder affecting 1% of the general population, and is characterized by symptoms such as delusions, hallucinations, and blunted affect. While many ideas regarding SZ pathogenesis have been put forth, the majority of research has focused on neurotransmitter function, particularly in relation to altered dopamine activity. However, treatments based on this paradigm have met with only modest success, and current medications fail to alleviate symptoms in 30-60% of patients. An alternative idea postulated a quarter of a century ago by Feldberg (Psychol. Med. 6 (1976) 359) and Horrobin (Lancet 1 (1977) 936) involves the theory that SZ is associated in part with phospholipid/fatty acid abnormalities. Since then, it has been repeatedly shown that in both central and peripheral tissue, SZ patients demonstrate increased phospholipid breakdown and decreased levels of various polyunsaturated fatty acids (PUFAs), particularly arachidonic acid (AA). Given the diverse physiological function of membrane phospholipids and PUFAs, an elucidation of their role in SZ pathophysiology may provide novel strategies in the treatment of this disorder. The purpose of this review is to summarize the relevant data on membrane phospholipid/PUFA defects in SZ, the physiological consequence of altered AA signaling, and how they relate to the neurobiological manifestations of SZ and therapeutic outcome. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15206 USA. Indiana Univ, Dept Psychol, Bloomington, IN USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, WPIC, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA USA. RP Yao, JK (reprint author), Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, 7180 Highland Dr,Bldg 13, Pittsburgh, PA 15206 USA. NR 227 TC 47 Z9 50 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 367 EP 384 DI 10.1016/j.plefa.2003.08.008 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500002 PM 14623490 ER PT J AU Reddy, RD Yao, JK AF Reddy, RD Yao, JK TI Environmental factors and membrane polyunsaturated fatty acids in schizophrenia SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE schizophrenia; smoking; polyunsaturated fatty acids; oxidative stress; diet; omega-3 fatty acids ID RED-BLOOD-CELLS; CIGARETTE-SMOKING; ERYTHROCYTE-MEMBRANES; LIPID-PEROXIDATION; SKIN FIBROBLASTS; PLASMA; SMOKERS; SUPPLEMENTATION; ANTIOXIDANTS; ASSOCIATION AB There is accumulating evidence of reductions in red blood cell membrane essential fatty acids in patients with schizophrenia. The mechanisms that may underlie these reductions have yet to be determined. It is possible that the observed membrane fatty acid deficits are associated with the development of schizophrenia. Alternatively, the membrane fatty acid deficits may be due to environmental factors, such as smoking and variations in diet, which may not be associated specifically with the pathophysiology of schizophrenia. Patients with schizophrenia smoke cigarettes at very high rates. Cigarette smoke contains many pro-oxidants that contribute directly to oxidative stress. Polyunsaturated fatty acids (PUFAs) are very susceptible to oxidative effects of free radicals. Thus, smoke-induced oxidative stress could plausibly account for reductions in membrane fatty acid in schizophrenia. Recent studies provide conflicting evidence for smoking effects on membrane fatty acid deficits. Likewise, the effects of diet on membrane PUFAs in schizophrenia are not entirely clear. Essential PUFAs need to be consumed in diet. Thus, differences in membrane PUFAs observed between patients and control subjects may be due to dietary variation. Few studies that have examined dietary effects differ in their interpretation of the effects of diet on membrane PUFAs. Thus, the jury is still out whether smoking or dietary effects are the primary causes of membrane PUFA deficits in patients with schizophrenia. Future studies will need to systematically examine the potential effects of smoking and diet, as well as other environmental factors such exercise, to definitively establish whether or not PUFA abnormalities are inherent to schizophrenia. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. RP Reddy, RD (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH 64118, MH58141, MH43742] NR 67 TC 21 Z9 23 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 385 EP 391 DI 10.1016/j.plefa.2003.08.009 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500003 PM 14623491 ER PT J AU Reddy, R Keshavan, MS AF Reddy, R Keshavan, MS TI Phosphorus magnetic resonance spectroscopy: its utility in examining the membrane hypothesis of schizophrenia SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE magnetic resonance spectroscopy; phosphorus; schizophrenia; polyunsaturated fatty acids; membranes ID FATTY-ACID COMPOSITION; HIGH-ENERGY PHOSPHATE; IN-VIVO; PHOSPHOLIPID-METABOLISM; PREFRONTAL CORTEX; TEMPORAL LOBES; METHODOLOGICAL ISSUES; DOCOSAHEXAENOIC ACID; FRONTAL LOBES; FED PIGLETS AB A novel approach to understanding the pathophysiology of schizophrenia has been the investigation of membrane composition and functional perturbations, referred to as the "Membrane Hypothesis of Schizophrenia." The evidence in support of this hypothesis has been accumulating in findings in patients with schizophrenia of reductions in phospholipids and essential fatty acids various peripheral tissues. Postmortem studies indicate similar reductions in essential fatty acids in the brain. However, the use of magnetic resonance spectroscopy (MRS) has provided an opportunity to examine aspects of membrane biochemistry in vivo in the living brain. MRS is a powerful, albeit complex, noninvasive quantitative imaging tool that offers several advantages over other methods of in vivo biochemical investigations. It has been used extensively in investigating brain biochemistry in schizophrenia. Phosphorus MRS (P-31 MRS) can provide important information about neuronal membranes, such as levels of phosphomonoesters that reflect the building blocks of neuronal membranes and phosphodiesters that reflect breakdown products. P-31 MRS can also provide information about bioenergetics. Studies in patients with chronic schizophrenia as well as at first episode prior to treatment show a variety of alterations in neuronal membrane biochemistry, supportive of the membrane hypothesis of schizophrenia. Below, we will briefly review the principles underlying P-31 MRS and findings to date. Magnetic resonance spectroscopy (MRS) is a powerful, albeit complex, imaging tool that permits investigation of brain biochemistry in vivo. It utilizes the magnetic resonance imaging hardware. It offers several advantages over other methods of in vivo biochemical investigations. MRS is noninvasive, there is no radiation exposure, does not require the use of tracer ligands or contrast media. Because of it is relatively benign, repeated measures are possible. It has been used extensively in investigating brain biochemistry in schizophrenia. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. RP Reddy, R (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH-45203, MH-64118] NR 45 TC 22 Z9 24 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 401 EP 405 DI 10.1016/j.plefa.2003.08.011 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500005 PM 14623493 ER PT J AU Yao, JK Sistilli, CG van Kammen, DP AF Yao, JK Sistilli, CG van Kammen, DP TI Membrane polyunsaturated fatty acids and CSF cytokines in patients with schizophrenia SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE schizophrenia; red blood cells; cerebrospinal fluid; polyunsaturated fatty acids; interleukin 6; interleukin 10 ID MAGNETIC-RESONANCE SPECTROSCOPY; DIETARY SUPPLEMENTATION; PHOSPHOLIPASE-A2 ACTIVITY; ARACHIDONIC-ACID; INTERLEUKIN-2 PRODUCTION; DRUG-FREE; ERYTHROCYTE-MEMBRANES; SERUM INTERLEUKIN-6; SIGNAL TRANSDUCTION; LIPID PEROXIDES AB Findings to date provide evidence that altered membrane structure and function are present in patients with either first-episode or chronic schizophrenia, suggesting defects in phospholipid metabolism and cell signaling in schizophrenia. The purpose of this investigation is to test whether decreased membrane polyunsaturated fatty acids (PUFAs) were associated with an increased secretion of proinflammatory cytokines. Thus, we measured interleukin 6 (IL-6) and interleukin 10 (IL-10) in cerebrospinal fluid (CSF) of patients with chronic schizophrenia as well as PUFAs of red blood cell (RBC) membranes from the same individuals. A significant and inverse correlation was found between CSF IL-6 (not IL-10) and RBC membrane PUFAs levels in both haloperidol-treated and medication-free patients with schizophrenia. Specifically, such an association was found in the n-6 (18:2, 20:4, and 22:4) and, to a lesser extent, the n-3 fatty acids. Taken together, the present findings suggest that decreased membrane PUFAs may be related to an immune disturbance in schizophrenia, possibly resulting from an increased phospholipase A, activity mediated through the proinflammatory cytokines. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15206 USA. Aventis Inc, Bridgewater, NJ 08807 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Yao, JK (reprint author), Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, 7180 Highland Dr,Bldg 13, Pittsburgh, PA 15206 USA. FU NIMH NIH HHS [MH43742, MH44841, MH58141] NR 91 TC 17 Z9 18 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 429 EP 436 DI 10.1016/j.plefa.2003.08.015 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500009 PM 14623497 ER PT J AU Monnier, J Knapp, RG Frueh, BC AF Monnier, J Knapp, RG Frueh, BC TI Recent advances in telepsychiatry: An updated review SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-HEALTH-SERVICE; COGNITIVE-BEHAVIORAL THERAPY; FACE-TO-FACE; CONTROLLED-TRIAL; COST-ANALYSIS; TELEMEDICINE; CARE; CHILD; PROGRAM; SATISFACTION AB Objective: In response to new developments and interest in the area of telepsychiatry, literature on this topic has greatly increased over the past three years. Because of this increase, the authors conducted a literature review of telepsychiatry to update a previously published review that covered the years 1970 to 2000. Methods: A search was conducted on the MEDLINE, PsycINFO, and Telemedicine Information Exchange (TIE) databases for literature published from March 2000 to March 2003 on telepsychiatry applications, using the following terms: telepsychiatry, telepsychology, telemental health, videoconferencing, and video conferencing. Results: Sixty-eight publications were identified over this three-year period, exceeding the 63 publications identified in the previous literature review. The authors summarize the results of findings in six areas: novel clinical demonstrations and current program descriptions; the reliability of clinical assessments; clinical outcomes; satisfaction of patients and clinicians; cost and cost-effectiveness; and legal, regulatory, and ethical issues. Studies describing existing programs and novel clinical applications support the belief that the use of telepsychiatry is expanding. Overall, studies continued to support the notion that telepsychiatry assessments can produce reliable results, telepsychiatric services can lead to improved clinical status, and patients and clinicians are satisfied with treatment delivered via telepsychiatry. Evidence supported the notion that telepsychiatry is a cost-effective means of delivering mental health services; however, this conclusion was based on limited studies of economic models of telepsychiatry programs. Also limited were papers on the topics of legal, regulatory, and ethical issues. Conclusions: Despite the rapid increase in information on telepsychiatry, methodologically sound studies in the area of telepsychiatry are still infrequent. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. RP Monnier, J (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave,POB 250681, Charleston, SC 29425 USA. EM monnierj@musc.edu NR 67 TC 103 Z9 104 U1 0 U2 9 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2003 VL 54 IS 12 BP 1604 EP 1609 DI 10.1176/appi.ps.54.12.1604 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BV UT WOS:000222759200012 PM 14645799 ER PT J AU Weissman, EM Kushner, M Marcus, SM Davis, DF AF Weissman, EM Kushner, M Marcus, SM Davis, DF TI Volume of VA patients with posttraumatic stress disorder in the New York metropolitan area after september 11 SO PSYCHIATRIC SERVICES LA English DT Article ID TERRORIST ATTACKS; PSYCHOLOGICAL SEQUELAE AB The authors examined data from the Veterans Integrated Service Network of New York and New Jersey to determine whether the number of veterans who were treated for posttraumatic stress disorder (PTSD) increased significantly after the terrorist attacks of September 11, 2001. They analyzed the number of veterans treated for PTSD at Veterans Healthcare Administration facilities in New York and New Jersey from September 1999 through June 2002. The number of veterans treated for PTSD in these facilities after September 11 exceeded projections based on secular trends, and the increase was more pronounced than for other, diagnostic groups. The results highlight the need to ensure adequate availability of services in the! wake of traumatic events. C1 MIRECC, Dept Vet Affairs Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. VISN 3, Mental Hlth Care Line, Bronx, NY USA. RP Weissman, EM (reprint author), Bronx Vet Adm Med Ctr, OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ellen.weissman@med.va.gov NR 9 TC 9 Z9 9 U1 2 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2003 VL 54 IS 12 BP 1641 EP 1643 DI 10.1176/appi.ps.54.12.1641 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BV UT WOS:000222759200018 PM 14645805 ER PT J AU Garb, HN AF Garb, HN TI Incremental validity and the assessment of psychopathology in adults SO PSYCHOLOGICAL ASSESSMENT LA English DT Review ID BORDERLINE PERSONALITY-DISORDER; NONCLINICAL YOUNG-ADULTS; RATING DEPRESSION SCALE; EGO IMPAIRMENT INDEX; ANXIETY SENSITIVITY; COMPREHENSIVE SYSTEM; PERCEIVED CONTROL; INTERPERSONAL PROBLEMS; SCHIZOPHRENIC-PATIENTS; PSYCHIATRIC-PATIENT AB Results from studies on incremental validity are described for (a) interviews, (b) personality inventories, (c) projective techniques, and (d) brief self-rated and clinician-rated measures. In some of the studies (clinical judgment studies), psychologists were given increasing amounts of information. In other studies (statistical prediction studies), increasing amounts of assessment information were entered into a statistical prediction rule. Although relatively little research has been conducted on incremental validity, results that have been obtained tend to favor the use of interviews, personality inventories (e.g., the Minnesota Multiphasic Personality Inventory-2; J. N. Butcher, W. G. Dahlstrom, J. R., Graham, A. Tellegen, & B. Kaemmer, 1989), and brief self-rated measures (e.g., the Anxiety Sensitivity Index, S. Reiss, R. A. Peterson, D. M. Gursky, & R. M. McNally, 1986). Results are generally less encouraging for projective techniques. C1 Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat & Psychol, Pittsburgh, PA 15260 USA. RP Garb, HN (reprint author), Wilford Hall USAF Med Ctr, Psychol Res Serv, 59 MDOS MMCPR,2200 Bergquist Dr,Suite 1, Lackland AFB, TX 78236 USA. NR 156 TC 30 Z9 31 U1 3 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 2003 VL 15 IS 4 BP 508 EP 520 DI 10.1037/1040-3590.15.4.508 PG 13 WC Psychology, Clinical SC Psychology GA 754VH UT WOS:000187352200007 PM 14692846 ER PT J AU Hasenfeld, R Shekelle, PG AF Hasenfeld, R Shekelle, PG TI Is the methodological quality of guidelines declining in the US? Comparison of the quality of US Agency for Health Care Policy and Research (AHCPR) guidelines with those published subsequently SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID SPECIALTY; APPRAISAL; REVIEWS AB Objective: To determine whether North American guidelines published subsequent to and in the same topic areas as those developed by the US Agency for Health Care Policy and Research (AHCPR) meet the same methodological criteria. Study design: A guideline appraisal instrument containing 30 criteria was used to evaluate the methodological quality of the AHCPR guidelines, "updates" of the AHCPR guidelines authored by others, and guidelines that referenced or were adapted from the AHCPR guidelines. The frequency with which the criteria appeared in each guideline was compared and an analysis was performed to determine guidelines with two key features of the ACHPR guidelines - multidisciplinary guideline development panels and systematic reviews of the literature. Data were extracted from the guidelines by one investigator and then checked for accuracy by the other. Results: Fifty two guidelines identified by broad based searches were evaluated. 50% of the criteria were present in every AHCPR guideline. The AHCPR guidelines scored 80% or more on 24 of the 30 criteria compared with 14 for the "updates" and 11 for those that referenced/adapted the AHCPR guidelines. All of the 17 AHCPR guidelines had both multidisciplinary development panels and systematic reviews of the literature compared with five from the other two categories (p < 0.05). Conclusions: North American guidelines developed subsequent to and in the same topic areas as the AHCPR guidelines are of substantially worse methodological quality and ignore key features important to guideline development. This finding contrasts with previously published conclusions that guideline methodological quality is improving over time. C1 RAND Hlth, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90406 USA. Greater Los Angeles VA Med Ctr, Dept Gen Internal Med, Los Angeles, CA USA. RP Hasenfeld, R (reprint author), RAND Corp, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. FU PHS HHS [290-97-0001] NR 18 TC 30 Z9 31 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD DEC PY 2003 VL 12 IS 6 BP 428 EP 434 DI 10.1136/qhc.12.6.428 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 754NY UT WOS:000187324300011 PM 14645758 ER PT J AU Aravagiri, M Marder, SR Nuechterlein, KH Gitlin, MJ AF Aravagiri, M Marder, SR Nuechterlein, KH Gitlin, MJ TI Intra- and interindividual variations in steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients treated chronically with various doses of risperidone SO THERAPEUTIC DRUG MONITORING LA English DT Article DE risperidone; 9-hydroxyrisperidone; steady-state plasma levels; inter- and intraindividual variations; plasma level monitoring; LC-MS-MS ID SERUM CONCENTRATIONS; ACTIVE METABOLITE; DRUG-INTERACTIONS; PHARMACOKINETICS; RAT; 5-HT2; BRAIN; D-2; ANTIPSYCHOTICS; PROPRANOLOL AB The intra- and interindividual variability in apparent steady-state plasma levels of risperidone (RSP) and its metabolite 9-hydroxyrisperidone (9-OHRSP) in schizophrenic patients was investigated. Patients (n = 46, age 26.4 +/- 5.3 years) with diagnosed schizophrenia were treated with a fixed daily oral dose of RSP (1-12 mg/d). The steady-state plasma samples from these patients were collected over a period of 5 years and a total of 549 visits. Plasma concentrations of RSP and 9-OHRSP were determined using a highly sensitive and specific LC-MS-MS method with a detection limit of 0.1 ng/mL. All plasma samples had measurable amounts of 9-OHRSP; however, RSP was nondetectable (<0.1 ng/mL) in 18% of the plasma samples. 9-OHRSP levels were, on average, similar to22 times higher than those of RSP. The plasma levels of RSP and 9-OHRSP varied widely among patients receiving similar doses of RSP, and the intra- and interindividual variations of RSP and 9-OHRSP plasma levels were found to be large. The data indicated that there was no significant change in the steady-state levels of either RSP or 9-OHRSP during the treatment period. Similarly, the dose-normalized concentration did not vary significantly during the treatment period or with the administered dose. The absence of RSP in many plasma samples (<0.1 ng/mL) and presence of 9-OHRSP at severalfold higher concentrations than RSP indicate that measuring plasma levels of RSP alone may lead to erroneous interpretation in plasma level monitoring studies. The current data support the fact that it is important to measure steady-state levels of total active moiety by analyzing both RSP and 9-OHRSP for plasma drug monitoring. C1 Univ Calif Los Angeles, Psychopharmacol Unit, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90073 USA. RP Aravagiri, M (reprint author), Univ Calif Los Angeles, Psychopharmacol Unit, VA Greater Los Angeles Healthcare Syst, Bldg 210 15,11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. NR 32 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD DEC PY 2003 VL 25 IS 6 BP 657 EP 664 DI 10.1097/00007691-200312000-00003 PG 8 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 747YG UT WOS:000186833500002 PM 14639051 ER PT J AU Aujesky, D Hayoz, D Yersin, B Perrier, A Barghouth, G Schnyder, P Bischof-Delaloye, A Cornuz, J AF Aujesky, D Hayoz, D Yersin, B Perrier, A Barghouth, G Schnyder, P Bischof-Delaloye, A Cornuz, J TI Exclusion of pulmonary embolism using C-reactive protein and D-dimer SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE pulmonary embolism; C-reactive protein; D-dimer; clinical probability assessment ID DEEP VENOUS THROMBOSIS; SIMPLE CLINICAL-MODEL; NONINVASIVE DIAGNOSIS; VEIN THROMBOSIS; THROMBOEMBOLISM; OUTPATIENTS; PERFORMANCE; PROBABILITY; EMERGENCY; PLASMA AB Our goal was to evaluate the diagnostic utility of C-reactive protein (CRP) alone or combined with clinical probability assessment in patients with suspected pulmonary embolism (PE), and to compare its performance to a D-dimer assay. We conducted a prospective study in which we performed a common immuno-turbidimetric CRP test and a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer test in 259 consecutive outpatients with suspected PE at the emergency department of a teaching hospital. We assessed clinical probability of PE by a validated prediction rule overridden by clinical judgment. Patients with D-dimer levels greater than or equal to 500 mug/l underwent a work-up consisting of lower-limb venous ultrasound, spiral computerized tomography, ventilation-perfusion scan, or pulmonary angiography. Patients were followed up for three months. Seventy-seven (30%) of the patients had PE. The CRP alone had a sensitivity of 84% (95% confidence interval [Cl).: 74 to 92%) and a negative predictive value (NPV) of 87% (95% Cl: 78 to 93%) at a cutpoint of 5 mg/l. Overall, 61 (24%) patients with a low clinical probability of PE had a CRP < 5 mg/l. Due to the low prevalence of PE (9%) in this subgroup, the NPV increased to 97% (95% Cl: 89 to 100%). The D-dimer (cutpoint 500 mug/l) showed a sensitivity of 100% (95% Cl: 95 to 100%) and a NPV of 100% (95% Cl: 94 to 100%) irrespective of clinical probability and accurately rule out PE in 56 (22%) patients. Standard CRP tests alone or combined with clinical probability assessment cannot safely exclude PE. C1 Univ Lausanne Hosp, Dept Med, Lausanne, Switzerland. Univ Lausanne Hosp, Div Angiol, Lausanne, Switzerland. Univ Lausanne Hosp, Dept Emergency Med, Lausanne, Switzerland. Univ Lausanne Hosp, Dept Radiol, Lausanne, Switzerland. Univ Lausanne Hosp, Dept Nucl Med, Lausanne, Switzerland. Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland. Univ Hosp Geneva, Dept Med, Geneva, Switzerland. RP Aujesky, D (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,11E127, Pittsburgh, PA 15240 USA. RI Perrier, Arnaud/M-2263-2014 NR 26 TC 15 Z9 17 U1 0 U2 3 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 DEC PY 2003 VL 90 IS 6 BP 1198 EP 1203 DI 10.1160/TH03-03-0175 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 755QW UT WOS:000187422800035 PM 14652657 ER PT J AU Lawrence, VA Silverstein, JH Cornell, JE Pederson, T Noveck, H Carson, JL AF Lawrence, VA Silverstein, JH Cornell, JE Pederson, T Noveck, H Carson, JL TI Higher Hb level is associated with better early functional recovery after hip fracture repair SO TRANSFUSION LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; BLOOD-CELL TRANSFUSIONS; INTENSIVE-CARE UNIT; HEMODIALYSIS-PATIENTS; EXERCISE CAPACITY; PHYSICAL PERFORMANCE; ABDOMINAL-SURGERY; VASCULAR PATIENTS; HEMOGLOBIN; RISK AB BACKGROUND: The benefits and indications for blood transfusion are controversial. One possible reason to transfuse is to improve functional recovery after major surgery. However, the data linking improved function with higher Hb concentration are limited. STUDY DESIGN AND METHODS: A retrospective cohort study was performed in 5793 patients at least 60 years old undergoing hip fracture repair at 20 academic and community hospitals. The primary outcome was distance walked at the time of discharge from the hospital. The mean postoperative Hb concentration was the main exposure variable and was defined as the average value from Day 1 after surgery to discharge. We used robust regression to assess the association between postoperative Hb level with distance walked, controlling for other preoperative variables that could influence functional recovery. RESULTS: On bivariate analysis, the predicted distance walked at discharge in feet (95% CI) increased with higher Hb levels (7 g/dL, 56 feet [42-70]; 8 g/dL, 61 feet [54-68]; 9 g/dL, 67 feet [64-70]; 10 g/dL, 74 feet [72-77]; 11 g/dL, 83 feet [80-85]; 12 g/dL, 92 feet [87-96]). After adjustment for other factors associated with ability to walk, higher average postoperative Hb level was independently associated with walking greater distance (p < 0.001). CONCLUSIONS: Higher postoperative Hb level may improve functional recovery after hip fracture repair. If confirmed with clinical trials, this finding would provide a rationale to maintain higher Hb concentrations in elderly patients recovering from surgery. C1 STVHCS, ALMD, VERDICT, 11C6, San Antonio, TX USA. VERDICT, Vet Affairs Hlth Serv Res & Dev Ctr Excellence, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Gen Med, Dept Med, San Antonio, TX 78285 USA. NYU, Mt Sinai Sch Med, Dept Anesthesiol, New York, NY USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, Dept Med, New Brunswick, NJ USA. RP Lawrence, VA (reprint author), STVHCS, ALMD, VERDICT, 11C6, 7400 Merton Minter Blvd, San Antonio, TX USA. FU AHRQ HHS [1R01HS07322] NR 44 TC 91 Z9 108 U1 0 U2 4 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2003 VL 43 IS 12 BP 1717 EP 1722 DI 10.1046/j.0041-1132.2003.00581.x PG 6 WC Hematology SC Hematology GA 750TT UT WOS:000187014900014 PM 14641869 ER PT J AU Kane, CJ Lubeck, DP Knight, SJ Spitalny, M Downs, TM Grossfeld, GD Pasta, DJ Mehta, SS Carroll, PR AF Kane, CJ Lubeck, DP Knight, SJ Spitalny, M Downs, TM Grossfeld, GD Pasta, DJ Mehta, SS Carroll, PR TI Impact of patient educational level on treatment for patients with prostate cancer: Data from CaPSURE SO UROLOGY LA English DT Article ID QUALITY-OF-LIFE; SOCIOECONOMIC-STATUS; RADICAL PROSTATECTOMY; DECISION-MAKING; MEN; AGE; THERAPY AB Objectives. To examine the effect of a patient's educational level on treatment selection for patients with newly diagnosed prostate cancer. A patient's educational level may impact a patient's understanding and perception of the risks and benefits of the treatment options for prostate cancer. Methods. We examined 3484 patients in CaPSURE with prostate cancer between 1992 and 2001. Chi-square and multinomial logistic regression analyses were performed to determine the role of education level in primary treatment received relative to other pretreatment predictors (age, race, insurance status, prostate cancer risk, comorbidity). Prostate cancer risk stratification was determined by serum prostate-specific antigen level and tumor stage and grade. Results. The mean patient age was 67.7 +/- 8.3 years, and the mean prostate-specific antigen level was 13.0 +/- 18.7 ng/mL. Of the 3484 patients, 16.7% had less than a high school education, 27.0% had completed high school or technical school, 19.5% had had some college, 18.0% had graduated from college, and 18.6% had had some graduate education. In bivariate analysis, the factors predictive of treatment selection were patient age, race, education, insurance status, risk group, and patient comorbidity (all P <0.001). In multinomial regression analysis, the factors predicting treatment received were age, race, cancer risk group, and comorbidity. For patients older than 75 years, those with a higher education level received more aggressive treatment (radiotherapy versus hormonal therapy) than did those with less education. Conclusions. Patient age, race, cancer risk group, comorbidity, and, for men older than 75 years, education level are the factors predictive of the primary treatment received by men with newly diagnosed prostate cancer. (C) 2003 Elsevier Inc. C1 Univ Calif San Francisco, Sch Med, Dept Urol, Program Urol Oncol,Urol Outcomes Res Grp, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Mt Zion Comprehens Canc Ctr, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Serv Urol, San Francisco, CA USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Kane, CJ (reprint author), Univ Calif San Francisco, Sch Med, Dept Urol, Program Urol Oncol,Urol Outcomes Res Grp, 1600 Divisadero St,Room A-607, San Francisco, CA 94143 USA. OI Pasta, David/0000-0003-2637-9293 NR 16 TC 26 Z9 26 U1 0 U2 1 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 DEC PY 2003 VL 62 IS 6 BP 1035 EP 1039 DI 10.1016/S0090-4295(03)00778-7 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 811RV UT WOS:000220789900013 PM 14665350 ER PT J AU Lacerda, ALT Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC AF Lacerda, ALT Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC TI Anatomical MRI study of basal ganglia in major depressive disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE neuroimaging; caudate; putamen; globus pallidus; mood disorders; unipolar depression; magnetic resonance imaging ID MAGNETIC-RESONANCE SPECTROSCOPY; PHOTON-EMISSION TOMOGRAPHY; MOOD DISORDERS; UNIPOLAR DEPRESSION; NEUROPSYCHIATRIC DISORDERS; PARKINSONS-DISEASE; BIPOLAR DISORDER; METABOLIC RATES; VOLUME; BRAIN AB The basal ganglia form a part of the brain neuroanatomic circuits that may be involved in mood regulation. Decreases in basal ganglia volumes have been previously reported in major depressive disorder patients in comparison to healthy controls. In this study, we measured caudate, putamen, and globus pallidus volumes in 25 patients with major depressive disorder (4 M; age +/- S.D. = 41 +/- 11 years) and 48 healthy controls (29 M; age +/- S.D. = 35 +/- 10 years), using high-resolution magnetic resonance imaging (MRI), in an attempt to replicate prior findings. Unlike most previous studies, we did not find significant differences between patient and control groups in basal ganglia volumetric measures. Nonetheless, there was a significant interaction between diagnosis and cerebral hemisphere, with MDD patients showing decreased asymmetry in globus pallidus volumes in comparison with healthy controls. Furthermore, in the patient group, left putamen volumes correlated inversely with length of illness, and left globus pallidus volume correlated directly with number of prior depressive episodes. These findings suggest that abnormalities in lateralization and possibly neurodegenerative changes in basal ganglia structures participate in the pathophysiology of major depressive disorder. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. State Univ Campinas, Sch Med Sci, Dept Med Psychol & Psychiat, Campinas, SP, Brazil. Univ Pavia, Sch Med, Dept Psychiat, Pavia, Italy. Univ Pittsburgh, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat MC7792, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Lacerda, Acioly/A-7052-2010; brambilla, paolo/B-4184-2010 OI Lacerda, Acioly/0000-0002-9370-0449; brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 01736, MH 30915] NR 59 TC 59 Z9 61 U1 3 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 30 PY 2003 VL 124 IS 3 BP 129 EP 140 DI 10.1016/S0925-4927(03)00123-9 PG 12 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 745VU UT WOS:000186711900001 PM 14623065 ER PT J AU Yun, TH Baglia, FA Myles, T Navaneetham, D Lopez, JA Walsh, PN Leung, LLK AF Yun, TH Baglia, FA Myles, T Navaneetham, D Lopez, JA Walsh, PN Leung, LLK TI Thrombin activation of factor XI on activated platelets requires the interaction of factor XI and platelet glycoprotein Ib alpha with thrombin anion-binding exosites I and II, respectively (Retracted Article. See vol 282, pg 29067, 2007) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article; Retracted Publication ID COAGULATION-FACTOR-XI; PRO-ARG CHLOROMETHYLKETONE; MOLECULAR-WEIGHT KININOGEN; BLOOD-COAGULATION; CRYSTAL-STRUCTURE; V COMPLEX; ANTITHROMBIN-III; HIGH-AFFINITY; FACTOR-VIII; FACTOR IXA AB Activation of factor XI (FXI) by thrombin on stimulated platelets plays a physiological role in hemostasis, providing additional thrombin generation required in cases of severe hemostatic challenge. Using a collection of 53 thrombin mutants, we identified 16 mutants with < 50% of the wild-type thrombin FXI-activating activity in the presence of dextran sulfate. These mutants mapped to anion-binding exosite (ABE) I, ABE-II, the Na(+)-binding site, and the 50-insertion loop. Only the ABE-II mutants showed reduced binding to dextran sulfate-linked agarose. Selected thrombin mutants in ABE-I (R68A, R70A, and R73A), ABE-II (R98A, R245A, and K248A), the 50-insertion loop (W50A), and the Na(+)-binding site ( E229A and R233A) with < 10% of the wildtype activity also showed a markedly reduced ability to activate FXI in the presence of stimulated platelets. The ABE-I, 50-insertion loop, and Na(+)-binding site mutants had impaired binding to FXI, but normal binding to glycocalicin, the soluble form of glycoprotein Ibalpha (GPIbalpha). In contrast, the ABE-II mutants were defective in binding to glycocalicin, but displayed normal binding to FXI. Our data support a quaternary complex model of thrombin activation of FXI on stimulated platelets. Thrombin bound to one GPIbalpha molecule, via ABE-II on its posterior surface, is properly oriented for its activation of FXI bound to a neighboring GPIalpha molecule, via ABE-I on its anterior surface. GPIbalpha plays a critical role in the co-localization of thrombin and FXI and the resultant efficient activation of FXI. C1 Stanford Univ, Sch Med, Dept Med, Div Hematol, Stanford, CA 94305 USA. Temple Univ, Sch Med, Sol Sherry Thrombosis Res Ctr, Philadelphia, PA 19140 USA. Temple Univ, Sch Med, Dept Med, Philadelphia, PA 19140 USA. Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19140 USA. Baylor Coll Med, Dept Med, Thrombosis Res Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Leung, LLK (reprint author), Stanford Univ, Sch Med, Dept Med, Div Hematol, 269 Campus Dr, Stanford, CA 94305 USA. EM lawrence.leung@stanford.edu FU NHLBI NIH HHS [HL70683, HL46213, HL57530, HL69493]; PHS HHS [P5065967] NR 56 TC 57 Z9 60 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 NOV 28 PY 2003 VL 278 IS 48 BP 48112 EP 48119 DI 10.1074/jbc.M306925200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746DM UT WOS:000186731400092 PM 12968031 ER PT J AU Rosenheck, R Perlick, D Bingham, S Liu-Mares, W Collins, J Warren, S Leslie, D Allan, E Campbell, EC Caroff, S Corwin, J Davis, L Douyon, R Dunn, L Evans, D Frecska, E Grabowski, J Graeber, D Herz, L Kwon, K Lawson, W Mena, F Sheikh, J Smelson, D Smith-Gamble, V AF Rosenheck, R Perlick, D Bingham, S Liu-Mares, W Collins, J Warren, S Leslie, D Allan, E Campbell, EC Caroff, S Corwin, J Davis, L Douyon, R Dunn, L Evans, D Frecska, E Grabowski, J Graeber, D Herz, L Kwon, K Lawson, W Mena, F Sheikh, J Smelson, D Smith-Gamble, V CA Dept Vet Affairs Cooperative Study TI Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-LIFE; ATYPICAL ANTIPSYCHOTICS; REFRACTORY SCHIZOPHRENIA; CLINICAL-TRIAL; RATING-SCALE; CLOZAPINE; OUTCOMES; CARE; IMPROVEMENT; MEDICATION AB Context Although olanzapine has been widely adopted as a treatment of choice for schizophrenia, its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a standard antipsychotic drug. Objective To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia. Design and Setting Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers. Participants Three hundred nine patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder, serious symptoms, and serious dysfunction for the previous 2 years. Fifty-nine percent fully completed and 36% partially completed follow-up assessments. Interventions Patients were randomly assigned to receive flexibly dosed olanzapine, 5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n=159); or haloperidol, 5 to 20 mg/d (n=150), for 12 months. Main Outcome Measures 'Standardized measures of symptoms, quality of life, neurocognitive status, and adverse effects of medication. Veterans Affairs administrative data and interviews concerning non-VA service use were used to estimate costs from the perspective of the VA health care system and society as a whole (ie, consumption of all resources on behalf of these patients). Results There were no significant differences between groups in study retention; positive, negative, or total symptoms of schizophrenia; quality of life; or extrapyramidal symptoms. Olanzapine was associated with reduced akathisia in the intention-to-treat analysis (P<.001) and with lower symptoms of tardive dyskinesia in a secondary analysis including only observations during blinded treatment with study drug. Small but significant advantages were also observed on measures of memory and motor function. Olanzapine was also associated with more frequent reports of weight gain and significantly greater VA costs, ranging from $3000 to $9000 annually. Differences in societal costs were somewhat smaller and were not significant. Conclusion Olanzapine does not demonstrate advantages compared with haloperidol (in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost. C1 Dept Vet Affairs Med Ctr, West Haven, CT USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Dept Vet Affairs, Cooperat Studies Program, Coordinating Ctr, Perry Point, MD USA. Dept Vet Affairs Med Ctr, Albuquerque, NM USA. Dept Vet Affairs, Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA. Dept Vet Affairs Med Ctr, Montrose, NY USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, New York, NY USA. Dept Vet Affairs Med Ctr, Tuscaloosa, AL USA. Dept Vet Affairs Med Ctr, Miami, FL USA. Dept Vet Affairs Med Ctr, Durham, NC USA. Dept Vet Affairs Med Ctr, Augusta, GA USA. Dept Vet Affairs Med Ctr, Bay Pines, FL USA. Dept Vet Affairs Med Ctr, Detroit, MI USA. Dept Vet Affairs Med Ctr, Bedford, MA USA. Dept Vet Affairs Med Ctr, Brecksville, OH USA. Howard Univ, Sch Med, Washington, DC 20059 USA. Dept Vet Affairs Med Ctr, Tuskegee, AL USA. Dept Vet Affairs Med Ctr, Palo Alto, CA USA. Dept Vet Affairs Med Ctr, Lyons, NJ USA. Dept Vet Affairs Med Ctr, Indianapolis, IN USA. RP Rosenheck, R (reprint author), VA Connecticut Hlth Care Syst, NE Program Evaluat Ctr 182, 950 Campbell Ave, West Haven, CT 06516 USA. OI Lawson, William/0000-0002-9324-7090 FU NCI NIH HHS [R25 CA092049] NR 62 TC 249 Z9 262 U1 3 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 26 PY 2003 VL 290 IS 20 BP 2693 EP 2702 DI 10.1001/jama.290.20.2693 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 747CR UT WOS:000186788100021 PM 14645311 ER PT J AU Tajouri, L Mellick, AS Ashton, KJ Tannenberg, AEG Nagra, RM Tourtellotte, WW Griffiths, LR AF Tajouri, L Mellick, AS Ashton, KJ Tannenberg, AEG Nagra, RM Tourtellotte, WW Griffiths, LR TI Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis SO MOLECULAR BRAIN RESEARCH LA English DT Article DE multiple sclerosis; plaque; chronic active; acute; cDNA microarray; quantitative PCR analysis ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; POLYMERASE-CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; MICROARRAY ANALYSIS; PARKINSONS-DISEASE; OXIDATIVE STRESS; PROTEIN; LESIONS; RECEPTOR; CLONING AB Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS with both genetic and environmental contributing factors. Clinical symptoms are broadly characterized by initial onset, and progressive debilitating neurological impairment. In this study, RNA from MS chronic active and MS acute lesions was extracted, and compared with patient matched normal white matter by fluorescent cDNA microarray hybridization analysis. This resulted in the identification of 139 genes that were differentially regulated in MS plaque tissue compared to normal tissue. Of these, 69 genes showed a common pattern of expression in the chronic active and acute plaque tissues investigated (P-value < 0.0001, rho = 0.73, by Spearman's rho analysis); while 70 transcripts were uniquely differentially expressed (greater than or equal to 1.5-fold) in either acute or chronic active tissues. These results included known markers of MS such as the myelin basic protein (MBP) and glutathione S-transferase (GS7) M1, nerve growth factors, such as nerve injury-induced protein 1 (NINJ1), X-ray and excision DNA repair factors (XRCC9 and ERCC5) and X-linked genes such as the ribosomal protein, RPS4X. Primers were then designed for seven array-selected genes, including transferrin (TF), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), GSTP1, crystallin, alpha-B (CRYAB), phosphomannomutase 1 (PMM1) and tubulin beta-5 (TBB5), and real time quantitative (Q)-PCR analysis was performed. The results of comparative Q-PCR analysis correlated significantly with those obtained by array analysis (r = 0.75, P-value < 0.01, by Pearson's bivariate correlation). Both chronic active and acute plaques shared the majority of factors identified suggesting that quantitative, rather than gross qualitative differences in gene expression pattern may define the progression from acute to chronic active plaques in MS. (C) 2003 Elsevier B.V. All rights reserved. C1 Griffith Univ, Sch Hlth Sci, Southport, Qld 4215, Australia. Queensland Med Labs, West End, Qld 4101, Australia. W Los Angeles Vet Affairs Med Ctr, Human Brain & Spinal Fluid Resources Ctr, Los Angeles, CA 90073 USA. RP Griffiths, LR (reprint author), Genome Res Ctr, Sch Hlth Sci, PMB 50 GCMC, Griffith, NSW 9726, Australia. RI Ashton, Kevin/R-2147-2016 OI Ashton, Kevin/0000-0001-6106-3425; Mellick, Albert/0000-0002-0668-2706; Griffiths, Lyn/0000-0002-6774-5475 NR 84 TC 72 Z9 72 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV 26 PY 2003 VL 119 IS 2 BP 170 EP 183 DI 10.1016/j.molbrainres.2003.09.008 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 748FV UT WOS:000186852600006 ER PT J AU Handforth, A Ondo, WG Tatter, S Mathern, GW Simpson, RK Walker, F Sutton, JP Hubble, JP Jankovic, J AF Handforth, A Ondo, WG Tatter, S Mathern, GW Simpson, RK Walker, F Sutton, JP Hubble, JP Jankovic, J TI Vagus nerve stimulation for essential tremor - A pilot efficacy and safety trial SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HARMALINE-INDUCED TREMOR; SYSTEM; CEREBELLUM; VAGAL; REPRESENTATION; SEIZURES; CAT AB Objective: To assess the safety and efficacy of vagus nerve stimulation (VNS) for essential tremor (ET). Methods: This was a pilot open-treatment trial at three centers, with masked videotape tremor assessments. Inclusion required a severity score of 3 or 4 on the Tremor Rating Scale (TRS) in one or both hands. At baseline, tremor was assessed with TRS and Unified Tremor Rating Assessment (UTRA), accelerometry, and a videotape protocol. The VNS device was implanted with leads placed around the left cervical vagus nerve. Stimulation was adjusted over 4 weeks before the repeat tremor assessments. Two raters masked to the study visit scored the videotapes. Results: Nine subjects participated, with a mean age of 65 years and a mean age at onset of tremor of 24. Investigators rated hand tremor as mildly improved (TRS 2.3+/-0.7 during VNS vs 3.0+/-0.4 during baseline, p=0.06). Accelerometry-measured total power improved 50.2+/-31.8% (p<0.01). Videotape tremor scores were highly correlated between the masked raters and revealed no changes in tremor scores with treatment. VNS was well tolerated, with the most common adverse events being stimulation related. Conclusions: VNS was judged by investigators to mildly improve upper extremity tremor. This finding was not confirmed in videotape scoring by masked raters. VNS is not likely to have a clinically meaningful effect on ET. C1 Vet Affairs Greater Los angeles Healthcare Syst, Neurol Serv W127, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Calif Neurosci Inst, Oxnard, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Ohio State Univ, Columbus, OH 43210 USA. RP Handforth, A (reprint author), Vet Affairs Greater Los angeles Healthcare Syst, Neurol Serv W127, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 18 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 25 PY 2003 VL 61 IS 10 BP 1401 EP 1405 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 746VF UT WOS:000186767800018 PM 14638963 ER PT J AU Rumsfeld, JS Havranek, E Masoudi, FA Peterson, ED Jones, P Tooley, JF Krumholz, HM Spertus, JA AF Rumsfeld, JS Havranek, E Masoudi, FA Peterson, ED Jones, P Tooley, JF Krumholz, HM Spertus, JA CA Cardiovascular Outcomes Res Consor TI Depressive symptoms are the strongest predictors of short-term declines in health status in patients with heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID QUALITY-OF-LIFE; CASE-FINDING INSTRUMENTS; RANDOMIZED-TRIAL; MAJOR DEPRESSION; ELDERLY PATIENTS; PRIMARY-CARE; DISEASE; RISK; OUTCOMES; CARDIOMYOPATHY AB OBJECTIVES The purpose of this study was to assess whether depressive symptoms are independently associated with changes in heart failure (HF)-specific health status. BACKGROUND Depression is common in patients with HF, but the impact of depressive symptoms on the health status of these patients over time is unknown. METHODS We conducted a multicenter prospective cohort study of outpatients with HF. Data from 460 patients who completed a baseline Medical Outcomes Study-Depression Questionnaire and both a baseline and follow-up (6 2 weeks) Kansas City Cardiomyopathy Questionnaire (KCCQ) were analyzed. The KCCQ measures HF-specific health status, including symptoms, physical and social function, and quality of life. Multivariable regression was used to evaluate depressive symptoms as a predictor of change in KCCQ scores, adjusting for baseline KCCQ scores and other patient variables. The primary outcome was change in KCCQ summary scores (range 0 to 100; higher scores indicate better health status; 5 points is a clinically meaningful change). RESULTS Approximately 30% (139/460) of the patients had significant depressive symptoms at baseline. Depressed patients had markedly lower baseline KCCQ summary scores (beta = -19.6; p < 0.001). After adjustment for potential confounders, depressed patients were at risk for significant worsening of their HF symptoms, physical and social function, and quality of life (average change in KCCQ summary score = -7.1 points; p < 0.001). Depressive symptoms were the strongest predictor of decline in health status in the multivariable, models. CONCLUSIONS Depressive symptoms are a strong predictor of short-term worsening of HF-specific health status. The recognition and treatment of depression may be an important component of HF care. (C) 2003 by the American College of Cardiology Foundation. C1 Denver VA Med Ctr, Denver, CO 80220 USA. Denver Hlth Med Ctr, Denver, CO USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ Missouri, Mid Amer Heart Inst, Columbia, MO 65211 USA. Pharmacia Corp, Skokie, IL USA. Yale Univ, Med Ctr, New Haven, CT 06520 USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, Cardiol 111B,1055 Clermont St, Denver, CO 80220 USA. FU NIA NIH HHS [KO8-AG01011] NR 36 TC 192 Z9 197 U1 2 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 NOV 19 PY 2003 VL 42 IS 10 BP 1811 EP 1817 DI 10.1016/j.jacc.2003.07.013 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 743NW UT WOS:000186580700018 PM 14642693 ER PT J AU Ackermann, RT Carroll, AE AF Ackermann, RT Carroll, AE TI Support for national health insurance among US physicians: A national survey SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CARE REFORM; ATTITUDES; VIEWS AB Background: Nearly 40 million persons in the United States were without health insurance for all of 2000. National health insurance would remedy this situation, and many believe the success of reform efforts in this direction may depend on physician support. Objective: To determine the general attitudes of U.S. physicians toward the financing of national health care. Design: Cross-sectional study. Setting: National mailed survey. Participants: 3188 randomly sampled physicians from the American Medical Association Physician Masterfile. Measurements: Physicians were asked whether they support or oppose 1) governmental legislation to establish national health insurance and 2) a national health insurance plan in which all health care is paid for by the federal government. Weighted multivariate logistic regression analyses were performed to identify factors that independently predicted support for each of these strategies. Results: Sixty percent of eligible participants returned a survey. Forty-nine percent of physicians supported governmental legislation to establish national health insurance, and 40% opposed it. Only 26% of all physicians supported a national health insurance plan in which all health care is paid for by the federal government. In analyses adjusting for differences in personal and practice characteristics, physicians in a primary care specialty, physicians reporting that at least 20% of their patients had Medicaid, and physicians practicing in a nonprivate setting or in an inner-city location were statistically significantly more likely to support governmental legislation to establish national health insurance. Conclusions: A plurality of U.S. physicians supports governmental legislation to establish national health insurance. This support may be relevant to the success of future efforts to reform national health care. C1 Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Carroll, AE (reprint author), Indiana Univ, Sch Med, 699 W Dr,Riley Res,Room 330, Indianapolis, IN 46202 USA. NR 15 TC 8 Z9 8 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 NOV 18 PY 2003 VL 139 IS 10 BP 795 EP 801 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 744ZV UT WOS:000186663500001 PM 14623616 ER PT J AU El-Serag, H Davila, JA Petersen, NJ McGlynn, KA AF El-Serag, H Davila, JA Petersen, NJ McGlynn, KA TI The continuing increase in the incidence of hepatocellular carcinoma in the United States: An update SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HEPATITIS-C-VIRUS; PRIMARY LIVER-CANCER; DIABETES-MELLITUS; RISING INCIDENCE; RISK-FACTORS; PREVALENCE; INFECTION; JAPAN AB Background: The incidence of hepatocellular carcinoma was reported to be increasing in the United States. However, alternate explanations were diagnostic or reclassification bias and changes in the demographic features of the general population. Objective: To examine the temporal trends in the incidence of hepatocellular carcinoma. Design: Retrospective cohort study. Setting: Information collected by population-based registries of the Surveillance, Epidemiology, and End Results (SEER) program. Patients: Persons given a diagnosis of hepatocellular carcinoma between 1975 and 1998. Measurements: Linear Poisson multivariate regression model, controlling for differences in age, sex, race or ethnicity, and geographic region among patients with hepatocellular carcinoma and in the underlying population. Results: The overall age-adjusted incidence rates of hepatocellular carcinoma increased from 1.4 per 100 000 in 1975 to 1977 to 3.0 per 100 000 in 1996 to 1998. There was a 25% increase during the last 3 years of the study compared with the preceding 3 years (1993 to 1995). The increase affected most age groups above 40 years, with the greatest increase in the 45- to 49-year-old age group. White men had the greatest increase (31%) in the last time period (1996 to 1998) compared with 1993 to 1995. The Poisson regression model confirmed an almost 2-fold increase in the incidence rate ratio for hepatocellular carcinoma between 1975 to 1978 and 1996 to 1998. Conclusions: The incidence of hepatocellular carcinoma continues to increase rapidly in the United States, with rates increasing the fastest in white men 45 to 54 years of age. These findings are consistent with a true increase and could be explained by consequences of hepatitis C virus acquired during the 1960s and 1970s. C1 Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP El-Serag, H (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 19 TC 612 Z9 633 U1 2 U2 19 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 NOV 18 PY 2003 VL 139 IS 10 BP 817 EP 823 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 744ZV UT WOS:000186663500005 PM 14623619 ER PT J AU Mandelblatt, J Saha, S Teutsch, S Hoerger, T Siu, AL Atkins, D Klein, J Helfand, M AF Mandelblatt, J Saha, S Teutsch, S Hoerger, T Siu, AL Atkins, D Klein, J Helfand, M CA Cost Work Grp US Preventive Serv TI The cost-effectiveness of screening mammography beyond age 65 years: A systematic review for the US Preventive Services Task Force SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BREAST-CANCER PATIENTS; OLDER WOMEN; LIFE-EXPECTANCY; ELDERLY-WOMEN; PATTERNS; SURVIVAL; MODEL; INTERVENTIONS; COMORBIDITY; DIAGNOSIS AB Purpose: There are few data on the effects of disease biology and competing mortality on the effectiveness of screening women for breast cancer after age 65 years. The authors performed a review to determine the costs and benefits of mammography screening after age 65 years. Data Sources: Cost-effectiveness articles published between January 1989 and March 2002. Study Selection: Studies were identified by using MEDLINE and the National Health Service Economic Evaluation Database. The authors included research on screening after age 65 years conducted from a societal or government perspective; reviews and analyses of other technologies were excluded. Data Synthesis: 115 studies were identified and 10 met inclusion criteria. One study modeled age-dependent assumptions of disease biology. No study fully captured the potential harms of screening, including anxiety associated with false-positive results, overdiagnosis, and previous knowledge of cancer or living longer with the consequences of treatment. Studies differed in the specific strategies compared and in analytic approaches. On average, extending biennial screening to age 75 or 80 years was estimated to cost $34 000 to $88 000 (2002 U.S. dollars) per life-year gained, compared with stopping screening at age 65 years. Two studies suggested that it was more cost-effective to target healthy women than those with several competing risks for death. Conclusions: Current estimates suggest that biennial breast cancer screening after age 65 years reduces mortality at reasonable costs for women without clinically significant comorbid conditions. More data are needed on disease biology and preferences for benefits and harms in older women. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Merck & Co Inc, W Point, PA USA. Univ N Carolina, Res Triangle Inst, Res Triangle Pk, NC USA. Mt Sinai Sch Med, New York, NY USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Univ Rochester, Rochester, NY USA. RP Mandelblatt, J (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, 2233 Wisconsin Ave,Suite 317, Washington, DC 20007 USA. FU NCI NIH HHS [KO5 CA96940, U01CA88283]; PHS HHS [290-97-0011, 290-97-0018] NR 44 TC 76 Z9 76 U1 2 U2 5 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 NOV 18 PY 2003 VL 139 IS 10 BP 835 EP 842 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 744ZV UT WOS:000186663500007 PM 14623621 ER PT J AU Mims, MP Maran, J Leal, SM Hayes, TG Ittmann, M Wheeler, T Guan, YL Prchal, JT AF Mims, MP Maran, J Leal, SM Hayes, TG Ittmann, M Wheeler, T Guan, YL Prchal, JT TI African American erythrocyte genetic polymorphisms in prostate cancer. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. Methodist Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3740 BP 10B EP 10B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100031 ER PT J AU Wang, H Tan, HM Jiang, XH Pastore, Y Yang, F Schafer, AI Prchal, JT AF Wang, H Tan, HM Jiang, XH Pastore, Y Yang, F Schafer, AI Prchal, JT TI Gain-of function mutation of human EPOR accelerates re-endothelialization and inhibits neointimal formation following carotid injury. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Texas Childrens Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 26 BP 11A EP 11A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700027 ER PT J AU Means, RT Fleury, TW Dallalio, GA Brunson, C AF Means, RT Fleury, TW Dallalio, GA Brunson, C TI Erythroid colony formation in sickle cell anemia patients is resistant to suppression by gamma interferon: Potential role of CD36. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3787 BP 21B EP 22B PN 2 PG 2 WC Hematology SC Hematology GA 742UU UT WOS:000186537100078 ER PT J AU Sun, L Feng, SJ Durante, W Kroll, MH AF Sun, L Feng, SJ Durante, W Kroll, MH TI Role of the Pyk2-MAP kinase-cPLA(2) signaling pathway in shear-dependent platelet aggregation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3959 BP 64B EP 64B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100250 ER PT J AU Heinrich, MC Yee, KWH Giese, NA Schittenhelm, M AF Heinrich, MC Yee, KWH Giese, NA Schittenhelm, M TI MLN518, a potent FLT3 inhibitor, displays synergistic effects with cytarabine and daunorubicin on FLT3 ITD leukemia cell lines. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 OHSU, Inst Canc, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Millennium Pharmaceut, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 330 BP 97A EP 97A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700330 ER PT J AU Alcantara, O Guo, Y Boldt, DH AF Alcantara, O Guo, Y Boldt, DH TI Iron availability influences binding of multiple transcription factors to the p21(WAF1/CIP1) gene promoter during myelopoiesis. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4345 BP 159B EP 159B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100636 ER PT J AU Maran, J Jedlickova, K Stockton, D Prchal, JT AF Maran, J Jedlickova, K Stockton, D Prchal, JT TI Finding the novel molecular defect in a family with high erythropoietin autosomal dominant polycythemia. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4359 BP 162B EP 162B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100650 ER PT J AU Means, RT Fleury, T Dallalio, G Bielawski, J AF Means, RT Fleury, T Dallalio, G Bielawski, J TI Role of sphingosine in cell death induced by erythropoietin withdrawal. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4398 BP 172B EP 172B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100689 ER PT J AU Schittenhelm, M Yee, KWH Braziel, R Bainbridge, T O'Farrell, AM Cherrington, J Schroeder, A Town, A McGreevey, L Heinrich, MC AF Schittenhelm, M Yee, KWH Braziel, R Bainbridge, T O'Farrell, AM Cherrington, J Schroeder, A Town, A McGreevey, L Heinrich, MC TI Mutation of the FLT3 TK1 domain: A new class of activating FLT3 mutations associated with AML. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. SUGEN Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 4535 BP 204B EP 204B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537100826 ER PT J AU Mielcarek, M Gooley, T Martin, PJ Chauncey, TR Young, BA Storb, R Torok-Storb, B AF Mielcarek, M Gooley, T Martin, PJ Chauncey, TR Young, BA Storb, R Torok-Storb, B TI Survival after hematopoietic cell transplantation according to ethnic background. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 841 BP 239A EP 240A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536700841 ER PT J AU Panse, JP Heimfeld, S Guthrie, KA Maris, M Maloney, DG Baril, B Little, MT Chauncey, T Storb, R Sandmaier, BM AF Panse, JP Heimfeld, S Guthrie, KA Maris, M Maloney, DG Baril, B Little, MT Chauncey, T Storb, R Sandmaier, BM TI Allogeneic peripheral blood graft composition affects early T-cell chimerism and later clinical outcomes after nonmyeloablative conditioning. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 843 BP 240A EP 240A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536700843 ER PT J AU Gokmen, E Callander, N Ehsan, A Dostalova, Z Ochoa, L Devore, P Freytes, C AF Gokmen, E Callander, N Ehsan, A Dostalova, Z Ochoa, L Devore, P Freytes, C TI A prospective analysis of B-cell reconstitution after autologous peripheral blood stem cell transplantation using grafts purged in vivo with rituximab in patients with non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ege Univ, Sch Med, Izmir, Turkey. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 4927 BP 301B EP 301B PN 2 PG 1 WC Hematology SC Hematology GA 742UU UT WOS:000186537101218 ER PT J AU Cavusoglu, E El Rouby, S Kunammeni, PB Lau, A Lee, T Hoppensteadt, D Colella, G Zucker, ML LaDuca, FM Fareed, J Marmur, JD AF Cavusoglu, E El Rouby, S Kunammeni, PB Lau, A Lee, T Hoppensteadt, D Colella, G Zucker, ML LaDuca, FM Fareed, J Marmur, JD TI Monitoring low molecular weight heparin (LMWH) during interventional coronary procedures using a sensitive point-of-care assay. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. ITC, Clin Affairs, Edison, NJ USA. ITC, R&D, Edison, NJ USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 1171 BP 326A EP 327A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701171 ER PT J AU Wang, H Jiang, XH Schildmeyer, L Liao, D Yang, F Yang, XF Durante, W Rumbaut, RE Bryan, RM Schafer, AI AF Wang, H Jiang, XH Schildmeyer, L Liao, D Yang, F Yang, XF Durante, W Rumbaut, RE Bryan, RM Schafer, AI TI Hyperhomocysteinemia impairs endothelial function by nitric oxide inhibition in cystathionine beta-synthase knockout mice and in aortic endothelial cells. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 1947 BP 531A EP 531A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701946 ER PT J AU Wang, H Tan, HW Yang, F Liao, D Shi, CV Yang, XF Durante, W Schafer, AI AF Wang, H Tan, HW Yang, F Liao, D Shi, CV Yang, XF Durante, W Schafer, AI TI Hyperhomocysteinemia promotes vascular fibrosis following vascular injury in cystathionine B-synthase knockout mice. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Nova Pharmaceut Corp, Summit, NJ USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 1952 BP 532A EP 533A PN 1 PG 2 WC Hematology SC Hematology GA 742UP UT WOS:000186536701951 ER PT J AU Patel, KV Wijelath, ES Patel, YM Sumathipala, R Sobel, MS Murray, J Seago, J Savidge, GF Rahman, S AF Patel, KV Wijelath, ES Patel, YM Sumathipala, R Sobel, MS Murray, J Seago, J Savidge, GF Rahman, S TI Hepatocyte growth factor (HGF) binding domains on fibronectin and vitronectin promote enhanced endothelial cell migration via a specific ras and PI3-kinase dependent pathway. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 St Thomas Hosp, GKT Sch Med, Div Med, Coagulat Res Lab, London, England. Univ Washington, Div Vasc Surg, Sch Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2003 VL 102 IS 11 MA 1955 BP 533A EP 533A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536701954 ER PT J AU Prchal, JT Pospisilova, D Mims, MP Priwitzerova, M Indrak, K Ponka, P Guan, YL Divoky, V AF Prchal, JT Pospisilova, D Mims, MP Priwitzerova, M Indrak, K Ponka, P Guan, YL Divoky, V TI Identification of the first human mutation of DMT1 (Nramp2) in a patient with microcytic anemia and iron overload. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. McGill Univ, Montreal, PQ, Canada. Houston VA Med Ctr, Houston, TX USA. RI Ponka, Prem/A-4123-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2781 BP 754A EP 754A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702781 ER PT J AU Means, RT Dallalio, G Fleury, T AF Means, RT Dallalio, G Fleury, T TI Serum hepcidin and cytokines in anemic patients. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. Med Univ S Carolina, Div Hematol Oncol, Charleston, SC USA. RI Means, Robert/A-4454-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2792 BP 757A EP 757A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702792 ER PT J AU Resendiz, JC Lassila, R Kroll, MH AF Resendiz, JC Lassila, R Kroll, MH TI Distinct mechanisms of protease-activated receptor (PAR) 1 - and PAR 4-induced phosphatidylinositol 3-kinase activation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Wihuri Res Inst, SF-00140 Helsinki, Finland. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2870 BP 777A EP 777A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702870 ER PT J AU Feng, SJ Lu, X Kroll, MH AF Feng, SJ Lu, X Kroll, MH TI The cytoplasmic domain of glycoprotein (Gp) Ib alpha couples von Willebrand factor (VWF) - Dependent cell contact with rolling and stable adhesion. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 2886 BP 781A EP 781A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536702886 ER PT J AU Gotlib, J Berube, C Ruan, J Growney, J Dugan, K Falkow, R Rosamilia, M Resta, D Cohen, P Fabbro, D Heinrich, M Gilliland, DG Coutre, S AF Gotlib, J Berube, C Ruan, J Growney, J Dugan, K Falkow, R Rosamilia, M Resta, D Cohen, P Fabbro, D Heinrich, M Gilliland, DG Coutre, S TI PKC412, inhibitor of the KIT tyrosine kinase, demonstrates efficacy in mast cell leukemia with the D816V KIT mutation. SO BLOOD LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Novartis Pharm Inc, E Hanover, NJ USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Harvard Univ, Sch Med, Boston, MA USA. Portland VA Med Ctr, Portland, OR USA. RI Heinrich, Michael/C-3727-2013 OI Heinrich, Michael/0000-0003-2611-6303 NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2003 VL 102 IS 11 MA 3420 BP 919A EP 919A PN 1 PG 1 WC Hematology SC Hematology GA 742UP UT WOS:000186536703420 ER PT J AU Gault, J Hopkins, J Berger, R Drebing, C Logel, J Walton, C Short, M Vianzon, R Olincy, A Ross, RG Adler, LE Freedman, R Leonard, S AF Gault, J Hopkins, J Berger, R Drebing, C Logel, J Walton, C Short, M Vianzon, R Olincy, A Ross, RG Adler, LE Freedman, R Leonard, S TI Comparison of polymorphisms in the alpha 7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; mutation; promoter; nicotinic receptor; sensory processing; auditory gating ID ACETYLCHOLINE-RECEPTOR; LINKAGE DISEQUILIBRIUM; CHROMOSOME-15 LOCUS; MENTAL-ILLNESS; SUBUNIT GENE; CHRNA7; EXPRESSION; SUSCEPTIBILITY; BUNGAROTOXIN; SMOKING AB The hypothesis that the 15q13-15 region of chromosome 15 contains a gene that contributes to the etiology of schizophrenia is supported by multiple genetic linkage studies. The alpha7 neuronal nicotinic acetylcholine receptor (CHRNA7) gene was selected as the best candidate gene in this region for molecular investigation, based on these linkage findings and biological evidence in both human and rodent models. CHRNA7 receptors are decreased in expression in postmortem brain of schizophrenic subjects. A dinucleotide marker, D15S1360, in intron two of the CHRNA7 gene is genetically linked to an auditory gating deficit found in schizophrenics and half of the first-degree relatives of patients. Single strand conformation polymorphism (SSCP) and sequence analyses of DNA from schizophrenic and control individuals identified 33 variants in the coding region and intron/exon borders of the CHRNA7 gene and its partial duplication, dupCHRNA7, common polymorphisms were mapped. Twenty-one variants were found in the exons, but non-synonymous changes were rare. Although the expression of CHRNA7 is decreased in schizophrenia, the general structure of the remaining receptors is likely to be normal. (C) 2003 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. RP Leonard, S (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Box C-268-71,4200 E 9th Ave, Denver, CO 80262 USA. FU NIDA NIH HHS [DA09457, DA12281]; NIMH NIH HHS [MH38321, MH42212] NR 45 TC 62 Z9 67 U1 2 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 15 PY 2003 VL 123B IS 1 BP 39 EP 49 DI 10.1002/ajmg.b.20061 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 735ZU UT WOS:000186145800006 PM 14582144 ER PT J AU Kraveka, JM Li, L Bielawski, J Obeid, LM Ogretmen, B AF Kraveka, JM Li, L Bielawski, J Obeid, LM Ogretmen, B TI Involvement of endogenous ceramide in the inhibition of telomerase activity and induction of morphologic differentiation in response to all-trans-retinoic acid in human neuroblastoma cells SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID EUKARYOTIC STRESS-RESPONSE; HUMAN NEURO-BLASTOMA; CATALYTIC SUBUNIT; N-MYC; REVERSE-TRANSCRIPTASE; SPHINGOLIPID METABOLISM; CRITICAL DETERMINANT; PROTEIN PHOSPHATASE; RNA COMPONENT; EXPRESSION AB In this study, we examined the role of endogenous ceramide in the inhibition of telomerase and induction of morphologic differentiation in response to all-trans-retinoic acid (ATRA) in the SK-N-SH and SK-N-AS human neuroblastoma cell lines. The results showed that ATRA inhibited the activity of telomerase significantly in a time- and dose-dependent manner, as determined by telomere repeat amplification protocol (TRAP). The inhibition of telomerase by ATRA was maximum (about 50-80% of untreated controls) at 5-10 muM for 4-8 days. Treatment of cells with ATRA (5 muM) also resulted in the inhibition of growth by about 30-70% after 4 and 8 days of treatment, respectively, which was measured by trypan blue exclusion method. Measurement of accumulation of endogenous ceramide by high pressure liquid chromatography coupled with mass spectroscopy (LC/MS) showed that treatment of cells with ATRA resulted in increased levels of mainly C24:0 and C24:1 ceramides at days 2, 4, and 8, respectively. Also, treatment of cells with ATRA in the presence of myriocin blocked the accumulation of ceramide significantly, and more importantly, presence of myriocin partially prevented the inhibition of telomerase. Mechanistically, inhibition of telomerase by endogenous ceramide in response to ATRA treatment involves, at least in part, down-regulation of the expression of telomerase reverse transcriptase (hTERT) mRNA, as determined by semi-quantitative RT-PCR, in these cells. In addition, the modulation of telomerase activity by ATRA correlated with the induction of morphologic differentiation, which was also blocked by myriocin, as determined by extension of neurites using phase-contrast microscopy. These results, therefore, reveal an important effect of ATRA on telomerase inhibition and induction of morphologic differentiation in human neuroblastoma cells. These data also demonstrate that endogenous ceramide is one of the upstream regulators of telomerase activity in human neuroblastoma cells in response to ATRA. (C) 2003 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Div Hematol & Oncol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Ogretmen, B (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA 88932]; NCRR NIH HHS [RR 17677-01]; NIA NIH HHS [AG 16583] NR 77 TC 31 Z9 35 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 2003 VL 419 IS 2 BP 110 EP 119 DI 10.1016/j.abb.2003.08.034 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 744CL UT WOS:000186610300003 PM 14592454 ER PT J AU Choy, HA Wang, XP Schotz, MC AF Choy, HA Wang, XP Schotz, MC TI Reduced atherosclerosis in hormone-sensitive lipase transgenic mice overexpressing cholesterol acceptors SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE hormone-sensitive lipase; atherosclerosis; efflux; cholesterol acceptor; macrophage ID LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN A-IV; MACROPHAGE FOAM CELLS; E-DEFICIENT MICE; MOUSE PERITONEAL-MACROPHAGES; ESTER HYDROLYSIS; MESSENGER-RNA; J774 MACROPHAGES; PROTEIN-KINASE; GENE-TRANSFER AB Macrophage-specific overexpression of cholesteryl ester hydrolysis in hormone-sensitive lipase transgenic (HSL Tg) female mice paradoxically increases cholesterol esterification and cholesteryl ester accumulation in macrophages, and thus susceptibility to diet-induced atherosclerosis compared to nontransgenic C57BL/6 mice. The current studies suggest that whereas increased cholesterol uptake could contribute to transgenic foam cell formation, there are no differences in cholesterol synthesis and the expression of cholesterol efflux mediators (ABCA1, ABCG1, apoE, PPARgamma, and LXRalpha) compared to wild-type macrophages. HSL Tg macrophages exhibit twofold greater efflux of cholesterol to apoA-I in vitro, suggesting the potential rate-limiting role of cholesteryl ester hydrolysis in efflux. However, macrophage cholesteryl ester levels appear to depend on the relative efficacy of alternate pathways for free cholesterol in either efflux or re-esterification. Thus, increased atherosclerosis in HSL Tg mice appears to be due to the coupling of the efficient re-esterification of excess free cholesterol to its limited removal mediated by the cholesterol acceptors in these mice. The overexpression of cholesterol acceptors in HSL-apoA-IV double-transgenic mice increases plasma HDL levels and decreases diet-induced atherosclerosis compared to HSL Tg mice, with aortic lesions reduced to sizes in nontransgenic littermates. The results in vivo are consistent with the effective efflux from HSL Tg macrophages supplemented with HDL and apoA-I in vitro, and highlight the importance of cholesterol acceptors in inhibiting atherosclerosis caused by imbalances in the cholesteryl ester cycle. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Schotz, MC (reprint author), Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Lipid Res Lab, Room 312,Bldg 113,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 76 TC 13 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD NOV 15 PY 2003 VL 1634 IS 3 BP 76 EP 85 DI 10.1016/j.bbalip.2003.09.001 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 750JL UT WOS:000186987500003 PM 14643795 ER PT J AU Prchal, JF Prchal, JT AF Prchal, JF Prchal, JT TI A specific test for polycythemia vera? SO BLOOD LA English DT Editorial Material C1 McGill Univ, Montreal, PQ H3A 2T5, Canada. Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. RP Prchal, JF (reprint author), McGill Univ, Montreal, PQ H3A 2T5, Canada. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2003 VL 102 IS 10 BP 3464 EP 3464 DI 10.1182/blood-2003-09-3089 PG 1 WC Hematology SC Hematology GA 741XT UT WOS:000186486200005 ER PT J AU O'Farrell, AM Foran, JM Fiedler, W Serve, H Paquette, RL Cooper, MA Yuen, HA Louie, SG Kim, H Nicholas, S Heinrich, MC Berdel, WE Bello, C Jacobs, M Scigalla, P Manning, WC Kelsey, S Cherrington, JM AF O'Farrell, AM Foran, JM Fiedler, W Serve, H Paquette, RL Cooper, MA Yuen, HA Louie, SG Kim, H Nicholas, S Heinrich, MC Berdel, WE Bello, C Jacobs, M Scigalla, P Manning, WC Kelsey, S Cherrington, JM TI An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; INTERNAL TANDEM DUPLICATION; GROWTH-FACTOR; CONSTITUTIVE ACTIVATION; CELL-GROWTH; MAP KINASE; RISK GROUP; C-KIT; MUTATIONS; DISEASE AB Purpose: Obtaining direct and rapid proof of molecular activity in early clinical trials is critical for optimal clinical development of novel targeted therapies. SU11248 is an oral multitargeted kinase inhibitor with selectivity for fms-related tyrosine kinase 3/Flk2 (FLT3), platelet-derived growth factor receptor alpha/beta, vascular endothelial growth factor receptor 1/2, and KIT receptor tyrosine kinases. FLT3 is a promising candidate for targeted therapy in acute myeloid leukemia (AML), because activating mutations occur in up to 30% of patients. We conducted an innovative single-dose clinical study with a primary objective to demonstrate inhibition of FLT3 phosphorylation by SU11248 in AML. Experimental Design: Twenty-nine AML patients each received a single dose of SU11248, escalated from 50 to 350 mg, in increments of 50 mg and cohorts of three to six patients. FLT3 phosphorylation and plasma pharmacokinetics were evaluated at seven time points over 48 h after SU11248 administration, and FLT3 genotype was deter-mined. Study drug-related adverse events occurred in 31% of patients, mainly grade 1 or 2 diarrhea and nausea, at higher dose levels. Results: Inhibition of FLT3 phosphorylation was apparent in 50% of FLT3-wild-type (WT) patients and in 100% of FLT3-mutant patients. FLT3 internal tandem duplication (ITD) mutants showed increased sensitivity relative to FLT3-WT, consistent with preclinical predictions. The primary end point, strong inhibition of FLT3 phosphorylation in >50% patients, was reached in 200 mg and higher dose cohorts. Downstream signaling pathways were also inhibited; signal transducer and activator of transcription 5 (STAT5) was reduced primarily in internal tandem duplication patients and at late time points in FLT3-WT patients, whereas extracellular signal-regulated kinase (ERK) activity was reduced in the majority of patients, independent of FLT3 inhibition. Conclusions: This novel translational study bridges preclinical models to the patient setting and provides the first evidence of anti-FLT3 activity in patients. Proof of target inhibition accomplishes a crucial milestone in the development of novel oncology therapeutics. C1 SUGEN Inc, San Francisco, CA USA. Univ Alabama, Birmingham, AL USA. Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. Univ Klinikum Munster, Munster, Germany. Community Canc Care Inc, Indianapolis, IN USA. Univ Calif Los Angeles, Stem Cell Serv, Los Angeles, CA 90024 USA. Oregon Hlth & Sci Canc Inst, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Pharmacia Corp, Bedminster, NJ USA. RP O'Farrell, AM (reprint author), 844 Fremont St 4, Menlo Pk, CA 94025 USA. NR 34 TC 217 Z9 227 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2003 VL 9 IS 15 BP 5465 EP 5476 PG 12 WC Oncology SC Oncology GA 750TM UT WOS:000187014200006 PM 14654525 ER PT J AU Randall, TC Armstrong, K AF Randall, TC Armstrong, K TI Differences in treatment and outcome between African-American and white women with endometrial cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RACIAL-DIFFERENCES; CARDIOVASCULAR PROCEDURES; ROGERS,WILL PHENOMENON; HOSPITAL VOLUME; SURVIVAL; CARCINOMA; SURGERY; IMPACT; STAGE; RACE AB Purpose: To investigate disparities in treatment and outcomes between African-American and white women with endometrial cancer. Patients and Methods: We analyzed 1992 to 1998 Surveillance, Epidemiology, and End Results data for 21,561 women with epithelial cancers of the endometrium. Sequential Cox proportional hazard models were used to determine the association between tumor characteristics (stage, grade, and histologic type), sociodemographic characteristics (age and marital status), and treatment (surgery and radiation therapy) and the racial difference in mortality. Results: The unadjusted hazard ratio (HR) for death from endometrial cancer for African-American women compared with white women was 2.57. However, African-American women were significantly more likely to present with advanced-stage disease and have poorly differentiated tumors or tumors with an unfavorable histologic type and were significantly less likely to undergo definitive surgery at all stages of disease. Adjusting for tumor and sociodemographic characteristics lowered the HR for African-American women to 1.80. Further adjustment for the use of surgery reduced the HR to 1.51. The association between surgery and survival was stronger among white women (HR, 0.26) than among African-American women (HR, 0.44). Conclusion: African-American women with endometrial cancer are significantly less likely to undergo primary surgery and have significantly shorter survival than white women with endometrial cancer. Racial differences in treatment are associated with racial differences in survival. The association between use of surgery and survival is weaker among African-American than white women, raising questions about potential racial differences in the effectiveness of surgery. (C) 2003 by American Society of Clinical Oncology. C1 Univ Penn, Sch Med, Dept Obstet & Gynecol, 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 Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1204 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 31 TC 60 Z9 60 U1 3 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 15 PY 2003 VL 21 IS 22 BP 4200 EP 4206 DI 10.1200/JCO.2003.01.218 PG 7 WC Oncology SC Oncology GA 745BW UT WOS:000186669300021 PM 14615448 ER PT J AU Brau, N AF Brau, N TI Update on chronic hepatitis C in HIV/HCV-coinfected patients: viral interactions and therapy SO AIDS LA English DT Review DE HIV; hepatitis C virus; coinfection; HAART; ribavirin; interferon; combination therapy; liver disease ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; ACTIVE ANTIRETROVIRAL THERAPY; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; SUSTAINED VIROLOGICAL RESPONSE; HEPATOCELLULAR-CARCINOMA; COMBINATION THERAPY; DRUG-USERS; INITIAL TREATMENT; RANDOMIZED-TRIAL AB With highly active antiretroviral therapy (HAART), HIV-infected patients can now live longer and healthier lives, and other comorbid diseases, such as chronic hepatitis C, have emerged as a significant health concern. Coinfection with the hepatitis C virus (HCV) may limit life expectancy because it can lead to serious liver disease including decompensated liver cirrhosis and hepatocellular carcinoma. HCV-induced fibrosis progresses faster in HIV/HCV-coinfected persons, although HAART may be able to decrease this disease acceleration. Combination therapy for HCV with interferon and ribavirin can achieve a sustained viral response, although at a lower rate than in HCV-monoinfected patients. Combination treatment with pegylated interferon and ribavirin will probably emerge as the next HCV therapy of choice for HIV/HCV-coinfected patients. HCV combination therapy is generally safe, but serious adverse reactions, like lactic acidosis, may occur. Cytopenia may present a problem leading to dose reductions, but the role of growth factors is under study. All HIV/HCV-coinfected patients should be evaluated for therapy against the hepatitis C virus. A sustained viral load will probably lead to regression of liver disease, and even interferon-based treatment without viral clearance may slow down progression of liver disease. HIV/HCV-coinfected patients who have progressed to end-stage liver disease have few therapeutic options other than palliative care, since liver transplants are generally unavailable. The mortality post-transplant may be higher than in HCV-monoinfected patients. We are entering an era where safe and effective HCV therapy is being defined for HIV/HCV-coinfected patients, and all eligible patients should be offered treatment. C1 Bronx Vet Affairs Med Ctr, Infect Dis Sect 111F, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY USA. RP Brau, N (reprint author), Bronx Vet Affairs Med Ctr, Infect Dis Sect 111F, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 101 TC 35 Z9 40 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 7 PY 2003 VL 17 IS 16 BP 2279 EP 2290 DI 10.1097/01.aids.0000088176.01779.19 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 809YO UT WOS:000220672200002 PM 14571179 ER PT J AU McGlynn, EA Asch, SM Kerr, EA AF McGlynn, EA Asch, SM Kerr, EA TI Quality of health care delivered to adults in the United States - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 RAND Hlth, Santa Monica, CA 90407 USA. Vet Affairs Greater Los Angeles Hlth Syst, Los Angeles, CA 90073 USA. Vet Affairs Ctr Practice Management & Outcomes Re, Ann Arbor, MI 48105 USA. RP McGlynn, EA (reprint author), RAND Hlth, Santa Monica, CA 90407 USA. NR 3 TC 4 Z9 4 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 NOV 6 PY 2003 VL 349 IS 19 BP 1867 EP 1868 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 739NR UT WOS:000186353800019 ER PT J AU Wenger, NS Solomon, DH Roth, CP MacLean, CH Saliba, D Kamberg, CJ Rubenstein, LZ Young, RT Sloss, EM Louie, R Adams, J Chang, JT Venus, PJ Schnelle, JF Shekelle, PG AF Wenger, NS Solomon, DH Roth, CP MacLean, CH Saliba, D Kamberg, CJ Rubenstein, LZ Young, RT Sloss, EM Louie, R Adams, J Chang, JT Venus, PJ Schnelle, JF Shekelle, PG TI The quality of medical care provided to vulnerable community-dwelling older patients SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; OF-CARE; PROJECT; ELDERS; BENEFICIARIES; IMPROVEMENT; OUTCOMES AB Background: Many people 65 years of age and older are at risk for functional decline and death. However, the resource-intensive medical care provided to this group has received little evaluation. Previous studies have focused on general medical conditions aimed at prolonging life, not on geriatric issues important for quality of life. Objective: To measure the quality of medical care provided to vulnerable elders by evaluating the process of care using Assessing Care of Vulnerable Elders quality indicators (Qls). Design: Observational cohort study. Setting: Managed care organizations in the northeastern and southwestern United States. Patients: Vulnerable older patients identified by a brief interview from a random sample of community-dwelling adults 65 years of age or older who were enrolled in 2 managed care organizations and received care between July 1998 and July 1999. Measurements: Percentage of 207 Qls passed, overall and for 22 target conditions; by domain of care (prevention, diagnosis, treatment, and follow-up); and by general medical condition (for example, diabetes and heart failure) or geriatric condition (for example, falls and incontinence). Results: Patients were eligible for 10 711 Qls, of which 55% were passed. There was no overall difference between managed care organizations. Wide variation in adherence was found among conditions, ranging from 9% for end-of-life care to 82% for stroke care. More treatment Qls were completed (81%) compared with other domains (follow-up, 63%; diagnosis, 46%; and prevention, 43%). Adherence to Qls was lower for geriatric conditions than for general medical conditions (31% vs. 52%; P < 0.001). Conclusions: Care for vulnerable elders falls short of acceptable levels for a wide variety of conditions. Care for geriatric conditions is much less optimal than care for general medical conditions. C1 RAND Corp, Hlth, Santa Monica, CA 90407 USA. RAND Corp, Hlth, Washington, DC USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Los Angeles Jewish Home Aging, Los Angeles, CA USA. Borun Ctr Gerontol Res, Los Angeles, CA USA. United Healthcare Corp, Ctr Hlth Care Policy & Evaluat, Minnetonka, MN USA. RP Wenger, NS (reprint author), RAND Corp, Hlth, 1700 Main St,M-26, Santa Monica, CA 90407 USA. NR 26 TC 236 Z9 237 U1 3 U2 10 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 NOV 4 PY 2003 VL 139 IS 9 BP 740 EP 747 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 738XJ UT WOS:000186312900004 PM 14597458 ER PT J AU Tamayo-Sarver, JH Dawson, NV Hinze, SW Cydulka, RK Wigton, RS Albert, JM Ibrahim, SA Baker, DW AF Tamayo-Sarver, JH Dawson, NV Hinze, SW Cydulka, RK Wigton, RS Albert, JM Ibrahim, SA Baker, DW TI The effect of race/ethnicity and desirable social characteristics on physicians' decisions to prescribe opioid analgesics SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE emergency department; analgesia prescription; race/ethnicity; usual source of care; communication; access ID IMPLICIT ASSOCIATION TEST; RHEUMATOID-ARTHRITIS; RACIAL-DIFFERENCES; AFRICAN-AMERICAN; PATIENT RACE; MANAGED-CARE; CANCER; PAIN; ETHNICITY; HEALTH AB Objective: Racial/ethnic disparities in physician treatment have been documented in multiple areas, including emergency department (ED) analgesia. The purpose of this study was to determine if physicians were predisposed to different treatment decisions based on patient race/ethnicity and if physicians' treatment predispositions changed when socially desirable information about the patient (occupation, socioeconomic status, and relationship with a primary care physician) was made explicit. Methods: The authors developed three clinical vignettes designed to engage physicians' decision-making processes. The patient's race/ethnicity was included. Each vignette randomly included or omitted explicit socially desirable information. The authors mailed 5,750 practicing emergency physicians three clinical vignettes and a one-page questionnaire about demographic and practice characteristics. Chi-square tests of significance for bivariate analyses and multiple logistic regression were used for multivariate analyses. Results: A total of 2,872 (53%) of the 5,398 potential physician subjects participated. Patient race/ethnicity had no effect on physician prescription of opioids at discharge for African Americans, Hispanics, and whites: absolute differences in rates of prescribing opioids at discharge were less than 2% for all three conditions presented. Making socially desirable information explicit increased the prescribing rates by 4% (95% CI = 0.1%, to 8%) for the migraine vignette and 6% (95% CI = 3% to 8%) for the back pain vignette. Conclusions: Patient race/ethnicity did not influence physicians' predispositions to treatment plans in clinical vignettes. Even knowing that the patient had a high-prestige occupation and a primary care provider only minimally increased prescribing of opioid analgesics for conditions with few objective findings. C1 Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Ctr Hlth Care Res & Policy, Metrohlth Med Ctr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Sociol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH 44106 USA. Univ Nebraska, Med Ctr, Coll Med, Dept Internal Med,Div Gen Internal Med, Omaha, NE 68182 USA. Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Div Gen Internal Med, Chicago, IL 60611 USA. RP Tamayo-Sarver, JH (reprint author), 4009 Cullen Dr, Cleveland, OH 44105 USA. NR 58 TC 65 Z9 66 U1 2 U2 6 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2003 VL 10 IS 11 BP 1239 EP 1248 DI 10.1197/S1069-6563903)00494-9 PG 10 WC Emergency Medicine SC Emergency Medicine GA 740WY UT WOS:000186426300014 PM 14597500 ER PT J AU Kampov-Polevoy, AB Garbutt, JC Khalitov, E AF Kampov-Polevoy, AB Garbutt, JC Khalitov, E TI Family history of alcoholism and response to sweets SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE sweet taste; alcoholism; genetic marker ID PITUITARY BETA-ENDORPHIN; SACCHARIN INTAKE; ETHANOL-CONSUMPTION; TASTE PREFERENCES; NUCLEUS-ACCUMBENS; HEDONIC RESPONSE; WISTAR RATS; BODY-WEIGHT; DRINKING; SUCROSE AB Background: The relationship between a hedonic response to sweet tastes and a propensity to excessive alcohol drinking is supported by both animal and human studies. This study was designed to test the hypothesis that the genetic risk for alcoholism as measured by a paternal history of alcoholism in young social drinkers is associated with sweet-liking, defined as rating the strongest offered sucrose solution (i.e., 0.83 M) as the most palatable during the standard sweet test. Methods: Participants were 163 subjects (39% male) without a lifetime history of alcohol or drug abuse or dependence. Eighty-one subjects had a paternal history of alcoholism (FH+), and 82 did not (FH-). Each subject rated a series of sucrose solutions for intensity of sweetness and palatability. Subjects were categorized as sweet-likers if they rated the highest sucrose concentration as the most pleasurable. Results: The estimated odds of being a sweet-liker were 2.5 times higher for FH+ than for FH- subjects. FH+ subjects disliked the tastes of the two weakest offered sucrose concentrations (0.05 and 0.10 M), whereas FH- subjects reported these tastes to be neutral. Conclusions: The results of this study support the hypothesis that sweet-liking is associated with a genetic vulnerability to alcoholism. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Univ N Carolina, Ctr Alcohol Studies, Chapel Hill, NC USA. Univ Minnesota, Sch Stat, Minneapolis, MN 55455 USA. RP Kampov-Polevoy, AB (reprint author), Bronx Vet Affairs Med Ctr, Dept Psychiat, 536 OOMH,130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 68 TC 52 Z9 53 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2003 VL 27 IS 11 BP 1743 EP 1749 DI 10.1097/01.ALC.0000093739.05809.DD PG 7 WC Substance Abuse SC Substance Abuse GA 747TF UT WOS:000186820400007 PM 14634489 ER PT J AU Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S AF Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S CA Veterans Affairs Cooperative Study TI I. Veterans affairs cooperative study of polyenylphosphatidylcholine in alcoholic liver disease: Effects on drinking behavior by nurse/physician teams SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE brief invention; control of drinking ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; BRIEF PHYSICIAN ADVICE; UNITED-STATES; FOLLOW-UP; CIRRHOSIS; DRINKERS; FIBROSIS; TRIAL AB Background: This multicenter prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the effectiveness of polyenylphosphatidylcholine against the progression of liver fibrosis toward cirrhosis in alcoholics. Seven hundred eighty-nine alcoholics with an average intake of 16 drinks per day were enrolled. To control excessive drinking, patients were referred to a standard 12-step-based alcoholism treatment program, but most patients refused to attend. Accordingly, study follow-up procedures incorporated the essential features of the brief-intervention approach. An overall substantial and sustained reduction in drinking was observed. Hepatic histological and other findings are described in a companion article. Methods: Patients were randomized to receive daily three tablets of either polyenylphosphatidylcholine or placebo. Monthly follow-up visits included an extensive session with a medical nurse along with brief visits with a study physician (hepatologist or gastroenterologist). A detailed physical examination occurred every 6 months. In addition, telephone consultations with the nurse were readily available. All patients had a liver biopsy before entry; a repeat biopsy was scheduled at 24 and, 48 months. Results: There was a striking decrease in average daily alcohol intake to approximately 2.5 drinks per day. This was sustained over the course of the trial, lasting from 2 to 6 years. The effect was similar both in early dropouts and long-term patients, i.e., those with a 24-month biopsy or beyond. Conclusions: In a treatment trial of alcoholic liver fibrosis, a striking reduction in alcohol consumption from 16 to 2.5 daily drinks was achieved with a brief-intervention approach, which consisted of a relative economy of therapeutic efforts that relied mainly on treatment sessions with a medical nurse accompanied by shorter reinforcing visits with a physician. This approach deserves generalization to address the heavy drinking problems commonly encountered in primary care and medical specialty practices. C1 Bronx Vet Affairs Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, Bronx, NY USA. Univ Maryland, Sch Med, Perry Point Vet Affairs Med Ctr, Perry Point, MD USA. W Haven Vet Affairs Med Ctr, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. San Antonio Vet Affairs Med Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Lieber, CS (reprint author), VA Med Ctr, Alcohol Res Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 25 TC 42 Z9 43 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2003 VL 27 IS 11 BP 1757 EP 1764 DI 10.1097/01.ALC.0000093744.12232.34 PG 8 WC Substance Abuse SC Substance Abuse GA 747TF UT WOS:000186820400009 PM 14634491 ER PT J AU Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S AF Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S CA Veterans Affairs Cooperative Study TI II. Veterans affairs cooperative study of polyenylphosphatidylcholine in alcoholic liver disease SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases DE phospholipids; ascites; cirrhosis ID CHRONIC ETHANOL-CONSUMPTION; CHRONIC HEPATITIS-C; CLINICAL-TRIALS; FIBROSIS; CIRRHOSIS; LEVEL AB Background: Polyenylphosphatidylcholine (PPC) has been shown to prevent alcoholic cirrhosis in animals. Our aims were to determine the effectiveness of PPC in preventing or reversing liver fibrosis in heavy drinkers and to assess the extent of liver injury associated with the reduced drinking achieved in these patients. Methods: This randomized, prospective, double-blind, placebo-controlled clinical trial was conducted in 20 Veterans Affairs Medical Centers with 789 patients (97% male; mean age, 48.8 years) averaging 16 drinks per day (1 drink = 14 g of alcohol) for 19 years. A baseline liver biopsy confirmed the presence of perivenular or septal fibrosis or incomplete cirrhosis. They were randomly assigned either PPC or placebo. Liver biopsy was repeated at 24 months, and the main outcome measure was the stage of fibrosis compared with baseline. Progression was defined as advancing to a more severe stage. Results: The 2-year biopsy was completed in 412 patients. PPC did not differ significantly from placebo in its effect on the main outcome. Alcohol intake was unexpectedly reduced in both groups to approximately 2.5 drinks per day. With this intake, 21.4% advanced at least one stage (22.8% of PPC patients and 20.0% of placebo patients). The hepatitis C virus-positive subgroup exhibited accelerated progression. Improvement in transaminases and bilirubin favoring PPC was seen at some time points in other subgroups (hepatitis C virus-positive drinkers or heavy drinkers). Conclusions: PPC treatment for 2 years did not affect progression of liver fibrosis. A trend in favor of PPC was seen for transaminases and bilirubin (in subgroups). One of five patients progressed even at moderate levels of drinking, and thus health benefits commonly associated with moderate drinking do not necessarily extend to individuals in the early stages of alcoholic liver disease. C1 Bronx Vet Affairs Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, Bronx, NY USA. Univ Maryland, Sch Med, Perry Point Vet Affairs Med Ctr, Perry Point, MD USA. W Haven Vet Affairs Med Ctr, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. San Antonio Vet Affairs Med Ctr, San Antonio, TX USA. Hlth & Sci Ctr, San Antonio, TX 78285 USA. RP Lieber, CS (reprint author), VA Med Ctr, Alcohol Res Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 36 TC 66 Z9 74 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2003 VL 27 IS 11 BP 1765 EP 1772 DI 10.1097/01.ALC.0000093743.03049.80 PG 8 WC Substance Abuse SC Substance Abuse GA 747TF UT WOS:000186820400010 PM 14634492 ER PT J AU Dieterich, DT Wasserman, R Brau, N Hassanein, TI Bini, EJ Bowers, PJ Sulkowski, MS AF Dieterich, DT Wasserman, R Brau, N Hassanein, TI Bini, EJ Bowers, PJ Sulkowski, MS TI Once-weekly epoetin alfa improves anemia and facilitates maintenance of ribavirin dosing in hepatitis C virus-infected patients receiving ribavirin plus interferon alfa SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week/102nd Annual Meeting of the American-Gastroenterological-Association CY MAY 20-23, 2001 CL ATLANTA, GEORGIA SP Amer Gastroenterol Assoc ID QUALITY-OF-LIFE; RANDOMIZED TRIAL; CHEMOTHERAPY PATIENTS; COMMUNITY ONCOLOGY; INITIAL TREATMENT; THERAPY; COMBINATION; DISEASE; CANCER; ERYTHROPOIETIN AB OBJECTIVE: The aim of this study was to determine the efficacy of epoetin alfa in alleviating anemia and minimizing ribavirin (RBV) dose reductions in patients with chronic hepatitis C virus (HCV) infection receiving combination RBV/interferon alfa (IFN) therapy. METHODS: HCV-infected patients who had Hb levels of 12 g/dl or less during the first 24 wk of combination RBV/IFN therapy (n = 64) were randomized to treatment with epoetin alfa (40,000 units) s.c. q.w. or to standard of care (SOC) for anemia management (RBV dose reduction or discontinuation, transfusions). Primary and secondary efficacy end-points were changes in Hb level and RBV dosage, respectively, from baseline to week 16 of epoetin alfa. therapy. RESULTS: Based on intent-to-treat analysis, the mean changes from baseline Hb levels at week 16 were +2.8 g/dl for epoetin alfa versus +0.4 g/dl for SOC (p < 0.0001), and the mean changes in RBV dosage were -34 mg/day for epoetin alfa versus -146 mg/day (p = 0.060) for SOC. The mean Hb level at week 16 in the epoetin alfa. group (13.8 g/dl) was significantly (p < 0.0001) higher than that of the SOC group (11.4 g/dl). At week 4 and subsequently, significantly more patients in the epoetin alfa group did not have RBV dosage reductions (p < 0.011). At study end, 83% of epoetin alfa-treated patients maintained RBV dosages of at least 800 mg/day, compared with 54% of patients receiving SOC (p = 0.022). Epoetin alfa was well tolerated. CONCLUSIONS: In anemic HCV-infected patients treated with RBV/IFN, epoetin alfa increases Hb levels and maintains RBV dosing. Based on these results, epoetin alfa seems to be promising in the treatment of HCV treatment-related anemia. Further research is warranted to determine the potential impact on outcomes, including quality of life and sustained viral response rate. (C) 2003 by Am. Coll. of Gastroenterology. C1 CUNY Mt Sinai Sch Med, Sch Med, Dept Med, New York, NY 10029 USA. New York VA Med Ctr, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Hepatitis Resource Ctr, Walnut Creek, CA USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Ortho Biotech Prod, Bridgewater, MA USA. Johns Hopkins Univ, Ctr Viral Hepatitis, Baltimore, MD USA. RP Dieterich, DT (reprint author), CUNY Mt Sinai Sch Med, Sch Med, Dept Med, Box 1118,1 Gustave L Levy Pl, New York, NY 10029 USA. NR 37 TC 143 Z9 145 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2003 VL 98 IS 11 BP 2491 EP 2499 DI 10.1016/j.amjgastroenterol.2003.08.006 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 746MQ UT WOS:000186750500025 PM 14638354 ER PT J AU Goodgame, B Shaheen, NJ Galanko, J El-Serag, HB AF Goodgame, B Shaheen, NJ Galanko, J El-Serag, HB TI The risk of end stage liver disease and hepatocellular carcinoma among persons infected with hepatitis C virus: Publication bias? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NON-B-HEPATITIS; TERM FOLLOW-UP; SINGLE-SOURCE OUTBREAK; NON-A; NATURAL-HISTORY; POSTTRANSFUSION HEPATITIS; IMMUNE GLOBULIN; ITALIAN PATIENTS; COHORT; TRANSFUSION AB OBJECTIVES: In persons infected with hepatitis C virus (HCV), the incidence of cirrhosis and hepatocellular carcinoma (HCC) can be estimated by examining over time entire cohorts with known onset of HCV infection. We performed a systematic review of the literature to identify and to analyze studies that examine such cohorts. METHODS: A search of all articles from 1980 to 2001 was performed. Published studies were included in which chronic HCV infection was defined by elevation of liver enzymes or persistent RNA. We excluded studies in which cohorts were selected from patients with prevalent liver disease or in whom the onset of infection could not be estimated. Two investigators abstracted the data. The incidences of cirrhosis and HCC were analyzed in all studies and in categories based on study design, mode of HCV acquisition, sample size and duration of follow-up, age at the onset of infection, and the quality of estimating the onset of HCV infection. RESULTS: Of the articles, 21 fulfilled the selection criteria. Studies varied in sample size (17-1,680), duration of follow-up (8-45 yr), total person-years (157-34,098), and the mean age at onset of HCV (5-58 yr). The mean time to end stage liver disease (ESLD) was 4-23 yr and to HCC was 9-31 yr. A funnel plot showed a possible publication bias against studies with low incidence of ESLD and HCC. The pooled weighted incidence rates for ESLD and HCC based on infection mode were as follows: community-acquired HCV, 1.9 and 0 per 1,000 person-years; transfusion associated, 4.5 and 0.7; hemophilia patients, 7.9 and 1.0; anti-D IgG, 0.7 and 0 per 1,000 person-years. Poisson regression modeling showed that the incidence of ESLD is increased in studies with a low quality estimate of the onset of HCV infection, in community-acquired and transfusion-associated HCV, and in studies with prospective design. CONCLUSIONS: We found large variation in the incidence estimates of cirrhosis and HCC. Short duration of follow-up, small sample size, and possible publication bias may explain some of this variation. Low quality estimates of the onset of HCV infection, a prospective study design, and a transfusion- or hemophilia-related mode of acquisition were independent predictors of high reported incidence of ESLD. (C) 2003 by Am. Coll. of Gastroenterology. C1 Houston Vet Affairs Med Ctr 152, Gastroenterol Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr 152, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ N Carolina, Div Digest Dis, Chapel Hill, NC 27515 USA. Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27515 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Shaheen, Nicholas/A-1898-2013 FU NIDDK NIH HHS [K23DK59311-01, P30DK34987] NR 55 TC 23 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2003 VL 98 IS 11 BP 2535 EP 2542 DI 10.1016/S0002-9270(03)00663-4 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 746MQ UT WOS:000186750500031 PM 14638360 ER PT J AU McKinley, LL Moriarty, HJ Short, TH Johnson, CC AF McKinley, LL Moriarty, HJ Short, TH Johnson, CC TI Effect of comparative data feedback on intensive care unit infection rates in a Veterans Administration Hospital Network System SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article ID WOUND-INFECTION; SURVEILLANCE; STATES AB Background: Infection control surveillance is not performed with standardized methodology within the Veterans Affairs (VA) health system. The purposes of this study were (1) to provide network hospitals with a standardized intensive care unit (ICU) surveillance system developed by the Centers for Disease Control and Prevention (CDC); (2) to compare ICU infection rates in hospitals that receive comparative data with those that do not; and (3) to compare network device-associated infection trends to national trends. Methods: One VA Medical Center served as the central coordination site where surveillance data were analyzed with CDC's criteria and reported back to the sites. During 1999, the experimental group received risk-adjusted infection rates with national comparative data, and the control group received only risk-adjusted infection rates without comparative data. In 2000, hospitals in both groups received risk-adjusted infection rates accompanied by national data. Results: In 1999, the device-associated infection rates were significantly higher in the control group compared with the experimental group. In the control group, the device-associated infection rates were significantly higher than the national comparative CDC rates; in the experimental group, the device-associated infection rates were not significantly different from the national comparative CDC rates. In 2000, the control group device-associated infection rates were not significantly different from the experimental group. The observed rates in both groups were not significantly different from the CDC rates. Conclusions: Study results suggest that infection rate outcomes may be reduced when national comparative data are provided. The study may serve as an infection control surveillance model for VA hospital networks. C1 Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. Vet Affairs Med Ctr, Patient Care Serv, Philadelphia, PA USA. Indiana Univ Penn, Indiana, PA USA. RP McKinley, LL (reprint author), VA Med Ctr, Dept Med, 2500 Overlake Terrace, Madison, WI 53705 USA. NR 20 TC 8 Z9 9 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD NOV PY 2003 VL 31 IS 7 BP 397 EP 404 DI 10.1067/mic.2003.46 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 742LU UT WOS:000186519700003 PM 14639435 ER PT J AU Saha, S Hickam, DH AF Saha, S Hickam, DH TI Explaining low ratings of patient satisfaction among Asian-Americans SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE Asian-Americans; ethnic groups; minority groups; patient satisfaction ID PRIMARY-CARE PERFORMANCE; HEALTH-CARE; QUALITY; SERVICES; VISITS AB Asian-Americans report lower levels of satisfaction with health care than other racial or ethnic groups. To determine potential reasons for this observation, we analyzed data from a national household telephone survey examining various aspects of health and health care across racial or ethnic groups. As in previous studies, Asians reported lower satisfaction with their physicians and health care services than other racial or ethnic groups, even after adjusting for demographic and health-related variables. However, Asians also reported lower satisfaction with their health insurance and with life in general and were less likely than non-Asians to have changed physicians due to dissatisfaction. We conclude that lower satisfaction ratings among Asians may be due to different response tendencies rather than to differences in quality of care. Further research is needed to explain this phenomenon and assess its potential impact on quality-of-care evaluations for clinicians and health care organizations providing care for large numbers of Asian-Americans. C1 Oregon Hlth & Sci Univ, Gen Internal Med Sect, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Hlth Serv Res & Dev Serv, Portland Vet Affairs Med Ctr, Div Gen Internal Med & Geriatr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. RP Saha, S (reprint author), Oregon Hlth & Sci Univ, Gen Internal Med Sect, P3MED,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 24 TC 16 Z9 16 U1 0 U2 0 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD NOV-DEC PY 2003 VL 18 IS 6 BP 256 EP 264 DI 10.1177/106286060301800606 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 752JD UT WOS:000187156600006 PM 14738037 ER PT J AU Lawrence, VA AF Lawrence, VA TI The relation between postoperative cardiac and noncardiac complications: Pathophysiological dominoes or doubles tennis? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID SURGERY; OUTCOMES; STAY C1 Univ Texas, Hlth Sci Ctr, Div Gen Med, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, Div Gen Med, San Antonio, TX 78229 USA. VERDICT, Audie Murphy Div, Div Gen Med, San Antonio, TX 78229 USA. RP Lawrence, VA (reprint author), Univ Texas, Hlth Sci Ctr, Div Gen Med, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM vlawrence@uthscsa.edu NR 7 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 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 2003 VL 115 IS 7 BP 580 EP 581 DI 10.1016/S0002-9343(03)00553-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 740PX UT WOS:000186411700012 PM 14599640 ER PT J AU Freitas, FRS Moriscot, AS Jorgetti, V Soares, AG Passarelli, M Scanlan, TS Brent, GA Bianco, AC Gouveia, CHA AF Freitas, FRS Moriscot, AS Jorgetti, V Soares, AG Passarelli, M Scanlan, TS Brent, GA Bianco, AC Gouveia, CHA TI Spared bone mass in rats treated with thyroid hormone receptor TR beta-selective compound GC-1 SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE thyrotoxicosis; osteopenia; osteoporosis; bone mineral density; bone histomorphometry ID GROWTH-FACTOR-I; BIOCHEMICAL MARKERS; MINERAL METABOLISM; MICE; EXPRESSION; ALPHA-1; TISSUE; HYPERTHYROIDISM; RESISTANCE; PHENOTYPE AB Thyrotoxicosis is frequently associated with increased bone turnover and decreased bone mass. To investigate the role of thyroid hormone receptor-beta (TRbeta) in mediating the osteopenic effects of triiodothyronine (T-3), female adult rats were treated daily ( 64 days) with GC-1 (1.5 mug/100 g body wt), a TRbeta-selective thyromimetic compound. Bone mass was studied by dual-energy X-ray absorptiometry of several skeletal sites and histomorphometry of distal femur, and the results were compared with T-3-treated (3 mug/100 g body wt) or control animals. As expected, treatment with T-3 significantly reduced bone mineral density (BMD) in the lumbar vertebrae (L-2-L-5), femur, and tibia by 10-15%. In contrast, GC-1 treatment did not affect the BMD in any of the skeletal sites studied. The efficacy of GC-1 treatment was verified by a reduction in serum TSH (-52% vs. control, P < 0.05) and cholesterol (-21% vs. control, P < 0.05). The histomorphometric analysis of the distal femur indicated that T-3 but not GC-1 treatment reduced the trabecular volume, thickness, and number. We conclude that chronic, selective activation of the TRbeta isoform does not result in bone loss typical of T-3-induced thyrotoxicosis, suggesting that the TRbeta isoform is not critical in this process. In addition, our findings suggest that the development of TR-selective T-3 analogs that spare bone mass represents a significant improvement toward long-term TSH-suppressive therapy. C1 Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508900 Sao Paulo, Brazil. Univ Sao Paulo, Inst Biomed Sci, Dept Histol, BR-05508900 Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, BR-05508900 Sao Paulo, Brazil. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Los Angeles, CA 91301 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 91301 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 91301 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Thyroid Div, Boston, MA 02115 USA. RP Gouveia, CHA (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof Lineu Prestes 2415,Rm 114, BR-05508900 Sao Paulo, Brazil. RI Bianco, Antonio/A-4965-2008; Moriscot, Anselmo/C-4506-2012; Moriscot, Anselmo/H-6985-2012; Freitas, Fatima/I-5678-2012; Soares, Antonio/C-9179-2016; JORGETTI, VANDA/C-9470-2012 OI Bianco, Antonio/0000-0001-7737-6813; Soares, Antonio/0000-0001-5814-3475; JORGETTI, VANDA/0000-0002-4824-8879 NR 39 TC 43 Z9 49 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV 1 PY 2003 VL 285 IS 5 BP E1135 EP E1141 DI 10.1152/ajpendo.00506.2002 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 730HB UT WOS:000185822500025 PM 12965872 ER PT J AU Levin, BE Dunn-Meynell, AA Ricci, MR Cummings, DE AF Levin, BE Dunn-Meynell, AA Ricci, MR Cummings, DE TI Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE ghrelin receptor; arcuate nucleus; dorsomedial nucleus; ventromedial nucleus; leptin receptor ID DIET-INDUCED OBESITY; GROWTH-HORMONE SECRETAGOGUE; SPRAGUE-DAWLEY RATS; FOOD-INTAKE; ARCUATE NUCLEUS; CIRCULATING GHRELIN; INSULIN-RESISTANCE; ACYLATED PEPTIDE; NEUROPEPTIDE-Y; NERVOUS-SYSTEM AB Rats selectively bred to develop diet-induced obesity (DIO) spontaneously gain more body weight between 5 and 7 wk of age than do those bred to be diet resistant (DR). Here, chow-fed DIO rats ate 9% more and gained 19% more body weight from 5 to 6 wk of age than did DR rats but had comparable leptin and insulin levels. However, 6-wk-old DIO rats had 29% lower plasma ghrelin levels at dark onset but equivalent levels 6 h later compared with DR rats. When subsequently fed a high-energy (HE; 31% fat) diet for 10 days, DIO rats ate 70% more, gained more body and adipose depot weight, had higher leptin and insulin levels, and had 22% lower feed efficiency than DR rats fed HE diet. In DIO rats on HE diet, leptin levels increased significantly at 3 days followed by increased insulin levels at 7 days. These altered DIO leptin and ghrelin responses were associated with 10% lower leptin receptor mRNA expression in the arcuate (ARC), dorsomedial (DMN), and ventromedial hypothalamic nuclei and 13 and 15% lower ghrelin receptor (GHS-R) mRNA expression in the ARC and DMN than in the DR rats. These data suggest that increased ghrelin signaling is not a proximate cause of DIO, whereas reduced leptin sensitivity might play a causal role. C1 Dept Vet Affairs Med Ctr, Serv Neurol, E Orange, NJ 07018 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurosci, Newark, NJ 07103 USA. Res Diets Inc, New Brunswick, NJ 08901 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Endocrine, Seattle, WA 98108 USA. RP Levin, BE (reprint author), Vet Affairs Med Ctr, Neurol Serv 127C, 385 Tremont Ave, E Orange, NJ 07018 USA. FU NIDDK NIH HHS [DK-61516, F32 DK-59682, R01 DK-30066] NR 51 TC 92 Z9 95 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV 1 PY 2003 VL 285 IS 5 BP E949 EP E957 DI 10.1152/ajpendo.00186.2003 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 730HB UT WOS:000185822500003 PM 12865257 ER PT J AU Mundinger, TO Mei, Q Figlewicz, DP Lernmark, A Taborsky, GJ AF Mundinger, TO Mei, Q Figlewicz, DP Lernmark, A Taborsky, GJ TI Impaired glucagon response to sympathetic nerve stimulation in the BB diabetic rat: effect of early sympathetic islet neuropathy SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE norepinephrine; 6-hydroxydopamine; neuropathy ID INSULIN-INDUCED HYPOGLYCEMIA; NOREPINEPHRINE SPILLOVER; EPINEPHRINE SECRETION; AUTONOMIC NEUROPATHY; PANCREATIC GLUCAGON; STRUCTURAL-CHANGES; CELL ACTIVITY; SYSTEM; SOMATOSTATIN; ACTIVATION AB We investigated the functional impact of a recently described islet-specific loss of sympathetic nerves that occurs soon after the autoimmune destruction of beta-cells in the BB diabetic rat (35). We found that the portal venous (PV) glucagon response to sympathetic nerve stimulation (SNS) was markedly impaired in newly diabetic BB rats ( BB D). We next found a normal glucagon response to intravenous epinephrine in BB D, eliminating the possibility of a generalized secretory defect of the BB D alpha-cell as the mediator of the impaired glucagon response to SNS. We then sought to determine whether the glucagon impairment to SNS in BB D was due solely to their loss of islet sympathetic nerve terminals or whether other effects of autoimmune diabetes contributed. We therefore reproduced, in nondiabetic Wistar rats, an islet nerve terminal loss similar to that in BB D with systemic administration of the sympathetic neurotoxin 6-hydroxydopamine. The impairment of the glucagon response to SNS in these chemically denervated, nondiabetic rats was similar to that in the spontaneously denervated BB D. We conclude that the early sympathetic islet neuropathy of BB D causes a functional defect of the sympathetic pathway to the alpha-cell that can, by itself, account for the impaired glucagon response to postganglionic SNS. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Mundinger, TO (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, 1660 S Columbian Wy, Seattle, WA 98108 USA. FU NIAID NIH HHS [AI-42380]; NIDDK NIH HHS [DK-50154, DK-12829, DK-12047] NR 46 TC 20 Z9 20 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV 1 PY 2003 VL 285 IS 5 BP E1047 EP E1054 DI 10.1152/ajpendo.00136.2003 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 730HB UT WOS:000185822500014 PM 12876072 ER PT J AU Derose, SF Asch, SM Fielding, JE Schuster, MA AF Derose, SF Asch, SM Fielding, JE Schuster, MA TI Developing quality indicators for local health departments - Experience in Los Angeles County SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PERFORMANCE; CARE AB Objectives: To develop public health quality indicators for local health department (LHD) use. Methods: An indicator development team utilized public health quality measurement concepts, reviewed existing quality measurement-related initiatives, and conducted interviews with LHD staff in order to identify and develop quality indicators for the Los Angeles County Health Department. Results: Sixty-one recommended and 50 acceptable (i.e., scientifically sound but less useful) indicators were developed, with an emphasis on measuring process quality in services delivery. Pre-existing indicators from external sources, when available, were often not well suited to the Health Department's needs. The indicator development process clarified conceptual issues, highlighted strengths and limitations of potential indicators, and revealed implementation barriers. Conclusions: A limited number of generally available, quantitative indicators of local public health quality exist. Indicators addressing the delivery of LHD services can be locally developed to fill an important gap in public health quality-improvement efforts. However, implementation of quality measurement is difficult due to limited evidence on public health practices, sparse data resources, unclear accountability, and inconsistent organizational motivation. C1 So Calif Kaiser Permanente, Dept Res & Evaluat, Pasadena, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Cty Los Angeles Dept Hlth Serv, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Cty Los Angeles Dept Hlth Serv, Dept Hlth Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Cty Los Angeles Dept Hlth Serv, Dept Pediat, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Derose, SF (reprint author), 393 E Walnut St,991, Pasadena, CA 91188 USA. FU ODCDC CDC HHS [U48/CCU 915773] NR 40 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2003 VL 25 IS 4 BP 347 EP 357 DI 10.1016/S0749-3797(03)00208-3 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 734HC UT WOS:000186048300014 PM 14580639 ER PT J AU Fagan, SP Awad, SS Rahwan, K Hira, K Aoki, N Itani, KMF Berger, DH AF Fagan, SP Awad, SS Rahwan, K Hira, K Aoki, N Itani, KMF Berger, DH TI Prognostic factors for the development of gangrenous cholecystitis SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAY 03-05, 2003 CL NASHVILLE, TENNESSEE SP Assoc VA Surg DE gangrenous cholecystitis; prognostic factors; multivariate logistic regression ID ACUTE ACALCULOUS CHOLECYSTITIS; LAPAROSCOPIC CHOLECYSTECTOMY; DIABETIC-PATIENTS; NATURAL-HISTORY; GALLBLADDER; RISK; PATIENT AB Background: The operative morbidity and mortality for patients with gangrenous cholecystitis (GC) remains high. Our objective was to identify preoperative prognostic factors for GC in order to distinguish this subset of patients with acute cholecystitis (AC). Methods: From 1/98 to 11/01 the medical records of patients who presented with the diagnosis of AC were reviewed. Univariate and multivariate analysis were performed on this retrospective data. Results: Of 113 patients with acute cholecystitis, 45 (39.8%) had histologically confirmed gangrenous cholecystitis. Nine variables were identified that were associated with GC by univariate analysis: age greater than or equal to51 years, African-American race, white blood cell count greater than or equal to15,000, diabetes, pericholecystic fluid, asparate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lipase. Two variables were identified by multivariate analysis: diabetes, and white blood cell count. Conclusions: Our data suggest that patients with a history of diabetes and white blood cell count >15,000 to be at an increased risk for having GC upon presentation and they should have urgent surgical intervention. (C) 2003 Excerpta Medica, Inc. All rights reserved. C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Houston Vet Affairs Med Ctr, Surg Serv Va 112, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Sch Hlth Informat, Houston, TX 77030 USA. RP Fagan, SP (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Houston Vet Affairs Med Ctr, Surg Serv Va 112, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 25 TC 39 Z9 43 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2003 VL 186 IS 5 BP 481 EP 485 DI 10.1016/j.amjsung.2003.08.001 PG 5 WC Surgery SC Surgery GA 738UY UT WOS:000186307300013 PM 14599611 ER PT J AU Knauer, EM Ailawadi, G Yahanda, A Obermeyer, RJ Millie, MP Ojeda, H Mulholland, MW Colletti, L Sweeney, J AF Knauer, EM Ailawadi, G Yahanda, A Obermeyer, RJ Millie, MP Ojeda, H Mulholland, MW Colletti, L Sweeney, J TI 101 Laparoscopic splenectomies for the treatment of benign and malignant hematologic disorders SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAY 03-05, 2003 CL NASHVILLE, TENNESSEE SP Assoc VA Surg DE splenectomy; Laparoscopic; idiopathic thrombocytopenic purpura; splenomegaly ID DISEASES; EXPERIENCE; MANAGEMENT; SPLEENS AB Background: Laparoscopic splenectomy (LS) is the surgical approach of choice for patients with hematologic disorders requiring splenectomy. Patients with idiopathic thrombocytopenic purpura (ITP) have normal to slightly enlarged spleens and benefit the most from LS. Methods: We reviewed the perioperative outcomes in 101 patients who underwent LS between May 1996 and December 2002. Patients were divided into three groups-ITP, other benign, and malignant hematologic disorders-and compared. Results: The ITP patients (n = 48) had significantly smaller spleens and operative times compared with the other groups. Splenomegaly in the other benign (n = 23) and malignant hematologic disorders (n = 30) groups was responsible for higher open conversion rates and greater need for hand-assisted laparoscopic splenectomy (HALS). Conclusions: Laparoscopic splenectomy and HALS can be performed with good results for benign and malignant hematologic disorders. The benefits of HALS are similar to LS, so there should be a low threshold for HALS in patients with large spleens. (C) 2003 Excerpta Medica, Inc. All rights reserved. C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Houston VA Med Ctr, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA. Minimally Invas Surg, Houston, TX 77030 USA. RP Sweeney, J (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Houston VA Med Ctr, Houston, TX 77030 USA. NR 18 TC 33 Z9 43 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2003 VL 186 IS 5 BP 500 EP 504 DI 10.1016/j.amjsurg.2003.07.026 PG 5 WC Surgery SC Surgery GA 738UY UT WOS:000186307300016 PM 14599614 ER PT J AU Etzioni, DA Liu, JH O'Connell, JB Maggard, MA Ko, CY AF Etzioni, DA Liu, JH O'Connell, JB Maggard, MA Ko, CY TI Elderly patients in surgical workloads: A population-based analysis SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID TOTAL GASTRECTOMY; RISK-FACTORS; POSTOPERATIVE COMPLICATIONS; MEDICAL SPECIALTIES; GASTRIC-CANCER; COLON SURGERY; AGE; MORTALITY; OLDER; SURVIVAL AB Elderly (80+ year old) individuals are the fastest-growing segment of the U.S. population. The objective of this study was to use population-based data to examine trends in the number of elderly undergoing major general, vascular, and cardiothoracic surgical procedures. California inpatient data from 1990-2000 was used to identify patients undergoing six procedures: abdominal aortic aneurysm repair (AAA), coronary artery bypass graft (CABG), carotid endarterectomy (CEA), colon resections, lung resections, and pancreatic resections. Despite comprising only 2.7 per cent of the California population, elderly patients were a significant percentage (6-22%) of the caseloads for the six procedures examined. For all six procedures, the percentage of patients that were elderly increased during the study period. The age-specific incidence rates for elderly individuals increased significantly for three of these procedures (CABG, CEA, lung resection), remained unchanged for two (AAA, pancreas resection), and decreased for one (colon resection). Elderly patients are a large and growing part of surgical caseloads. In the near future, the number of elderly individuals in the California state and the U.S. populations will increase dramatically (41% and 35% between 2000 and 2020). To provide the best quality of care, surgeons should embrace research, training, and educational opportunities regarding the treatment of elderly patients. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Adm Med Ctr, Dept Gen Internal Med, Los Angeles, CA USA. RP Etzioni, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 911 Broxton Ave, Los Angeles, CA 90024 USA. NR 31 TC 56 Z9 57 U1 1 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD NOV PY 2003 VL 69 IS 11 BP 961 EP 965 PG 5 WC Surgery SC Surgery GA 741BZ UT WOS:000186440000009 PM 14627256 ER PT J AU Zingmond, D Maggard, M O'Connell, J Liu, J Etzioni, D Ko, C AF Zingmond, D Maggard, M O'Connell, J Liu, J Etzioni, D Ko, C TI What predicts serious complications in colorectal cancer resection? SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID OPERATIVE MORTALITY; COLON-CANCER; SURGERY; VOLUME; OUTCOMES; HOSPITALS AB Virtually all volume-outcome studies use mortality as their outcome measure, yet most general surgical procedures have low in-patient death rates. We examined whether hospital surgical volume impacts other colorectal cancer resection outcomes and complications. Colorectal cancer (CRC) resections from 1996 to 2000 were identified using the California hospital discharge database. Comorbidity was graded using a modified Charlson index. Hospital CRC resection volume was calculated. Serious medical complications were defined as life-threatening cardiac or respiratory events, renal failure, or shock. Serious surgical complications were defined as vascular events, need for reoperation, or bleeding. Multivariate logistic regression analyses were performed to estimate the impact of predictors on complications. We identified 56,621 resections. Median age was 70 to 74 years. Eighty-one per cent of patients were white. Most had localized (57%) versus distant (22%) disease. Serious medical (17.5%) and surgical (9.8%) complications were not infrequent. In multivariate analyses, greater annual CRC surgical volume predicted lower odds of serious complication, but patient characteristics (age, comorbidity, and acuity of surgery) were more important. Although patients receiving CRC resection at lower-volume hospitals have greater odds of complication than patients treated at higher-volume institutions, patient factors remain the most important determinants of complication. C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. W Los Angeles VA, Los Angeles, CA USA. RP Ko, C (reprint author), 10833 LeConte Ave,72-215 CHS, Los Angeles, CA 90095 USA. NR 16 TC 19 Z9 19 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD NOV PY 2003 VL 69 IS 11 BP 969 EP 974 PG 6 WC Surgery SC Surgery GA 741BZ UT WOS:000186440000011 PM 14627258 ER PT J AU Dieter, RS Murtaugh, T Black, J Russell, DC AF Dieter, RS Murtaugh, T Black, J Russell, DC TI Coronary arteriomegaly in a patient with Ehlers-Danlos syndrome and multiple aneurysms - A case report SO ANGIOLOGY LA English DT Article ID ABDOMINAL AORTIC-ANEURYSMS; LOCALIZATION; LOCUS AB The authors report a case of coronary arteriomegaly in a patient with Ehlers-Danlos syndrome and multiple aneurysms who presented with myocardial infarction. Coronary arteriography revealed distal "pruning" of vessels without occlusive disease. Fibroblast cultures excluded Ehlers-Danlos syndrome types IV and VII. Literature review suggests this may represent a previously unidentified vascular syndrome. C1 William S Middleton Mem Vet Adm Med Ctr, Cardiol Sect 111CA, Madison, WI 53705 USA. Univ Wisconsin, Madison, WI USA. RP Russell, DC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Cardiol Sect 111CA, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NHLBI NIH HHS [T32 HL07936] NR 10 TC 6 Z9 6 U1 0 U2 1 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 0003-3197 J9 ANGIOLOGY JI Angiology PD NOV-DEC PY 2003 VL 54 IS 6 BP 733 EP 736 DI 10.1177/000331970305400616 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 746LP UT WOS:000186748100016 PM 14666965 ER PT J AU Etzioni, DA Liu, JH Maggard, MA O'Connell, JB Ko, CY AF Etzioni, DA Liu, JH Maggard, MA O'Connell, JB Ko, CY TI Workload projections for surgical oncology: Will we need more surgeons? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Society-of-Surgical-Oncology CY MAR 07, 2003 CL LOS ANGELES, CALIFORNIA SP Soc Surg Oncol DE workload; workforce; aging; projection; surgery ID FECAL OCCULT-BLOOD; COLORECTAL-CANCER; GENERAL-SURGERY; SCREENING PRACTICES; UNITED-STATES; TRENDS; CALIFORNIA; PROGRESS; IMPACT AB Background: Over the next two decades, the US population will experience dramatic growth in the number and relative proportion of older individuals. The aim of this study was to quantify the effect of these changes on the demand for oncological procedures. Methods: The 2000 Nationwide Inpatient Sample and the 1996 National Survey of Ambulatory Surgery were used to compute age-specific incidence rates for oncological procedures of the breast, colon, rectum, stomach, pancreas, and esophagus. Procedure rates were combined with census projections for 2010 and 2020 to estimate the future utilization of each procedure. Results: By 2020, the number of patients undergoing oncological procedures is projected to increase by 24% to 51%. The bulk of growth in procedures is derived from outpatient procedures, but significant growth will also be seen in inpatient procedures. Conclusions: The aging of the population will generate an enormous growth in demand for oncological procedures. If a shortage of surgeons performing these procedures does occur, the result will inevitably be decreased access to care. To prevent this from happening, the ability of surgeons to cope with an increased burden of work needs to be critically evaluated and improved. C1 Univ Calif Berkeley, Dept Surg, David Geffen Sch Med, Santa Monica, CA 90403 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Etzioni, DA (reprint author), Univ Calif Berkeley, Dept Surg, David Geffen Sch Med, 1015 9th St,Apt 106, Santa Monica, CA 90403 USA. NR 20 TC 36 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD NOV PY 2003 VL 10 IS 9 BP 1112 EP 1117 DI 10.1245/ASO.2003.03.034 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 740NU UT WOS:000186409100021 PM 14597452 ER PT J AU Rumsfeld, JS AF Rumsfeld, JS TI In the world of heart valves size matters - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80220 USA. RP Rumsfeld, JS (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, 1055 Clermont St 111B, Denver, CO 80220 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2003 VL 76 IS 5 BP 1604 EP 1604 DI 10.1016/S0003-4975(03)01033-6 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 739QU UT WOS:000186358600050 ER PT J AU Schellenberg, GD AF Schellenberg, GD TI Alzheimer Disease genes - Presenilin 2 mutation number 9 and still counting SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID MISSENSE MUTATIONS C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Schellenberg, GD (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,Mail Code 182B,Box 358280, Seattle, WA 98108 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2003 VL 60 IS 11 BP 1521 EP 1522 DI 10.1001/archneur.60.11.1521 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 744DC UT WOS:000186611800002 PM 14623722 ER PT J AU Boninger, ML Dicianno, BE Cooper, RA Towers, JD Koontz, AM Souza, AL AF Boninger, ML Dicianno, BE Cooper, RA Towers, JD Koontz, AM Souza, AL TI Shoulder magnetic resonance imaging abnormalities, wheelchair propulsion, and gender SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE biomechanics; gender; magnetic resonance imaging; paraplegia; rehabilitation; shoulder; wheelchairs ID BEARING UPPER EXTREMITY; LONG-TERM PARAPLEGIA; IMPINGEMENT SYNDROME; PUSHRIM FORCES; 2 SPEEDS; WEIGHT; PAIN; BIOMECHANICS; INDIVIDUALS; INJURIES AB Objective: To investigate the relationship between pushrim forces and the progression of shoulder injuries in manual wheelchair users. Design: Longitudinal case series. Setting: Biomechanics laboratory and magnetic resonance imaging (MRI) facility at a Veterans Health Administration medical center and university hospital, respectively. Participants: Fourteen individuals with spinal cord injury (8 men. 6 women) who used manual wheelchairs. Intervention: Subjects propelled their own wheelchairs on a dynamometer at 0.9 and 1.8m/s. Bilateral biomechanical data were obtained by using force and moment sensing pushrims at time 1. Bilateral shoulder MR images were also completed on 2 occasions. at time I and, approximately 2 years later, at time 2. Main Outcome Measures: The peak pushrim forces in a pushrim coordinate system were calculated, weight normalized and averaged over 5 strokes (presented as % body weight). MRI abnormalities were graded by using a summated scale Differences between scores between times I and 2 were calculated. Results: Subjects were divided into 2 groups based on change in MRI score. Seven subjects were in the group with worsening scores (MRI+: mean, 8.14 points, range, 5-16), and 7 were in the group with improving or unchanging scores (MRI-: mean. -1.00 point; range, -5 to 1). There was no significant difference between groups with respect to age, body mass index. or years from injury. There were significantly more women in the MRI+ group (6 women, I man) than in the MRI- group (7 men) (P=.001). The MRI+ group used significantly greater weight-normalized radial force, or force directed toward the axle at time 1, to propel their wheelchairs at each speed (P<.01): MRI+ at 0.9m/s (mean radial force standard deviation, 5.2%+/-1.0%) and MRI- at 0.9m/s (mean radial force, 3.2%+/-1.7%) (P=.028); and MRI+ at 1.8m/s (mean radial force, 6.6%+/-1.2%) (P=.023) and MRI- at 1.8m/s (mean radial force, 4.1%+/-2.2%). In a separate analysis, women were found to propel with a significantly higher radial force. A logistic regression found a significant relationship between radial force at time I and increased risk of progression of MRI findings over time. Conclusion: Individuals who propel with a greater percentage of force directed toward the axle were at increased risk of progression of MRI findings over time. Most people in this group were women. Clinicians should instruct wheelchair users in effective propulsion techniques and should pay particular attention to women who use wheelchairs. Reducing forces during wheelchair propulsion may minimize the likelihood of developing shoulder injuries. C1 VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Human Engn Res Labs, Dept Phys Med & Rehabil, Sch Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Sch Hlth & Rehabil Sci, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Radiol, Med Ctr, Pittsburgh, PA 15260 USA. RP Boninger, ML (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, 5180 Highland Dr,151R-1, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X; Dicianno, Brad/0000-0003-0738-0192 FU NICHD NIH HHS [1 P01 HD33989] NR 33 TC 41 Z9 45 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2003 VL 84 IS 11 BP 1615 EP 1620 DI 10.1053/S0003-9993(03)00282-X PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 741PR UT WOS:000186466900007 PM 14639560 ER PT J AU Petchkrua, W Burns, SA Stiens, SA James, JJ Little, JW AF Petchkrua, W Burns, SA Stiens, SA James, JJ Little, JW TI Prevalence of vitamin B-12 deficiency in spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE rehabilitation; spinal cord injuries; vitamin B12 deficiency ID SUBTLE COBALAMIN DEFICIENCY; METHYLMALONIC ACID; DIAGNOSIS; ABNORMALITIES; OUTPATIENTS; INDIVIDUALS; POPULATION; ANEMIA; FOLATE; RISK AB Objective: To assess the prevalence of vitamin B-12 deficiency in persons with spinal cord injury (SCI) or disease (SCD). Design: Cross-sectional study with prospective blood collection and retrospective medical record review. Setting: Regional Veterans Affairs SCI service. Participants: One hundred six adult men with chronic SCI or SCD and without other acute medical or surgical complications; most had SCI or SCD due to trauma or cervical spinal stenosis. Interventions: Not applicable. Main Outcome Measures: Fasting blood samples were obtained at annual evaluation for serum B12, folic acid, methylmalonic acid (MMA), and homocysteine. Serum levels were analyzed graphically and associated with patient variables by using statistical tests. Results: The vitamin B-12 level was subnormal in 5.7% of subjects: of those. all had supranormal MMA levels, all were age 40 to 59. most had complete SCI, and 67% had symptoms suggestive of B-12 deficiency. Low-normal B-12 levels were associated with a high prevalence of supranormal MMA. Subjects with either subnormal B-12 or low normal B-12 with supranormal MMA. both suggestive of vitamin 13, deficiency, comprised 13.3% of the total group of subjects. Conclusion: Vitamin B-12 deficiency is most common in middle-aged SCI or SCD persons with complete or near-complete spinal cord involvement (ie, American Spinal Injury Association class A-C injuries). Treatment with either parenteral or oral B-12 replacement may optimize health and prevent irreversible neuropsychiatric complications in those with subnormal and low-normal B-12 levels. C1 VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv S128, Dept Vet Affairs, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Little, JW (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv S128, Dept Vet Affairs, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 33 TC 11 Z9 12 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2003 VL 84 IS 11 BP 1675 EP 1679 DI 10.1053/S0003-9993(03)00318-6 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 741PR UT WOS:000186466900016 PM 14639569 ER PT J AU Yaffe, K Edwards, ER Lui, LY Zmuda, JM Ferrell, RE Cauley, JA AF Yaffe, K Edwards, ER Lui, LY Zmuda, JM Ferrell, RE Cauley, JA TI Androgen receptor CAG repeat polymorphism is associated with cognitive function in older men SO BIOLOGICAL PSYCHIATRY LA English DT Article DE androgen receptor; CAG repeat; polymorphism; cognitive decline; older men ID GENE; HIPPOCAMPUS; EXPRESSION; CORTEX; MEMORY; CELLS; BRAIN AB Background: Androgen receptors are located throughout the brain, especially in regions involved with learning and memory. Different lengths of a CAG (glutamine) repeat polymorphism in exon 1 of the androgen receptor gene may influence androgen action, with longer repeat lengths conferring decreased androgen sensitivity. Methods: We sought to determine if this CAG polymorphism was associated with cognition in older men. Results: Among 301 community-dwelling white men (mean age, 73.0 +/- 7.1), greater CAG repeat length was associated with lower scores on three cognitive tests (p < .05 for all). In addition, 12 participants (9.8%) had cognitive impairment in the low tertile of CAG repeat length whereas 29 (16.3%) had cognitive impairment in the two higher tertiles (odds ratio = 1.8; 95% confidence interval = .9-3.7). Conclusions: Research should be directed at identifying the mechanism for this association and to determine if treatment with testosterone prevents cognitive decline. (C) 2003 Society of Biological Psychiatry. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St, San Francisco, CA 94121 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [K23-AG00888]; NIAMS NIH HHS [P60-AR44811] NR 18 TC 40 Z9 40 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2003 VL 54 IS 9 BP 943 EP 946 DI 10.1016/S0006-3223(03)00115-X PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 734NH UT WOS:000186062000012 PM 14573323 ER PT J AU Vaiva, G Ducrocq, F Jezequel, K Averland, B Lestavel, P Brunet, A Marmar, CR AF Vaiva, G Ducrocq, F Jezequel, K Averland, B Lestavel, P Brunet, A Marmar, CR TI Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma SO BIOLOGICAL PSYCHIATRY LA English DT Article DE posttraumatic stress disorder; immediate treatment; propranolol; peritraumatic distress; short-term outcome ID PTSD AB Background: This study investigated the efficacy of propranolol prescribed shortly after trauma exposure in the prevention of posttraumatic stress disorder (PTSD) symptoms and diagnosis. Methods: Eleven patients received 40 mg of propranolol 3 times daily for 7 days, followed by a taper period of 8-12 days. They were compared with eight patients who refused propranolol but agreed to participate in the study. Though nonrandomized, the two groups did not differ on demographics, exposure characteristics, physical injury severity, or peritraumatic emotional responses. Results: Posttraumatic stress disorder rates were higher in the group who refused propranolol (318) compared with those who received the medication (1/11), as were the levels of PTSD symptoms (U = 85, p = .037). Conclusions: Our results are consistent with earlier findings and suggest that propranolol may be useful for mitigating PTSD symptoms or perhaps even preventing the development of PTSD. (C) 2003 Society of Biological Psychiatry. C1 Univ Lille 2, Clin Sch Psychiat, Lille, France. McGill Univ, Dept Psychiat, Montreal, PQ, Canada. Douglas Hosp, Res Ctr, Montreal, PQ, Canada. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Vaiva, G (reprint author), CHRU, Clin Michel Fontan, 6 Rue Prof Laguesse, F-59037 Lille, France. RI DUCROCQ, Francois/O-7342-2014; VAIVA, Guillaume/J-8983-2015 OI DUCROCQ, Francois/0000-0002-0664-761X; VAIVA, Guillaume/0000-0003-2462-008X NR 14 TC 274 Z9 281 U1 3 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2003 VL 54 IS 9 BP 947 EP 949 DI 10.1016/S0006-3223(03)00412-8 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 734NH UT WOS:000186062000013 PM 14573324 ER PT J AU Jedlickova, K Stockton, DW Prchal, JT AF Jedlickova, K Stockton, DW Prchal, JT TI Possible primary familial and congenital polycythemia locus at 7q22.1-7q22.2 SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article ID ERYTHROPOIETIN RECEPTOR GENE; DOMINANT PRIMARY POLYCYTHEMIA; ERYTHROID PROGENITORS; LINKAGE ANALYSIS; ACTIVATION; MUTATION; ERYTHROCYTOSIS; DIMERIZATION AB Primary familial and congenital polycythemia (PFCP), inherited as an autosomal dominant trait, has been reported to be associated with mutations in the gene encoding the erythropoietin receptor (EpoR). The clinical features include the presence of isolated erythrocytosis, low erythropoietin (Epo) levels, normal hemoglobin-oxygen dissociation curve, hypersensitivity of erythroid progenitors to exogenous Epo in vitro and no progression to leukemia or myelodysplastic syndrome. Less than 15% of PFCP families have an identifiable EPOR mutation. Abnormalities of other genes are therefore likely responsible for the phenotype of the majority PFCP patients. In this study we report a family segregating PFCP with an autosomal dominant pattern of inheritance, where 7 of 14 members of the family were affected in four generations. This family was studied previously and an EPOR mutation was ruled out by sequencing and by genetic means. Here, we confirmed by linkage analysis that the disease phenotype was not linked to the Epo and EPOR genes. We then performed a genomewide screen with 410 polymorphic markers at average spacing 7.67 cM to locate the chromosomal region responsible for PFCP. We identified a region in 7q22.1-7q22.2 with a suggestive LOD score of 1.84, from our data this is the most likely location of a candidate region responsible for PFCP in this family. (C) 2003 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Texas Med Ctr, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX 77030 USA. RP Prchal, JT (reprint author), Baylor Coll Med, Texas Med Ctr, 1 Baylor Plaza,MS 525D, Houston, TX 77030 USA. NR 23 TC 10 Z9 11 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD NOV-DEC PY 2003 VL 31 IS 3 BP 327 EP 331 DI 10.1016/S1079-9796(03)00167-0 PG 5 WC Hematology SC Hematology GA 748DD UT WOS:000186846200006 PM 14636647 ER PT J AU Mitchell, BD Kammerer, CM Schneider, JL Perez, R Bauer, RL AF Mitchell, BD Kammerer, CM Schneider, JL Perez, R Bauer, RL TI Genetic and environmental determinants of bone mineral density in Mexican Americans: results from the San Antonio Family Osteoporosis Study SO BONE LA English DT Article DE bone mineral density; osteoporosis; heritability; family study; Mexican Americans ID ETHNIC-DIFFERENCES; PHYSICAL-ACTIVITY; PEDIGREE ANALYSIS; HIP FRACTURE; US ADULTS; MASS; EXTENSIONS; WOMEN; RISK; TWIN AB Osteoporosis is a major cause of disability in the United States. Numerous factors contribute to the decline in bone mineral density (BMD) that characterizes this disease, and the importance of heredity is now widely appreciated. We evaluated the joint contributions of genes and environmental factors on variation in BMD in 895 participants of the San Antonio Family Osteoporosis Study (SAFOS). Participants of the SAFOS ranged in age from 18 to 96 years and were members of 34 large families of Mexican American ancestry. BMD was measured at the spine, hip, and forearm by dual-energy X-ray absorptiometry. Information about medical history, lifestyle habits, dietary intake, and physical activity patterns was obtained by questionnaire. Age and body mass index were strongly associated with BMD at nearly every site; these and other measured risk factors accounted in aggregate for up to 46% of the total variation in BMD. In general, the environmental risk factors accounted for proportionately more of the total variation in BMD in men than in women. Genes accounted for 65-80% of the residual variation in spine and hip BMD, and 25-55% of the residual variability in forearm BMD. Although residual heritabilities were generally comparable between men and women across all ages combined, heritabilities at all sites tended to be higher in premenopausal women than in men younger than 50 years of age. Identifying the individual genes involved will shed insights into the processes that govern bone remodeling and may suggest strategies for the prevention of osteoporosis. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Mitchell, BD (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, 660 W Redwood St,Room 492, Baltimore, MD 21201 USA. OI Mitchell, Braxton/0000-0003-4920-4744 FU NCRR NIH HHS [M01-RR-01346]; NHLBI NIH HHS [P01-HL45522]; NIAMS NIH HHS [R01-AR43351] NR 32 TC 42 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 8756-3282 J9 BONE JI Bone PD NOV PY 2003 VL 33 IS 5 BP 839 EP 846 DI 10.1016/S8756-3282(03)00246-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746XF UT WOS:000186772400011 PM 14623060 ER PT J AU Ludtke, CB Coutinho, ML Jouglard, SDD Moreira, CN Fernandes, CHP Brod, CS Haake, DA Ko, AI Dellagostin, OA Aleixo, JAG AF Luedtke, Charli Beatriz Coutinho, Mariana Loner Dorneles Jouglard, Sandra Denise Moreira, Cecilia Nunes Pinho Fernandes, Claudia Hartleben Brod, Claudiomar Soares Haake, David A. Ko, Albert Icksang Dellagostin, Odir Antonio Guimaraes Aleixo, Jose Antonio TI MONOCLONAL ANTIBODIES AGAINST AN OUTER MEMBRANE PROTEIN FROM PATHOGENIC LEPTOSPIRA SO BRAZILIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE leptospirosis; monoclonal antibodies; LipL32 AB Two hybridomas secreting monoclonal antibodies (MAbs) that react with a lipoprotein (LipL32) of the outer membrane of pathogenic Leptospira were obtained. For hybridoma production, spleen cells from BALB/c mice imunized with recombinant LipL32 (rLipL32) were fused to SP2/O-Ag14 cells, selected in HAT medium and screened in an indirect ELISA. One MAb produced was of the IgG2b isotype and the other was an IgM. MAbs specificity was confirmed by indirect ELISA and immunoblotting using purified rLipL32 and whole-cell antigen preparations from Escherichia coli (E. coli) expressing LipL32 and from pathogenic and nonpathogenic serovars. Both Mabs reacted with most of the pathogenic serovars tested and none reacted with non-pathogenic Leptospira. The MAbs described have potential for use in diagnostic tests for leptospirosis. C1 [Luedtke, Charli Beatriz; Coutinho, Mariana Loner; Dorneles Jouglard, Sandra Denise; Moreira, Cecilia Nunes; Pinho Fernandes, Claudia Hartleben; Dellagostin, Odir Antonio; Guimaraes Aleixo, Jose Antonio] Univ Fed Pelotas, Ctr Biotecnol, BR-96019900 Pelotas, RS, Brazil. [Brod, Claudiomar Soares] Univ Fed Pelotas, Ctr Control Zoonoses, BR-96019900 Pelotas, RS, Brazil. [Haake, David A.] Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Ko, Albert Icksang] Fundacao Oswaldo Cruz, Ctr Pesquisa Goncalo Moniz, Salvador, BA, Brazil. [Dellagostin, Odir Antonio] Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, New York, NY 10021 USA. RP Aleixo, JAG (reprint author), Univ Fed Pelotas, Ctr Biotecnol, Campus Univ Capao Leao S-N, BR-96019900 Pelotas, RS, Brazil. RI Dellagostin, Odir/C-2331-2009; Coutinho, Mariana/J-9024-2012; Ko, Albert/P-2343-2015 OI Dellagostin, Odir/0000-0003-2803-4088; Ko, Albert/0000-0001-9023-2339 NR 12 TC 5 Z9 5 U1 0 U2 3 PU SOC BRASILEIRA MICROBIOLOGIA PI SAO PAULO PA AV PROF LINEU PRESTES,1374, 05508 SAO PAULO, BRAZIL SN 1517-8382 EI 1678-4405 J9 BRAZ J MICROBIOL JI Braz. J. Microbiol. PD NOV PY 2003 VL 34 SU 1 BP 1 EP 4 DI 10.1590/S1517-83822003000500001 PG 4 WC Microbiology SC Microbiology GA V04NQ UT WOS:000207065500001 ER PT J AU Bohning, DE Denslow, S Bohning, PA Walker, JA George, MS AF Bohning, DE Denslow, S Bohning, PA Walker, JA George, MS TI A TMS coil positioning/holding system for MR image-guided TMS interleaved with fMRI SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial magnetic stimulation; TMS; MR-guided positioning; interleaved TMS and fMRI ID TRANSCRANIAL MAGNETIC STIMULATION; BOLD-FMRI; CORTEX AB Objective: Transcranial magnetic stimulation (TMS) can be interleaved with fMRI to visualize regional brain activity in response to direct, non-invasive, cortical stimulation, making it a promising tool for studying brain function. A major practical difficulty is accurately positioning the TMS coil within the MRI scanner for stimulating a particular area of brain cortex. The objective of this work was to design and build a self-contained hardware/software system for MR-guided TMS coil positioning in interleaved TMS/fMRI studies. Methods: A compact, manually operated, articulated TMS coil positioner/holder with 6 calibrated degrees of freedom was developed for use inside a cylindrical RF head coil, along with a software package for transforming between MR image coordinates, MR scanner space coordinates, and positioner/holder settings. Results: Phantom calibration studies gave an accuracy for positioning within setups of dx = +/- 1.9 mm, dy = +/- 1.4 mm, dz = +/- 0.8 mm and a precision for multiple setups of dx = +/- 0.8 mm, dy = +/- 0.1 mm, dz = +/- 0.1 mm. Conclusions: This self-contained, integrated MR-guided TMS system for interleaved TMS/fMRI studies provides fast, accurate location of motor cortex stimulation sites traditionally located functionally, and a means of consistent, anatomy-based TMS coil positioning for stimulation of brain areas without overt response. (C) 2003 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 Med Univ S Carolina, Dept Radiol, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP Bohning, DE (reprint author), Med Univ S Carolina, Dept Radiol, Ctr Adv Imaging Res, 169 Ashley Ave, Charleston, SC 29425 USA. NR 15 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2003 VL 114 IS 11 BP 2210 EP 2219 DI 10.1016/S1388-2457(03)00232-3 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 743GH UT WOS:000186563700025 PM 14580621 ER PT J AU Goy, E Ganzini, L AF Goy, E Ganzini, L TI End-of-life care in geriatric psychiatry SO CLINICS IN GERIATRIC MEDICINE LA English DT Review ID ILL CANCER-PATIENTS; TERMINALLY-ILL; ALZHEIMERS-DISEASE; PALLIATIVE CARE; ADVANCED DEMENTIA; DEPRESSION SCALE; STAGE DEMENTIA; BEHAVIORAL DISTURBANCES; POSTOPERATIVE DELIRIUM; COGNITIVE IMPAIRMENT AB Depression, anxiety and delirium are relatively common during the final stages of terminal disease, and each can profoundly impact the quality of those last days for both patient and involved family. In this article the authors review the assessment and treatment of each syndrome in the context of palliative care for older adults. Treatment of mental disorders at the end of life warrants special consideration due to the need to balance the benefits of treatment against the potential burden of the intervention, especially those that might worsen quality of life. Dementia and the complications of depression and behavioral disturbance within dementia are also discussed. Finally, caregivers of dying patients are vulnerable to stress, depression, grief, and complicated bereavement. Interventions for caregivers who are debilitated by these states are briefly summarized. C1 Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. RP Goy, E (reprint author), Portland Vet Affairs Med Ctr, P3MHDC,POB 1034, Portland, OR 97207 USA. NR 113 TC 10 Z9 11 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD NOV PY 2003 VL 19 IS 4 BP 841 EP + DI 10.1016/S0749-0690(03)00029-6 PG 18 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 746KE UT WOS:000186744900010 PM 15024815 ER PT J AU Huh, J Wall, MJ Soltero, ER AF Huh, J Wall, MJ Soltero, ER TI Treatment of combined coronary and carotid artery disease SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE coronary; carotid; coronary artery bypass; carotid endarterectomy ID OFF-PUMP; MYOCARDIAL REVASCULARIZATION; CARDIOPULMONARY BYPASS; CONCOMITANT CORONARY; CARDIAC-SURGERY; RISK-FACTORS; FOLLOW-UP; ENDARTERECTOMY; STROKE; STENOSIS AB Despite a large volume of data present in the literature, the treatment indications and surgical options remain controversial. We currently advocate treatment of symptomatic territory first in favor of staged procedures and reserve combined procedures for patients with critical stenosis or symptoms in both territories. C1 Ben Taub Gen Hosp, Div Cardiothorac Surg, Houston Vet Affairs Med Ctr, Baylor Coll Med, Houston, TX 77030 USA. RP Huh, J (reprint author), Houston Vet Affairs Med Ctr 112, 2002 Holcombe Blvd, Houston, TX 77401 USA. EM joseph.huh@med.va.gov NR 51 TC 31 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD NOV PY 2003 VL 18 IS 6 BP 447 EP 453 DI 10.1097/00001573-200311000-00005 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 864IE UT WOS:000224626400005 PM 14597885 ER PT J AU Bi, LC Kaunitz, JD AF Bi, LC Kaunitz, JD TI Gastroduodenal mucosal defense: an integrated protective response SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE stomach; injury; Helicobacter pylori; nonsteroidal anti-inflammatory drugs; trefoil peptides; adrenomedullin ID HELICOBACTER-PYLORI INFECTION; TRANSMEMBRANE CONDUCTANCE REGULATOR; GASTRIC-ULCER; ACID-SECRETION; DUODENAL-ULCER; RAT; ADRENOMEDULLIN; STOMACH; CELLS; MICE AB Purpose of review The remarkable resistance of the mucosal lining the upper gastrointestinal tract to concentrated gastric acid remains one of the biggest unsolved mysteries of upper gastrointestinal physiology. Even with the discovery of the involvement of Helicobacter pylori in gastroduodenal injury, the mechanism by which the organism causes injury remains unresolved. In the past year, there have been striking findings regarding trefoil peptides, the protective effect of regulatory peptides such as adrenomedullin, and the influence of H. pylori on the junctions that join the epithelial cells. Recent findings Trefoil peptide-2-deficient mice were more susceptible to gastric injury from nonsteroidal anti-inflammatory agents, confirming that trefoil peptides increased the barrier properties of the pre-epithelial mucus gel. With regard to H. pylori, the gastric mucosa of mice deficient in the tyrosine phosphatase receptor type Z were not damaged by H. pylori vacuolating cytotoxin. Proton pump inhibition appears to be equally or more effective in upper gastrointestinal mucosal protection compared with other interventions such as exogenous prostaglandins or H. pylori eradication. Summary Peptic ulcer disease, although declining in prevalence, appears to be increasing in virulence, perhaps because of the overall aging of the population and improved intensive care unit care. Although H. pylori and nonsteroidal anti-inflammatory drugs have been identified as key pro-ulcerogenic factors, many ulcers may also result from a deficiency of other, unknown host protective factors. A more detailed understanding of the host factors involved in mucosal protection will thus help identify novel therapeutic targets aimed at the prevention and treatment of upper gastrointestinal mucosal injury. C1 W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Irvine, Irvine, CA USA. Long Beach VA Med Ctr, Long Beach, CA USA. Univ Calif Los Angeles, Sch Med, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Los Angeles, CA 90024 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Bldg 114,Suite 217, Los Angeles, CA 90073 USA. NR 49 TC 7 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2003 VL 19 IS 6 BP 526 EP 532 DI 10.1097/00001574-200311000-00003 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 735VM UT WOS:000186135300003 PM 15703600 ER PT J AU Wrobel, JS Charns, MP Diehr, P Robbins, JM Reiber, GE Bonacker, KM Haas, LB Pogach, L AF Wrobel, JS Charns, MP Diehr, P Robbins, JM Reiber, GE Bonacker, KM Haas, LB Pogach, L TI The relationship between provider coordination and diabetes-related foot outcomes SO DIABETES CARE LA English DT Article ID LOWER-EXTREMITY ULCERS; SURGICAL SERVICES; CARE; QUALITY; ASSOCIATION; UNITS AB OBJECTIVE - To investigate the relationship between provider coordination and amputations in patients with diabetes. RESEARCH DESIGN AND METHODS- The study design was a cross-sectional descriptive study of process and outcomes for diabetes-related foot care at 10 Department of Veterans Affairs (VA) medical centers representing different geographic regions, population densities, patient populations, and amputation rates. The subjects included all providers of diabetes foot care and a random sample of primary care providers at each medical center. The main outcome measures were the Foot Systems Assessment Tool (FootSAT), nontraumatic lower extremity amputation rates, and investigators' ordinal ranking of site effectiveness based on site visits. RESULTS - The survey response rate was 48%. Scale reliability, as measured by Cronach's alpha, ranged from 0.73 to 0.93. The scale scores for programming coordination ( medical record, policies, reminders, protocols, and educational seminars) and feedback coordination (i.e., discharge planning, quality of care meetings, and curbside consultations) were negatively associated with amputation rates, suggesting centers with higher levels of coordination had lower amputation rates. Statistically significant associations were found for programming coordination with minor amputations (P = 0.02) and total amputations (P = 0.04). CONCLUSIONS - The FootSAT demonstrated a stronger association with amputation rates than site visit rankings. Among these 10 VA facilities, those with higher levels of programming and feedback coordination had significantly lower amputation rates. C1 VA Med & Reg Off Ctr, Dept Vet Affairs, White River Jct, VT USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. Boston Univ, Sch Publ Hlth, VA Management Decis & Res Ctr, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Program Hlth Policy & Management, Boston, MA 02215 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Cleveland VA Med Ctr, Dept Vet Affairs, Cleveland, OH USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv & Res & Dev, Dept Vet Affairs, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Dept Vet Affairs, Seattle, WA USA. VA New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. RP Wrobel, JS (reprint author), VA White River Junct, Surg Serv, 112E, White River Jct, VT 05009 USA. NR 27 TC 23 Z9 23 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2003 VL 26 IS 11 BP 3042 EP 3047 DI 10.2337/diacare.26.11.3042 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738CL UT WOS:000186269100012 PM 14578237 ER PT J AU Maggard, MA Beanes, SR Ko, CY AF Maggard, MA Beanes, SR Ko, CY TI Anal canal cancer - A population-based reappraisal SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY JUN 03-09, 2002 CL CHICAGO, ILLINOIS SP Amer Soc Colon & Rectal Surg DE anal canal cancer; incidence rates; survival; racial/ethnic disparities ID RADIATION-THERAPY; RANDOMIZED TRIAL; CERVICAL-CANCER; CARCINOMA; CHEMOTHERAPY; CHEMORADIATION; RADIOTHERAPY; MITOMYCIN; OUTCOMES; PROGRAM AB PURPOSE: This study was designed to obtain an updated population-based perspective on anal canal cancer incidence rates, demographics, and outcomes using a nationwide database. Eight-five percent of all carcinomas of the anus are anal canal cancers, and previous studies suggest that incidence rates may be rising. Although the most successful treatment for anal canal cancer has been chemoradiation, little information at the population-level exists regarding demographics, treatment, and survival. METHODS: All patients diagnosed with anal canal cancer from 1973 to 1998 in the Surveillance Epidemiology and End Results cancer registry were analyzed. Data regarding demographics, cancer characteristics, treatment, and survival were assessed. Univariate and multivariate survival analyses were performed. RESULTS: A total of 4,841 patients were studied (mean age was 61 years; 62 percent female). Female patients were significantly older than male patients (65 vs. 58 years; P < 0.0001). There was a yearly increase in incidence of anal canal cancers (from 1973-1998). Disease prevalence by stage was localized (53 percent), regional (38 percent), and distant (9 percent). Racial/stage differences were seen, because black patients had less localized disease than white patients (46 vs. 53 percent; P < 0.01). Overall five-year survival for the entire cohort was 53 percent, and cancer-specific survival was 84 percent. Survival improved per decade (based on year of diagnosis). Significant survival differences in race were noted, but were less when the receipt of treatment was considered. CONCLUSION: Although most anal canal cancer reviews are single institutional series, this study was performed with population-based data. The incidence of anal canal cancer is increasing, and overall survival rates are improving. Important disparities in care were identified, which need to be addressed. C1 Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Robert Wood Johnson VA Clin Scholars Program, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm, Dept Surg, Los Angeles, CA USA. RP Maggard, MA (reprint author), Univ Calif Los Angeles, Sch Med, Dept Surg, 10833 Le Conte Ave,CHS Room 72-215, Los Angeles, CA 90095 USA. NR 28 TC 36 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD NOV PY 2003 VL 46 IS 11 BP 1517 EP 1523 DI 10.1097/01.DCR.0000093722.63657.B4 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 743FF UT WOS:000186561200012 PM 14605572 ER PT J AU Williams, DL Bowers, RR Bartness, TJ Kaplan, JM Grill, HJ AF Williams, DL Bowers, RR Bartness, TJ Kaplan, JM Grill, HJ TI Brainstem melanocortin 3/4 receptor stimulation increases uncoupling protein gene expression in brown fat SO ENDOCRINOLOGY LA English DT Article ID ROSTRAL VENTROLATERAL MEDULLA; NUCLEUS-TRACTUS-SOLITARIUS; CENTRAL-NERVOUS-SYSTEM; AGOUTI-RELATED PROTEIN; BETA-ENDORPHIN; MESSENGER-RNA; ADAPTIVE THERMOGENESIS; ADIPOSE-TISSUE; HORMONE GENE; BODY-WEIGHT AB Central administration of melanocortin 3 and 4 receptor (MC3/4-R) agonists increases energy expenditure, with the hypothalamus commonly held as the primary site of action. It is also clear, however, that MC4-R are expressed in caudal brainstem structures of relevance to the control of energy expenditure. Three experiments investigated whether hindbrain MC-R contribute to the energy expenditure effects of central MC3/4-R agonist treatments; in each, we examined the effect of fourth intracerebroventricular (icv) administration of a MC3/4-R agonist, MTII ( three injections, each separated by 12 h), on uncoupling protein 1 (UCP-1) gene expression in brown adipose tissue ( BAT). First, we compared the effects of fourth and third icv administration of MTII and found that the hindbrain and forebrain treatments were equally effective at elevating UCP-mRNA expression in BAT compared with the respective vehicle-treated group results. A second experiment demonstrated that the fourth icv MTII-induced rise in UCP-1 expression was mediated by sympathetic outflow to BAT by showing that this response was abolished by surgical denervation of BAT. In the third experiment, we showed that chronic decerebrate rats, like their neurologically intact controls, elevated UCP-1 mRNA expression in response to fourth icv MTII administration. Taken together, the results indicate that: 1) there is an independent caudal brainstem MC3/4-R trigger for a sympathetically stimulated elevation in BAT UCP-1 gene expression, and 2) the MTII-induced rise in UCP-1 expression can be mediated by circuitry intrinsic to the caudal brainstem and spinal cord. C1 Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. RP Williams, DL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111 Endo, Seattle, WA 98108 USA. RI Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 FU NIDDK NIH HHS [DK-42284, DK32524, DK-21397] NR 50 TC 71 Z9 71 U1 2 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2003 VL 144 IS 11 BP 4692 EP 4697 DI 10.1210/en.2003-0440 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 736PB UT WOS:000186178300004 PM 12960080 ER PT J AU Ostrow, JD Pascolo, L Shapiro, SM Tiribelli, C AF Ostrow, JD Pascolo, L Shapiro, SM Tiribelli, C TI New concepts in bilirubin encephalopathy SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Review DE bilirubin; jaundice; neonates; nuerotoxicity; encephalopathy; kernicterus ID RESISTANCE-ASSOCIATED PROTEIN; APOPTOSIS INHIBITORY PROTEIN; CENTRAL-NERVOUS-SYSTEM; BRAIN-STEM RESPONSES; JAUNDICED GUNN-RATS; EVOKED-POTENTIAL ABNORMALITIES; GLUTATHIONE-S-TRANSFERASES; ORGANIC ANION TRANSPORTER; MDR1 P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE AB Revised concepts of bilirubin encephalopathy have been revealed by studies of bilirubin toxicity in cultured CNS cells and in congenitally jaundiced Gunn rats. Bilirubin neurotoxicity is related to the unbound (free) fraction of unconjugated bilirubin (B-f), of which the dominant species at physiological pH is the protonated diacid, which can passively diffuse across cell membranes. As the binding affinity of plasma albumin for bilirubin decreases strikingly as albumin concentration increases, previously reported B-f values were underestimated. Newer diagnostic tests can detect reversible neurotoxicity before permanent damage occurs from precipitation of bilirubin (kernicterus). Early toxicity can occur at B-f only modestly above aqueous saturation and affects astrocytes and neurons, causing mitochondrial damage, resulting in impaired energy metabolism and apoptosis, plus cell-membrane perturbation, which causes enzyme leakage and hampers transport of neurotransmitters. The concentrations of unbound bilirubin in the cerebro-spinal fluid and CNS cells are probably limited mainly by active export of bilirubin back into plasma, mediated by ABC transporters present in the brain capillary endothelium and choroid plexus epithelium. Intracellular bilirubin levels may be diminished also by oxidation, conjugation and binding to cytosolic proteins. These new concepts may explain the varied susceptibility of neonates to develop encephalopathy at any given plasma bilirubin level and the selective distribution of CNS lesions in bilirubin encephalopathy. They also can suggest better strategies for predicting, preventing and treating this syndrome. C1 Univ Washington, Sch Med, Dept Med, GI Hepatol Div, Seattle, WA 98195 USA. Univ Trieste, Liver Res Ctr, Trieste, Italy. Univ Trieste, Dept BBCM, Trieste, Italy. Virginia Commonwealth Univ, Med Coll Virginia, Dept Neurol, Div Pediat Neurol, Richmond, VA 23298 USA. RP Ostrow, JD (reprint author), VA Puget Sound Hlth Care Syst, Res Serv 151 L, Seattle Div, 1600 S Columbian Way, Seattle, WA 98108 USA. FU NIDCD NIH HHS [R01-DC00369] NR 149 TC 79 Z9 85 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD NOV PY 2003 VL 33 IS 11 BP 988 EP 997 DI 10.1046/j.1365-2362.2003.01261.x PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 737NA UT WOS:000186237600009 PM 14636303 ER PT J AU Barger, JL Walford, RL Weindruch, R AF Barger, JL Walford, RL Weindruch, R TI The retardation of aging by caloric restriction: its significance in the transgenic era SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE aging; dwarf mice; insulin-like growth factor-1; growth hormone; transgenic mice ID AMES DWARF MICE; LIFE-SPAN EXTENSION; GROWTH-FACTOR-I; INSULIN-RECEPTOR; OXIDATIVE STRESS; DROSOPHILA-MELANOGASTER; EXTENDED LONGEVITY; SIGNALING PATHWAY; ADIPOSE-TISSUE; HORMONE AB The retardation of aging and diseases by caloric restriction (CR) is a widely-studied and robust phenomenon. Recent publications describe transgenic and other mutant rodents displaying lifespan extension, and the rapid pace at which these animals are being generated raises the possibility that the importance of the CR paradigm is declining. Here we discuss these models and evaluate the evidence whether or not the aging process is retarded based on longevity, disease patterns and age-associated biological changes. A comparison to rodents on CR is made. Because CR has been investigated for similar to70 years with increasing intensity, there exists extensive data to document aging retardation. In contrast, for nearly all of the genetically abnormal models of lifespan extension, such data are minimal and often unconvincing; additional studies will be required to validate these strains as suitable models for aging research. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. RP Weindruch, R (reprint author), Univ Wisconsin, William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, 2500 Overlook Terrace, Madison, WI 53705 USA. EM rhweindr@wisc.edu OI Barger, Jamie/0000-0001-8694-0068 FU NIA NIH HHS [T32AG00213, P01 AG11915, R01 AG18922] NR 44 TC 103 Z9 106 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 2003 VL 38 IS 11-12 BP 1343 EP 1351 DI 10.1016/j.exger.2003.10.017 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 766ZC UT WOS:000188412800015 PM 14698815 ER PT J AU Liang, HY Masoro, EJ Nelson, JF Strong, R McMahon, CA Richardson, A AF Liang, HY Masoro, EJ Nelson, JF Strong, R McMahon, CA Richardson, A TI Genetic mouse models of extended lifespan SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE dwarf mice; caloric restriction; insulin like growth factor-I; insulin receptor; growth hormone receptor binding protein ID RECEPTOR/BINDING PROTEIN GENE; AMES DWARF MICE; GROWTH-HORMONE LEVELS; FED AD-LIBITUM; OXIDATIVE STRESS; SIGNALING PATHWAY; CALORIC RESTRICTION; DIETARY RESTRICTION; INSULIN-RECEPTOR; DISRUPTED MICE AB Since 1996, seven genetic mouse models have been reported to show increased lifespan: Ames and Snell dwarf mice, the 'little mouse' (Ghrhr(lit/lit)), mice null for either growth hormone receptor/binding protein (GHR/BP-/-) or p66(shc) (p66(shc-/-)), mice heterozygous for the IGF-I receptor (Igflr(+/-)), and fat-specific insulin receptor knockout mice. In this article, we describe and evaluate these mouse models with respect to their relevance for aging studies. While these seven genetic models all show a significant increase in lifespan, issues of sample size and animal husbandry procedures require further evaluation before firm conclusions can be drawn on the reproducibility of life extension in most of these mouse models. Because data on the age-related pathology and physiological functions are lacking for all of the models, except the dwarf mice, it is too early to conclude that aging is retarded in these mouse models. However, these mouse models are already providing new information about the mechanism underlying mammalian aging. (C) 2003 Elsevier Inc. 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, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78284 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr,MSC 7762, San Antonio, TX 78229 USA. EM richardsona@uthscsa.edu RI Liang, Hanyu/A-1066-2010 NR 79 TC 138 Z9 140 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 2003 VL 38 IS 11-12 BP 1353 EP 1364 DI 10.1016/j.exger.2003.10.019 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 766ZC UT WOS:000188412800016 PM 14698816 ER PT J AU Stackman, RW Eckenstein, F Frei, B Kulhanek, D Nowlin, J Quinn, JF AF Stackman, RW Eckenstein, F Frei, B Kulhanek, D Nowlin, J Quinn, JF TI Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment SO EXPERIMENTAL NEUROLOGY LA English DT Article DE amyloid; oxidative stress; spatial learning; spatial memory; hippocampus; Alzheimer; Tg2576; antioxidant ID AMYLOID-BETA-PROTEIN; EXTRACT EGB 761; HEALTHY-YOUNG VOLUNTEERS; GLOBAL BRAIN ISCHEMIA; RAT HIPPOCAMPAL CELLS; OXIDATIVE STRESS; IN-VIVO; A-BETA; PHOSPHOLIPID BREAKDOWN; GINSENG COMBINATION AB Alzheimer's disease (AD) is characterized by cognitive decline and deposition of beta-amyloid (Abeta) plaques in cortex and hippocampus. A transgenic mouse AD model (Tg2576) that overexpresses a mutant form of human Abeta precursor protein exhibits age-related cognitive deficits, Abeta plaque deposition, and oxidative damage in the brain. We tested the ability of Ginkgo biloba, a flavonoid-rich antioxidant, to antagonize the age-related behavioral impairment and neuropathology exhibited by Tg2576 mice. At 8 months of age, 16 female Tg2576 and 15 female wild-type (wt) littermate mice were given ad lib access to tap water or Ginkgo biloba (70 mg/kg/day in water). After 6 months of treatment, all mice received Morris water maze training (4 trials/day for 10 days) to assess hippocampal dependent spatial learning. All mice received a 60-s probe test of spatial memory retention 24 It after the 40th trial. Untreated Tg2576 mice exhibited a spatial learning impairment, relative to wt mice, while Ginkgo biloba-treated Tg2576 mice exhibited spatial memory retention comparable to wt during the probe test. Spatial learning was not different between Ginkgo biloba-treated and untreated wt mice. There were no group differences in learning to swim to a visible platform. Soluble Abeta and hippocampal Abeta plaque burden did not differ between the Tg2576 groups. Brain levels of protein carbonyls were paradoxically elevated in Ginkgo biloba-treated mice. These data indicate that chronic Ginkgo biloba treatment can block an age-dependent decline in spatial cognition without altering Abeta levels and without suppressing protein oxidation in a transgenic mouse model of AD. (C) 2003 Elsevier Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon State Univ, Linus Pauling Inst Sci & Med, Corvallis, OR 97331 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Stackman, RW (reprint author), Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. OI Stackman Jr, Robert/0000-0002-5950-046X FU NCCIH NIH HHS [NIH-AT00066]; NIA NIH HHS [AG07424, NIA AG08017] NR 81 TC 144 Z9 159 U1 2 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2003 VL 184 IS 1 BP 510 EP 520 DI 10.1016/S0014-4886(03)00399-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 747KZ UT WOS:000186804800052 PM 14637120 ER PT J AU Ledoux, WR Shofer, JB Ahroni, JH Smith, DG Sangeorzan, BJ Boyko, EJ AF Ledoux, WR Shofer, JB Ahroni, JH Smith, DG Sangeorzan, BJ Boyko, EJ TI Biomechanical differences among pes cavus, neutrally aligned, and pes planus feet in subjects with diabetes SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE diabetes mellitus; flatfoot; foot deformities ID MEDIAL LONGITUDINAL ARCH; FOOT; RELIABILITY AB The purpose of this study was to quantify differences in joint range of motion, foot deformity, and foot morphology among pes cavus, neutrally aligned, pes planus rigid, and pes planus flexible feet. A cohort of 1047 veterans with diabetes (contributing 2047 feet) was enrolled in a prospective study of diabetic ulcer risk factors (the Seattle Diabetic Foot Study). Significant differences between foot types were found. Pes cavus feet had an increased percentage of prominent metatarsal heads, bony prominences, and hammer/claw toes (p < .0001), as well as significantly increased amounts of hallux dorsiflexion and decreased amounts of hallux plantarflexion (p < .0001) with a total range of motion equal to the other foot types (p = .3). Neutrally aligned feet had a lower percentage of intrinsic muscle atrophy, bony prominences, and hammer/claw toes (p < .0001). Pes planus feet had an increased lateral talometatarsal angle (p < .0001) and an increased second metatarsal length. These data demonstrate structural differences between foot types in a population with diabetes. C1 VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Epidemiol Res & Informat Ctr, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Res & Dev Serv, Epidemiol Res & Informat Ctr, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Gen Internal Med Sect, Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Epidemiol Res & Informat Ctr, MS 151,1660 S Columbian Way, Seattle, WA 98108 USA. RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714; Boyko, Edward/0000-0002-3695-192X NR 25 TC 34 Z9 34 U1 0 U2 3 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD NOV PY 2003 VL 24 IS 11 BP 845 EP 850 PG 6 WC Orthopedics SC Orthopedics GA 745AH UT WOS:000186664700007 PM 14655889 ER PT J AU Rattan, R Giri, S Singh, AK Singh, I AF Rattan, R Giri, S Singh, AK Singh, I TI Rho A negatively regulates cytokine-mediated inducible nitric oxide synthase expression in brain-derived transformed cell lines: Negative regulation of IKK alpha SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE statins; RhoA; geranylgeranylation; NF-kappa B; iNOS; IKK alpha; CBP/p300; free radicals ID SMOOTH-MUSCLE-CELLS; DIFFICILE TOXIN-B; REDUCTASE INHIBITORS; MULTIPLE-SCLEROSIS; KAPPA-B; PROTEINS; INDUCTION; GTPASE; STATINS; GERANYLGERANYLATION AB The present study describes the role of RhoA as a negative regulator of iNOS expression via the inactivation of NF-kappaB in transformed brain cell lines [C-6 glioma, human astrocytoma (T98G, A172), neuroblastoma (NEB), and immortal rat astrocytes]. Treatment with lovastatin resulted in the induction of LPS/IFN-gamma-mediated iNOS mRNA and increased nitric oxide (NO) production. The addition of mevalonate and geranylgeranylpyrophosphate (GGPP) reversed the lovastatin-mediated effect, whereas FPP had no effect. An inhibitor of geranylgeranyltransferase inhibitor (GGTI 298) further induced the cytokine and lovastatin-mediated iNOS expression, suggesting the involvement of geranylgeranylated proteins in the regulation of iNOS. Bacterial toxin B (inactivates RhoA, B, and C; CDC42; Rac proteins), C3 ADP-ribosyltransferase (0) toxin from C. botulinum (inactivates RhoA, B, and C proteins), and Y-27632 (selective inhibitor of Rho-associated kinases) increased the LPS/IFN-gamma-mediated iNOS expression. Lovastatin treatment induced NO by increasing NF-kappaB translocation and its association with the CREB-binding protein (CBP/p300) via the downregulation of RhoA. Inhibition of RhoA resulted in increased activation of IKKalpha. Cotransfection studies with dominant-negative form of RhoA and iNOS-luciferase or NF-kappaB-luciferase reporter constructs further support these observations. Taken together, these studies show that downregulation of RhoA by lovastatin resulted in increased iNOS expression via the activation of NF-kappaB-CBP/p300 pathway in transformed brain cells. (C) 2003 Elsevier Inc. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Ctr, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 96 Jonathan Lucas St,316 Clin Sci Bldg, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-34741, NS 37766, NS-40810, NS-22576] NR 35 TC 41 Z9 41 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2003 VL 35 IS 9 BP 1037 EP 1050 DI 10.1016/S0891-5849(03)00459-3 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 734JP UT WOS:000186052400005 PM 14572607 ER PT J AU Ran, QT Van Remmen, H Gu, MJ Qi, WB Roberts, LJ Prolla, T Richardson, A AF Ran, QT Van Remmen, H Gu, MJ Qi, WB Roberts, LJ Prolla, T Richardson, A TI Embryonic fibroblasts from Gpx4(+/-) mice: A novel model for studying the role of membrane peroxidation in biological processes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE phospholipid hydroperoxide glutathione peroxidase; oxidative stress; knockout mice; lipid peroxidation; free radicals ID OXIDATIVE DNA-DAMAGE; GLUTATHIONE-PEROXIDASE; LIPID-PEROXIDATION; HYDROPEROXIDE; CELLS; APOPTOSIS; MITOCHONDRIA; HEPATOCYTES; SENESCENCE; CULTURES AB A previous study using mice null for Gpx4 indicates that PHGPx plays a critical role in antioxidant defense and is essential for the survival of the mouse. In the present study, we further analyzed the stress response of MEFs (murine embryonic fibroblasts) derived from mice heterozygous for the Gpx4 gene (Gpx4(+/-) mice). MEFs from Gpx4(+/-) mice have a 50% reduction in PHGPx expression without any changes in the activities of other major antioxidant defense enzymes. Compared to MEFs from Gpx4(+/+) mice, MEFs from Gpx4(+/-) mice were more sensitive to exposure to the oxidizing agent t-butyl hydroperoxide (t-BuOOH), and t-BuOOH exposure induced increased apoptosis in MEFs from Gpx4(+/-) mice. When cultured at low cell density, MEFs from Gpx4(+/-) mice also showed retarded growth under normal culture conditions (20% oxygen) that was reversed by culturing under low oxygen (2% oxygen). In addition, oxidative damage was increased in the MEFs from the Gpx4(+/-) mice, as indicated by increased levels of F-2-isoprostanes and 8-oxo-2-deoxyguanosine in these cells. Our data demonstrate that MEFs from Gpx4(+/-) mice are more sensitive to oxidative stress because of reduced expression of PHGPx. (C) 2003 Elsevier Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Vanderbilt Univ, Dept Med & Pharmacol, Nashville, TN USA. Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, Mail Code 7756,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCI NIH HHS [CA68485]; NIA NIH HHS [1P30-AG13319, AG015908, AG19316]; NIDDK NIH HHS [DK26657]; NIGMS NIH HHS [GM15431, GM42056] NR 29 TC 32 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2003 VL 35 IS 9 BP 1101 EP 1109 DI 10.1016/S0891-5849(03)00466-0 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 734JP UT WOS:000186052400010 PM 14572612 ER PT J AU Sonnenberg, A Lieberman, DA AF Sonnenberg, A Lieberman, DA TI Calculating the benefit of a negative endoscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID COST-EFFECTIVENESS; RENAL-FAILURE; DYSPEPSIA; CANCER C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2003 VL 58 IS 5 BP 752 EP 754 AR PII S0016-5107(03)02022-4 DI 10.1016/S0016-5107(03)02022-4 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 739GY UT WOS:000186337800017 PM 14595313 ER PT J AU Epstein, JB Feldman, R Dolor, RJ Porter, SR AF Epstein, JB Feldman, R Dolor, RJ Porter, SR TI The utility of tolonium chloride rinse in the diagnosis of recurrent or second primary cancers in patients with prior upper aerodigestive tract cancer SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE diagnostic sensitivity; oropharyngeal cancer; tolonium chloride ID TOLUIDINE BLUE APPLICATION; SQUAMOUS-CELL CARCINOMAS; ORAL-CANCER; EPITHELIAL DYSPLASIA; STAINING TEST; RISK; TOBACCO; LESIONS; LEUKOPLAKIA; SENSITIVITY AB Background. The clinical utility of tolonium chloride rinse was compared with unaided visual examination alone in the diagnosis of oral carcinoma in patients previously treated for carcinoma of the upper aerodigestive tract. Methods. A total of 668 patients were enrolled in this multicenter study. At each site, an oral clinical visual examination was completed by one investigator followed by tolonium chloride rinse and examination by a second investigator blinded to the examination findings of the first investigator. If a lesion was considered suspicious (urgent biopsy required at the first visit), the lesion was biopsied after tolonium chloride rinsing. Patients with lesions characterized at the first visit as not suspicious (biopsy not urgent) or that stained with tolonium chloride were asked to return for a second visit. At the second visit, any residual lesion or lesions that retained tolonium chloride were biopsied. Results. A total of 96 biopsies was performed in 81 of the 668 patients (12.1%), of which 30 (31.3%) were diagnosed histologically as carcinoma/carcinoma in situ (CIS) and the remainder as inflammation (31.3%), keratosis (26.6%), dysplasia (21.9%), ulcer (2.1%), other (3.1%), or no abnormality (1.0%). Of the 30 lesions with the diagnosis of carcinoma/CIS, 12 (sensitivity 40.0%) were considered to be clinically suspicious (CS+), whereas 29 (sensitivity 96.7%) retained tolonium chloride (p = .0002). The predictive values of a positive test for clinical examination and tolonium chloride staining were similar (36.4% vs 32.6%; p = .5871), indicating that the greater sensitivity of tolonium chloride was not associated with an excessive number of unnecessary biopsies (false positives). Conclusions. Tolonium chloride rinse is more sensitive than clinical examination alone in detecting lesions that might be found on biopsy to be carcinoma or CIS. The increased sensitivity is largely attributed to lesions that stain but were not detected clinically on visual examination. (C) 2003 Wiley Periodicals, Inc. C1 British Columbia Canc Agcy, Div Dent, Vancouver, BC V5Z 4E6, Canada. Univ & Woodland Ave, Dent Serv, Vet Affairs Med Ctr, Philadelphia, PA USA. Vet Affairs Med Ctr, Durham, NC USA. UCL Eastman Dent Inst, London, England. RP Epstein, JB (reprint author), British Columbia Canc Agcy, Div Dent, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM jepstein@uic.edu NR 46 TC 52 Z9 53 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD NOV PY 2003 VL 25 IS 11 BP 911 EP 921 DI 10.1002/hed.10309 PG 11 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 736FJ UT WOS:000186160500004 PM 14603451 ER PT J AU Wu, J Haugk, K Plymate, SR AF Wu, J Haugk, K Plymate, SR TI Activation of pro-apoptotic p38-MAPK pathway in the prostate cancer cell line M12 expressing a truncated IGF-IR SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE pAkt; PI3K; ERK; 486/STOP; insulin-like growth factor I (IGF-I) ID DOMINANT-NEGATIVE MUTANT; GROWTH-FACTOR RECEPTOR; SIGNAL-TRANSDUCTION; TUMOR-GROWTH; IN-VIVO; INSULIN; PHOSPHORYLATION; TUMORIGENESIS; INHIBITION; SURVIVAL AB The type I insulin-like growth factor receptor (IGF-IR) plays a critical role in signaling survival and proliferation in many cell types. Activation of IGF-IR by its ligands promotes cell proliferation via mitogen-activated protein kinase (MAPK) cascade and cell survival via phosphoinositide 3-kinase (PI3K) cascade. The IGF-IR emerges as a powerful growth factor for many tumor cells. A truncated IGF-IR 486/STOP, described as a dominant negative IGF-IR mutant, was shown to induce apoptosis and inhibit tumor growth in vivo while endogenous IGF-IR was activated. To investigate the mechanism(s) of the action of 486/STOP, we have introduced 486/STOP into the prostate tumor model cell line M12 and its derivative M12lisn that expresses high levels of wild type IGF-IR. We have found that 486/STOP induces apoptosis in M12 and M12lisn cells in culture and that 486/STOP acts through activation of the pro-apoptotic p38-MAPK without interfering with wild type IGF-IR activation. In addition, our results have indicated that 486/STOP induced activation of p38-MAPK increases through activation of endogenous IGF-IR. These data suggest that activation of the IGF-IR by 486/STOP can selectively enhance the previously reported IGF-IR pro-apoptotic signaling pathways. C1 Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Plymate, SR (reprint author), Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Box 359755,325 9th Ave, Seattle, WA 98104 USA. EM splymate@u.washington.edu FU NCI NIH HHS [P01 CA85859]; NIDDK NIH HHS [R01DK52683] NR 27 TC 12 Z9 13 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV-DEC PY 2003 VL 35 IS 11-12 BP 751 EP 757 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761UB UT WOS:000187932900014 PM 14710354 ER PT J AU Butts, BD Linseman, DA Le, SS Laessig, TA Heidenreich, KA AF Butts, BD Linseman, DA Le, SS Laessig, TA Heidenreich, KA TI Insulin-like growth factor-I suppresses degradation of the pro-survival transcription factor myocyte enhancer factor 2D (MEF2D) during neuronal apoptosis SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE cerebellar granule neurons; neurodegeneration; programmed cell death; caspases; signal transduction ID CEREBELLAR GRANULE NEURONS; FACTOR 2A; IGF-I; BINDING-PROTEINS; GENE-EXPRESSION; CELL-SURVIVAL; CANCER CELLS; PHOSPHORYLATION; ACTIVATION; DEATH AB Cultured rat cerebellar granule neurons (CGNs) require depolarization-mediated calcium influx for survival. Calcium regulates the activity of the pro-survival transcription factor, myocyte enhancer factor 2D (MEF2D). MEF2D is hyperphosphorylated and degraded in CGNs undergoing apoptosis induced by lowering the extracellular potassium concentration from 25 mM to 5 mM. Since insulin-like growth factor-I (IGF-I) is known to protect CGNs from apoptotic cell death, we investigated the effects of IGF-I on MEF2D processing during apoptosis. IGF-I administered during the apoptotic insult did not prevent the hyperphosphorylation of MEF2D and consequential loss of DNA binding. However, IGF-I significantly blocked the degradation of MEF2D. Furthermore, IGF-I had no effect on the initial loss of MEF2 transcriptional activity following hyperphosphorylation, but the recovery of MEF2 activity following restoration of intracellular calcium was significantly increased by IGF-I. We conclude that IGF-I blocks the degradation of MEF2D and enhances recovery of MEF2 activity by protecting MEF2D from caspase-dependent cleavage during apoptosis. These results suggest that IGF-I can prolong the time of commitment to irreversible cell death and enhance the recovery of neurons subjected to an acute apoptotic stimulus by preserving the activity of the pro-survival factor MEF2D. C1 Denver VAMC, Denver, CO 80220 USA. Univ Colorado, Ctr Hlth Sci, Dept Pharmacol, Denver, CO 80202 USA. RP Heidenreich, KA (reprint author), Denver VAMC, 111H,1055 Clermont St, Denver, CO 80220 USA. EM kim.heidenreich@uchsc.edu FU NINDS NIH HHS [NS38619-01A1] NR 52 TC 10 Z9 10 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV-DEC PY 2003 VL 35 IS 11-12 BP 763 EP 770 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761UB UT WOS:000187932900016 PM 14710356 ER PT J AU Sharma, S Batra, RK Yang, SC Hillinger, S Zhu, L Atianzar, K Strieter, RM Riedl, K Huang, M Dubinett, SM AF Sharma, S Batra, RK Yang, SC Hillinger, S Zhu, L Atianzar, K Strieter, RM Riedl, K Huang, M Dubinett, SM TI Interleukin-7 gene-modified dendritic cells reduce pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma SO HUMAN GENE THERAPY LA English DT Article ID GROWTH-FACTOR-BETA; COLONY-STIMULATING FACTOR; ANGIOGENESIS IN-VIVO; MHC CLASS-I; T-CELL; LUNG-CANCER; ANTITUMOR IMMUNITY; INTERFERON-GAMMA; DOWN-REGULATION; INTRATUMORAL INJECTION AB The antitumor efficiency of dendritic cells transduced with an adenovirus vector expressing interleukin (IL)-7 (DC-AdIL-7) was evaluated in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg), expressing the SV40 large T antigen under the Clara cell promoter, develop bilateral multifocal pulmonary adenocarcinomas and die at 4 months as a result of progressive pulmonary tumor burden. Injection of DC-AdIL-7 in the axillary lymph node region (ALNR) weekly for 3 weeks led to a marked reduction in tumor burden with extensive lymphocytic infiltration of the tumors and enhanced survival. The antitumor responses were accompanied by the enhanced elaboration of interferon (IFN)-gamma and IL-12 as well as an increase in the antiangiogenic chemokines, IFN-gamma-inducible protein 10 (IP-10/CXCL10) and monokine induced by IFN-gamma (MIG/CXCL9). In contrast, production of the immunosuppressive mediators IL-10, transforming growth factor (TGF)-beta, prostaglandin E-2 (PGE(2)), and the proangiogenic modulator vascular endothelial growth factor ( VEGF) decreased in response to DC-AdIL-7 treatment. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for further evaluation of DC-AdIL-7 in regulation of tumor immunity and its use in lung cancer genetic immunotherapy. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med,Dept Med, Ctr Hlth Sci 37 131,Lung Canc Res Program, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA 90073 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med,Dept Med, Ctr Hlth Sci 37 131,Lung Canc Res Program, 0833 LeConte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [P50 CA090388, CA 85686, P50 CA 90388, R01 CA 78654, R01 CA078654, R01 CA085686] NR 76 TC 23 Z9 24 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2003 VL 14 IS 16 BP 1511 EP 1524 DI 10.1089/104303403322495025 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 736MX UT WOS:000186175500002 PM 14577913 ER PT J AU Huang, TT Zong, YM Dalwadi, H Chung, C Miceli, MC Spicher, K Birnbaumer, L Braun, J Aranda, R AF Huang, TT Zong, YM Dalwadi, H Chung, C Miceli, MC Spicher, K Birnbaumer, L Braun, J Aranda, R TI TCR-mediated hyper-responsiveness of autoimmune G alpha i2(-/-) mice is an intrinsic naive CD4(+) T cell disorder selective for the G alpha i2 subunit SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE autoimmunity; mucosa; signal transduction; T lymphocytes; TCR ID PERTUSSIS TOXIN; G-PROTEINS; ALPHA-SUBUNITS; MEMORY CELLS; LYMPHOCYTES; RECEPTOR; EXPRESSION; ACTIVATION; CHANNELS; ANTIGEN AB Heterotrimeric Gi signaling regulates immune homeostasis, since autoimmunity occurs upon disruption of this pathway. However, the role of the lymphocyte-expressed Galphai subunits (Galphai2 and 3) on T cell activation and cytokine production is poorly understood. To examine this role, we studied T lymphocytes from mice deficient in the Galphai2 or Galphai3 subunits. Galphai2(-/-) but not Galphai3(-/-) splenocytes were hyper-responsive for IFN-gamma and IL-4 production following activation through the TCR. Galphai2(-/-) T cells had a relaxed costimulatory requirement for IL-2 secretion and proliferation compared to wild-type cells. Purified naive Galphai2(-/-) T cells produced more IL-2 than naive wild-type T cells following TCR activation, indicating that the hyper-responsive cytokine profile was not due to the expanded Galphai2(-/-), memory T cells, but involved an intrinsic T cell alteration. Cytokine hyper-responsiveness was not seen when purified Galphai2(-/-) T cells were stimulated with phorbol myristic acetate/ionomycin, localizing the alteration to a proximal TCR-specific signaling pathway. Galphai2(-/-) CD4(+) T cells were distinguished from wild-type or Galphai3(-/-) T cells by a globally augmented TCR-induced calcium response. These findings indicate that Galphai2(-/-) mice have an intrinsic CD4(+) T cell abnormality in TCR signaling which may be one cause of augmented T cell effector function and Galphai2(-/-) autoimmune susceptibility. C1 Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. VA GReater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Braun, J (reprint author), Univ Calif Los Angeles, Inst Mol Biol, Box 951732,CHS 13-222, Los Angeles, CA 90095 USA. FU NCI NIH HHS [CA 16042, R01 CA 65979]; NIAID NIH HHS [5T32 AI 07325, AI 07126-23, AI 28697]; NIDDK NIH HHS [DK 43026, DK 46763] NR 45 TC 44 Z9 46 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2003 VL 15 IS 11 BP 1359 EP 1367 DI 10.1093/intimm/dxg135 PG 9 WC Immunology SC Immunology GA 739CX UT WOS:000186325600010 PM 14565934 ER PT J AU Chen, F Ng, PS Faull, KF Lee, RH AF Chen, F Ng, PS Faull, KF Lee, RH TI Cone photoreceptor beta gamma-transducin: Posttranslational modification and interaction with phosducin SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL ROD; CRYSTAL-STRUCTURE; PROTEIN-BINDING; ALPHA-SUBUNIT; CELLS; IDENTIFICATION; COMPLEX; ISOPRENYLATION/METHYLATION; PHOSPHODIESTERASE; PHOSPHORYLATION AB PURPOSE. To characterize the structure of cone betagamma-transducin (Tbeta3gamma8) and its interaction with phosducin (pdc). METHODS. The Tgamma8 subunit of Tbeta3gamma8 was isolated by column chromatography for peptide mapping with mass spectrometry. Tbeta3gamma8 was compared with rod betagamma-transducin (Tbeta1gamma1) in terms of the electrophoretic mobility, pdc binding affinity, and the effects of phosphorylation and methylation, and then the correlation to the crystal structures and functional domains of Tbeta1gamma1 was determined. RESULTS. The mature Tgamma8 is a 65-amino-acid peptide encoded by the Ggamma8 gene with an acetylated and a farnesylated-methylated N- and C-terminus, respectively. Purified Tbeta3gamma8 is similar to Tbeta1gamma1 in that (1) both are heterogeneous, containing methylated and demethylated Tgamma subunits; (2) each demethylated dimer migrates faster than its methylated counterpart during native gel electrophoresis, and the methylation-associated mobility differential is masked by pdc binding; and (3) both dimers bind pdc with the same affinity, and the affinity is reduced threefold by PKA phosphorylation of pdc and twofold by demethylation at the C-terminus of Tgamma. Tbeta3gamma8 differs from Tbeta1gamma1 in. exhibiting lower intrinsic electrophoretic mobility, and the difference is unaffected by either pdc binding or the status of Tgamma methylation. CONCLUSIONS. Tbeta3gamma8 is identical with Tbeta1gamma1 in Tgamma isoprenylation, the spatial organization, and the mode of pdc binding, indicating that its interaction with pdc does not play an important role in the specialization of cones. Changes in Tbetagamma characteristics by Tgamma methylation reveal conformational changes on a surface domain that is essential for Tbetagamma functions and support a regulatory role for reversible methylation. C1 VA Greater LA Healthcare Syst Sepulveda, Mol Neurol Lab, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Pasaraw Mass Spectormetry Lab, Dept Chem Biochem Psychiat & Behav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Lee, RH (reprint author), VA Greater LA Healthcare Syst Sepulveda, Mol Neurol Lab, Mail Code 151B9,16111 Plummer St, Sepulveda, CA 91343 USA. EM rlee@ucla.edu FU NEI NIH HHS [EY09936] NR 41 TC 5 Z9 5 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2003 VL 44 IS 11 BP 4622 EP 4629 DI 10.1167/iovs.03-0420 PG 8 WC Ophthalmology SC Ophthalmology GA 737LL UT WOS:000186231800004 PM 14578377 ER PT J AU Neuzil, KM Coffey, CS Mitchel, EF Griffin, MR AF Neuzil, KM Coffey, CS Mitchel, EF Griffin, MR TI Cardiopulmonary hospitalizations during influenza season in adults and adolescents with advanced HIV infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE influenza; HIV infection; AIDS ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; VACCINATION; MORTALITY; MORBIDITY; VIRUS AB The etiologic role of influenza in hospitalizations and deaths among persons infected with HIV since the introduction of highly active antiretroviral therapy (HAART) is not known. A retrospective cohort study was performed of all persons aged 15 to 50 years with AIDS or advanced HIV infection enrolled in the Tennessee Medicaid program from 1995 through 1999, representing 7368 person-years of follow-up. The influenza season was defined based on local virus surveillance, and hospitalizations were measured for acute cardiopulmonary causes and deaths from any cause throughout the year. From 1995 through 1999, cardiopulmonary hospitalization rates in HIV-infected patients declined by 53% and death rates declined by 77%. The influenza-attributable hospitalization rate was 48 (95% confidence interval [CI]: 16-91) per 1000 persons in 1995 and 5 (95% CI: -0.5-11) per 1000 persons per year during 1996 through 1999, after the introduction of HAART. Influenza-associated hospitalizations have declined in patients with HIV infection in the post-HAART era. Rates remain comparable to rates in other high-risk groups for which annual influenza vaccination is recommended, however. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Tennessee Valley Healthcare Syst, Ctr Geriatr Res Educ & Clin, Nashville, TN USA. RP Neuzil, KM (reprint author), 1660 S Columbian Way,Med Serv 111, Seattle, WA 98108 USA. FU ODCDC CDC HHS [UR6 CCU417579] NR 11 TC 50 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2003 VL 34 IS 3 BP 304 EP 307 DI 10.1097/00126334-200311010-00008 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 740YW UT WOS:000186431700008 PM 14600576 ER PT J AU Narr, KL Green, MF Capetillo-Cunliffe, L Toga, AW Zaidel, E AF Narr, KL Green, MF Capetillo-Cunliffe, L Toga, AW Zaidel, E TI Lateralized lexical decision in schizophrenia: Hemispheric specialization and interhemispheric lexicality priming SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID BILATERAL TRANSFER DEFICIT; ERROR-CORRECTING BEHAVIOR; CORPUS-CALLOSUM SIZE; THOUGHT-DISORDER; WORD PRONUNCIATION; DYSFUNCTION; ASYMMETRIES; PERFORMANCE; PEOPLE; GENDER AB Reports of left-hemisphere dysfunction and abnormal interhemispheric transfer in schizophrenia are mixed. The authors used a unified paradigm, the lateralized lexical decision task, to assess hemispheric specialization in word recognition, hemispheric error monitoring, and interhemispheric transfer in male, right-handed participants with schizophrenia (n = 34) compared with controls (n = 20). Overall, performance and error monitoring were worse in patients. However, patients like controls showed left-hemisphere superiority for lexical processing and right-hemisphere superiority for error monitoring. Only patients showed selective-interhemispheric lexicality priming for accuracy, in which performance improved when the lexical status of target and distractor stimuli presented to each hemifield was congruent. Results suggest that schizophrenia is associated with impaired monitoring and with increased interhemispheric automatic information transfer rather than with changed hemispheric specialization for language or error monitoring. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP Narr, KL (reprint author), Univ Calif Los Angeles, Dept Neurol, 710 Westwood Plaza,Room 4238, Los Angeles, CA 90095 USA. FU NIMH NIH HHS [MH-43292]; NINDS NIH HHS [NS-20187, NS38253]; NLM NIH HHS [LM/MH05639] NR 81 TC 9 Z9 10 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2003 VL 112 IS 4 BP 623 EP 632 DI 10.1037/0021-843X.112.4.623 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 750QK UT WOS:000187008100008 PM 14674874 ER PT J AU Mairbaurl, H Schwobel, F Hoschele, S Maggiorini, M Gibbs, S Swenson, ER Bartsch, P AF Mairbaurl, H Schwobel, F Hoschele, S Maggiorini, M Gibbs, S Swenson, ER Bartsch, P TI Altered ion transporter expression in bronchial epithelium in mountaineers with high-altitude pulmonary edema SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE nasal potential; alveolar fluid clearance; airway Na-K-ATPase; epithelial Na channels ID BETA-ADRENERGIC AGONIST; POTENTIAL DIFFERENCE; FLUID TRANSPORT; SODIUM-CHANNEL; A549 CELLS; HYPOXIA; LUNG; NA,K-ATPASE AB Hypoxia inhibits activity and expression of transport proteins of cultured lung alveolar epithelial cells. Here we tested whether hypoxia at high altitude affected the expression of ion transport proteins in tissues obtained from controls and mountaineers with high-altitude pulmonary edema (HAPE) at the Capanna Margherita (4,559 m). Expression was determined by RT-PCR and Western blots from brush biopsies of bronchial epithelium and from leukocytes obtained before and during the stay at high altitude. At low altitude, amounts of mRNAs were not different between control and HAPE-susceptible subjects. At high altitude, the amount of mRNA of Na-K-ATPase, CFTR, and beta-actin of brush biopsies did not change in controls but decreased significantly (-60%) in HAPE-susceptible subjects. There was no change in Na channel mRNAs at high altitude in controls and HAPE. No statistically significant correlation was found between the expression of Na transporters and PO2 and O-2 saturation. In leukocytes, 28S-rRNA and Na-K-ATPase decreased at altitude in control and HAPE-susceptible subjects, but no significant change in Na-K-ATPase protein was found. Hypoxia-inducible factor-1alpha mRNA and GAPDH mRNA tended to increase in leukocytes obtained from HAPE-susceptible subjects at high altitude but did not change in controls. These results show that hypoxia induces differences in mRNA expression of ion transport-related proteins between HAPE-susceptible and control subjects but that these changes may not necessarily predict differences in protein concentration or activity. It is therefore unclear whether these differences are related to the pathophysiology of HAPE. C1 Univ Heidelberg, Dept Med, Div Sports Med, D-69115 Heidelberg, Germany. Univ Hosp, Dept Internal Med, Intens Care Unit, Zurich, Switzerland. Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Med & Res Serv, Seattle, WA 98195 USA. RP Mairbaurl, H (reprint author), Univ Heidelberg, Dept Med, Div Sports Med, Luisenstr 5,Geb 4100, D-69115 Heidelberg, Germany. NR 26 TC 22 Z9 22 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV 01 PY 2003 VL 95 IS 5 BP 1843 EP 1850 DI 10.1152/japplphysiol.01156.2002 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 730VF UT WOS:000185850300012 PM 14555664 ER PT J AU Lan, J Li, WJ Zhang, F Sun, FY Nagayama, T O'Horo, C Chen, J AF Lan, J Li, WJ Zhang, F Sun, FY Nagayama, T O'Horo, C Chen, J TI Inducible repair of oxidative DNA lesions in the rat brain after transient focal ischemia and reperfusion SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE DNA damage; base excision repair; 8-hydroxyl-2 '; deoxyguanosine-; AP site; stroke ID BASE-EXCISION-REPAIR; COLI ENDONUCLEASE-III; POLYMERASE-BETA; CEREBRAL-ISCHEMIA; ABASIC SITES; MAMMALIAN-CELLS; APURINIC/APYRIMIDINIC ENDONUCLEASE; STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE; INDUCED CYTOTOXICITY AB To determine the role of oxidative DNA damage and repair in brain injury after focal ischemia and reperfusion, the authors investigated DNA base damage and DNA base excision repair (BER) capacity, the predominant repair mechanism for oxidative DNA lesions, in the rat model of temporary middle cerebral artery occlusion. Contents of 8-hydroxyl-2'-deoxyguanosine (8-oxodG) and apurinic/apyrimidinic abasic site (AP site), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains 0.25 to 72 hours after I hour of middle cerebral artery occlusion. In parallel to the detection of DNA lesions, the capacity for 8-oxodG- or AP site-dependent DNA repair synthesis was measured in nuclear protein extracts using specific in vitro DNA repair assays. After postischemic reperfusion, the levels of 8-oxodG and AP sites were markedly increased in ischemic tissues. In frontal/parietal cortex, regions that survived ischemia, 8-oxodG and AP sites were efficiently repaired during reperfusion. However, in the caudate, a region that was destined to infarct, the DNA lesions were poorly repaired. In consistent with the patterns of endogenous lesion repair, a markedly induced and long-lasting (at least 72 hours) BER activity was detected in the cortex but not in the caudate after ischemia. The induced BER activity in ischemic cortex was attributed to the upregulation of gene expression and activation of selective BER enzymes, particularly DNA polymerase-beta and OGG1. These results strongly suggest that inducible DNA BER constitutes an important endogenous mechanism that protects brain against ischemia-induced oxidative neuronal injury. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Disorders, Pittsburgh, PA USA. Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [NS35965, NS38560, NS36736] NR 71 TC 41 Z9 42 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 2003 VL 23 IS 11 BP 1324 EP 1339 DI 10.1097/01.WCB.0000091540.60196.F2 PG 16 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 741TY UT WOS:000186477500009 PM 14600440 ER PT J AU Hayden, KM Khachaturian, AS Tschanz, JT Corcoran, C Nortond, M Breitner, JCS AF Hayden, KM Khachaturian, AS Tschanz, JT Corcoran, C Nortond, M Breitner, JCS CA Cache Cty Study Grp TI Characteristics of a two-stage screen for incident dementia SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE receiver-operating characteristic analysis; sensitivity; specificity; dementia; mass screening; validation sample ID ALZHEIMERS-DISEASE; CACHE COUNTY; RELIABILITY; POPULATION; PREVALENCE; DECLINE; AD AB Background and Objectives: To avoid costly evaluation of healthy individuals, efficient methods of screening for incident dementia must combine adequate sensitivity and high specificity. Two-stage screening may offer improvements over single-stage methods. We therefore investigated a two-stage screening protocol for incident dementia among 3,308 elderly. Methods: We administered the Modified Mini-Mental-State (3MS) or, rarely, Jorm's IQCODE, to a validation sample of 441 high-risk respondents. Informants then completed the Dementia Questionnaire (DQ). Finally, all 441 sample members underwent physical, neurologic, and neuropsychologic assessment. We studied the sensitivity and specificity of the 3MS/IQCODE and DQ using Receiver-Operating Characteristic analyses. Results: A 3MS cut point of 82/83 (of 100) yielded sensitivity and specificity of 91.5 and 90.1%. With 3MS scores of less than or equal to82, a DQ cut point of 2/3 (of five) yielded conditional sensitivity and specificity of 90.2 and 55.3%. Combining these instruments yielded sensitivity and specificity of 82.5 and 95.6%. Age stratification and use of longitudinal decline score criteria did not materially improve these figures. Conclusions: The improved specificity of the two-stage approach offers economies that are attractive, particularly if sensitivity can be enhanced, for example, by examination of a high-risk validation sample. (C) 2003 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD 21205 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. RP Breitner, JCS (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Dept Mental Hyg, 624 N Broadway, Baltimore, MD 21205 USA. RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [R01AG11380]; NIMH NIH HHS [T32MH14592] NR 17 TC 34 Z9 34 U1 0 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 NOV PY 2003 VL 56 IS 11 BP 1038 EP 1045 DI 10.1016/S0895-4356(03)00247-6 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 745ND UT WOS:000186694000003 PM 14614994 ER PT J AU Barron, MA Sutton, DA Veve, R Guarro, J Rinaldi, M Thompson, E Cagnoni, PJ Moultney, K Madingerl, NE AF Barron, MA Sutton, DA Veve, R Guarro, J Rinaldi, M Thompson, E Cagnoni, PJ Moultney, K Madingerl, NE TI Invasive mycotic infections caused by Chaetomium perlucidum, a new agent of cerebral phaeohyphomycosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TRANSPLANT RECIPIENT; DACTYLARIA-GALLOPAVA; SUCCESSFUL THERAPY; PATIENT; GLOBOSUM; SUSCEPTIBILITY; CLADOSPORIUM; LEUKEMIA AB We report the first two cases of invasive human mycoses caused by the phaeoid ascomycete, Chaetomium perlucidum, and review the English literature regarding invasive Chaetomium infections. Fatal disseminated disease involving the brain, heart, lungs, and spleen is described in an acute myelogenous leukemia patient. A second patient with a history of asthma and chronic bronchiectasis experiencing right-middle-lobe syndrome grew C. perlucidum from lung tissue. This study adds C. perlucidum to the list of other known neurotropic Chaetomium species, C. atrobrunneum and C. strumarium, and also documents this organism's ability to disseminate beyond the central nervous system. C1 Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Bone Marrow Transplant Program, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado Hosp, Clin Microbiol Lab, Denver, CO 80262 USA. Univ Rovira & Virgili, Fac Med, Unitat Microbiol, Tarragona 43201, Spain. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Lab Serv, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX USA. RP Barron, MA (reprint author), Univ Colorado, Hlth Sci Ctr, Div Infect Dis, 4200 E 9th Ave,Box B168, Denver, CO 80262 USA. OI Guarro, Josep/0000-0002-7839-7568 NR 21 TC 30 Z9 33 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 NOV PY 2003 VL 41 IS 11 BP 5302 EP 5307 DI 10.1128/JCM.41.11.5302-5307.2003 PG 6 WC Microbiology SC Microbiology GA 745AR UT WOS:000186665500073 PM 14605190 ER PT J AU Lewis, JH Andersen, RM Gelberg, L AF Lewis, JH Andersen, RM Gelberg, L TI Health care for homeless women - Unmet needs and barriers to care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE barriers; homeless; unmet need; vulnerable population; women ID MEDICAL-CARE; LOS-ANGELES; URBAN HOMELESS; HOUSED POOR; ADULTS; SERVICES; FAMILIES; OUTCOMES; CHILDREN; HISTORY AB Objective: Homelessness is a significant and growing problem in the United States. Women and families are the fastest growing segments of the homeless population. Homelessness increases the risk of having health problems and encountering barriers to care. This study determines how much perceived unmet need for medical care there is among homeless women, what homeless women perceive to be barriers to health care, and how barriers and other factors are associated with unmet needs. Design: Cross-sectional study of homeless women, utilizing structured interviews. Setting and Participants: Community-based probability sample of 974 homeless women aged 15 to 44 years. Main Outcome Measures: Perceived unmet need for medical care in the past 60 days. Relationship between unmet need and demographic variables, place of stay, source of health care, insurance, and perceived barriers to care. Results: Of the 974 women, 37% reported unmet need for medical care. Controlling for other factors, the odds of unmet need were lower among those with a regular source of care (odds ratio [OR] to .35, 95% confidence interval [CI], .21 to 58), while having health insurance was not significantly associated. The odds of unmet need were higher among those who experienced the barriers: not knowing where to go (OR 2.27, 95% CI, 1.40 to 3.69), long office waiting times (OR 1.89, 95% CI 1.27 to 2.83) and being too sick to seek care (OR 2.03, 95% CI, 1.14 to 3.62). Conclusions: There is significant unmet need for medical care among homeless women. Having a regular source of care was more important than health insurance in lowering the odds of unmet need. Homeless women must be educated regarding sources of care, and clinics serving the homeless must decrease waiting times. C1 Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Lewis, JH (reprint author), POB 1765, Wilson, WY 83014 USA. FU AHRQ HHS [R01 HS008323, R01 HS08323]; NIAAA NIH HHS [R21 AA013398, R21 AA 13398]; NIDA NIH HHS [R01 DA014835, R01 DA14835] NR 43 TC 54 Z9 54 U1 1 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2003 VL 18 IS 11 BP 921 EP 928 DI 10.1046/j.1525-1497.2003.20909.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 743FW UT WOS:000186562600007 PM 14687278 ER PT J AU O'Toole, TP Conde-Martel, A Gibbon, JL Hanusa, BH Fine, MJ AF O'Toole, TP Conde-Martel, A Gibbon, JL Hanusa, BH Fine, MJ TI Health care of homeless veterans - Why are some individuals falling through the safety net? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE homelessness; mental health; needs assessment; substance abuse; veterans ID URBAN HOMELESS; MENTAL-ILLNESS; HOUSED POOR; SERVICE USE; OUTCOMES; MODEL AB It is important to understand the needs of those veterans who are homeless. We describe characteristics of homeless male veterans and factors associated with needing VA benefits from a two-city, community survey of 531 homeless adults. Overall, 425 were male, of whom 127 were veterans (29.9%). Significantly more veterans had a chronic medical condition and two or more mental health conditions. Only 35.1% identified a community clinic for care compared with 66.8% of non-veterans (P<.01); 47.7% identified a shelter-based clinic and 59.1% reported needing VA benefits. Those reporting this need were less likely to report a medical comorbidity (58.7% vs 76.9%; P=.04), although 66.7% had a mental health comorbidity and 82.7% met Diagnosic Screening Manual (DSM)-IIIR criteria for substance abuse/dependence. They were also significantly more likely to access shelter clinics compared with veterans without this need. Homeless veterans continue to have substantial health issues. Active outreach is needed for those lacking access to VA services. C1 Johns Hopkins Univ, Welch Ctr, Sch Med, Baltimore, MD 21205 USA. Hosp Univ Gran Canaria, Las Palmas Gran Canaria, Spain. Maricopa Cty Dept Publ Hlth, Phoenix, AZ USA. Univ Pittsburgh, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP O'Toole, TP (reprint author), Johns Hopkins Univ, Welch Ctr, Sch Med, Rm 2-513,2024 E Monument St, Baltimore, MD 21205 USA. FU NIDA NIH HHS [K23 DA013988, K23DA13988-01] NR 19 TC 46 Z9 46 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2003 VL 18 IS 11 BP 929 EP 933 DI 10.1046/j.1525-1497.2003.21209.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 743FW UT WOS:000186562600008 PM 14687279 ER PT J AU Kobza, PE Budoff, JE Yeh, ML Luo, ZP AF Kobza, PE Budoff, JE Yeh, ML Luo, ZP TI Management of the scaphoid during four-corner fusion - A cadaveric study SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE midcarpal fusion; partial wrist arthrodesis ID PROXIMAL ROW CARPECTOMY; WRIST; ARTHRODESIS; MOTION; JOINT AB Purpose: To examine the effects of scaphoid retention, inclusion, and excision on wrist motion and radiolunate contact characteristics in a cadaveric model after simulated 4-corner fusion with rigid, internal fixation. Methods: Seven. fresh-frozen cadaveric upper extremities were examined. For all surgical manipulations the motion was measured and contact characteristics were assessed using ultra-low prescale pressure-sensitive film. Results: Compared with the intact specimen, simple 4-corner fusion with scaphoid retention led to a significant decrease in extension, radial deviation, and ulnar deviation, but no change in radiolunate contact characteristics. After 4-corner fusion there was no significant difference in motion or radiolunate contact characteristics between scaphoid retention and scaphoid inclusion. After, 4-corner fusion scaphoid excision allowed significantly greater radial deviation compared with scaphoid retention and scaphoid inclusion. Compared with the intact specimen 4-corner fusion with-scaphoid excision also led to a significant increase in radiolunate contact area and mean contact pressure. Conclusions:. When performing 4-corner arthrodesis in the absence of radioscaphoid arthritis; scaphoid excision may improve motion at the cost of increased mean radiolunate contact pressure Copyright (C) 2003 by the American Society for Surgery of the Hand. C1 Baylor Coll Med, Dept Orthopaed Surg, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. RP Budoff, JE (reprint author), 6550 Fannin 2525, Houston, TX 77030 USA. NR 14 TC 10 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO 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 NOV PY 2003 VL 28A IS 6 BP 904 EP 909 DI 10.1016/S0363-5023(03)00372-1 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 745VE UT WOS:000186710500004 PM 14642504 ER PT J AU Moreland, ME AF Moreland, ME TI Practitioner application SO JOURNAL OF HEALTHCARE MANAGEMENT LA English DT Editorial Material C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Moreland, ME (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 USA SN 1096-9012 J9 J HEALTHC MANAG JI J. Healthc. Manag. PD NOV-DEC PY 2003 VL 48 IS 6 BP 406 EP 407 PG 2 WC Health Policy & Services SC Health Care Sciences & Services GA 746RZ UT WOS:000186762600010 ER PT J AU Rao, AR Quinones, MP Garavito, E Kalkonde, Y Jimenez, F Gibbons, C Perez, J Melby, P Kuziel, W Reddick, RL Ahuja, SK Ahuja, SS AF Rao, AR Quinones, MP Garavito, E Kalkonde, Y Jimenez, F Gibbons, C Perez, J Melby, P Kuziel, W Reddick, RL Ahuja, SK Ahuja, SS TI CC chemokine receptor 2 expression in donor cells serves an essential role in graft-versus-host-disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; ALLOREACTIVE T-CELLS; INTERFERON-GAMMA; ALLOGRAFT TOLERANCE; APLASTIC-ANEMIA; DENDRITIC CELLS; IFN-GAMMA; IN-VIVO; MICE AB The complete repertoire of cellular and molecular determinants that influence graft-vs-host disease (GVHD) is not known. Using a well-established murine model of GVHD (B6-->bm12 mice), we sought to elucidate the role of the donor non-T cell compartment and molecular determinants therein in the pathogenesis of GVHD. In this model the acute GVHD-inducing effects of purified B6 wild-type (wt) CD4(+) T cells was inhibited by wt non-T cells in a dose-dependent manner. Paradoxically, unlike the chronic GVHD phenotype observed in bm12 mice transplanted with B6wt unfractionated splenocytes, bm12 recipients of B6ccr2-null unfractionated splenocytes developed acute GVHD and died of IFN-gamma-mediated bone marrow aplasia. This switch from chronic to acute GVHD was associated with increased target organ infiltration of activated CD4(+) T cells as well as enhanced expression of Th1/Th2 cytokines, chemokines, and the antiapoptotic factor bfl1. In vitro, ccr2(-/-) CD4(+) T cells in unfractionated splenocytes underwent significantly less activation-induced cell death than B6wt CD4(+) T cells, providing another potential mechanistic basis along with enhanced expression of bfl1 for the increased numbers of activated T cells in target organs of B6ccr2(-/-) splenocyte-->bm12 mice. Collectively, these findings have important clinical implications, as they implicate the donor non-T cell compartment as a critical regulator of GVHD and suggest that ccr2 expression in this cellular compartment may be an important molecular determinant of activation-induced cell death and GVHD pathogenesis. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. Vet Adm Ctr, Res AIDS & HIV Infect 1, San Antonio, TX 78229 USA. Univ Texas, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. RP Ahuja, SS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr,MC 7870, San Antonio, TX 78229 USA. FU PHS HHS [A148644, 5K12C801723] NR 58 TC 27 Z9 28 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2003 VL 171 IS 9 BP 4875 EP 4885 PG 11 WC Immunology SC Immunology GA 735WD UT WOS:000186136800050 PM 14568968 ER PT J AU Egan, BM Basile, JN AF Egan, BM Basile, JN TI Controlling blood pressure in 50% of all hypertensive patients: An achievable goal in the healthy people 2010 report? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE Healthy People 2010; hypertension; high blood pressure ID CORONARY HEART-DISEASE; AFRICAN-AMERICAN WOMEN; CARDIOVASCULAR-DISEASE; RESISTANT HYPERTENSION; SYSTOLIC HYPERTENSION; UNCONTROLLED HYPERTENSION; TIME-PREFERENCES; CONTROLLED TRIAL; OLDER PATIENTS; SELF-EFFICACY AB Background: One important objective defined in the Healthy People 2010 report was to improve blood pressure (BP) control to < 140/90 mm Hg in 50% of all hypertensive patients. Because the US population is becoming older, more obese, and ethnically diverse, the health and economic benefits of reaching this goal become more valuable each year. Hypertension control rates are currently at similar to31% of all hypertensives and have risen slowly and erratically since 1988. In the absence of a coordinated strategic plan, achieving this critically important goal for BP control is highly unlikely. Methods: A selected literature review was undertaken to briefly assess the cardiovascular benefits of controlling hypertension. Greater focus was placed on variables that impact hypertension awareness, treatment, and control. The impact on hypertension control rates of theoretic changes in awareness, treatment, and control individually and collectively was examined. Four categories of potential barriers to optimizing BP control are discussed: systems, provider, patient, and treatment factors. Results: Raising awareness to 80% of all hypertensives, ensuring treatment of 90% of aware hypertensives, and controlling BP to < 140/90 mm Hg in 70% of treated patients would achieve control rates of 50%. Conclusions: The barriers to achieving the Healthy People 2010 goal of controlling hypertension in 50% of all patients are formidable but appear to be resolvable with a coordinated strategic plan. Given projected demographic changes in the United States, the health and economic benefits of attaining the national goal for hypertension control would seem to merit a serious integrated effort. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Div Gen Internal Med Geriatr & Hypertens, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Primary Care Serv Line, Charleston, SC USA. RP Egan, BM (reprint author), Med Univ S Carolina, Dept Med, 96 Jonathan Lucas St, Charleston, SC 29425 USA. FU AHRQ HHS [P01HS1087-03]; NHLBI NIH HHS [HL04290]; NIMHD NIH HHS [P60-MD00267] NR 100 TC 16 Z9 18 U1 2 U2 3 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 NOV PY 2003 VL 51 IS 6 BP 373 EP 385 DI 10.2310/6650.2003.8979 PG 13 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 751XN UT WOS:000187115500017 PM 14686641 ER PT J AU Montanez, S Daws, LC Gould, GG Frazer, A AF Montanez, S Daws, LC Gould, GG Frazer, A TI Serotonin (5-HT) transporter (SERT) function after graded destruction of serotonergic neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 5; 7-DHT; CA3 region of hippocampus; chronoamperometry; degeneration; rat; serotonin transporter ID IN-VIVO; RAT-BRAIN; EXTRACELLULAR DOPAMINE; ANIMAL-MODEL; CLEARANCE; STRIATUM; ANTIDEPRESSANTS; AUTORADIOGRAPHY; HIPPOCAMPUS; CITALOPRAM AB The degree of occupancy of the serotonin transporter (SERT) by selective serotonin reuptake inhibitors (SSRIs) appears to be critical in determining therapeutic response. To gain insight into the extent of occupancy required to alter serotonergic neurotransmission we used high-speed chronoamperometry to determine the extent of serotonergic destruction required to reduce the clearance of exogenously administered serotonin from extracellular fluid in the CA3 region of the hippocampus. Rats were pretreated with various doses of 5,7-dihydroxytryptamine to produce either a low, intermediate or high loss of SERTs. Clearance of 5-HT was reduced only in rats with > 90% loss of SERT. In these rats, there was also a trend for peak signal amplitudes to be greater. There was no significant difference in these parameters between the sham group and those with low or intermediate loss of SERTs. The SSRI, fluvoxamine, prolonged clearance of 5-HT in sham, low and intermediate groups, whereas there was no effect of fluvoxamine in those rats with > 90% loss of SERT. Functional loss of SERT activity occurs when destruction of serotonergic innervation is greater than 90% but serotonin clearance and efficacy of fluvoxamine is maintained with as few as one fifth of a full complement of SERTs. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Montanez, S (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr,MS 7792, San Antonio, TX 78229 USA. OI Gould, Georgianna/0000-0002-5470-8763 FU NIMH NIH HHS [MH64489, MH57001] NR 35 TC 16 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2003 VL 87 IS 4 BP 861 EP 867 DI 10.1046/j.1471-4159.2003.02032.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 737QJ UT WOS:000186243000007 PM 14622117 ER PT J AU Ahmadi, FA Linseman, DA Grammatopoulos, TN Jones, SM Bouchard, RJ Freed, CR Heidenreich, KA Zawada, WM AF Ahmadi, FA Linseman, DA Grammatopoulos, TN Jones, SM Bouchard, RJ Freed, CR Heidenreich, KA Zawada, WM TI The pesticide rotenone induces caspase-3-mediated apoptosis in ventral mesencephalic dopaminergic neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE DEVD; dopamine neurons; midbrain; neurotoxin; Parkinson's disease; tyrosine hydroxylase ID CALCIUM-BINDING PROTEINS; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; BASAL GANGLIA; INHIBITION; CALBINDIN-D28K; DAMAGE; BRAIN; DEATH; MPTP AB In vivo, the pesticide rotenone induces degeneration of dopamine neurons and parkinsonian-like pathology in adult rats. In the current study, we utilized primary ventral mesencephalic (VM) cultures from E15 rats as an in vitro model to examine the mechanism underlying rotenone-induced death of dopamine neurons. After 11 h of exposure to 30 nm rotenone, the number of dopamine neurons identified by tyrosine hydroxylase (TH) immunostaining declined rapidly with only 23% of the neurons surviving. By contrast, 73% of total cells survived rotenone treatment, indicating that TH+ neurons are more sensitive to rotenone. Examination of the role of apoptosis in TH+ neuron death, revealed that 10 and 30 nm rotenone significantly increased the number of apoptotic TH+ neurons from 7% under control conditions to 38 and 55%, respectively. The increase in apoptotic TH+ neurons correlated with an increase in immunoreactivity for active caspase-3 in TH+ neurons. The caspase-3 inhibitor, DEVD, rescued a significant number of TH+ neurons from rotenone-induced death. Furthermore, this protective effect lasted for at least 32 h post-rotenone and DEVD exposure, indicating lasting neuroprotection achieved with an intervention prior to the death commitment point. Our results show for the first time in primary dopamine neurons that, at low nanomolar concentrations, rotenone induces caspase-3-mediated apoptosis. Understanding the mechanism of rotenone-induced apoptosis in dopamine neurons may contribute to the development of new neuroprotective strategies against Parkinson's disease. C1 Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Clin Pharmacol & Toxicol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA. RP Zawada, WM (reprint author), Univ Colorado, Hlth Sci Ctr, Div Clin Pharmacol, 4200 E 9th Ave,C-237, Denver, CO 80262 USA. OI Grammatopoulos, Tom/0000-0001-7175-051X FU NIAAA NIH HHS [AA13473]; NINDS NIH HHS [NS 38619] NR 39 TC 67 Z9 70 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2003 VL 87 IS 4 BP 914 EP 921 DI 10.1046/j.1471-4159.2003.02068.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 737QJ UT WOS:000186243000012 PM 14622122 ER PT J AU Chou, R Clark, E Helfand, M AF Chou, R Clark, E Helfand, M TI Comparative efficacy and safety of long-acting oral Opioids for chronic non-cancer pain: A systematic review SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Review DE analgesics; opioid; pain; meta-analysis; fentanyl; morphine; oxycodone; codeine ID CHRONIC NONMALIGNANT PAIN; PLACEBO-CONTROLLED-TRIAL; CONTROLLED-RELEASE OXYCODONE; TRANSDERMAL FENTANYL; NEUROPATHIC PAIN; DOUBLE-BLIND; POSTHERPETIC NEURALGIA; RANDOMIZED TRIAL; SUBSTANCE-ABUSE; CANCER PAIN AB Opioids have been endorsed as appropriate treatment for refractory chronic non-cancer pain when used according to published guidelines. They are widely used for this indication. However, there appear to be gaps in our understanding of the efficacy and safety of individual long acting opioids compared to each other or as a class compared to short-acting opioids. This systematic review summarizes and assesses the evidence for the comparative efficacy and safety of long acting opioids in the management of chronic non,efficacy and adverse events) and cancer pain. Randomized trials (for comparative observational studies (for adverse events only) that included non-parenteral long-acting opioids were sought using electronic databases, handsearching reference lists, and soliciting pharmaceutical company submissions. Searches were performed through October 2002. The validity of each included study was assessed using a data abstraction form and predefined criteria. An overall grade was allocated for the body of evidence for each key question. A total of 16 randomized trials (comparative efficacy and adverse events), enrolling 1427 patients, and 8 observational studies (adverse events) of 1190 patients were included in this review. No randomized trial was rated good quality; observational studies were generally of poorer quality than the trials. There was insufficient evidence to prove that different long-acting opioids are associated with different efficacy or safety profiles. There was also insufficient evidence to determine whether long-acting opioids as a class are more effective or safer than short-acting opioids. A subgroup of three studies on long acting versus short-acting oxycodone was more homogeneous and provided fair evidence that these formulations are equally effective for pain control. (C) 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Family Med, Portland, OR 97201 USA. Oregon Evidence Based Practice Ctr, Portland, OR USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Chou, R (reprint author), 9721 SW Morrison St, Portland, OR 97225 USA. NR 42 TC 114 Z9 117 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2003 VL 26 IS 5 BP 1026 EP 1048 DI 10.1016/j.jpainsymman.2003.03.003 PG 23 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 740WZ UT WOS:000186426400006 PM 14585554 ER PT J AU Chae, JH Nahas, Z Lomarev, M Denslow, S Lorberbaum, JP Bohning, DE George, MS AF Chae, JH Nahas, Z Lomarev, M Denslow, S Lorberbaum, JP Bohning, DE George, MS TI A review of functional neuroimaging studies of vagus nerve stimulation (VNS) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Review DE vagus nerve stimulation (VNS); functional neuroimaging; positron emission tomography (PET); single-photon emission computed tomography (SPECT); functional magnetic resonance imaging (fMRI) ID CEREBRAL BLOOD-FLOW; RESISTANT DEPRESSION; REFRACTORY EPILEPSY; SLEEP-DEPRIVATION; NEURONAL-ACTIVITY; MAJOR DEPRESSION; BRAIN; ACTIVATION; CORTEX; SPECT AB Vagus nerve stimulation (VNS) is a new method for preventing and treating seizures, and shows promise as a potential new antidepressant. The mechanisms of action of VNS are still unknown, although the afferent direct and secondary connections of the vagus nerve are well established and are the most likely route of VNS brain effects. Over the past several years, many groups have used functional brain imaging to better understand VNS effects on the brain. Since these studies differ somewhat in their methodologies, findings and conclusions, at first glance, this literature may appear inconsistent. Although disagreement exists regarding the specific locations and the direction of brain activation, the differences across studies are largely due to different methods, and the results are not entirely inconsistent. We provide an overview of these functional imaging studies of VNS. PET (positron emission tomography) and SPECT (single photon emission computed tomography) studies have implicated several brain areas affected by VNS, without being able to define the key structures consistently and immediately activated by VNS. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), with its relatively high spatio-temporal resolution, performed during VNS, can reveal the location and level of the brain's immediate response to VNS. As a whole, these studies demonstrate that VNS causes immediate and longer-term changes in brain regions with vagus innervations and which have been implicated in neuropsychiatric disorders. These include the thalamus, cerebellum, orbitofrontal cortex, limbic system, hypothalamus, and medulla. Functional neuroimaging studies have the potential to provide greater insight into the brain circuitry behind the activity of VNS. (C) 2003 Elsevier Ltd. All rights reserved. C1 Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Catholic Univ Korea, Dept Psychiat, Seoul, South Korea. Inst Human Brain, St Petersburg, Russia. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP George, MS (reprint author), Inst Psychiat, Brain Stimulat Lab, 67 President St,Room 502 N, Charleston, SC 29425 USA. NR 64 TC 92 Z9 93 U1 1 U2 8 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 NOV-DEC PY 2003 VL 37 IS 6 BP 443 EP 455 DI 10.1016/S0022-3956(03)00074-8 PG 13 WC Psychiatry SC Psychiatry GA 737NY UT WOS:000186239700001 PM 14563375 ER PT J AU Taub, E Uswatte, G AF Taub, E Uswatte, G TI The case for C1 therapy SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Letter ID INDUCED MOVEMENT THERAPY; CHRONIC STROKE PATIENTS; REHABILITATION C1 Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Taub, E (reprint author), Univ Alabama, Dept Psychol, 1530 3rd Ave S,CH 415, Birmingham, AL 35294 USA. RI Uswatte, Gitendra/C-4913-2009 FU NICHD NIH HHS [HD 34273] NR 11 TC 2 Z9 2 U1 0 U2 0 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 NOV-DEC PY 2003 VL 40 IS 6 BP XIII EP XV PG 3 WC Rehabilitation SC Rehabilitation GA 753JD UT WOS:000187227500003 PM 15077656 ER PT J AU Robinson-Whelen, S Rintala, DH AF Robinson-Whelen, S Rintala, DH TI Informal care providers for veterans with SCI: Who are they and how are they doing? SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE caregivers; long-term care; spinal cord injuries ID SPINAL-CORD-INJURY; LIFE SATISFACTION; DISABILITY; OUTCOMES; MODEL AB Veterans with spinal cord injury (SCI) who received care at the Houston Department of Veterans Affairs Medical Center were interviewed about their use of formal and informal assistance to meet their daily physical needs. Informal caregivers were found to play an important role in the daily care of veterans with SCI, with 37% receiving some informal, unpaid assistance with personal care. Primary informal caregivers were mostly women, had a mean age of 53, and provided an average of almost 12 hours of care a day. Nearly one-third of participants rated their primary caregiver as being only in fair or poor health, and one-fourth thought their caregiver was unlikely to be able to provide the same level of care 5 years from now. Of particular concern, more than half reported that they did not have anyone else willing and able to provide assistance if their primary family caregiver became permanently unable to care for them. C1 VA Med Ctr, Dept Vet Affairs, VA Rehabil Res & Dev Serv, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Robinson-Whelen, S (reprint author), Houston VAMC 153, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 19 TC 10 Z9 10 U1 1 U2 1 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 NOV-DEC PY 2003 VL 40 IS 6 BP 511 EP 516 DI 10.1682/JRRD.2003.11.0511 PG 6 WC Rehabilitation SC Rehabilitation GA 753JD UT WOS:000187227500012 PM 15077663 ER PT J AU Vig, EK Pearlman, RA AF Vig, EK Pearlman, RA TI Quality of life while dying: A qualitative study of terminally ill older men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quality of life; attitude to death; terminal care; patient-centered care; qualitative research ID ADVANCE DIRECTIVES; FAMILY MEMBERS; PATIENTS PERSPECTIVES; CONTROLLED-TRIAL; CARE; END; DEATH; PERCEPTIONS; PREFERENCES; CANCER AB OBJECTIVES: To characterize the experience of quality of life while dying from the perspective of terminally ill men. DESIGN: Descriptive study involving semistructured interviews. SETTING: Patients attending clinics at two university-affiliated medical centers were interviewed in a private conference room or in their homes. PARTICIPANTS: Twenty-six men identified by their physicians as having terminal heart disease or cancer. Eligible participants acknowledged that they had serious illness. MEASUREMENTS: The interview contained open-ended questions such as: "What are the most important things in your life right now?" The interview also contained closed-ended questions about symptom intensity, presence of depressed mood, and other items related to overall quality of life. The open-ended questions were tape-recorded, transcribed, and analyzed using grounded theory methods. The closed-ended questions were analyzed using descriptive statistics. RESULTS: Participants believed that death was near. Participants saw engaging in hobbies and other enjoyable activities as an alternative to moving into the final stage of illness, in which they saw themselves as actively dying. They admitted to occasionally ignoring prescribed diets; these actions improved their overall quality of life but worsened symptoms. New symptoms brought concerns about progression to active dying. They anticipated what their dying would be like and how it would affect others. Participants believed that their actions in the present could improve the quality of their dying and lessen the burden of their deaths on others. Many participants therefore were preparing for death by engaging in such tasks as putting their finances in order and planning their funerals, to relieve anticipated burden on loved ones. CONCLUSION: To help terminally ill patients plan for the end of life, clinicians are encouraged to become familiar with their patients' experiences of living with terminal illness, to identify each patient's unique priorities, and to incorporate that information into care plans aimed at maximizing quality of life at the end of life. C1 VAPSHCS, GEC S182, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Vig, EK (reprint author), VAPSHCS, GEC S182, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 43 TC 36 Z9 37 U1 4 U2 14 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2003 VL 51 IS 11 BP 1595 EP 1601 DI 10.1046/j.1532-5415.2003.51505.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 736KE UT WOS:000186169300011 PM 14687389 ER PT J AU Gooch, JL Guler, RL Vanden Heuvel, GB AF Gooch, JL Guler, RL Vanden Heuvel, GB TI Defects in nephrogenic zone development and mesangial cell proliferation in calcineurin A alpha knockout mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 18A EP 18A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100081 ER PT J AU Gooch, JL Guler, RL Toro, JJ AF Gooch, JL Guler, RL Toro, JJ TI Calcineurin A alpha is required for normal AQP2 trafficking and function. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 32A EP 32A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100145 ER PT J AU Procino, G Carmosino, M Tamma, G Gouraud, S Laera, A Svelto, M Valenti, G AF Procino, G Carmosino, M Tamma, G Gouraud, S Laera, A Svelto, M Valenti, G TI Calcium-sensing receptors signaling counteracts forskolin-induced aquaporin-2 trafficking in kidney collecting duct contributing to hypercalciuria-induced polyuria SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Ctr Hlth Sci, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. RI Carmosino, Monica/O-2594-2014; Tamma, Grazia/F-8823-2016 OI Carmosino, Monica/0000-0001-7600-8816; 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 32A EP 32A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100146 ER PT J AU Rincon-Choles, H Vasylyeva, TL Bhandari, K Barnes, JL Bhandari, B Simon, M Pergola, PE Gorin, Y Abboud, HE AF Rincon-Choles, H Vasylyeva, TL Bhandari, K Barnes, JL Bhandari, B Simon, M Pergola, PE Gorin, Y Abboud, HE TI Regulation of ZO-1 expression and phosphorylation in experimental diabetes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 47A EP 47A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100216 ER PT J AU Chen, Y Polci, R Litchfield, P Gaczynska, M Riley, DJ AF Chen, Y Polci, R Litchfield, P Gaczynska, M Riley, DJ TI Nek1 regulates renal epithelial cell apoptosis through phosphorylation of the mitochondrial transition pore channel VDAC. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, Inst Biotechnol, San Antonio, TX USA. Univ Roma La Sapienza, Policlin Umberto I, Div Nephrol, Rome, Italy. S Texas Vet Hlth Care Syst, Div Res, San Antonio, TX 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 50A EP 50A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100231 ER PT J AU Nagami, GT Warech, EM AF Nagami, GT Warech, EM TI Metabolic acidosis enhances the stimulatory effects of angiotensin II on ammonia production and secretion by mouse S3 proximal tubule segments. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 VA Greater Los Angeles Healthcare Syst, Nephrol Sect, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 69A EP 69A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100318 ER PT J AU Nagami, GT Patel, S Warech, EM AF Nagami, GT Patel, S Warech, EM TI High pH increases cell surface expression of type 2 angiotensin II receptors in cultured proximal tubule cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 VA Greater Los Angeles Healthcare Syst, Nephrol Sect, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 70A EP 70A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100323 ER PT J AU Mariappan, M Duraisamy, S Choudhury, GG Kasinath, BS AF Mariappan, M Duraisamy, S Choudhury, GG Kasinath, BS TI Novel role of SRC and PLC in regulation of VEGF-induced ERK activation in proximal tubular epithelial cells and its role in protein synthesis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 87A EP 87A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100410 ER PT J AU Gorin, Y Ricono, JM Kim, NH Bhandari, B Choudhury, GG Abboud, HE AF Gorin, Y Ricono, JM Kim, NH Bhandari, B Choudhury, GG Abboud, HE TI Nox4 mediates angiotensin II-induced mesangial cell hypertrophy via activation of Akt/protein kinase B. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Hosp Div, S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 91A EP 91A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100430 ER PT J AU Achinger, SG Polci, R Litchfield, P Riley, DJ Chen, Y AF Achinger, SG Polci, R Litchfield, P Riley, DJ Chen, Y TI Dynamic association between Nek1 protein kinase and VDAC1 in renal tubular epithelial cells after reversible or lethal DNA damage. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 93A EP 93A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100438 ER PT J AU Weisbord, SD Kip, KE Saul, MI Palevsky, PM AF Weisbord, SD Kip, KE Saul, MI Palevsky, PM TI Defining clinically significant radiocontrast nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 280A EP 281A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101300 ER PT J AU Balkovetz, DF Gerrard, ER Li, SX AF Balkovetz, DF Gerrard, ER Li, SX TI Cell contact dependent regulation of ERK 1/2 and cyclin D1 controls Madin Darby canine kidney epithelial cell proliferation. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Dept Med, Birmingham, AL 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 342A EP 342A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101584 ER PT J AU Riley, DJ Achinger, SG Chen, YM AF Riley, DJ Achinger, SG Chen, YM TI Expression of Nek1 protein kinase during kidney development and after ischemic tubular injury. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 366A EP 366A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101700 ER PT J AU Feliers, D Senthil, D Ghosh-Choudhury, G Barnes, J Kasinath, BS AF Feliers, D Senthil, D Ghosh-Choudhury, G Barnes, J Kasinath, BS TI Selective translational regulation of vascular endothelial growth factor (VEGF) expression in proximal tubular cells (MCT) by angiotensin II (AII). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 402A EP 402A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101871 ER PT J AU Palevsky, PM O'Connor, TZ Zhang, JH Star, R AF Palevsky, PM O'Connor, TZ Zhang, JH Star, R CA VA NIH Acute Renal Failure Trial N TI VA/NIH acute renal failure trial network: Study design. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. CSPCC, VA Connecticut Healthcare Syst, West Haven, CT USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 512A EP 512A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102359 ER PT J AU Eslami, P Corry, DB Nyby, MD Tuck, ML AF Eslami, P Corry, DB Nyby, MD Tuck, ML TI Angiotensin II AT1 receptor Blockers and antioxidants reverse the inhibition of nitric oxide production by uric acid in vascular smooth muscle cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CA SP Amer Soc Nephrol C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, SFVP, Sylmar, CA USA. VA Greater Los Angeles Healthcare, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 523A EP 523A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102406 ER PT J AU Mahimainathan, L Ghosh-Choudhury, G AF Mahimainathan, L Ghosh-Choudhury, G TI TGF beta and high glucose downregulate the tumor suppressor protein PTEN (Phosphatase and tensin homolog deleted on chromosome 10) to regulate mesangial cell hypertrophy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 551A EP 551A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102539 ER PT J AU Chen, XY Feliers, D Akis, N Choudhury, GG Madaio, MS Kasinath, BS AF Chen, XY Feliers, D Akis, N Choudhury, GG Madaio, MS Kasinath, BS TI Vascular endothelial growth factor (VEGF) regulation of eNOS in glomerular endothelial (G Endo) cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 553A EP 553A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102549 ER PT J AU Faulkner, JL Barnes, JL AF Faulkner, JL Barnes, JL TI TGF beta-1 and angiotensin II (AII) have distinct effects on renal fibroblast phenotype, hypertrophy and fibronectin synthesis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 590A EP 590A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102730 ER PT J AU Tofovic, SP Mady, H Jackson, EK AF Tofovic, SP Mady, H Jackson, EK TI Estradiol metabolites attenuate renal and cardiovascular injury induced by chronic angiotensin II administration. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, Pittsburgh, PA USA. Sch Med, Dept Pathol, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 620A EP 620A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102872 ER PT J AU Kestenbaum, B Seliger, SL Gillen, DL Wasse, H Young, B Sherrard, DJ Weiss, NS Stehman-Breen, CO AF Kestenbaum, B Seliger, SL Gillen, DL Wasse, H Young, B Sherrard, DJ Weiss, NS Stehman-Breen, CO TI Parathyroidectomy rates among US dialysis patients: 1990-1999. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Washington, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Healthcare Syst, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RI Wasse, Haimanot/A-5726-2013 OI Wasse, Haimanot/0000-0001-5756-0242 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 684A EP 684A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103162 ER PT J AU Palevsky, PM Zgibor, JC Stevenson, JA Rohay, JM Perry, SB Dyer, NJ Freed, B AF Palevsky, PM Zgibor, JC Stevenson, JA Rohay, JM Perry, SB Dyer, NJ Freed, B TI Influenza immunization in ESRD patients: Comparison between medicare billing and facility data. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. ESRD Network 4, Pittsburgh, PA USA. Pinney Associates, Pittsburgh, PA 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 719A EP 719A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103316 ER PT J AU Young, BA Boyko, EJ McDonell, M Fihn, SS AF Young, BA Boyko, EJ McDonell, M Fihn, SS TI Risk of cardiovascular events with renal insufficiency: Results from the ambulatory care quality improvement project SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. VA Puget Sound Hlth Care Syst, ERIC, Seattle, WA USA. Univ Washington, Div Gen Internal Med, 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 816A EP 816A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103760 ER PT J AU Watnick, SG Angelo, D Paul, K John, C AF Watnick, SG Angelo, D Paul, K John, C TI Depression as a potential barrier to renal transplantation. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Portland VA Med Ctr, Portland, OR USA. Yale Univ, New Haven, CT 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 830A EP 830A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103822 ER PT J AU Arar, M Ye, P Barnes, J Abboud, H AF Arar, M Ye, P Barnes, J Abboud, H TI Mesangial cell development: Role of PDGF. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 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 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 873A EP 873A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219104021 ER PT J AU Mittalhenkle, A Meligro, CM Sherrard, DJ AF Mittalhenkle, A Meligro, CM Sherrard, DJ TI The changing relationship between intact parathyroid hormone (iPTH) and bone histology in dialysis patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Washington, Div Nephrol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 894A EP 894A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219104115 ER PT J AU Santamaria, R Almaden, Y Felsenfeld, A Martin-Malo, A Gao, P Cantor, T Aljama, P Rodriguez, M AF Santamaria, R Almaden, Y Felsenfeld, A Martin-Malo, A Gao, P Cantor, T Aljama, P Rodriguez, M TI Dynamics of PTH secretion in hemodialysis patients as determined by the intact and whole PTH assays SO KIDNEY INTERNATIONAL LA English DT Article DE calcium; hemodialysis; PTH; PTH fragments; secondary hyperparathyroidism ID IONIZED CALCIUM-CONCENTRATION; CARBOXYL-TERMINAL FRAGMENTS; PARATHYROID-HORMONE RELEASE; CHRONIC-RENAL-FAILURE; SECONDARY HYPERPARATHYROIDISM; BONE TURNOVER; SET-POINT; METABOLISM; DIAGNOSIS; RECEPTOR AB Background. Renal hyperparathyroidism is assessed by measurement of parathyroid hormone (PTH) levels. The intact PTH assay (I-PTH) not only reacts with 1-84 PTH but also with large, truncated fragments of non-1-84 PTH. Because the whole PTH assay (W-PTH) is specific for 1-84 PTH, non-1-84 PTH is determined by subtracting W-PTH from I-PTH values. These large circulating PTH fragments may exert a hypocalcemic effect by contributing to skeletal resistance to 1-84 PTH. Methods. The dynamic secretion of both 1-84 PTH and non-1-84 PTH was evaluated during the induction of hypo- and hypercalcemia in eight hemodialysis patients. Results. The basal ionized calcium concentration was 1.23 +/- 0.03 mmol/L at which time I-PTH, W-PTH, and non-1-84 PTH values were 276 +/- 78 pg/mL, 164 +/- 48 pg/mL, and 102 +/- 28 pg/mL, respectively. The induction of hypo- and hypercalcemic changes resulted in a sigmoidal response for all three PTH moieties, I-PTH, W-PTH, and non-1-84 PTH. During hypocalcemia, maximal values of W-PTH were greater than those of non-1-84 PTH. But during hypercalcemia, minimal values of W-PTH and non-1-84 PTH were similar. Neither the set points nor the basal/maximal ratios for W-PTH, I-PTH, and non-1-84 PTH were different. At the baseline ionized calcium concentration, the W-PTH (1-84 PTH)/non-1-84 PTH ratio was 1.53 +/- 0.15. Changes in ionized calcium resulted in a sigmoidal relationship with hypocalcemia, increasing this ratio to a maximum of 2.01 +/- 0.30 and hypercalcemia decreasing this ratio to a minimum of 1.18 +/- 0.15 (P < 0.01 vs baseline for both hypo- and hypercalcemia). Conclusion. Although acute changes in serum calcium produce similar secretory responses in 1-84 PTH and non-1-84 PTH, the secretory responses are not proportional for these PTH moieties. Changes in the serum calcium concentration modulate the ratio of 1-84 PTH/non-1-84 PTH in a sigmoidal pattern with hypocalcemia maximizing this ratio. Whether changes in the 1-84 PTH/non-1-84 PTH ratio specifically modulate the calcemic action and other biologic effects of 1-84 PTH remain to be determined. C1 Reina Sofia Univ Hosp, Serv Nephrol, Cordoba 14004, Spain. Reina Sofia Univ Hosp, Res Unit, Cordoba, Spain. W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Scantibodies Lab Inc, Dept R&D & Diagnost, Santee, CA USA. RP Santamaria, R (reprint author), Reina Sofia Univ Hosp, Serv Nephrol, Avda Menendez Pidal S-N, Cordoba 14004, Spain. RI Rodriguez, teresa/H-5452-2011 NR 28 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2003 VL 64 IS 5 BP 1867 EP 1873 DI 10.1046/j.1523-1755.2003.00262.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 730HH UT WOS:000185824300036 PM 14531822 ER PT J AU Coburn, JW AF Coburn, JW TI An update on vitamin D as related to nephrology practice: 2003 SO KIDNEY INTERNATIONAL LA English DT Article DE renal osteodystrophy; vitamin D; calcitriol ID CHRONIC-RENAL-FAILURE; DOXERCALCIFEROL 1-ALPHA-HYDROXYVITAMIN D-2; INTERMITTENT CALCITRIOL THERAPY; PARATHYROID-HORMONE SECRETION; SECONDARY HYPERPARATHYROIDISM; DOUBLE-BLIND; D-DEFICIENCY; HEMODIALYSIS-PATIENTS; CALCIUM HOMEOSTASIS; DIALYSIS PATIENTS AB In this article, an up-to-date consideration of vitamin D therapeutics in nephrology is reviewed. The condition of vitamin D insufficiency is defined as the level of serum 25(OH)vitamin D at which vitamin D-2 or D-3 supplementation leads to a reduction of levels of parathyroid hormone (PTH). The risks of such vitamin D insufficiency in the normal population and likely risks in individuals with chronic kidney disease (CKD) stages 3 and 4 are reviewed. The potential for its safe treatment and prevention using moderate supplements of vitamin D-2 or vitamin D-3 are outlined. The role of altered "vitamin D nutrition" in leading to the observed greater incidence of secondary hyperparathyroidism in African Americans with ESRD compared to other racial groups is considered. The actions of active vitamin D sterols to augment intestinal absorption of both calcium and phosphorus, the effect to reduce levels of PTH, and to be a factor contributing to the rising incidence of low bone turnover (adynamic bone) are discussed. Growing evidence for contributions of elevated levels of serum calcium, serum phosphorus, and the calcium x phosphorus product as factors contributing to vascular and cardiac calcification in ESRD patients are cited. Questions are raised about whether the current practice of vitamin D usage in ESRD patients might be a contributing factor to such vascular abnormalities. The economic factors that likely affect the usage of intravenous vitamin D sterols in the United States are reviewed. It is recommended that potential adverse vascular effects of vitamin D sterols related to the increments of serum Ca and P be carefully evaluated. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Med Serv, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Coburn, JW (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect, 111L,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 56 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2003 VL 64 SU 87 BP S125 EP S130 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 730CQ UT WOS:000185812000020 ER PT J AU Rosen, HR AF Rosen, HR TI Hepatitis C pathogenesis: Mechanisms of viral clearance and liver injury SO LIVER TRANSPLANTATION LA English DT Article ID VIRUS ENVELOPE PROTEIN; CD8(+) T-CELLS; HYPERVARIABLE REGION 1; NATURAL-KILLER-CELLS; DENDRITIC CELLS; IMMUNE-RESPONSES; INFECTION; CD4(+); INTERFERON; PERSISTENCE AB 1. The development of hepatitis C virus (HCV) quasispecies has a number of biological consequences, including the development of escape mutants to humoral or cellular immunity, the generation of "defective" viral particles, variable cell tropism, and the development of drug resistance. 2. Accumulating evidence shows that HCV affects the early innate immune response mediated by natural killer and dendritic cells. 3. Recent data suggest that clearance of HCV bestows antibody to HCV immunity that affords partial protection against persistent infection. However, after spontaneous recovery from HCV infection, titers of HCV-specific antibodies decline and disappear in a subset of patients, whereas viral-specific CD4(+) and CD8(+) T-cell responses persist for decades. 4. HCV-specific CD8(+) T-cell responses are phenotypically and functionally diverse and may be associated with either viral eradication or chronic hepatic immunopathologic states. 5. Novel HCV genome-wide screening approaches have shown that the breadth of the immune response is considerably greater than was initially appreciated using more conventional assays, but why the majority of patients remain chronically infected despite the presence of vital-specific immune responses remains undefined. C1 Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. RP Rosen, HR (reprint author), Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, SW US Vet Hosp 371 0, P3-G1, Portland, OR 97207 USA. FU NIDDK NIH HHS [R01 DK60590-1, U01-DK60342-01] NR 57 TC 32 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2003 VL 9 IS 11 SU 3 BP S35 EP S43 DI 10.1053/jlts.2003.50253 PG 9 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 738DC UT WOS:000186270600006 PM 14586893 ER PT J AU Chatterjee, B AF Chatterjee, B TI The role of the androgen receptor in the development of prostatic hyperplasia and prostate cancer SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE androgen receptor; prostate; prostate cancer; androgen; antiandrogen; growth factor; apoptosis; signal cross talk ID LIGAND-BINDING DOMAIN; CARCINOMA-CELLS; TRANSACTIVATION FUNCTION; HORMONE-RECEPTOR; INTERFERING RNAS; TUMOR-SUPPRESSOR; MAMMALIAN-CELLS; GENE-EXPRESSION; PROTEIN; KINASE AB The androgen receptor (AR) is an androgen-inducible transcription factor characterized by a modular primary structure, with each module representing a distinct functional unit. After its interaction with androgens, the cytoplasmic AR is activated and translocated to the nucleus where it binds to target genes at the androgen responsive element(s) and recruits coregulators to form a multiprotein complex that interacts with transcriptional mediators and the basal transcription machinery to regulate gene transcription. Androgens play an essential role in the morphogenesis and physiology of the normal prostate. The etiology of benign prostatic hyperplasia (BPH) and prostatic neoplasia, which can progress to adenocarcinoma, is androgen-dependent, and reduction/obliteration of androgen action in the prostate has been the therapy of choice for BPH and prostate cancer. After androgen withdrawal and antiandrogen treatment, the androgen responsive prostate cancer cells cease to proliferate and undergo apoptosis, causing tumor regression. However, relapses are seen invariably, when tumors emerge as androgen-independent and apoptosis-resistant. Gene amplification and amino acid substitutions in the AR are detected at a high frequency in recurrent tumors. These changes confer growth advantage to the tumor cells due to either hypersensitivity of AR to low, castrate-level androgens or a realignment of the receptor conformation, leading to altered ligand specificity that enables antiandrogens, adrenal androgens and non-androgen steroids act agonistically to increase AR activity. Persistence of signaling by the wildtype AR in therapy-resistant tumors is due to the increased receptor activity caused by cross talk of AR with multiple intracellular signaling cascades, especially the growth factor activated MAP kinase/ERK and PI3 kinase/Akt pathways. Ablation of AR function using antisense oligodeoxynucleotides, ribozymes or small interference RNAs (RNAi) holds promise as future approaches to the successful treatment of hormone-refractory, apoptosis-resistant prostate tumors. C1 Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Chatterjee, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, 15355 Lambda Dr, San Antonio, TX 78245 USA. FU NIA NIH HHS [R01 AG19660] NR 81 TC 85 Z9 89 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2003 VL 253 IS 1-2 BP 89 EP 101 DI 10.1023/A:1026057402945 PG 13 WC Cell Biology SC Cell Biology GA 727LN UT WOS:000185660200011 PM 14619959 ER PT J AU Nelson, PS Montgomery, B AF Nelson, PS Montgomery, B TI Unconventional therapy for prostate cancer: Good, bad or questionable? SO NATURE REVIEWS CANCER LA English DT Review ID RANDOMIZED CLINICAL-TRIAL; CELL-CYCLE PROGRESSION; PC-SPES; VITAMIN-E; GREEN TEA; ALPHA-TOCOPHEROL; BETA-CAROTENE; UNITED-STATES; SAW PALMETTO; IN-VITRO AB Complementary and alternative medicine (CAM) encompasses a wide range of interventions that are often used for the prevention and treatment of malignant disease. As prostate cancer is characterized by strong dietary influences, a long disease latency period and limited treatment strategies for advanced disease, many patients turn to CAM with the belief that they represent a viable therapeutic option that is free of adverse side effects. Although the efficacy of many CAM therapies seems compelling, definitive studies are underway and the potentially harmful effects of these 'natural' interventions need to be recognized. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98105 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98105 USA. Univ Washington, Dept Med, Seattle, WA 98108 USA. VA Puget Sound HCS, Seattle, WA 98108 USA. RP Nelson, PS (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave, Seattle, WA 98105 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 106 TC 32 Z9 33 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD NOV PY 2003 VL 3 IS 11 BP 845 EP 858 DI 10.1038/nrc1210 PG 14 WC Oncology SC Oncology GA 739AJ UT WOS:000186319800015 PM 14668815 ER PT J AU Casey, DE Daniel, DG Wassef, AA Tracy, LA Wozniak, P Sommerville, KW AF Casey, DE Daniel, DG Wassef, AA Tracy, LA Wozniak, P Sommerville, KW CA Depakote psychosis grp TI Effect of Divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia - Reply SO NEUROPSYCHOPHARMACOLOGY LA English DT Letter ID VALPROATE C1 Portland VA Med Ctr, Mental Illness Res Educ & Clin Ctr P3MIRECC, Portland, OR 97201 USA. George Washington Univ, Washington, DC 20052 USA. Bioniche Dev, Falls Church, VA USA. Univ Texas, HCPC, Houston, TX USA. Abbott Labs, Abbott Pk, IL 60064 USA. Univ Illinois, Chicago, IL USA. RP Casey, DE (reprint author), Portland VA Med Ctr, Mental Illness Res Educ & Clin Ctr P3MIRECC, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 7 TC 5 Z9 6 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2003 VL 28 IS 11 BP 2052 EP 2053 DI 10.1038/sj.npp.1300246 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 743AU UT WOS:000186550900019 ER PT J AU Hartig, GK Connor, NP Heisey, DM Conforti, ML AF Hartig, GK Connor, NP Heisey, DM Conforti, ML TI Comparing a mechanical device with medicinal leeches for treating venous congestion SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 106th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 22-25, 2002 CL SAN DIEGO, CALIFORNIA SP Amer Acad Otolaryngol Head & Neck Surg ID SURGERY AB OBJECTIVE. To compare mechanical device therapy to medicinal leech therapy for treating venous congestion. STUDY DESIGN. Fasciocutaneous flaps of 9 x 7-cm (porcine model, n = 11) were elevated and the associated veins clamped for 15 hours. Device-treated flaps (n = 6) were treated with up to 3 devices/flap. Leech-treated flaps (n = 5) were treated with 75 leeches/flap (5 leeches/hour). Treatment evaluation parameters included: blood volume removed, skin color, surface perfusion, tissue oxygen tension, and endpoint histology. RESULTS: No significant differences were seen in blood volume removed, surface perfusion, and oxygen tension. However, significant differences were seen in skin color change over time. Histological assessment showed mild congestion in 5/5 leech-treated flaps and 2/6 device-treated flaps. CONCLUSION: Device therapy was comparable to leech therapy for decongesting a 9 x 7-cm flap over a 15-hour period. However, digital images and significant differences in skin color change over time demonstrate that device therapy promotes more global decongestion versus leech therapy. C1 Univ Wisconsin, Sch Med, Clin Sci Ctr K4720, Dept Surg,Div Otolaryngol, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Res, Dept Vet Affairs, Madison, WI USA. RP Hartig, GK (reprint author), Univ Wisconsin, Sch Med, Clin Sci Ctr K4720, Dept Surg,Div Otolaryngol, Madison, WI 53792 USA. NR 11 TC 9 Z9 9 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2003 VL 129 IS 5 BP 556 EP 564 DI 10.1016/S0194-5998(03)01587-0 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 741CA UT WOS:000186440100013 PM 14595279 ER PT J AU Pandol, SJ Gukovsky, I Satoh, A Lugea, A Gukovskaya, AS AF Pandol, SJ Gukovsky, I Satoh, A Lugea, A Gukovskaya, AS TI Animal and in vitro models of alcoholic pancreatitis: Role of cholecystokinin SO PANCREAS LA English DT Article DE alcohol; cholecystokinin; pancreatitis; nuclear factor kappa B; activator protein 1; protein kinase C ID NF-KAPPA-B; ACINAR-CELLS; GENE-EXPRESSION; ACTIVATION; INJURY; CURCUMIN; ETHANOL; KINASE; RATS; TRANSCRIPTION AB Although ethanol abuse is the major etiologic factor in the development of acute and chronic pancreatitis, the mechanisms of ethanol effects to cause pancreatitis are poorly understood. The major reason for the lack of progress is the relative lack of animal models that reproduce the deleterious effects of ethanol on the pancreas that are observed in human disease. We propose that the effect of ethanol on the pancreas is due to its ability to sensitize animals and humans to the potentially injurious effects of other stimuli. We have developed models of ethanol-induced acute and chronic pancreatitis in rats as well as pancreatic acinar cells in primary culture demonstrating that ethanol sensitizes the pancreas to the inflammatory, cell death, and fibrosing responses caused by cholecystokinin (CCK). Our results indicate that the ethanol-sensitized inflammatory response is the key or trigger event for the development of the other pathologic responses in both acute and chronic pancreatitis, such as cell death, intracellular digestive enzyme activation, and fibrosis. These findings suggest that experimental strategies designed to reveal the modulating effects of ethanol on the mechanisms underlying the inflammatory, cell death, and fibrosing responses stimulated by CCK will provide the key information needed to understand how ethanol abuse causes pancreatitis. C1 VA Greater Los Angeles Healthcare Syst, Dept Med, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. USC UCLA, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. RP Pandol, SJ (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, W Los Angeles Healthcare Ctr, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIAAA NIH HHS [P50-AA11999]; NIDDK NIH HHS [DK59508] NR 40 TC 29 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2003 VL 27 IS 4 BP 297 EP 300 DI 10.1097/00006676-200311000-00004 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 737GV UT WOS:000186222800004 PM 14576490 ER PT J AU Whitcomb, DC AF Whitcomb, DC TI Genetic predisposition to alcoholic chronic pancreatitis SO PANCREAS LA English DT Article DE pancreatitis; pancreatic secretory trypsin inhibitor; alcohol; cystic fibrosis transmembrane conductance regulator; trypsinogen; trypsin ID CYSTIC-FIBROSIS GENE; IDIOPATHIC CHRONIC-PANCREATITIS; CATIONIC TRYPSINOGEN GENE; SERINE-PROTEASE INHIBITOR; HEREDITARY PANCREATITIS; KAZAL TYPE-1; MUTATIONS; RISK; SPINK1; POLYMORPHISMS AB The mechanisms leading to alcoholic chronic pancreatitis in humans have remained elusive. Numerous questions surround the apparent random nature of the disease in which 1 person is hit with alcoholic chronic pancreatitis while the next is spared. Why do fewer than 10% of chronic, heavy alcohol users ever develop pancreatitis, while others develop alcoholic liver disease, neuropathy, or other alcohol-associated problems? Why do laboratory animals, fed large amounts of alcohol for prolonged periods of time, fail to develop typical chronic pancreatitis? Why are heavy alcohol users from a black African background more likely to develop pancreatic diseases than Caucasians, whereas the opposite is true for the development of liver disease? The answers underlying these questions appear to reflect the differences in underlying genetic susceptibility, environmental exposure, and the interaction between these factors. Thus, even cases of "typical" alcoholic chronic pancreatitis or other forms of pancreatitis appear to be complex diseases. Recently, several genetic mutations have been identified that increase the susceptibility to pancreatitis. However, the major common gene mutations in CFTR, PRSS1, and SPINK1 only slightly increase the risk of alcoholic chronic pancreatitis. New genetic, environmental, and triggering factors must be considered to gain further insight into the mechanisms leading to alcoholic chronic pancreatitis so that strategies for treatment and prevention can be developed. C1 Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Whitcomb, DC (reprint author), UPMC Presbyterian Hosp, Mezzanine Level,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 35 TC 26 Z9 26 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2003 VL 27 IS 4 BP 321 EP 326 DI 10.1097/00006676-200311000-00009 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 737GV UT WOS:000186222800009 PM 14576495 ER PT J AU Fried, L Bernardini, J Piraino, B AF Fried, L Bernardini, J Piraino, B TI Comparison of the Charlson Comorbidity Index and the Davies score as a predictor of outcomes in PD patients SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article; Proceedings Paper CT 9th Congress of the International-Society-of-Peritoneal-Dialysis CY JUN 26-29, 2001 CL MONTREAL, CANADA SP Int Soc Peritonial Dialysis DE comorbidity; hospitalization; mortality ID PERITONEAL-DIALYSIS PATIENTS; HOSPITAL UTILIZATION; COEXISTENT DISEASE; CLINICAL-OUTCOMES; SURVIVAL; MORBIDITY; HEMODIALYSIS; ADEQUACY; ILLNESS; CANCER AB Background: Comorbidity is a strong predictor and confounds many studies of outcomes. Previous studies have shown that the Charlson Comorbidity Index (CCI) and the Davies score predict mortality in peritoneal dialysis (PD) patients. However, there are few data on the comparison of comorbidity scores. Objective: To compare the CCI (combines comorbidity and age) and Davies score (comorbidity score without age) to see if one score was superior to the other in predicting outcomes. Design: Prospective database study. Setting: Seven dialysis centers in Western Pennsylvania. Participants: 415 incident PD patients, starting PD from 1/1/90 to 2/1/00. Measurements: The CCI and Davies score calculated at the start of PD; serum albumin levels and demographics at the start of PD; total hospitalizations and mortality, collected prospectively. Results: The correlation between CCI and Davies was 0.80, p < 0.0001. The CCI was inversely correlated with serum albumin (-0.31, p < 0.0001). Davies was significantly correlated with age (0.32, p < 0.0001) and inversely correlated with albumin (-0.27, p < 0.0001). The CCI alone was a stronger predictor than Davies alone (score by best subsets regression 49.6 vs 42.0, p = 0.0058). The CCI and Davies with age appeared to be equivalent models of survival (49.61 vs; 49.64). The best predictive models were CCI and initial albumin, or Davies, age, and initial albumin. Both CCI and Davies were predictors of hospitalization rates, but the model with the Davies score was better (Akaike information criterion 799.2 vs; 850.2). The best predictive model was Davies, albumin, age, and race. Conclusions: Both comorbidity scores were significant predictors of outcomes, with CCI the stronger predictor for mortality, but the Davies was a stronger predictor of hospitalizations. One or both should be done at the start of dialysis to predict outcome. C1 Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Renal Sect,VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Med, Sch Med, Pittsburgh, PA 15261 USA. RP Fried, L (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Renal Sect,VA Pittsburgh Healthcare Syst, A919 Scaife Hall, Pittsburgh, PA 15261 USA. NR 22 TC 26 Z9 26 U1 0 U2 1 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD NOV-DEC PY 2003 VL 23 IS 6 BP 568 EP 573 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 752MQ UT WOS:000187165000007 PM 14703198 ER PT J AU Ritsher, JB Otilingam, PG Grajales, M AF Ritsher, JB Otilingam, PG Grajales, M TI Internalized stigma of mental illness: psychometric properties of a new measure SO PSYCHIATRY RESEARCH LA English DT Article DE stereotyping; social alienation; risk factors; mental disorders; questionnaires; psychometrics ID PERCEIVED STIGMA; HEALTH-SERVICES; CONSEQUENCES; EMPOWERMENT; CONSUMERS; CONSTRUCT; RECOVERY; VALIDITY AB The study evaluated the Internalized Stigma of Mental Illness (ISMI) scale, designed to measure the subjective experience of stigma, with subscales measuring Alienation, Stereotype Endorsement, Perceived Discrimination, Social Withdrawal and Stigma Resistance. The ISMI was developed in collaboration with people with mental illnesses and contains 29 Likert items. The validation sample included 127 mental health outpatients. Results showed that the ISMI had high internal consistency and test-retest reliability. Construct validity was supported by comparisons against scales measuring related constructs with the same methodology. As expected, the ISMI had positive correlations with measures of stigma beliefs and depressive symptoms, and it had negative correlations with measures of self-esteem, empowerment and recovery orientation. Factor analyses of the joint set of items from the ISMI and each scale supported the distinction between constructs. Having a validated measure of internalized stigma may encourage clinicians to include stigma reduction as a verifiable treatment goal in addition to symptom reduction. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 US Dept Vet Affairs, Ctr Hlth Care Evaluat, Menlo Park, CA USA. Stanford Univ, Sch Med, Menlo Park, CA USA. Univ Calif San Francisco, Dept Psychiat 116A, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ So Calif, Dept Psychol, Los Angeles, CA USA. San Francisco State Univ, Dept Social Psychol, San Francisco, CA 94132 USA. RP Ritsher, JB (reprint author), US Dept Vet Affairs, Ctr Hlth Care Evaluat, Menlo Park, CA USA. NR 28 TC 340 Z9 362 U1 5 U2 55 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 1 PY 2003 VL 121 IS 1 BP 31 EP 49 DI 10.1016/j.physchres.2003.08.008 PG 19 WC Psychiatry SC Psychiatry GA 736LG UT WOS:000186171800004 PM 14572622 ER PT J AU Oslin, DW Sayers, S Ross, J Kane, V Ten Have, T Conigliaro, J Cornelius, J AF Oslin, DW Sayers, S Ross, J Kane, V Ten Have, T Conigliaro, J Cornelius, J TI Disease management for depression and at-risk drinking via telephone in an older population of veterans SO PSYCHOSOMATIC MEDICINE LA English DT Article DE telephone; depression; at-risk drinking; primary care ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PATIENTS; LATE-LIFE; FAMILY PHYSICIANS; MENTAL-DISORDERS; MAJOR DEPRESSION; VALIDATION; ALCOHOLISM; ATTITUDES; KNOWLEDGE AB Objectives: The purpose of this study was to explore the efficacy in a primary care setting of a telephone-based disease management program for the acute management of depression and/or at-risk drinking. Materials and Methods: Veterans (N = 97) with depression and/or at-risk drinking were identified by systematic screening and assessment. Eligible subjects received either telephone disease management (TDM) program or usual care based on random assignment of their clinician. The TDM program consisted of regular contacts with each subject by a behavioral health specialist (BHS) to assist in assessment, education, support, and treatment planning. Symptomatic outcomes were assessed at 4 months. Results: Overall response rates favored those assigned to TDM compared with those assigned to usual care (39.1% responded vs. 17.6%,p = 0.022). Response rates within the separate diagnostic groups also favored TDM, but this was only significant for depressive disorders. Conclusions: Although the sample size was modest and the sample was limited to veterans, findings strongly suggest that a telephone-based disease management program can improve outcomes for patients with a behavioral health problem. Findings also suggest that a health specialist can focus and manage patients with different diagnoses, thus expanding the role beyond just depression care. TDM may be a viable, low-cost, model for primary care clinicians to deliver manual guideline-adherent behavioral health care, especially in a VA clinical setting. C1 Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA USA. Univ Penn, Ctr Study Addict, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. VISN 4 MIRECC, Philadelphia, PA USA. Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Oslin, DW (reprint author), Univ Penn, Sect Geriatr Psychiat, 3535 Market St,Room 3002, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [1K08 MH01599-01] NR 49 TC 53 Z9 53 U1 6 U2 7 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 NOV-DEC PY 2003 VL 65 IS 6 BP 931 EP 937 DI 10.1097/01.PSY.0000097335.35776.FB PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 748QK UT WOS:000186872400002 PM 14645769 ER PT J AU Grant, EG Benson, CB Moneta, GL Alexandrov, AV Baker, JD Bluth, EI Carroll, BA Eliasziw, M Gocke, J Hertzberg, BS Katanick, S Needleman, L Pellerito, J Polak, JF Rholl, KS Wooster, DL Zierler, E AF Grant, EG Benson, CB Moneta, GL Alexandrov, AV Baker, JD Bluth, EI Carroll, BA Eliasziw, M Gocke, J Hertzberg, BS Katanick, S Needleman, L Pellerito, J Polak, JF Rholl, KS Wooster, DL Zierler, E TI Carotid artery stenosis: Gray-scale and Doppler US diagnosis - Society of Radiologists in Ultrasound consensus conference SO RADIOLOGY LA English DT Article DE carotid arteries, flow dynamics; carotid arteries, stenosis or obstruction; carotid arteries, US; Special Reports ID MAGNETIC-RESONANCE ANGIOGRAPHY; DUPLEX CRITERIA; ENDARTERECTOMY TRIAL; SYMPTOMATIC PATIENTS; SYSTOLIC VELOCITY; SURGERY-TRIAL; ULTRASONOGRAPHY; 70-PERCENT; STANDARDIZATION; 60-PERCENT AB The Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts in the field of vascular ultrasonography (US) to come to a consensus regarding Doppler US for assistance in the diagnosis of carotid artery stenosis. The panel's consensus statement is believed to represent a reasonable position on the basis of analysis of available literature and panelists' experience. Key elements of the statement include the following: (a) All internal carotid artery (ICA) examinations should be performed with gray-scale, color Doppler, and spectral Doppler US. (b) The degree of stenosis determined at gray-scale and Doppler US should be stratified into the categories of normal (no stenosis), <50% stenosis, 50%-69% stenosis, greater than or equal to70% stenosis to near occlusion, near occlusion, and total occlusion. (c) ICA peak systolic velocity (PSV) and presence of plaque on gray-scale and/or color Doppler images are primarily used in diagnosis and grading of ICA stenosis; two additional parameters, ICA-to-common carotid artery PSV ratio and ICA end-diastolic velocity may also be used when clinical or technical factors raise concern that ICA PSV may not be representative of the extent of disease. (d) ICA should be diagnosed as (i) normal when ICA PSV is less than 125 cm/sec and no plaque or intimal thickening is visible; (ii) <50% stenosis when ICA PSV is less than 125 cm/sec and plaque or intimal thickening is visible; (iii) 50%-69% stenosis when ICA PSV is 125-230 cm/sec and plaque is visible; (iv) greater than or equal to70% stenosis to near occlusion when ICA PSV is greater than 230 cm/sec and visible plaque and lumen narrowing are seen; (v) near occlusion when there is a markedly narrowed lumen at color Doppler US; and (vi) total occlusion when there is no detectable patent lumen at gray-scale US and no flow at spectral, power, and color Doppler US. (e) The final report should discuss velocity measurements and gray-scale and color Doppler findings. Study limitations should be noted when they exist. The conclusion should state an estimated degree of ICA stenosis as reflected in the above categories. The panel also considered various technical aspects of carotid US and methods for quality assessment and identified several important unanswered questions meriting future research. (C) RSNA, 2003. C1 Univ So Calif, Keck Sch Med, Dept Radiol, Los Angeles, CA 90033 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Univ Texas, Houston Med Sch, Cerebrovasc Ultrasound & Stroke Treatment Team, Houston, TX USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA USA. Alton Ochsner Med Fdn & Ochsner Clin, Dept Radiol, New Orleans, LA 70121 USA. Duke Univ, Sch Med, Dept Radiol, Durham, NC 27706 USA. Univ Calgary, Dept Biostat, Calgary, AB T2N 1N4, Canada. Midw Heart Specialists Vasc Lab, Downers Grove, IL USA. La Grange Mem Vasc Lab, Downers Grove, IL USA. Intersocietal Accreditat Commiss, Columbia, MD USA. Thomas Jefferson Univ, Dept Radiol, Philadelphia, PA 19107 USA. NYU, N Shore Univ Hosp, Sch Med, Dept Radiol, New York, NY USA. Inova Alexandria Hosp, Dept Radiol, Alexandria, VA USA. Univ Toronto, Dept Surg, Toronto, ON, Canada. Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. RP Grant, EG (reprint author), Univ So Calif, Keck Sch Med, Dept Radiol, 1500 San Pablo St, Los Angeles, CA 90033 USA. RI Bluth, Edward/A-8613-2011 OI Alexandrov, Andrei V/0000-0001-8871-1023 NR 40 TC 580 Z9 599 U1 2 U2 18 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 NOV PY 2003 VL 229 IS 2 BP 340 EP 346 DI 10.1148/radiol.2292030516 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 736KJ UT WOS:000186169700009 PM 14500855 ER PT J AU Buchsbaum, MS Shihabuddin, L Brickman, AM Miozzo, R Prikryl, R Shaw, R Davis, K AF Buchsbaum, MS Shihabuddin, L Brickman, AM Miozzo, R Prikryl, R Shaw, R Davis, K TI Caudate and putamen volumes in good and poor outcome patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE caudate; putamen; Kraepelinian subtype ID GLUCOSE METABOLIC-RATE; BASAL GANGLIA VOLUMES; VENTRICULAR ENLARGEMENT; EPISODE SCHIZOPHRENIA; STRIATAL SIZE; MRI; SYMPTOMS; CLOZAPINE; DISORDER AB Magnetic resonance images of 37 patients with schizophrenia and 37 age- and sex-matched volunteers were acquired. The caudate nucleus and putamen were traced on axial slices from the most superior extent of the caudate to the most inferior point where the caudate and putamen merge. Two subtypes of schizophrenia were compared, the Kraepelinian subtype (n = 13), characterized by an unremitting and severe course, and the non-Kraepelinian subtype (n = 24), characterized by a remitting course and some periods of self-care. Patients with good outcome schizophrenia had larger relative mean putamen size (0.0129) than poor outcome patients (0.0123) or normal controls (0.0121), but not caudate size. This enlargement was most marked for the dorsal putamen and right hemisphere. Striatal size was not related to whether patients were currently being treated with atypical or typical neuroleptics or whether they had been predominantly treated with typical or atypical neuroleptics over the past 3 years. This suggests the possibility that the expansion of putamen size may be a physiological correlate of neuroleptic responsiveness or that small putamen size at disease onset may be a predictor of outcome. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Fac Hosp Brno, Dept Psychiat, Brno, Czech Republic. RP Buchsbaum, MS (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIMH NIH HHS [MH60023, MH56489] NR 31 TC 53 Z9 54 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 1 PY 2003 VL 64 IS 1 BP 53 EP 62 DI 10.1016/S0920-9964(02)00526-1 PG 10 WC Psychiatry SC Psychiatry GA 729ZK UT WOS:000185804600006 PM 14511801 ER PT J AU Vergnes, L Phan, J Strauss, M Tafuri, S Reue, K AF Vergnes, L Phan, J Strauss, M Tafuri, S Reue, K TI Cholesterol and cholate components of an atherogenic diet induce distinct stages of hepatic inflammatory gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENSITY-LIPOPROTEIN LEVELS; HIGH-FAT DIETS; TRANSGENIC MICE; STELLATE CELLS; ATHEROSCLEROSIS; MOUSE; FIBROSIS; SUSCEPTIBILITY; IV; HYPERCHOLESTEROLEMIA AB Atherosclerosis in inbred mouse strains has been widely studied by using an atherogenic (Ath) diet containing cholesterol, cholic acid, and fat, but the effect of these components on gene expression has not been systematically examined. We employed DNA microarrays to interrogate gene expression levels in liver of C57BL/6J mice fed the following five diets: mouse chow, the Ath diet, or modified versions of the Ath diet in which either cholesterol, cholate, or fat were omitted. Dietary cholesterol and cholate produced discrete gene expression patterns. Cholesterol was required for induction of genes involved in acute inflammation, including three genes of the serum amyloid A family, three major histocompatibility class II antigen genes, and various cytokine-related genes. In contrast, cholate induced expression of genes involved in extracellular matrix deposition in hepatic fibrosis, including five collagen family members, collagen-interacting proteins, and connective tissue growth factor. The gene expression findings were confirmed by biochemical measurements showing that cholesterol was required for elevation of circulating serum amyloid A, and cholate was required for accumulation of collagen in the liver. The possibility that these gene expression changes are relevant to atherogenesis in C57BL/6J mice was supported by the observation that the closely related, yet atherosclerosis-resistant, C57BL/ 6ByJ strain was largely resistant to dietary induction of the inflammatory and fibrotic response genes. These results establish that cholesterol and cholate components of the Ath diet have distinct proatherogenic effects on gene expression and suggest a strategy to study the contribution of acute inflammatory response and fibrogenesis independently through dietary manipulation. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Pfizer Global Res & Dev, Ann Arbor Labs, Ann Arbor, MI 48105 USA. RP Reue, K (reprint author), 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL28481, HL58627] NR 35 TC 106 Z9 109 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 OCT 31 PY 2003 VL 278 IS 44 BP 42774 EP 42784 DI 10.1074/jbc.M306022200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 736EA UT WOS:000186157000008 PM 12923166 ER PT J AU Shimizu, S Ugi, S Maegawa, H Egawa, K Nishio, Y Yoshizaki, T Shi, K Nagai, Y Morino, K Nemoto, K Nakamura, T Bryer-Ash, M Kashiwagi, A AF Shimizu, S Ugi, S Maegawa, H Egawa, K Nishio, Y Yoshizaki, T Shi, K Nagai, Y Morino, K Nemoto, K Nakamura, T Bryer-Ash, M Kashiwagi, A TI Protein-tyrosine phosphatase 1B as new activator for hepatic lipogenesis via sterol regulatory element-binding protein-1 gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN SENSITIVITY; RESISTANCE; MICE; PATHWAY; GLUCOSE; LIVERS; SP1; 2A; PHOSPHORYLATION; OVEREXPRESSION AB Like hyperglycemia, postprandial (diet-induced) hypertriglyceridemia is thought to play crucial roles in the pathogenesis of insulin resistant/metabolic syndrome. Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcription factor to induce postprandial hypertriglyceridemia. We found that insulin-resistant rats fed a diet high in fructose showed an increased protein-tyrosine phosphatase 1B (PTP1B) content with strong expression of SREBP-1 mRNA in the liver. To clarify the association of PTP1B with SREBP-1 gene expression, we overexpressed PTP1B in rat hepatocytes, which led to increased mRNA content and promoter activity of SREBP-1a and -1c, resulting in the increased mRNA expression of fatty-acid synthase, one of the SREBP-1-responsive lipogenic genes. Because PTP1B overexpression increased phosphatase 2A (PP2A) activity, we inhibited PP2A activity by expression of its selective inhibitor, SV40 small t antigen and found that this normalized the PTP1B-enhanced SREBP-1a and -1c mRNA expressions through activation of the Sp1 site. These results indicate that PTP1B may regulate gene expression of SREBP-1 via enhancement of PP2A activity, thus mediating hepatic lipogenesis and postprandial hypertriglyceridemia. We demonstrate here a unique serial activation of the PTP1B-PP2A axis as a novel mechanism for the regulation of gene expression in the biosynthesis of triglyceride. C1 Shiga Univ Med Sci, Dept Med, Div Endocrinol & Metab, Shiga 5202192, Japan. Shiga Univ Med Sci, Dept Anat, Shiga 5202192, Japan. Univ Calif Los Angeles, Dept Med, Div Endocrinol Diabet & Hypertens, Gonda Goldschmied Diabet Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90095 USA. RP Maegawa, H (reprint author), Shiga Univ Med Sci, Dept Med, Div Endocrinol & Metab, Shiga 5202192, Japan. NR 32 TC 54 Z9 59 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 31 PY 2003 VL 278 IS 44 BP 43095 EP 43101 DI 10.1074/jbc.M306880200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 736EA UT WOS:000186157000048 PM 12941932 ER PT J AU DeArmond, D Brattain, MG Jessup, JM Kreisberg, J Malik, S Zhao, SJ Freeman, JW AF DeArmond, D Brattain, MG Jessup, JM Kreisberg, J Malik, S Zhao, SJ Freeman, JW TI Autocrine-mediated ErbB-2 kinase activation of STAT3 is required for growth factor independence of pancreatic cancer cell lines SO ONCOGENE LA English DT Article DE growth factors; ErbB-2; cell signaling; pancreatic cancer ID CYCLIN D1; FACTOR-ALPHA; CONSTITUTIVE ACTIVATION; BREAST-CANCER; SIGNAL TRANSDUCERS; TYROSINE KINASES; CDK INHIBITORS; ABERRANT REGULATION; DEPENDENT KINASE; FACTOR RECEPTORS AB Pancreatic ductal adenocarcinoma (PDAC) cell lines, MIA PaCa-2, and UK Pan-1, were used to investigate the role of ErbB2 in PDAC oncogenesis. Both these cell lines exhibit exogenous growth factor-independent proliferation that was attributed to the production of autocrine growth factors and/or overexpression of growth factor receptors. The exogenous growth factor-independent phenotype displayed by these PDAC cell lines was dependent on ErbB2 kinase activity since treatment of cells with tyrphostin AG879 prevented serum-free media (SFM) induction of cell proliferation. We determined that ErbB2 kinase contributed to aberrant cell cycle regulation in PDAC through the induction of cyclin D1 levels and the suppression of p21(Cip1) and p27(Kip1). Inhibition of ErbB2 kinase led to cell cycle arrest marked by an increased association of p27(Kip1) with cdk2 and reduced levels of phosphorylated pRb. We further observed constitutive STAT3 activation in the PDAC cell lines and an increase in STAT3 activation upon stimulating quiescent cells with SFM. Inhibitors of ErbB2 kinase blocked STAT3 activation, whereas inhibition of EGFR kinase led to a slight reduction of STAT3 activation. STAT3 was coimmunoprecipitated with ErbB2. SFM stimulation caused an increase in the association of ErbB2 and STAT3, which was blocked by inhibition of ErbB2 kinase. Expression of a STAT3 dominant negative prevented SFM-stimulated cell proliferation of MIA PaCa-2 cells, suggesting that activation of STAT3 by ErbB2 is required for a growth factor-independent phenotype of these cells. Consistent with this observation in PDAC cell lines, we found that most PDAC tumor specimens ( 10 of 11) showed constitutive activation of STAT3 and that ErbB2 was readily detected in most of these tumors ( nine of 11). We believe that these findings indicate a novel mechanism of oncogenesis in PDAC and may suggest future therapeutic strategies in the treatment of PDAC. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Res & Dev, San Antonio, TX 78229 USA. Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20007 USA. RP Freeman, JW (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCI NIH HHS [R01 CA69122, P30 CA 54174] NR 70 TC 41 Z9 42 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 OCT 30 PY 2003 VL 22 IS 49 BP 7781 EP 7795 DI 10.1038/sj.onc.1206966 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 737PD UT WOS:000186240200008 PM 14586404 ER PT J AU Greenberg, BH Banish, D Goldman, S Thomas, I Havranek, E Bijou, R O'Leary, M Zhu, Y Ticho, B Massie, B Abraham, W AF Greenberg, BH Banish, D Goldman, S Thomas, I Havranek, E Bijou, R O'Leary, M Zhu, Y Ticho, B Massie, B Abraham, W TI BG9928, an oral adenosine antagonist, preserves renal function, improves sodium excretion and is well tolerated in heart failure patients SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Calif San Diego, San Diego, CA 92103 USA. New Orleans Clin Trial Management, New Orleans, LA USA. VA Healthcare Syst, Tucson, AZ USA. Med Res Inst, Slidell, LA USA. Denver Hlth Med Ctr, Denver, CO USA. Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. Biogen Inc, Cambridge, MA 02142 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Ohio State Univ, Columbus, OH 43210 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 OCT 28 PY 2003 VL 108 IS 17 SU S MA 1602 BP 342 EP 342 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601660 ER PT J AU Ferguson, TB Shroyer, LA Coombs, LP DeLong, ER Grover, FL Peterson, ED AF Ferguson, TB Shroyer, LA Coombs, LP DeLong, ER Grover, FL Peterson, ED TI Risk-adjusted mortality, revascularization completeness and the learning curve effect in off-pump CABG SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 LSU, HSC, New Orleans, LA USA. Denver VA Med Ctr, Denver, CO USA. Duke Clin Res Inst, Durham, NC USA. Univ Colorado, HSC, Denver, CO 80202 USA. Duke Clin Rsch Inst, Durham, NC USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1810 BP 391 EP 391 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601867 ER PT J AU Howard, G Hobson, RW Brott, TG Howard, VJ Cohen, SN Petrossian, G Levy, D Mishkel, G Barnwell, SL AF Howard, G Hobson, RW Brott, TG Howard, VJ Cohen, SN Petrossian, G Levy, D Mishkel, G Barnwell, SL TI Does the stroke risk of stenting increase at older ages? Thirty-day stroke - Death rates in the CREST lead-in phase SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Alabama, Birmingham, AL USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. St Francis Hosp, Port Washington, NY USA. Kaiser Permanente Med Ctr, San Diego, CA USA. Prairie Cardiol St Johns Hosp & Mem Med Ctr, Springfield, IL USA. Oregon Hlth Sci Cntr, Portland, OR 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2116 BP 461 EP 461 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602173 ER PT J AU Corvera-Tindel, T Doering, LV Casimiro, L Dracup, K Khan, S AF Corvera-Tindel, T Doering, LV Casimiro, L Dracup, K Khan, S TI Estimating daily activity in heart failure patients: What do exercise tests mean? SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 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 OCT 28 PY 2003 VL 108 IS 17 SU S MA 2291 BP 502 EP 502 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602348 ER PT J AU Corvera-Tindel, T Doering, LV Aquino, C Roper, J Dracup, K AF Corvera-Tindel, T Doering, LV Aquino, C Roper, J Dracup, K TI Quality of life in heart failure: Feelings or performance? SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 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 OCT 28 PY 2003 VL 108 IS 17 SU S MA 2295 BP 503 EP 503 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602352 ER PT J AU Latini, R Wong, M Masson, S Barlera, S Staszewsky, L Salio, M Maggioni, AP Anand, IS Tognoni, G Cohn, JN AF Latini, R Wong, M Masson, S Barlera, S Staszewsky, L Salio, M Maggioni, AP Anand, IS Tognoni, G Cohn, JN CA Val HeFT Investigators TI Predicting outcomes in chronic heart failure from short-term change in BNP as a surrogate end-point: Val-HeFT data SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Ist Mario Negri, Milan, Italy. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. ANMCO Res Ctr, Florence, Italy. VA Med Ctr, Minneapolis, MN 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 OCT 28 PY 2003 VL 108 IS 17 SU S MA 2542 BP 557 EP 558 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602597 ER PT J AU Erkkila, AT Lichtenstein, AH MAyer, J Mozaffarian, D Herrington, DM AF Erkkila, AT Lichtenstein, AH MAyer, J Mozaffarian, D Herrington, DM TI Fish intake is associated with reduced progression of coronary-artery atherosclerosis in diabetic women with coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RI Mozaffarian, Dariush/B-2276-2008 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 OCT 28 PY 2003 VL 108 IS 17 SU S MA 3543 BP 785 EP 785 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603592 ER PT J AU Mendez, MF Clark, DG Shapira, JS Cummings, JL AF Mendez, MF Clark, DG Shapira, JS Cummings, JL TI Speech and language in progressive nonfluent aphasia compared with early Alzheimer's disease SO NEUROLOGY LA English DT Article ID CONDUCTION APHASIA; FRONTOTEMPORAL DEMENTIA; DEGENERATION; FEATURES; NETWORK AB Background: Progressive nonfluent aphasia (PA) is a slow deterioration of language that remains relatively isolated from other cognitive or behavioral deficits for at least 2 years. The differentiation of PA from early Alzheimer's disease (AD) is important, given the presence of early language changes in AD. Methods: A language assessment was administered to 15 patients who met established criteria for PA, 15 patients with clinically probable AD and mild dementia, and 15 normal control subjects. The language battery included verbal fluency, the Boston Naming Test with cuing and recognition, and an aphasia test battery with a motor speech exam. Results: Pronounced literal paraphasic errors distinguished the PA patients from the AD patients. The PA group had anomia, decreased letter fluency, neologisms, difficulty on phrase repetition, decreased phrase length, and a decreased rate of verbal output. Interference from paraphasic anomia accounted for much of their decreased fluency. Conclusion: Many patients with PA have a primary defect in accessing sound-based representation of speech ( phonemes), similar to conduction aphasia, possibly as a consequence of disturbed white matter tracts in the left superior temporal region. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 39 TC 29 Z9 32 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 28 PY 2003 VL 61 IS 8 BP 1108 EP U7 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 736QK UT WOS:000186184500017 PM 14581673 ER PT J AU Balasubramanian, S Kuppuswamy, D AF Balasubramanian, S Kuppuswamy, D TI RGD-containing peptides activate S6K1 through beta(3) integrin in adult cardiac muscle cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KINASE SIGNALING PATHWAY; FOCAL COMPLEX-FORMATION; MATRIX METALLOPROTEINASES; MONOCLONAL-ANTIBODIES; PROTEIN-SYNTHESIS; HEART-FAILURE; IN-VIVO; C-SRC; P70; PHOSPHORYLATION AB The enzyme p70S6 kinase (S6K1) is critical for cell growth, and we have reported its activation during cardiac hypertrophy. Because cardiac hypertrophy also involves integrin activation, we analyzed whether integrins could contribute to S6K1 activation. Using adult feline cardiomyocytes, here we report that integrin-interacting Arg-Gly-Asp (RGD) peptides activate S6K1 as observed by band shifting, kinase activity and phosphorylation at Thr-389 and Thr-421/Ser-424 of S6K1, and S6 protein phosphorylation. Perturbation of specific integrin function with blocking antibodies and by overexpressing the beta(1A) cytoplasmic tail revealed that beta(3) but not beta(1) integrin mediates the RGD-induced S6K1 activation. This activation is focal adhesion complex-independent and is accompanied by the activation of extracellular signal-regulated kinases 1/2 (ERK) and mammalian target of rapamycin (mTOR). Studies using specific inhibitors and dominant negative c-Raf expression in cardiomyocytes indicate that the S6K1 activation involves mTOR, MEK/ERK, and phosphatidylinositol 3-kinase pathways and is independent of protein kinase C and c-Raf. Finally, addition of fluorescent-labeled RGD peptide to cardiomyocytes exhibits its internalization and localization to the endocytic vesicles, and pretreatment of cardiomyocytes with endocytic inhibitors reduced the S6K1 activation. These data suggest that RGD interaction with beta(3) integrin and its subsequent endocytosis trigger specific signaling pathway(s) for S6K1 activation in cardiomyocytes and that this process may contribute to hypertrophic growth and remodeling of myocardium. C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, 114 Doughty St, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL 48788] NR 65 TC 32 Z9 36 U1 2 U2 3 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 OCT 24 PY 2003 VL 278 IS 43 BP 42214 EP 42224 DI 10.1074/jbc.M303428200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733FP UT WOS:000185989500080 PM 12909616 ER PT J AU Fihn, SD AF Fihn, SD TI Acute uncomplicated urinary tract infection in women (vol 349, pg 259, 2003) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Correction C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Fihn, SD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 4 TC 0 Z9 0 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 OCT 23 PY 2003 VL 349 IS 17 BP 1675 EP 1676 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 734ZT UT WOS:000186088400032 ER PT J AU Sonnenberg, A Lieberman, D AF Sonnenberg, A Lieberman, D TI Optimal intervals and techniques for screening sigmoidoscopy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID ASYMPTOMATIC ADULTS; COLORECTAL-CANCER C1 Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 22 PY 2003 VL 290 IS 16 BP 2122 EP 2123 DI 10.1001/jama.290.16.2122-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 734CB UT WOS:000186036700011 PM 14570940 ER PT J AU Yan, LJL Liu, K Matthews, KA Daviglus, ML Ferguson, TF Kiefe, CI AF Yan, LJL Liu, K Matthews, KA Daviglus, ML Ferguson, TF Kiefe, CI TI Psychosocial factors and risk of hypertension - The Coronary Artery Risk Development in Young Adults (CARDIA) study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HIGH BLOOD-PRESSURE; A BEHAVIOR PATTERN; NUTRITION EXAMINATION SURVEY; HEART-DISEASE; PSYCHOLOGICAL PREDICTORS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; EDUCATION-PROGRAM; NATIONAL-HEALTH; HOSTILITY AB Context Although psychosocial factors are correlated, previous studies on risk factors for hypertension have typically examined psychosocial factors individually and have yielded inconsistent findings. Objective To examine the role of psychosocial factors of time urgency/impatience (TUI), achievement striving/competitiveness (ASC), hostility, depression, and anxiety on long-term risk of hypertension. Design, Setting, and Study Population A population-based, prospective, observational study using participant data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. A total of 3308 black and white adults aged 18 to 30 years (when recruited in 1985 and 1986) from 4 US metropolitan areas and followed up through 2000 to 2001. Main Outcome Measures Fifteen-year cumulative incidence of hypertension (systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, or taking anti hypertensive medication). Results The incidence of hypertension at year 15 was 15% from baseline and 13.6% from year 5. After adjusting for the same set of hypertension risk factors and each of the psychosocial factors of TUI, ASC, hostility, depression, and anxiety in 5 separate logistic regression models, higher TUI and hostility were significantly associated with risk of developing hypertension at 15-year follow-up for the total sample. Compared with the lowest score group, the adjusted odds ratio (OR) for TUI was 1.51 (95% confidence interval [CI], 1.12-2.03) for a score of 1; 1.47 (95% Cl, 1.08-2.02) for a score of 2; and 1.84 (95% Cl, 1.29-2.62) for a score of 3 to 4 (P for trend =.001). Compared with the lowest quartile group, the adjusted OR for hostility was 1.06 (95% Cl, 0.76-1.47) for quartile 2; 1.38 (95% Cl, 1.00-1.91) for quartile 3; and 1.84 (95% Cl, 1.33-2.54) for quartile 4 (P for trend <.001). No consistent patterns were found for ASC, depression, or anxiety. Race- and sex-specific analyses and multivariable models with simultaneous adjustment for all 5 psychosocial factors and other hypertension risk factors had generally similar results. Conclusion Among young adults, TUI and hostility were associated with a dose-response increase in the long-term risk of hypertension. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Dent, Chicago, IL 60611 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Yan, LJL (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Dent, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095] NR 55 TC 181 Z9 195 U1 1 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 22 PY 2003 VL 290 IS 16 BP 2138 EP 2148 DI 10.1001/jama.290.16.2138 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 734CB UT WOS:000186036700023 PM 14570949 ER PT J AU Linseman, DA Bartley, CM Le, SS Laessig, TA Bouchard, RJ Meintzer, MK Li, MT Heidenreich, KA AF Linseman, DA Bartley, CM Le, SS Laessig, TA Bouchard, RJ Meintzer, MK Li, MT Heidenreich, KA TI Inactivation of the myocyte enhancer factor-2 repressor histone deacetylase-5 by endogenous Ca2+/calmodulin-dependent kinase II promotes depolarization-mediated cerebellar granule neuron survival SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; MEF2 TRANSCRIPTION FACTOR; CULTURED HIPPOCAMPAL-NEURONS; INDUCED NEURITE-OUTGROWTH; CENTRAL-NERVOUS-SYSTEM; FACTOR 2C EXPRESSION; MUSCLE FIBER-TYPE; GROWTH-FACTOR-I; CARDIAC-HYPERTROPHY; BRAIN-DEVELOPMENT AB Cerebellar granule neuron (CGN) survival depends on activity of the myocyte enhancer factor-2 (MEF2) transcription factors. Neuronal MEF2 activity is regulated by depolarization via a mechanism that is presently unclear. Here, we show that depolarization-mediated MEF2 activity and CGN survival are compromised by overexpression of the MEF2 repressor histone deacetylase-5 (HDAC5). Furthermore, removal of depolarization induced rapid cytoplasm-to-nuclear translocation of endogenous HDAC5. This effect was mimicked by addition of the calcium/calmodulin-dependent kinase ( CaMK) inhibitor KN93 to depolarizing medium. Removal of depolarization or KN93 addition resulted in dephosphorylation of HDAC5 and its co-precipitation with MEF2D. HDAC5 nuclear translocation triggered by KN93 induced a marked loss of MEF2 activity and subsequent apoptosis. To selectively decrease CaMKII, CGNs were incubated with an antisense oligonucleotide to CaMKIIalpha. This antisense decreased CaMKIIalpha expression and induced nuclear shuttling of HDAC5 in CGNs maintained in depolarizing medium. Selectivity of the CaMKIIalpha antisense was demonstrated by its lack of effect on CaMKIV-mediated CREB phosphorylation. Finally, antisense to CaMKIIalpha induced caspase-3 activation and apoptosis, whereas a missense control oligonucleotide had no effect on CGN survival. These results indicate that depolarization-mediated calcium influx acts through CaMKII to inhibit HDAC5, thereby sustaining high MEF2 activity in CGNs maintained under depolarizing conditions. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Heidenreich, KA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol C236, 4200 E 9th Ave, Denver, CO 80262 USA. RI Bartley, Christopher/G-4226-2012 OI Bartley, Christopher/0000-0002-1391-4130 FU NIGMS NIH HHS [T32 GM007205]; NINDS NIH HHS [NS38619-01A1] NR 59 TC 87 Z9 87 U1 0 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 OCT 17 PY 2003 VL 278 IS 42 BP 41472 EP 41481 DI 10.1074/jbc.M307245200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730TX UT WOS:000185847200127 PM 12896970 ER PT J AU Bent, S Xu, L Lui, LY Nevitt, M Schneider, E Tian, GQ Guo, SS Cummings, S AF Bent, S Xu, L Lui, LY Nevitt, M Schneider, E Tian, GQ Guo, SS Cummings, S TI A randomized controlled trial of a Chinese herbal remedy to increase energy, memory, sexual function, and quality of life in elderly adults in Beijing, China SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID OLDER ADULTS; MEDICINE; DYSFUNCTION; STRENGTH AB BACKGROUND: Chinese herbal medicines are commonly used to improve general health and well-being despite limited scientific data to support their efficacy. We conducted a randomized, double-blind, placebo-controlled trial to determine whether an herbal remedy that is used widely in China was associated with changes in quality of life, energy, memory, sexual function, and qi (the Chinese concept of "vital energy" that is important in general health). METHODS: Residents (n = 237) of Beijing, China, who were aged greater than or equal to60 years and had self-reported decreased energy, memory, or sexual function, were randomly assigned to take four tablets of a Chinese herbal formula or of an identical placebo, three times a day for 30 days. Patients returned for one follow-up visit after 30 days for assessment of all outcomes. The main outcome measures were changes in quality of life at 30 days as measured by the 12-Item Short Form Health Survey (SF-12) Mental and Physical Component Summary scales. RESULTS: Use of Chinese herbs was associated with a small benefit in the Mental Component scale (difference of 1.9 points; 95% confidence interval [Cl]: 0.1 to 3.6) and no benefit in the Physical Component scale (difference of -0.1 points; 95% CI: -1.7 to 1.5) as compared with placebo. A small improvement in the qi scale was no longer significant after adjusting for baseline differences in this score between groups. There was no improvement in physical performance, memory, or sexual function. The herbal product was well tolerated. CONCLUSION: Short-term use of a mixture of Chinese herbs was associated with a small benefit in one measure of mental health that is of unclear clinical importance. (C) 2003 by Excerpta Medica Inc. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA USA. Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. Beijing Union Med Coll Hosp, Beijing, Peoples R China. RP Bent, S (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, 4150 Clement St,111A1, San Francisco, CA 94121 USA. FU NCCIH NIH HHS [KO8 AT01338-01] NR 20 TC 12 Z9 12 U1 3 U2 12 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 15 PY 2003 VL 115 IS 6 BP 441 EP 447 DI 10.1016/S0002-9343(03)00421-2 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 733AX UT WOS:000185978700003 PM 14563500 ER PT J AU Qin, M Chen, S Yu, T Escuadro, B Sharma, S Batra, RK AF Qin, M Chen, S Yu, T Escuadro, B Sharma, S Batra, RK TI Coxsackievirus adenovirus receptor expression predicts the efficiency of adenoviral gene transfer into non-small cell lung cancer xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID DEACETYLASE INHIBITOR FR901228; EPITHELIAL-CELLS; APICAL SURFACE; 5 FIBER; THERAPY; ENDOCYTOSIS; INFECTION; EFFICACY; PROTEIN; VIRUSES AB Purpose: Current paradigms postulate that inefficient adenoviral (Ad) gene transfer is a consequence of poor Coxsackievirus adenovirus receptor (CAR) expression in tumors in vivo. To test whether exuberant CAR expression alone is sufficient to mediate efficient Ad gene transfer, we compared Ad gene transfer efficiency in a panel of non-small cell lung cancer (NSCLC) cell model systems in which we systematically measured CAR expression in vitro and in vivo. Experimental Design: NSCLC cells were selected for study on the basis of (a) differences in Ad transduction, (b) identical requirements for growth in vitro, (c) capacity to grow as xenografts in immunocompromised mice, and (d) similar amounts of alpha(nu) integrin expression as measured by flow cytometry. CAR expression and Ad transduction profiles of these NSCLC cells were generated in vitro and in vivo. Results: Ad transduction efficiency of NSCLC cells in vitro can be directly related to CAR expression at both the mRNA and protein level. CAR expression in vitro favorably predicts a comparable pattern of expression in transplanted NSCLC xenografts in vivo. Xenografts generated from NSCLC cells exhibiting increased CAR expression showed of transduction was reduced compared with in vitro measurements. Thus, in NSCLC cells with high basal expression of CAR, Ad vector doses that enabled uniform transduction in vitro achieve a gene transfer efficiency ranging from 10% to 70% after a single intratumoral injection in the xenografts. Conclusions: These studies indicate CAR expression is predictive for more efficient gene transfer into NSCLC cells in vitro and in vivo but is not sufficient to achieve uniform transduction by Group C Ad vectors in vivo. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. RP Batra, RK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [R01 CA078654-02, R01-CA78654]; PHS HHS [1P50-90388] NR 42 TC 28 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2003 VL 9 IS 13 BP 4992 EP 4999 PG 8 WC Oncology SC Oncology GA 737CW UT WOS:000186212000042 PM 14581374 ER PT J AU McCabe, K Tyler, K Tanabe, J AF McCabe, K Tyler, K Tanabe, J TI Diffusion-weighted MRI abnormalities as a clue to the diagnosis of herpes simplex encephalitis SO NEUROLOGY LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; INFECTIONS C1 Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, 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 VA Med Ctr, Neurol Serv, Denver, CO USA. RP Tanabe, J (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Radiol, Campus Box A034,4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 7 TC 47 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 14 PY 2003 VL 61 IS 7 BP 1015 EP 1016 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 731XH UT WOS:000185911400038 PM 14557588 ER PT J AU Fitten, LJ AF Fitten, LJ TI Driver screening for older adults SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DEMENTIA C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Sepulveda, CA 91343 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Fitten, LJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, VHA 16111 Plummer St, Sepulveda, CA 91343 USA. NR 8 TC 11 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 13 PY 2003 VL 163 IS 18 BP 2129 EP 2131 DI 10.1001/archinte.163.18.2129 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 732GB UT WOS:000185931500003 PM 14557207 ER PT J AU Whiting, J AF Whiting, J TI Singular loyalties SO LANCET LA English DT Letter C1 Portland VA Med Ctr, Dept Imaging, Portland, OR 97207 USA. RP Whiting, J (reprint author), Portland VA Med Ctr, Dept Imaging, Portland, OR 97207 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 11 PY 2003 VL 362 IS 9391 BP 1243 EP 1243 DI 10.1016/S0140-6736(03)14527-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 732CW UT WOS:000185924100040 PM 14568762 ER PT J AU Song, BB Marvizon, JCG AF Song, BB Marvizon, JCG TI Dorsal horn neurons firing at high frequency, but not primary afferents, release opioid peptides that produce mu-opioid receptor internalization in the rat spinal cord SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C-fiber; dynorphin; endocytosis; endomorphin; enkephalin; dorsal horn; dorsolateral funiculus; internalization; neurokinin; neurokinin 1 receptor; mu-opioid receptor; opioid; primary afferent; rat; release; spinal cord; substance P; tachykinin ID ENKEPHALIN-LIKE MATERIAL; SUBSTANCE-P RELEASE; GABA-IMMUNOREACTIVE NEURONS; NOXIOUS MECHANICAL STIMULI; CAPSAICIN-EVOKED RELEASE; D-ASPARTATE RECEPTORS; LONG-TERM DEPRESSION; IN-VIVO RELEASE; MET-ENKEPHALIN; NEUROKININ-1 RECEPTOR AB To determine what neural pathways trigger opioid release in the dorsal horn, we stimulated the dorsal root, the dorsal horn, or the dorsolateral funiculus (DLF) in spinal cord slices while superfusing them with peptidase inhibitors to prevent opioid degradation. Internalization of mu-opioid receptors (MOR) and neurokinin 1 receptors (NK1R) was measured to assess opioid and neurokinin release, respectively. Dorsal root stimulation at low, high, or mixed frequencies produced abundant NK1R internalization but no MOR internalization, indicating that primary afferents do not release opioids. Moreover, capsaicin and NMDA also failed to produce MOR internalization. In contrast, dorsal horn stimulation elicited MOR internalization that increased with the frequency, being negligible at <10 Hz and maximal at 500 Hz. The internalization was abolished by the MOR antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), in the presence of low Ca2+ and by the Na+ channel blocker lidocaine, confirming that it was caused by opioid release and neuronal firing. DLF stimulation in "oblique" slices (encompassing the DLF and the dorsal horn of T11-L4) produced MOR internalization, but only in areas near the stimulation site. Moreover, cutting oblique slices across the dorsal horn (but not across the DLF) eliminated MOR internalization in areas distal to the cut, indicating that it was produced by signals traveling in the dorsal horn and not via the DLF. These findings demonstrate that some dorsal horn neurons release opioids when they fire at high frequencies, perhaps by integrating signals from the rostral ventromedial medulla, primary afferents, and other areas of the spinal cord. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis,Ctr Neurovisceral Sci & Womens Hlt, Los Angeles, CA 90073 USA. RP Marvizon, JCG (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 115,Room 119,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDA NIH HHS [R01 DA012609, R01 DA012609-01A1, R01 DA012609-02, R01 DA012609-03, R01-DA12609] NR 89 TC 32 Z9 32 U1 0 U2 2 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 OCT 8 PY 2003 VL 23 IS 27 BP 9171 EP 9184 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 730GZ UT WOS:000185822200018 PM 14534251 ER PT J AU Margolis, ML Christie, JD Silvestri, GA Kaiser, L Santiago, S Hansen-Flaschen, J AF Margolis, ML Christie, JD Silvestri, GA Kaiser, L Santiago, S Hansen-Flaschen, J TI Racial differences pertaining to a belief about lung cancer surgery - Results of a multicenter survey SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 96th International Conference of the American-Thoracic-Society CY MAY 03-10, 2000 CL TORONTO, CANADA SP Amer Thorac Soc ID AFRICAN-AMERICANS; BREAST-CANCER; LOW-INCOME; ATTITUDES; BLACK; CARCINOMA; SURVIVAL; RACE AB Background: Patients at the Philadelphia Veterans Affairs Medical Center frequently voice concern that air exposure during lung cancer surgery might cause tumor spread. Several African-American patients asserted that this belief was common in the African-American community.. I. Objective: To assess the prevalence of the belief that air exposure during lung cancer surgery might cause tumor spread and gauge the influence of this belief on the willingness of African-American and white patients to have lung cancer surgery. Design: Prospective questionnaire survey. Setting: Philadelphia Veterans Affairs Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Los Angeles Veterans Affairs Medical Center, Los Angeles, California; and Medical University of South Carolina, Charleston, South Carolina. Patients: 626 consecutive patients in pulmonary and lung cancer clinics. Results: 38% of patients (61% of whom were African American and 29% of whom were white) stated that they believe air exposure at surgery causes tumor spread. The most significant predictor of belief was African-American race (odds ratio, 3.5 [95% Cl, 1.9 to 6.5]), even after controlling for other relevant variables in a multivariable analysis. Nineteen percent of African Americans stated that this belief was a reason for opposing surgery, and 14% would not accept their physicians' assertion that the belief is false. These rates were also statistically significantly higher among African-American than white patients. Conclusions: Belief in accelerated tumor spread at surgery is prevalent among general pulmonary outpatients and lung cancer clinic patients facing lung surgery, particularly among African-American patients. Our findings may pertain to key racial disparities in lung cancer surgery and survival rates and suggest that culturally sensitive physician training or outreach programs directed at disparate beliefs and attitudes may help to address racial discrepancies in health care outcomes. C1 Philadelphia Vet Affairs Med Ctr, Pulm Sect, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Margolis, ML (reprint author), Philadelphia Vet Affairs Med Ctr, Pulm Sect, Room 8A112,Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 29 TC 128 Z9 129 U1 3 U2 4 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 OCT 7 PY 2003 VL 139 IS 7 BP 558 EP 563 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 729AP UT WOS:000185748800003 PM 14530226 ER PT J AU Landefeld, CS Callahan, CM Woolard, N AF Landefeld, CS Callahan, CM Woolard, N TI General internal medicine and geriatrics: Building a foundation to improve the training of general internists in the care of older adults SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID 21ST-CENTURY; RESIDENTS AB Internists-"doctors for adults"-provide most of the medical care given to older Americans, especially those with serious chronic disease. Nonetheless, the United States lacks an adequate physician workforce with mastery in caring for older persons and with expertise in building knowledge about how best to provide this care. This supplement aims to strengthen the physician workforce by fostering incremental and sustained improvements in the training of internal medicine residents in the care of older adults and in the development of geriatrics-oriented general internal medicine faculty. It identifies 3 major barriers to these improvements: lack of adequately trained teachers and mentors, the belief that explicit training in geriatrics has little to offer the generalist, and inadequate funding. Three strategies offer particular promise in over-coming these barriers: engaging directors of internal medicine residency programs, funding centers to promote collaboration between teaching and research programs in general internal medicine and geriatrics, and providing substantial incremental funding on the national level to pay for the time required to care for frail older patients and to teach and do research about this care. The barriers and strategies identified in this supplement may also inform efforts to enhance the skills of practicing physicians and improve training and faculty development in family medicine and other disciplines. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Indiana Univ, Indianapolis, IN 46204 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, Box 1265, San Francisco, CA 94143 USA. FU NIA NIH HHS [K07 AG000912, K-07 AG00912] NR 23 TC 28 Z9 28 U1 0 U2 0 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 OCT 7 PY 2003 VL 139 IS 7 BP 609 EP 614 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 729AP UT WOS:000185748800026 PM 14530244 ER PT J AU Hayashi, T Boyko, EJ Leonetti, DL McNeely, MJ Newell-Morris, L Kahn, SE Fujimoto, WY AF Hayashi, T Boyko, EJ Leonetti, DL McNeely, MJ Newell-Morris, L Kahn, SE Fujimoto, WY TI Visceral adiposity and the prevalence of hypertension in Japanese Americans SO CIRCULATION LA English DT Article DE epidemiology; hypertension; visceral fat; obesity; risk factors ID IMPAIRED GLUCOSE-TOLERANCE; FASTING PLASMA-INSULIN; BODY-FAT DISTRIBUTION; BLOOD-PRESSURE; MEN; OBESITY; WOMEN; DISEASE; TISSUE; RISK AB Background-Visceral adiposity is generally considered to play a key role in the metabolic syndrome, including hypertension. The purpose of this study was to evaluate cross-sectionally whether visceral adiposity is associated with prevalence of hypertension independent of other adipose depots and fasting plasma insulin. Methods and Results-Study subjects included 563 Japanese Americans with normal or impaired glucose tolerance or diabetes but not taking oral hypoglycemic medication or insulin at entry. Variables included plasma glucose and insulin measured after an overnight fast and during an oral glucose tolerance test, and abdominal, thoracic, and thigh fat areas by CT. Total fat area (TFA) was calculated as the sum of these fat areas. Hypertension was defined as having a systolic blood pressure greater than or equal to140 mm Hg, having a diastolic blood pressure greater than or equal to90 mm Hg, or taking antihypertensive medications. Intra-abdominal fat area (IAFA) was associated with a higher prevalence of hypertension. Adjusted odds ratio of hypertension by IAFA was 1.68 for a 1-SD increase (95% CI, 1.20 to 2.37) after adjusting for age, sex, fasting plasma insulin, a nonlinear transformation of 2-hour plasma glucose, and TFA. IAFA remained a significant predictor of prevalence of hypertension even after adjustment for total subcutaneous fat area, abdominal subcutaneous fat area, body mass index, or waist circumference, but no measure of regional or total adiposity was associated with the odds of prevalence of hypertension in models that contained IAFA. Conclusions-Greater visceral adiposity increases the odds of hypertension in Japanese Americans independent of other adipose depots and fasting plasma insulin. C1 Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst S152E, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Hayashi, Tomoshige/N-8508-2015 OI Kahn, Steven/0000-0001-7307-9002; Boyko, Edward/0000-0002-3695-192X FU NCRR NIH HHS [RR-00037]; NHLBI NIH HHS [HL-49293]; NIDDK NIH HHS [DK-02654, DK-17047, DK-31170, DK-35816] NR 23 TC 63 Z9 68 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 OCT 7 PY 2003 VL 108 IS 14 BP 1718 EP 1723 DI 10.1161/01.CIR.0000087597.59169.8D PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 729HE UT WOS:000185767000013 PM 12975250 ER PT J AU Liu, YY Schultz, JJ Brent, GA AF Liu, YY Schultz, JJ Brent, GA TI A thyroid hormone receptor alpha gene mutation (P398H) is associated with visceral adiposity and impaired catecholamine-stimulated lipolysis in mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOMINANT-NEGATIVE MUTATION; BETA-ADRENERGIC-RECEPTOR; RETINOID-X-RECEPTOR; FAT-CELL FUNCTION; INSULIN-RESISTANCE; DEFICIENT MICE; POSTNATAL-DEVELOPMENT; COREPRESSOR RELEASE; EXPRESSION; TISSUE AB Thyroid hormone has profound effects on metabolic homeostasis, regulating both lipogenesis and lipolysis, primarily by modulating adrenergic activity. We generated mice with a point mutation in the thyroid hormone receptor alpha (TRalpha) gene producing a dominant-negative TRalpha mutant receptor with a proline to histidine substitution (P398H). The heterozygous P398H mutant mice had a 3.4-fold (p < 0.02) increase in serum thyrotropin (TSH) levels. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were slightly elevated compared with wild-type mice. The P398H mice had a 4.4-fold increase in body fat (as a fraction of total body weight) (p < 0.001) and a 5-fold increase in serum leptin levels (p < 0.005) compared with wild-type mice. A 3-fold increase in serum fasting insulin levels (p < 0.002) and a 55% increase in fasting glucose levels (p < 0.01) were observed in P398H compared with wild-type mice. There was a marked reduction in norepinephrine-induced lipolysis, as reflected in reduced glycerol release from white adipose tissue isolated from P398H mice. Heart rate and cold-induced adaptive thermogenesis, mediated by thyroid hormone-catecholamine interaction, were also reduced in P398H mice. In conclusion, the TRα P398H mutation is associated with visceral adiposity and insulin resistance primarily due to a marked reduction in catecholamine-stimulated lipolysis. The observed phenotype in the TRα P398H mouse is likely due to interference with TRα action as well as influence on other metabolic signaling pathways. The physiologic significance of these findings will ultimately depend on understanding the full range of actions of this mutation. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med,Mol Endocrinol Lab, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol,Mol Endocrinol Lab, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med,Mol Endocrinol Lab, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 114,Rm 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA-89364] NR 62 TC 98 Z9 101 U1 0 U2 4 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 OCT 3 PY 2003 VL 278 IS 40 BP 38913 EP 38920 DI 10.1074/jbc.M306120200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 726AM UT WOS:000185575100100 PM 12869545 ER PT J AU Ferguson, JJ Antman, EM Bates, ER Cohen, M Every, NR Harrington, RA Pepine, CJ Theroux, P AF Ferguson, JJ Antman, EM Bates, ER Cohen, M Every, NR Harrington, RA Pepine, CJ Theroux, P CA NICE-3 Investigators TI Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: Final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study SO AMERICAN HEART JOURNAL LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; WAVE MYOCARDIAL-INFARCTION; UNFRACTIONATED HEPARIN; UNSTABLE ANGINA; RANDOMIZED-TRIAL; ARTERY-DISEASE; TIMI 11B; TIROFIBAN; ESSENCE; BLOCKADE AB Background In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI). Methods The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST-elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia. Results A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively). Conclusions The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin. C1 St Lukes Episcopal Hosp, Houston, TX 77225 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Newark Beth Israel Med Ctr, Newark, NJ USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Florida, Gainesville, FL USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. RP Ferguson, JJ (reprint author), St Lukes Episcopal Hosp, POB 20269, Houston, TX 77225 USA. NR 27 TC 67 Z9 72 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2003 VL 146 IS 4 BP 628 EP 634 DI 10.1067/S0002-8703(03)00165-0 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 733UN UT WOS:000186019200012 PM 14564315 ER PT J AU Beinart, SC Sales, AE Spertus, JA Plomondon, ME Every, NR Rumsfeld, JS AF Beinart, SC Sales, AE Spertus, JA Plomondon, ME Every, NR Rumsfeld, JS TI Impact of angina burden and other factors on treatment satisfaction after acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Article ID QUALITY-OF-LIFE; PATIENT SATISFACTION; MEDICAL-CARE; COMMUNICATION-SKILLS; GENERAL-PRACTICE; ARTERY-DISEASE; HOSPITAL-CARE; CONSUMER SATISFACTION; FUNCTIONAL STATUS; VETERANS-AFFAIRS AB Purpose Although of great importance to clinicians, hospitals, and health care systems, little is known about factors that influence treatment satisfaction after acute coronary syndromes (ACS). The objective of this study was to identify potentially modifiable factors associated with treatment satisfaction 7 months after ACS. Methods The study population included 1957 patients with ACS who were enrolled in the multicenter, prospective Veterans' Health Administration Access to Cardiology Study. The primary outcome was treatment satisfaction 7 months after ACS as measured by the Seattle Angina Questionnaire. Multivariable regression models were developed to determine the association between treatment satisfaction and patient characteristics, physician-patient communication, and current angina frequency. Results Patient characteristics associated with reduced treatment satisfaction included a history of depression, atrial fibrillation, prior heart surgery, arthritis, hypertension, younger age, and a discharge diagnosis of unstable angina (as opposed to myocardial infarction). After adjusting for patient characteristics, patient-reported inability to reach one or more of their physicians (OR, 2.40; 95% CI, 1.47 to 3.91), being given confusing information (OR, 3.48; 95% CI, 2.08 to 5.83), and poor overall communication with one or more of their physicians (OR, 4.94; 95% CI, 2.93 to 8.34) were all associated with reduced satisfaction. Finally, after adjustment for both patient characteristics and physician communication, weekly (OR, 3.52; 95% CI, 2.28 to 5.45) and daily angina (OR, 3.88; 95% CI, 2.23 to 6.75) were associated with worse treatment satisfaction. Conclusions Current angina symptoms and aspects of physician communication are independently associated with treatment satisfaction after ACS. These results suggest that treatment satisfaction may be improved through better communication and better control of angina symptoms. C1 Denver VA Med Ctr, Denver, CO 80220 USA. VA Puget Sound Hlth Care Syst, Cardiovasc Outcomes Res Ctr, Seattle, WA USA. Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. Univ Missouri, Kansas City, MO 64110 USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, 111B,1055 Clermont St, Denver, CO 80220 USA. OI Sales, Anne/0000-0001-9360-3334 NR 47 TC 24 Z9 26 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2003 VL 146 IS 4 BP 646 EP 652 DI 10.1016/S0002-8703(03)00256-4 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 733UN UT WOS:000186019200015 PM 14564318 ER PT J AU Fine, MJ Stone, RA Lave, JR Hough, LJ Obrosky, DS Mor, MK Kapoor, WN AF Fine, MJ Stone, RA Lave, JR Hough, LJ Obrosky, DS Mor, MK Kapoor, WN TI Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: A randomized controlled trial SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; RESEARCH TEAM COHORT; EARLY SWITCH; MEDICAL LITERATURE; USERS GUIDES; OUTCOMES; DISCHARGE; CARE; RECOMMENDATIONS; COSTS AB PURPOSE: Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia. METHODS: In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days. RESULTS: Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] = 1.23; 95% confidence interval [Cl]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (FIR = 1.16; 95% Cl: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms. CONCLUSION: The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes. (C) 2003 by Excerpta Medica Inc. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Div Gen Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Div Gen Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Dept Hlth Policy & Management, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Dept Biostat, Pittsburgh, PA USA. VA Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Fine, MJ (reprint author), Vet Adm Med Ctr, 130-U,11th Floor,11E127,Univ Dr C, Pittsburgh, PA 15240 USA. FU AHRQ HHS [HS08282] NR 36 TC 60 Z9 61 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 1 PY 2003 VL 115 IS 5 BP 343 EP 351 DI 10.1016/S0002-9343(03)00395-4 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 729MA UT WOS:000185776400001 PM 14553868 ER PT J AU Hathout, GM Duh, MJ El-Saden, SM AF Hathout, GM Duh, MJ El-Saden, SM TI Accuracy of contrast-enhanced MR angiography in predicting angiographic stenosis of the internal carotid artery: Linear regression analysis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Radiological-Society-of-North-America CY DEC, 2002 CL CHICAGO, ILLINOIS SP Radiolog Soc North Amer ID MAGNETIC-RESONANCE ANGIOGRAPHY; CONVENTIONAL ANGIOGRAPHY; DIGITAL SUBTRACTION; SUPRAAORTIC VESSELS; HIGH-RESOLUTION; ENDARTERECTOMY; SONOGRAPHY; COMPLICATIONS; VARIABILITY; ULTRASOUND AB BACKGROUND AND PURPOSE: We sought to assess whether contrast-enhanced MR angiography is able to predict the degree of angiographic stenosis of the internal carotid artery within a clinically acceptable margin of error, thereby decreasing the need for angiography. In addition, we sought to assess whether adding ultrasound peak systolic velocity (PSV) as an additional regressor improves the accuracy of prediction. METHODS: A retrospective review of our institution's records for a 4-year period was conducted to identify all patients who had undergone evaluation of their carotid arteries using digital subtraction angiography, contrast-enhanced MR angiography, and ultrasonography. All internal carotid artery stenoses ranging from 10% to 90% at carotid angiography were selected (n = 22). Measurements were then obtained based on the North American Symptomatic Carotid Endarterectomy Trial style by using the digital subtraction angiograms and contrast-enhanced MR angiograms in a blinded fashion. The correlation between digital subtraction angiography data and contrast-enhanced MR angiography data was assessed by conducting linear regression analysis. Multiple regression analysis was then conducted to determine whether the inclusion of ultrasound PSV as an additional regressor increased the accuracy of prediction. RESULTS: The correlation between the degree of stenosis measured by digital subtraction angiography and that measured by contrast-enhanced MR angiography was r = 0.967. The 95% confidence interval for the line of means showed low errors bounds, ranging as low as +/-2.8%. The 95% confidence interval for individual prediction of angiographic stenosis based on a given contrast-enhanced MR angiographic measurement, however, was significantly larger, being no less than +/-13.6%. With the inclusion of PSV, the adjusted correlation was r = 0.965. CONCLUSION. A clear linear relationship exists between digital subtraction angiographic and contrast-enhanced MR angiographic measurements of carotid stenosis. Increasing severity of stenosis as measured by contrast-enhanced MR angiography corresponds to increasing severity at angiography. Although the predictive value of contrast-enhanced MR angiography is excellent in the mean, it is less reliable for predicting the degree of angiographic stenosis in the individual patient, showing rather wide confidence intervals. Furthermore, the inclusion of PSV as an additional regressor does not improve the predictive accuracy beyond that of contrast-enhanced MR angiography alone. C1 Calif State Univ Los Angeles, W Los Angeles Vet Adm Hosp, Dept Radiol, Los Angeles, CA 90073 USA. Calif State Univ Los Angeles, Ctr Med, Los Angeles, CA 90073 USA. RP Hathout, GM (reprint author), Calif State Univ Los Angeles, W Los Angeles Vet Adm Hosp, Dept Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 33 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2003 VL 24 IS 9 BP 1747 EP 1756 PG 10 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 733WC UT WOS:000186022800006 PM 14561597 ER PT J AU Polanczyk, M Zamora, A Subramanian, S Matejuk, A Hess, DL Blankenhorn, EP Teuscher, C Vandenbark, AA Offner, H AF Polanczyk, M Zamora, A Subramanian, S Matejuk, A Hess, DL Blankenhorn, EP Teuscher, C Vandenbark, AA Offner, H TI The protective effect of 17b-estradiol on experimental autoimmune encephalomyelitis is mediated through estrogen receptor-a SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; ALPHA-DEFICIENT MICE; MULTIPLE-SCLEROSIS; KNOCKOUT MICE; FEMALE MICE; BETA; EXPRESSION; PREGNANCY; CHEMOKINE; IMMUNOSUPPRESSION AB Low-dose estrogen (E2) treatment significantly inhibits the clinical signs and histopathological lesions of experimental autoimmune encephalomyelitis (EAE), and is being used in clinical trials to treat multiple sclerosis. To assess the role of intracytoplasmic estrogen receptors in mediating suppression of EAE, we studied mice with disrupted estrogen receptor-alpha (Esr1) and -beta (Esr2) genes. We demonstrate that the protective effect of E2 is abrogated in B6.129-Esr1(tm1Unc) mice (Esr1-/-) but not in B6.129-Esr2(tm1Unc) mice (Esr2(-/-)). The loss of E2-mediated protection from EAE in Esr1(-/-) mice immunized with the encephalitogenic MOG-35-55 peptide was manifested phenotypically by the development of severe acute clinical signs and histopathological lesions even in the presence of moderately high serum E2 levels. This is in contrast to C57BL/6 wild-type (WT) mice and Esr2(-/-) mice in which E2 treatment resulted in comparable serum levels and markedly suppressed clinical signs of EAE and abolished inflammatory lesions in the CNS. This pattern showing a lack of E2-dependent inhibition of EAE in Esr1-/- mice was mirrored by an enhanced rather than a reduced secretion of TNF-alpha, IFN-gamma, and interleukin (IL)-6 in MOG-specific splenocytes; and a lack of inhibition of message for inflammatory cytokines, chemokines and chemokine receptors in CNS tissue. These results indicate that the immunomodulatory effects of E2 in EAE are dependent on Esr1 and not Esr2 signaling. C1 Portland VA Med Ctr, Neuroimmunol Res, R&D 31, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Agr Univ Warsaw, Fac Vet Med, Dept Food Hyg, Warsaw, Poland. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Div Reprod Sci, Portland, OR USA. Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. Univ Vermont, Dept Med, Burlington, VT USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR USA. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res, R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIAID NIH HHS [AI41747, AI42376, AI45105, R01 AI041747]; NINDS NIH HHS [NS23444, NS23221, NS36526, R01 NS023221, R01 NS023444, R01 NS036526] NR 32 TC 100 Z9 104 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2003 VL 163 IS 4 BP 1599 EP 1605 DI 10.1016/S0002-9440(10)63516-X PG 7 WC Pathology SC Pathology GA 724ZE UT WOS:000185517500036 PM 14507666 ER PT J AU Ackermann, RT Cheadle, A Sandhu, N Madsen, L Wagner, EH LoGerfo, JP AF Ackermann, RT Cheadle, A Sandhu, N Madsen, L Wagner, EH LoGerfo, JP TI Community exercise program use and changes in healthcare costs for older adults SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID INTERVENTIONS AB Background: Regular exercise is associated with many health benefits. Community-based exercise programs may increase exercise participation, but little is known about cost implications. Methods: A retrospective, matched cohort study was conducted to determine if changes in healthcare costs for Medicare-eligible adults who choose to participate in a community-based exercise program were different from similar individuals who did not participate. Exercise program participants included 1114 adults aged greater than or equal to65 years, who were continuously enrolled in Group Health Cooperative of Puget Sound (GHQ between October 1, 1997 and December 31, 2000 and who participated in the Lifetime Fitness (exercise) Program(R), (LFP) at least once; three GHC enrollees who never attended LFP were randomly selected as controls for each participant by matching on age and gender. Cost and utilization estimates from GHC administrative data for the time from LFP enrollment to December 31, 2000 were compared using multivariable regression models. Results: The average increase in annual total healthcare costs was less in participants compared to controls (+$642 vs +$1175; p=0.05). After adjusting for differences in age, gender, enrollment date, comorbidity index, and pre-exposure cost and utilization levels, total healthcare costs for participants were 94.1% (95% confidence interval [CI], 85.6%-103.5%) of control costs. However, for participants who attended the exercise program at an average rate of greater than or equal to1 visit weekly, total adjusted follow-up costs were 79.3% (95% Cl, 71.3%-88.2%) of controls. Conclusions: Including a community exercise program as a health insurance benefit shows promise as a strategy for helping some Medicare-eligible adults to improve their health through exercise. C1 Univ Washington, Robert Wood Johnson Clin Scholars Program, Hlth Sci Ctr H220, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Grp Hlth Cooperat Puget Sound, Hlth Improvement Program, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Hlth Promot Res Ctr, Seattle, WA 98195 USA. RP Ackermann, RT (reprint author), Univ Washington, Robert Wood Johnson Clin Scholars Program, Hlth Sci Ctr H220, Box 357183, Seattle, WA 98195 USA. FU ODCDC CDC HHS [U48/CCU009654-09] NR 14 TC 48 Z9 49 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2003 VL 25 IS 3 BP 232 EP 237 DI 10.1016/S0749-3797(03)00196-X PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 728MD UT WOS:000185720200008 PM 14507530 ER PT J AU Ibrahim, SA Thomas, SB Fine, MJ AF Ibrahim, SA Thomas, SB Fine, MJ TI Achieving health equity: An incremental journey SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID RACIAL-DIFFERENCES C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Pub Hlth, Ctr Minor Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,11-E 130 A-U, Pittsburgh, PA 15240 USA. NR 22 TC 13 Z9 13 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2003 VL 93 IS 10 BP 1619 EP 1621 DI 10.2105/AJPH.93.10.1619 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 731JT UT WOS:000185881100006 PM 14534208 ER PT J AU Fine, MJ Demakis, JG AF Fine, MJ Demakis, JG TI The Veterans Health Administration's promotion of health equity for racial and ethnic minorities SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res & Hlth Care, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15260 USA. VA Hlth Serv Res & Dev Serv, Washington, DC USA. RP Fine, MJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 130-U, Pittsburgh, PA 15240 USA. NR 10 TC 9 Z9 9 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2003 VL 93 IS 10 BP 1622 EP 1624 DI 10.2105/AJPH.93.10.1622 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 731JT UT WOS:000185881100007 PM 14534209 ER PT J AU Ibrahim, SA Whittle, J Bean-Mayberry, B Kelley, ME Good, C Conigliaro, J AF Ibrahim, SA Whittle, J Bean-Mayberry, B Kelley, ME Good, C Conigliaro, J TI Racial/ethnic variations in physician recommendations for cardiac revascularization SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OF-VETERANS-AFFAIRS; CORONARY HEART-DISEASE; BYPASS GRAFT-SURGERY; RACIAL-DIFFERENCES; UNITED-STATES; BLACK POPULATIONS; ARTERY DISEASE; RATES; RACE; MORTALITY AB Objectives. We sought to examine whether physician recommendations for cardiac revascularization vary according to patient race. Methods. We studied patients scheduled for coronary angiography at 2 hospitals, one public and one private, between November 1997 and June 1999. Cardiologists were interviewed regarding their recommendations for cardiac resvacularization. Results. African American patients were less likely than Whites to be recommended for revascularization at the public hospital (adjusted odds ratio [OR]=0.31; 95% confidence interval [Cl]=0.12, 0.77) but not at the private hospital (adjusted OR=1.69; 95% CI=0.69, 4.14). Conclusions. Physician recommendations for cardiac revascularization vary by patient race. Further studies are needed to examine physician bias as a factor in racial disparities in cardiac care and outcomes. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Ibrahim, SA (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. NR 29 TC 47 Z9 47 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2003 VL 93 IS 10 BP 1689 EP 1693 DI 10.2105/AJPH.93.10.1689 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 731JT UT WOS:000185881100021 PM 14534223 ER PT J AU McGinnis, KA Fine, MJ Sharma, RK Skanderson, M Wagner, JH Rodriguez-Barradas, MC Rabeneck, L Justice, AC AF McGinnis, KA Fine, MJ Sharma, RK Skanderson, M Wagner, JH Rodriguez-Barradas, MC Rabeneck, L Justice, AC TI Understanding racial disparities in HIV using data from the veterans aging cohort 3-site study and VA administrative data SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ANTIRETROVIRAL THERAPY; CARE SYSTEM; RACE/ETHNICITY; MORTALITY AB Objectives. We identified race-associated differences in survival among HIV-positive US veterans to examine possible etiologies for these differences. Methods. We used national administrative data to compare survival by race and used data from the Veterans Aging Cohort 3-Site Study (VACS 3) to compare patients' health status, clinical management, and adherence to medication by race. Results. Nationally, minority veterans had higher mortality rates than did white veterans with HIV. Minority veterans had poorer health than white veterans with HIV. No significant differences were found in clinical management or adherence. Conclusions. HIV-positive minority veterans experience poorer survival than white veterans. This difference may derive from differences in comorbidities and in the severity of illness of HIV-related disease. C1 W Haven VA Healthcare Syst, West Haven, CT 06516 USA. VA Pittsburgh Healthcare Syst, Vet Aging Cohort Study Ctr, Pittsburgh, PA USA. Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. VA Med Ctr, VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX USA. RP Justice, AC (reprint author), W Haven VA Healthcare Syst, 950 Campbell Ave,11-ACSLG, West Haven, CT 06516 USA. FU NIA NIH HHS [K23 AG00826]; NIAAA NIH HHS [U01 AA013566, U01 AA 13566]; NIAID NIH HHS [K24 AI001769, K24 AI01769-04]; NIDDK NIH HHS [K24 DK59318] NR 17 TC 73 Z9 73 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2003 VL 93 IS 10 BP 1728 EP 1733 DI 10.2105/AJPH.93.10.1728 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 731JT UT WOS:000185881100027 PM 14534229 ER PT J AU Strack, S AF Strack, S TI Herman Feifel (1915-2003) - Obituary SO AMERICAN PSYCHOLOGIST LA English DT Biographical-Item C1 US Dept Vet Affairs, Los Angeles Ambulatory Care Ctr, Los Angeles, CA USA. RP Strack, S (reprint author), US Dept Vet Affairs, Los Angeles Ambulatory Care Ctr, Los Angeles, CA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD OCT PY 2003 VL 58 IS 10 BP 810 EP 810 DI 10.1037/0003-066X.58.10.810 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 735RF UT WOS:000186127800007 ER PT J AU Liu, JH Zingmond, D Etzioni, DA O'Connell, JB Maggard, MA Livingston, EH Liu, CD Ko, CY AF Liu, JH Zingmond, D Etzioni, DA O'Connell, JB Maggard, MA Livingston, EH Liu, CD Ko, CY TI Characterizing the performance and outcomes of obesity surgery in California SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID GASTRIC BYPASS-SURGERY; UNITED-STATES; MORBID-OBESITY; RISK-FACTORS; VOLUME; MORTALITY; EPIDEMIC AB Between 1991 and 2000, the prevalence of obesity increased 65 per cent. As a result, increasing research is being directed at gastric bypass (GB) surgery, an operation that appears to achieve long-term weight reduction. Despite the rapid proliferation of this surgery, the quality of care at a population level is largely unknown. This study examines longitudinal trends in quality and identifies significant predictors of adverse outcomes. Using the California inpatient discharge database, all GB operations from 1996 to 2000 were identified. Demographic, comorbidity, complication, and volume data were obtained. Complications were defined as life-threatening cardiac, respiratory, or medical (renal failure or shock) events. Comorbidity was graded on a modified Charlson score. Annual hospital volume was categorized into four groups: <50, 50-99, 100-199, and 200+ cases. Based on these data, we calculated longitudinal trends in complication rate and performed logistic regression to identify predictors of complications. A total of 16,232 patients were included. The average age was 41 years; 84 per cent were female, and 83.5 per cent were white. The complication rate was 10.4 per cent. Between 1996 and 2000, rates of cardiac and respiratory complications decreased while rates of medical complications remained unchanged. Complications were more likely in men [odd ratio (OR) = 1.69 compared to women] and in patients with comorbidities (OR = 1.60 for each additional comorbid disease). Furthermore, when examining the effect of volume, patients at very low (<50) and low (50-99) volume hospitals were much more likely to have complications (OR = 2.72 and 2.70, respectively) compared to patients at high-volume hospitals (200+), even after controlling for differences in case-mix. The quality of care for obesity surgery has improved between 1996 and 2000. Despite operating on patients with more comorbidity, rates of cardiac and respiratory complications have decreased. Furthermore, this study identifies three independent predictors of complications: gender, comorbidity, and hospital volume. These findings are important initial steps toward improving quality in obesity surgery. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Adm, Dept Gen Internal Med, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX 75235 USA. RP Liu, JH (reprint author), 11301 W Olympic Blvd,648, Los Angeles, CA 90064 USA. NR 27 TC 60 Z9 60 U1 0 U2 1 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2003 VL 69 IS 10 BP 823 EP 828 PG 6 WC Surgery SC Surgery GA 729KD UT WOS:000185771600001 PM 14570356 ER PT J AU O'Connell, JB Maggard, MA Liu, JH Etzioni, DA Livingston, EH Ko, CY AF O'Connell, JB Maggard, MA Liu, JH Etzioni, DA Livingston, EH Ko, CY TI Rates of colon and rectal cancers are increasing in young adults SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID 40 YEARS OLD; COLORECTAL-CANCER; PATIENTS LESS; LARGE-BOWEL; 3 DECADES; CARCINOMA; AGE; ADENOCARCINOMA; LIFE; PROGNOSIS AB Incidence rates for colorectal cancer are decreasing in the United States, possibly due to preventative cancer screening. Because these programs target older patients, their beneficial effects may not apply to young patients. The purpose of this study was to compare incidence rates and tumor characteristics of colon and rectal cancers for young versus older patients using a population-based cancer registry. Colon and rectal cancer patients reported in the Surveillance, Epidemiology, and End Results registry (1973-1999) were separately analyzed. Incidence rates over time stage, and grade were compared for two age groups: young patients (20-40 years, n = 5383) And older patients (60+ years, n = 256,401). For older patients, colon cancer incidence remained stable while rectal cancer incidence decreased 11 per cent to 72.1/100,000 persons (P < 0.05). For the young, colon cancer incidence increased 17 per cent to 2.1 (P < 0.05), and rectal incidence rose 75 per cent to 1.4 (P < 0.05). Young patients had less localized tumors than older patients: colon (25.8% vs. 35.3%, P < 0.001); rectal (38.4% vs. 41.7%, P = 0.005). Young patients also had more poorly differentiated tumors: colon (22.2% vs. 14.7%, P < 0.001); rectal (16.4% vs. 12.3%, P < 0.001). Incidence rates for colon and rectal cancers in young patients are rising, and they have more advanced disease. Although the overall prevalence is low in this population, the increasing incidence suggests health-care providers should have heightened awareness when caring for this population. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. W Los Angles Vet Affairs Hosp, Dept Surg, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX 75235 USA. RP O'Connell, JB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 19833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA. NR 51 TC 132 Z9 135 U1 0 U2 7 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2003 VL 69 IS 10 BP 866 EP 872 PG 7 WC Surgery SC Surgery GA 729KD UT WOS:000185771600010 PM 14570365 ER PT J AU Arteaga, JR Huerta, S Basa, NR Livingston, EH AF Arteaga, JR Huerta, S Basa, NR Livingston, EH TI Interval Jejunoileal bypass reduces the morbidity and mortality of Roux-en-y gastric bypass in the super-obese SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID VERTICAL BANDED GASTROPLASTY; FOLLOW-UP; SURGERY; EPIDEMIC; WOMEN; TRIAL AB Among Roux-en-Y gastric bypass (RYGB) patients, large male patients carry the greatest risk for severe, life-threatening complications. The higher complication rate is partly related to large amounts of intra-abdominal fat that increases the technical difficulty of the RYGB. In order to minimize the risk for complications, we established a staged approach for weight loss surgery for high-risk, super-obese patients. Patients with intra-abdominal fat at exploration which precluded the performance of RYGB underwent jejunoileal bypass (JIB). Following an initial period of weight loss (6-24 months), they were converted to a RYGB during a second operation. Twenty-four patients underwent initial JIB that was associated with a major complication rate of 8.3 per cent (2/24) and no mortality. Eight patients lost 53.4 +/- 6.3 kg prior to their conversion to RYGB (mean, 14.1 months). There was one major complication (12%) and no deaths (0%). Following RYGB, an additional period of weight loss resulted in overall excess weight loss (EWL) totaling 62 per cent. A two-step procedure is a safe and effective approach for minimizing complications for high-risk patients undergoing RYGB. The initial JIB was associated with low morbidity and no mortality, and the follow-up RYGB procedure was a technically simple operation that could be performed with few complications. C1 Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA 90095 USA. VA Greater LA Healthcare Syst, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Div Gastrointestinal & Endocrine Surg, Dallas, TX USA. RP Arteaga, JR (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, 900 Vet Ave,Rm 12-217, Los Angeles, CA 90095 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2003 VL 69 IS 10 BP 873 EP 878 PG 6 WC Surgery SC Surgery GA 729KD UT WOS:000185771600011 PM 14570366 ER PT J AU Guccione, JM Salahieh, A Moonly, SM Kortsmit, J Wallace, AW Ratcliffe, MB AF Guccione, JM Salahieh, A Moonly, SM Kortsmit, J Wallace, AW Ratcliffe, MB TI Myosplint decreases wall stress without depressing function in the failing heart: A finite element model study SO ANNALS OF THORACIC SURGERY LA English DT Article ID MYOCARDIAL OXYGEN-CONSUMPTION; PARTIAL LEFT VENTRICULECTOMY; VOLUME REDUCTION SURGERY; LEFT-VENTRICLE; DILATED CARDIOMYOPATHY; RESIDUAL-STRESS; FAILURE; HYPERTROPHY; DYSFUNCTION; EXPRESSION AB Background. The Myocor Myosplint is a transcavitary tensioning device designed to change left ventricular (LV) shape and reduce wall stress. Regional wall stress cannot be measured in the intact heart and LV function after surgical remodeling is often confounded by inotropic agents and mitral repair. We used a realistic mathematical (finite element) model of the dilated human LV to test the hypothesis that Myosplint decreased regional ventricular fiber stress and improved LV function. Methods. A finite element model was used to simulate the effects of Myosplint on the LV stroke volume/enddiastolic pressure (Starling) relationship and regional distributions of stress in the local muscle fiber direction (fiber stress) for a wide range of diastolic and endsystolic material properties. The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction. An elastance model for active fiber stress was incorporated in an axisymmetric geometric model of the globally dilated LV wall. Results. Both diastolic compliance and end-systolic elastance shifted to the left on the pressure-volume diagram. LV end-diastolic volume and end-systolic volumes were reduced by 7.6% and 8.6%, respectively. Mean end-diastolic and end-systolic fiber stress was decreased by 24% and 16%, respectively. Although the effect of Myosplint on the Starling relationship was not significant, there were trends toward an improvement in this relationship at low diastolic stiffness, C, high peak intracellular calcium concentration, Ca-0, and high arterial elastance, E-A. Of note, the effect of C was twice that of Ca-0 and E-A. Diastolic function would, therefore, be expected to be the prime determinant of success with Myosplint. Conclusions. Myosplint reduces fiber stress without a decrement in the Starling relationship. Myosplint should be much more effective than partial ventriculectomy as a surgical therapy for patients with dilated cardiomyopathy and end-stage congestive heart failure. C1 San Francisco Vet Affairs Med Ctr, Div Surg Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Dept Surg, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Anesthesia, Div Cardiothorac Surg, San Francisco, CA 94143 USA. Maastricht Univ, Dept Biophys, Maastricht, Netherlands. RP Guccione, JM (reprint author), San Francisco Vet Affairs Med Ctr, Div Surg Serv, 112D,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [R01-HL-58759, R01-HL-63348] NR 35 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2003 VL 76 IS 4 BP 1171 EP 1180 AR PII S0003-4975(03)00731-8 DI 10.1016/S0003-4975(03)00731-8 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 728LD UT WOS:000185717900046 PM 14530007 ER PT J AU Serena, C Ortoneda, M Capilla, J Pastor, FJ Sutton, DA Rinaldi, MG Guarro, J AF Serena, C Ortoneda, M Capilla, J Pastor, FJ Sutton, DA Rinaldi, MG Guarro, J TI In vitro activities of new antifungal agents against Chaetomium spp. and inoculum standardization SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FILAMENTOUS FUNGI; AMPHOTERICIN-B; SUSCEPTIBILITY; ASPERGILLUS; CASPOFUNGIN; ITRACONAZOLE; FUSARIUM; MK-0991; SYNERGY AB Chaetomium is an unusual etiological agent of human infections, but the mortality rate among immunocompromised patients is considerably greater than that among nonimmunocompromised individuals. We investigated the in vitro antifungal susceptibilities to novel antifungal agents of 19 strains belonging to three species of Chaetomium which have been involved in human infections, i.e., Chaetomium globosum, C. atrobrunneum, and C. nigricolor, and one strain of the closely related species Achaetomium strumarium. A modification of the NCCLS reference microdilution method (M38-A) was used to evaluate the in vitro activities of ravuconazole, voriconazole, albaconazole, and micafungin. Micafungin was not active at all, while the geometric mean MICs and minimum effective concentrations of the three triazoles were less than 0.5 and 0.4 mug/ml, respectively. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. Univ Rovira & Virgili, Fac Med & Ciencies Salut, Unitat Microbiol, E-43201 Reus, Spain. RP Guarro, J (reprint author), Univ Rovira & Virgili, Fac Med, Unitat Microbiol, Carrer St Llorenc 21, E-43201 Reus, Spain. RI Capilla, Javier/H-4689-2015 OI Capilla, Javier/0000-0002-0765-6403; Serena, Carolina/0000-0003-2251-0856; Guarro, Josep/0000-0002-7839-7568 NR 18 TC 28 Z9 28 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2003 VL 47 IS 10 BP 3161 EP 3164 DI 10.1128/AAC.47.10.3161-3164.2003 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 726RH UT WOS:000185612600021 PM 14506025 ER PT J AU Liu, JH Etzioni, DA O'Connell, JB Maggard, MA Hiyama, DT Ko, CY AF Liu, JH Etzioni, DA O'Connell, JB Maggard, MA Hiyama, DT Ko, CY TI Inpatient surgery in California: 1990-2000 SO ARCHIVES OF SURGERY LA English DT Article ID COMORBIDITY INDEX; TRENDS AB Background: The practice environment for surgery is changing. However, little is known regarding the trends or current status of inpatient surgery at a population level. Hypothesis: inpatient surgical care has changed significantly over the last 10 years. Design: Longitudinal analysis of California inpatient discharge data (January 1, 1990, through December 31, 2000). Setting: All 503 nonfederal acute care hospitals in California. Patients: All inpatients undergoing general, vascular, and cardiothoracic surgery in California from January 1, 1990, through December 31, 2000, were obtained. Main Outcome Measures: Volume, mean age, comorbidity profile, length of hospital stay, and inhospital mortality were obtained for inpatient general, vascular, and cardiothoracic surgical procedures performed during the period 1990 to 2000. Rates of change and trends were evaluated for the 10-year period. Results: Between January 1, 1990, and December 31, 2000, 1.64 million surgical procedures were performed. The number of surgical procedures increased 20.4%, from 135 795 in 1990 to 163 468 in 2000. Overall, patients were older and had more comorbid disease in 2000 compared with 1990. Both crude and adjusted (by type of operation) in-hospital mortality decreased from 3.9% in 1990 to 2.75% (P<.001) and 2.58% (P<.001), respectively, in 2000. Length of hospital stay decreased over the period for all operations analyzed. Conclusions: The total number of inpatient general, vascular, and cardiothoracic surgical procedures has increased over the past decade. Furthermore, our findings indicate that the outcomes of care (eg, in-hospital mortality and length of hospital stay) for patients who undergo general, vascular, and cardiothoracic surgical procedures have improved. However, continued evaluations at the population level are needed. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Admin, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Admin, Dept Gen Internal Med, Los Angeles, CA USA. RP Liu, JH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. NR 11 TC 13 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD OCT PY 2003 VL 138 IS 10 BP 1106 EP 1111 DI 10.1001/archsurg.138.10.1106 PG 6 WC Surgery SC Surgery GA 734UG UT WOS:000186075900013 PM 14557128 ER PT J AU Budoff, JE Nirschl, RP Ilahi, OA Rodin, DM AF Budoff, JE Nirschl, RP Ilahi, OA Rodin, DM TI Internal impingement in the etiology of rotator cuff tendinosis revisited SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE internal impingement; rotator cuff; Labrum; impingement syndrome; throwing injuries ID SUPERIOR GLENOID IMPINGEMENT; THROWING ATHLETE; THICKNESS TEARS; EMG ANALYSIS; SHOULDER; ACROMIOPLASTY; INSTABILITY; DEBRIDEMENT; OVERHAND; LABRUM AB Purpose: The theory of internal impingement holds that, in overhead athletes, repeated contact between the undersurface of the rotator cuff and the posterosuperior glenoid rim leads to articular-sided partial-thickness rotator cuff tears and superior labral lesions. However, we have noted this same constellation of lesions in our general patient population. These recreational athletic patients do not routinely assume the position of extreme abduction and external rotation, and thus are unlikely to experience significant internal impingement forces. The goal of this study was to document the prevalence of superior labral lesions in patients being treated for partial-thickness undersurface rotator cuff tears. Type of Study: Retrospective case series. Methods: We retrospectively reviewed the records of 75 shoulders arthroscopically treated for partial-thickness articular-sided rotator cuff tears. With the exception of one professional tennis player, no patients were playing sports at a professional or major college level. No professional or collegiate throwing athletes were included. The prevalence of these lesions and their association with recreational athletics was noted. Results: We found that 55 of 75 (73.3%) shoulders with articular-sided partial-thickness rotator cuff tears also had superior labral lesions. A statistically significant increased prevalence of superior labral lesions in the dominant shoulder was seen (P =.03). In addition, our patients who engaged in overhand throwing had significantly fewer superior labral lesions in the dominant shoulders than did nonthrowers (P =.017). Conclusions: The "kissing lesions" of undersurface rotator cuff tears and posterosuperior labral damage may be explained by mechanisms other than "internal impingement." C1 Baylor Coll Med, Dept Orthopaed Surg, Houston, TX 77030 USA. Houston VAMC, Houston, TX USA. Georgetown Univ, Dept Orthopaed Surg, Arlington, VA USA. RP Budoff, JE (reprint author), 6550 Fannin,2525, Houston, TX 77030 USA. NR 30 TC 28 Z9 29 U1 0 U2 12 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD OCT PY 2003 VL 19 IS 8 BP 810 EP 814 DI 10.1053/S0749-8063(03)00732-1 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 735WQ UT WOS:000186137900002 PM 14551541 ER PT J AU Blackburn, ML Chansky, HA Zielinska-Kwiatkowska, A Matsui, Y Yang, L AF Blackburn, ML Chansky, HA Zielinska-Kwiatkowska, A Matsui, Y Yang, L TI Genomic structure and expression of the mouse ESET gene encoding an ERG-associated histone methyltransferase with a SET domain SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE historic H3; methyltransferase; chromatin; transcription initiation; splicing ID RNA POLYMERASE-II; SUPPRESSOR GENE; DNA METHYLATION; H3; TRANSCRIPTION; CHROMATIN; PROTEINS; SU(VAR)3-9; INTERACTS; COMPLEXES AB ESET (ERG-associated protein with a SET domain, also called SETDB1) is a novel histone methyltransferase that catalyzes methylation of histone H3-lysine 9 (H3-K9). Here we describe the genomic structure and expression of the mouse ESET gene that gives rise to ESET protein and its alternative splicing product. ESET is a 36-kb single copy gene and full-length ESET transcript consisting of 22 exons. The splicing variant retains only the first 12 exons and thus lacks sequences encoding the methyl CpG-binding domain and the catalytic SET domain. The U2 type conserved GT/AG consensus sequence is present at all of the splicing junctions within the ESET gene. The transcription initiation site of the ESET gene was determined by 5'-RACE experiment and by primer extension. The 5'-flanking sequence of the ESET gene does not contain the consensus TATA box. Instead, this ESET promoter region has features such as SP1-binding sites that are typical of housekeeping genes. The ESET promoter was functionally active when tested in transfection and luciferase assay. Full-length ESET transcript appears to be ubiquitously expressed. While the SET domain-deficient splicing variant is present in immortalized cell lines, it is undetectable by RT-PCR in the majority of normal mouse tissues. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Washington, Sch Med, Dept Orthoped & Sports Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Hematol, Seattle, WA 98195 USA. RP Yang, L (reprint author), Univ Washington, Sch Med, Dept Orthoped, 1660 S Columbian Way,GMR 151, Seattle, WA 98108 USA. FU NCI NIH HHS [1R01CA90941] NR 26 TC 19 Z9 20 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD OCT 1 PY 2003 VL 1629 IS 1-3 BP 8 EP 14 DI 10.1016/S0167-4781(03)00155-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 731HD UT WOS:000185877500002 PM 14522075 ER PT J AU Shuster, E AF Shuster, E TI Human cloning: Category, dignity, and the role of bioethics SO BIOETHICS LA English DT Article; Proceedings Paper CT 6th World Congress of the International-Association-of-Bioethics CY 2001 CL BRASILIA, BRAZIL SP Int Assoc Bioeth AB Human cloning has been simultaneously a running joke for. massive worldwide publicity of fringe groups like the Raelians, and the core issue Of an international movement at the United Nations in support of a treaty to ban the use of cloning techniques to produce a child (so called reproductive cloning). Yet, even though debates on human cloning have greatly increased since the birth of Dolly, the clone sheep, in 1997, we, continue to wonder whether cloning is after all any different from other methods of medically assisted reproduction, and what exactly makes cloning an. 'affront. to the dignity of humans.' Categories we adopt matter mightily as they inform but can also misinform and lead to mistaken and unproductive decisions. And thus bioethicists have a responsibility to ensure that the proper categories are used in the cloning debates and denounce those who try to win the ethical debate through well-crafted labels rather than well-reasoned argumentations. But it is as important for bioethicists to take a position on broad issues such as human cloning and species altering interventions. One 'natural question' would be, for example, should there be an international treaty to ban human reproductive cloning? C1 Univ Penn, Vet Affairs Med Ctr, Human Rights & Eth Program, Philadelphia, PA 19104 USA. RP Shuster, E (reprint author), Univ Penn, Vet Affairs Med Ctr, Human Rights & Eth Program, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 10 TC 10 Z9 10 U1 2 U2 7 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0269-9702 J9 BIOETHICS JI Bioethics PD OCT PY 2003 VL 17 IS 5-6 BP 517 EP 525 DI 10.1111/1467-8519.00365 PG 9 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 734PD UT WOS:000186065000012 PM 14959720 ER PT J AU Pashek, GV Bachman, DL AF Pashek, GV Bachman, DL TI Cognitive, linguistic, and motor speech effects of donepezil hydrochloride in a patient with stroke-related aphasia and apraxia of speech SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID NONFLUENT APHASIA; DOUBLE-BLIND; BROMOCRIPTINE C1 Univ Florida, Commun Sci & Disorders Dept, Tampa, FL USA. Ralph H Johnson VAMC, Charleston, SC USA. NR 13 TC 6 Z9 6 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 2003 VL 87 IS 1 BP 179 EP 180 DI 10.1016/S0093-934X(03)00259-1 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 730ND UT WOS:000185836100091 ER PT J AU Merrell, M Suarez-Cuervo, C Harris, KW Vaananen, HK Selander, KS AF Merrell, M Suarez-Cuervo, C Harris, KW Vaananen, HK Selander, KS TI Bisphosphonate induced growth inhibition of breast cancer cells is augmented by p38 inhibition SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT 3rd North American Symposium on Skeletal Complications of Malignancy CY APR 25-27, 2002 CL BETHESDA, MARYLAND SP Paget Fdn DE bisphosphonates; breast cancer; p38 ID NITROGEN-CONTAINING BISPHOSPHONATES; ADJUVANT CLODRONATE TREATMENT; PLACEBO-CONTROLLED TRIAL; BONE-RESORPTION; IN-VITRO; SKELETAL METASTASES; MAP KINASE; PROTEIN PRENYLATION; MEVALONATE PATHWAY; ZOLEDRONIC ACID AB Bisphosphonates (BPs) inhibit osteoclast-mediated bone resorption. They also protect from cancer-induced osteolysis and inhibit breast cancer growth in vitro. Some breast cancer cell lines, however, are relatively resistant to the growth inhibitory effects of BPs. We studied the mechanism of BP resistance in human MDA-MB-231 breast cancer cells. We show that both pyrophosphate-resembling (p-) and nitrogen-containing (n-) BPs induce activation of p38 mitogen activated protein (MAP) kinase pathway in MDA-MB-231 cells in vitro. MDA-MB-231 cells stably expressing a dominant negative form of the p38 MAP kinase (p38/AF) exhibited a dramatic increase in growth inhibition in response to BPs in vitro, compared to control cells. SB203580, a specific inhibitor of the p38 MAP kinase, also augmented BP-induced growth inhibition of parental MDA-MB-231 cells. Similar results were obtained also in murine macrophage-like J774 cells in vitro. Finally, no BP-induced phosphorylation of p38, or augmentation of BP-induced growth inhibition by SB203580 were detected in MCF-7 or HCC38 breast cancer cells, which are more sensitive than MDA-MB-231 cells especially to n- BP induced growth inhibition. In conclusion, these results suggest that BPs activate the p38 pathway in MDA-MB-231 and J774 cells. This activation may be associated with increased survival or proliferation because inhibition of p38 augments BP-induced growth inhibition. These findings may apply to the development of novel approaches for the treatment of breast cancer. C1 Univ Alabama, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Turku, Inst Biomed, Dept Anat, FIN-20520 Turku, Finland. RP Selander, KS (reprint author), Univ Alabama, Dept Med, Div Hematol Oncol, WTI T558,1824 6th Ave S, Birmingham, AL 35294 USA. NR 46 TC 24 Z9 24 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2003 VL 81 IS 3 BP 231 EP 241 DI 10.1023/A:1026126430905 PG 11 WC Oncology SC Oncology GA 732BG UT WOS:000185920500006 PM 14620918 ER PT J AU Prindiville, SA Byers, T Hirsch, FR Franklin, WA Miller, YE Vu, KO Wolf, HJ Baron, AE Shroyer, KR Zeng, C Kennedy, TC Bunn, PA AF Prindiville, SA Byers, T Hirsch, FR Franklin, WA Miller, YE Vu, KO Wolf, HJ Baron, AE Shroyer, KR Zeng, C Kennedy, TC Bunn, PA TI Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ASPIRIN USE; FOLLOW-UP; RISK; MORTALITY; DISEASE; CHEMOPREVENTION; INTERVENTION; PROJECT; TRIAL AB Individuals with cytological atypia in sputum may be at increased risk for lung cancer. We conducted a longitudinal analysis of the association between lung cancer incidence and cytological atypia in sputum samples collected prospectively from an ongoing cohort of adults at high risk for lung cancer. Cohort members had a smoking history of 2:30 pack-years and chronic obstructive pulmonary disease documented by pulmonary airflow testing. Sputum samples collected at baseline and periodically thereafter were examined by standard cytological methods. From the cohort of 2006 people, there were 83 incident lung cancers over 4469 person-years of observation. At baseline, the association between personal and behavioral characteristics, and sputum cytological atypia was assessed by multiple logistic regression. The association between sputum cytological atypia and incident lung cancer was then assessed by hazard ratios using proportional hazards regression analysis, adjusting for potential confounding factors. Cytological atypia graded as moderate or worse was associated with continuing cigarette smoking (adjusted odds ratio, 2.5; 95% confidence interval, 1.5-4.1), and with lower levels of intake of fruits and vegetables (P for trend = 0.04). Atypia was not associated with several other factors, including the degree of airflow obstruction, the use of vitamin supplements, nonsteroidal anti-inflammatory drugs, or metered-dose steroid inhalers. Incident lung cancer was increased among those with moderate or worse cytological atypia (adjusted hazards ratio, 2.8; 95% confidence interval, 1.4-5.5). This association was not confounded by other risk factors. We conclude that in this high-risk cohort, cytological atypia is associated with continuing smoking and low intake of fruits and vegetables, but that independent of these and other factors, the risk of incident lung cancer is increased among those with moderate or worse grades of cytological atypia in their sputum. C1 Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Prevent Med & Biostat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Pathol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Lung Canc Inst Colorado, Denver, CO 80218 USA. RP Byers, T (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Med, 4200 E 9th Ave, Denver, CO 80262 USA. FU NCI NIH HHS [K07CA75159, P50CA58187] NR 38 TC 61 Z9 63 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2003 VL 12 IS 10 BP 987 EP 993 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 736CR UT WOS:000186153500006 PM 14578133 ER PT J AU Levine, GN Ferguson, JJ AF Levine, GN Ferguson, JJ TI Low-molecular-weight heparin during percutaneous coronary interventions: Rationale, results, and recommendations SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE enoxaparin; angioplasty; anticoagulation ID PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; UNFRACTIONATED HEPARIN; UNSTABLE ANGINA; MYOCARDIAL-INFARCTION; SUBCUTANEOUS ENOXAPARIN; INTRAVENOUS ENOXAPARIN; ACC/AHA GUIDELINES; AMERICAN-COLLEGE; RANDOMIZED TRIAL C1 Houston VAMC, Cardiol Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Houston, TX 77030 USA. Texas Heart Inst, Houston, TX 77025 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Houston, TX USA. RP Levine, GN (reprint author), Houston VAMC, Cardiol Sect, 3C-310,111-B, Houston, TX 77030 USA. NR 48 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT PY 2003 VL 60 IS 2 BP 185 EP 193 DI 10.1002/ccd.10640 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 728DD UT WOS:000185699200008 PM 14517923 ER PT J AU Hirshkowitz, M AF Hirshkowitz, M TI Modafinil adjunctive therapy improves excessive sleepiness and functional status in obstructive sleep apnea: A 12-month open-label extension study SO CHEST LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Chest-Physicians CY OCT 25-30, 2003 CL ORLAMDO, FLORIDA SP Amer Coll Chest Physicians C1 VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2003 VL 124 IS 4 SU S BP 75S EP 75S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 734RG UT WOS:000186070400013 ER PT J AU Flemons, WW Littner, MR AF Flemons, WW Littner, MR TI Measuring agreement between diagnostic devices SO CHEST LA English DT Review DE diagnosis; likelihood ratios; methods; polysomnography; research design; sensitivity and specificity; sleep apnea syndromes AB There is growing interest in using portable monitoring for investigating patients with suspected sleep apnea. Research studies typically report portable monitoring results in comparison with the results of sleep laboratory-based polysomnography. A systematic review of this research has recently been completed by a joint working group of the American College of Chest Physicians, the American Thoracic Society, and the American Academy of Sleep Medicine. The methods for comparing the results of portable monitors and polysomnography include product-moment correlation, intraclass correlation, mean differences/limits of agreement, sensitivity, specificity, and likelihood ratios. Each approach has advantages and limitations, which are highlighted in this review. C1 Univ Calgary, Fac Med, Calgary, AB T2N 2T9, Canada. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Flemons, WW (reprint author), Univ Calgary, Fac Med, 1403 29th Sw NW, Calgary, AB T2N 2T9, Canada. NR 5 TC 58 Z9 60 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2003 VL 124 IS 4 BP 1535 EP 1542 DI 10.1378/chest.124.4.1535 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 733LU UT WOS:000186002500051 PM 14555591 ER PT J AU An, JB Sun, YP Adams, J Fisher, M Belldegrun, A Rettig, MB AF An, JB Sun, YP Adams, J Fisher, M Belldegrun, A Rettig, MB TI Drug interactions between the proteasome inhibitor bortezomib and cytotoxic chemotherapy, tumor necrosis factor (TNF) alpha, and TNF-related apoptosis-inducing ligand in prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; APO-2 LIGAND; CONSTITUTIVE ACTIVATION; IN-VIVO; CELLS; RESISTANCE; PS-341; PATHWAY; PROTEIN; MODEL AB Purpose: Proteasome inhibition has been shown to be an effective anticancer therapy in many tumor models, including prostate cancer. We sought to identify drug interactions between the proteasome inhibitor bortezomib and other apoptotic stimuli, including cytotoxic chemotherapy and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In addition, we wanted to gain insight into the role of nuclear factor kappaB inhibition as a mediator of bortezomib cytotoxic effects. Experimental Design: Prostate cancer cell lines (LNCaP, LAPC4, CL1, and DU145) were treated with bortezomib and apoptotic stimuli (TRAIL, chemotherapy, and tumor necrosis factor alpha), alone or in combination. Apoptosis and cell viability were measured, and median effect/combination index analyses were used to quantitate drug interactions. Nuclear factor kappaB activity at baseline and in response to drug treatment was determined by gel shift and reporter gene assays. Results: Bortezomib induced cell death of androgen-dependent (LNCaP and LAPC4) and androgen-independent (CL1 and DU145) prostate cancer cell lines, although androgen-dependent cells were more sensitive to proteasome inhibition. Bortezomib synergized with TRAIL and tumor necrosis factor a to induce death in both androgen-dependent and androgen-independent cells. Conclusions: Bortezomib and TRAIL represent a synergistic drug combination that warrants further evaluation in in vivo models of prostate cancer. C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. RP Rettig, MB (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Bldg 304,Room E1-113,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 38 TC 57 Z9 59 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2003 VL 9 IS 12 BP 4537 EP 4545 PG 9 WC Oncology SC Oncology GA 730KV UT WOS:000185830700032 PM 14555528 ER PT J AU Rhew, DC Bernal, M Aguilar, D Iloeje, U Goetz, MB AF Rhew, DC Bernal, M Aguilar, D Iloeje, U Goetz, MB TI Association between protease inhibitor use and increased cardiovascular risk in patients infected with human immunodeficiency virus: A systematic review SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1-INFECTED PATIENTS; INSULIN-RESISTANCE; METABOLIC ALTERATIONS; LIPID ABNORMALITIES; AQUITAINE COHORT; HIV-1 INFECTION; LIPODYSTROPHY; DISEASE; HYPERLIPIDEMIA AB Some studies have shown that currently available protease inhibitors (PIs) are associated with an increased risk of cardiovascular disease. We have systematically reviewed the published literature and conference abstracts for studies evaluating cardiovascular risk factors and events in patients receiving highly active antiretroviral therapy, with and without PIs. The majority of studies showed that the use of PIs was associated with increased levels of total cholesterol ( 36 [75%] of 48 studies), triglycerides ( 35 [73%] of 48 studies), and low-density lipoprotein ( 12 [100%] of 12 studies). PI use was often associated with morphological signs of cardiovascular disease, such as increased carotid intima thickness or atherosclerotic lesions ( 7 [88%] of 8 studies). Finally, 2 (67%) of 3 long-term observational studies that met our inclusion criteria demonstrated an association between use of PIs and subsequent myocardial infarction. The benefits of the currently available PIs should be balanced against the long-term risk of cardiovascular disease. C1 Zynx Hlth, Cedars Sinai Dept Med, Beverly Hills, CA 90212 USA. Zynx Hlth, Cedars Sinai Dept Hlth Serv, Beverly Hills, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. David Geffen UCLA Sch Med, Los Angeles, CA USA. Bristol Myers Squibb Co, Outcomes Res, Wallingford, CT 06492 USA. RP Rhew, DC (reprint author), Zynx Hlth, Cedars Sinai Dept Med, 9100 Wilshire Blvd,Ste 655E, Beverly Hills, CA 90212 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 92 TC 41 Z9 42 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2003 VL 37 IS 7 BP 959 EP 972 DI 10.1086/378064 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 727TR UT WOS:000185677400014 PM 13130409 ER PT J AU Bierer, LM Yehuda, R Schmeidler, J Mitropoulou, V New, AS Silverman, JM Siever, LJ AF Bierer, LM Yehuda, R Schmeidler, J Mitropoulou, V New, AS Silverman, JM Siever, LJ TI Abuse and neglect in childhood: Relationship to personality disorder diagnoses SO CNS SPECTRUMS LA English DT Article ID SEXUAL ABUSE; SUICIDAL-BEHAVIOR; TRAUMA QUESTIONNAIRE; EARLY ADULTHOOD; PHYSICAL ABUSE; RISK-FACTORS; PSYCHOPATHOLOGY; SELF; INPATIENTS; INTERVIEW AB Background: Childhood history of abuse and neglect has been associated with personality disorders and has been observed in subjects with lifetime histories of suicidality and self-injury. Most of these findings have been generated from inpatient clinical samples. Methods: This study evaluated self-rated indices of sustained childhood abuse and neglect in an outpatient sample of well-characterized personality disorder subjects (n=182) to determine the relative associations of childhood trauma indices to specific personality disorder diagnoses or clusters and to lifetime history of suicide attempts or gestures. Subjects met criteria for similar to2.5 Axis II diagnoses and 24% reported past suicide attempts. The Childhood Trauma Questionnaire was administered to assess five dimensions of childhood trauma exposure (emotional, physical, and sexual abuse, and emotional and physical neglect). Logistic regression was employed to evaluate salient predictors among the trauma measures for each cluster, personality disorder, and history of attempted suicide and self-harm. All analyses controlled for gender distribution. Results: Seventy-eight percent of subjects met dichotomous criteria for some form of childhood trauma; a majority reported emotional abuse and neglect. The dichotomized criterion for global trauma severity was predictive of cluster B, borderline, and antisocial personality disorder diagnoses. Trauma scores were positively associated with cluster A, negatively with cluster C, but were not significantly associated with cluster B diagnoses. Among the specific diagnoses comprising cluster A, paranoid disorder alone was predicted by sexual, physical, and emotional abuse. Within cluster B, only antisocial personality disorder showed significant associations with trauma scores, with specific prediction by sexual and physical abuse. For borderline personality disorder, there were gender interactions for individual predictors, with emotional abuse being the only significant trauma predictor, and only in men. History of suicide gestures was associated with emotional abuse in the entire sample and in women only; self-mutilatory behavior was associated with emotional abuse in men. Conclusion: These results suggest that childhood emotional abuse and neglect are broadly represented among personality disorders, and associated with indices of clinical severity among patients with borderline personality disorder. Childhood sexual and physical abuse are highlighted as predictors of both paranoid and antisocial personality disorders.. These results help qualify prior observations of the association of childhood sexual abuse with borderline personality disorder. C1 Gen Clin Res Ctr, Dept Psychiat, New York, NY USA. Gen Clin Res Ctr, Dept Biomath Sci, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Bierer, LM (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIMH NIH HHS [R01-MH5606] NR 42 TC 98 Z9 105 U1 9 U2 41 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD OCT PY 2003 VL 8 IS 10 BP 737 EP + PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 736EB UT WOS:000186157100006 PM 14712172 ER PT J AU Goodman, M Weiss, DS Koenigsberg, H Kotlyarevsky, V New, AS Mitropoulou, V Silverman, JM O'Flynn, K Siever, LJ AF Goodman, M Weiss, DS Koenigsberg, H Kotlyarevsky, V New, AS Mitropoulou, V Silverman, JM O'Flynn, K Siever, LJ TI The role of childhood trauma in differences in affective instability in those with personality disorders SO CNS SPECTRUMS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PSYCHOLOGICAL RISK-FACTORS; BORDERLINE PERSONALITY; SEXUAL-ABUSE; DISSOCIATIVE EXPERIENCES; SELF-MUTILATION; FEMALE-PATIENTS; HERITABILITY; AGGRESSION; NEGLECT AB Background: This study examined the relationship of self-reported histories of childhood trauma to measures of affective instability in a sample of unmedicated outpatients with various personality disorders (n=174). Methods: Childhood trauma was measured by the Childhood Trauma Questionnaire. Affective instability comprises at least two dimensions: affective lability, assessed using the Affective Lability Scale, and affective intensity, assessed using the Affective Intensity Measure. Results: A history of emotional abuse was the only trauma variable that significantly correlated with the affect measures in the total sample (r=.21-.30). More fine-grained analyses revealed that the relationship of emotional abuse and affective instability measures varied as a function of both gender and personality disorder type. In subjects with borderline personality disorder, the correlation for emotional abuse was greatly attenuated for both Affective Lability Scale (r=.10) and Affective Intensity Measure (r=.15) total scores. Conclusion: This suggests that nontrauma-related factors may be more predominant in affective dyscontrol in individuals with borderline personality disorder. C1 Gen Clin Res Ctr, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Goodman, M (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIMH NIH HHS [R01-MH606] NR 70 TC 15 Z9 15 U1 1 U2 3 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD OCT PY 2003 VL 8 IS 10 BP 763 EP 770 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 736EB UT WOS:000186157100008 PM 14712174 ER PT J AU Swenson, ER AF Swenson, ER TI A comparative approach to carbonic anhydrase: the work of Thomas H. Maren SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Physiological-Society CY AUG 27, 2002 CL SAN DIEGO, CALIFORNIA SP Amer Physiolog Soc DE Thomas H. Maren; carbonic anhydrase; kidney; cerebrospinal fluid; bicarbonate; acid; comparative physiology; marine fish ID CAT CHOROID-PLEXUS; CEREBROSPINAL-FLUID; BICARBONATE SECRETION; MARINE TELEOST; RAT-KIDNEY; CELL PH; ACETAZOLAMIDE; EXCRETION; EXCHANGE; DISSOCIATION AB Thomas H. Maren studied carbonic anhydrase (CA) for half a century, venturing into all aspects of this powerful enzyme from active site chemistry to clinical medicine. He was a keen proponent of comparative physiology to illuminate basic principles of the chemistry and biology of CA and spent 47 Summers at the Mt. Desert Island Biological Laboratory (MDIBL) studying many non-mammalian species. Following the venerable strategy of selecting the right creature to explore a particular question, Maren derived important insights into the role of CA in ion transport, acid-base regulation and gas exchange. Using the fact that tissue CAs are expressed variably in different species, and that these animals differ in temperature, acid-base status and metabolic rate, he defined the contributions of un-catalyzed and catalyzed CO, reactions in many physiological processes. Often this strategy simplified a problem and offered answers not easily obtainable in mammals. As examples, he verified the primary role of HCO3- as lead ion in CSF formation in fish and extended this to mammals. Using marine fish whose kidneys have very little CA, he uncovered mechanisms of acid-base transfer independent of CA that help to explain why CA inhibition does not lead to total bicarbonate depletion. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Swenson, ER (reprint author), Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, S-111-Pulm,1660 S Columbian Way, Seattle, WA 98108 USA. NR 46 TC 7 Z9 7 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD OCT PY 2003 VL 136 IS 2 BP 229 EP 241 DI 10.1016/S1095-6433(03)00174-0 PG 13 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 728AZ UT WOS:000185694200002 PM 14511743 ER PT J AU Glorioso, JC Mata, M Fink, DJ AF Glorioso, JC Mata, M Fink, DJ TI Gene therapy for chronic pain SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE enkephalin; GDNF; gene therapy; HSV; pain ID HERPES-SIMPLEX-VIRUS; INITIAL CLINICAL-EXPERIENCE; SPINAL SUBARACHNOID SPACE; CHRONIC NEUROPATHIC PAIN; CHROMAFFIN CELL THERAPY; IMMEDIATE-EARLY GENES; BONE CANCER PAIN; NEUROTROPHIC-FACTOR; NERVE INJURY; LUMBAR TRANSPLANT AB The dorsal horn of the spinal cord represents an attractive site for interventions designed to treat chronic pain, but it has been difficult to identify small molecules that act selectively on pain transmission at the spinal level. One approach is the use of viral vector-mediated gene transfer to achieve focal production and release of short-lived analgesic peptides. Herpes simplex virus-based vectors, expressing proenkephalin delivered by subcutaneous inoculation, transduce neurons of the dorsal root ganglion, leading to release of enkephalin from nerve terminals in dorsal horn to produce an analgesic effect in several models of chronic pain. A clinical trial is set to commence. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15206 USA. RP Fink, DJ (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, 200 Lothrop St, Pittsburgh, PA 15213 USA. NR 45 TC 16 Z9 20 U1 0 U2 2 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD OCT PY 2003 VL 5 IS 5 BP 483 EP 488 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 735GE UT WOS:000186103400005 PM 14601516 ER PT J AU Kashyap, S Belfort, R Gastaldelli, A Pratipanawatr, T Berria, R Pratipanawatr, W Bajaj, M Mandarino, L DeFronzo, R Cusi, K AF Kashyap, S Belfort, R Gastaldelli, A Pratipanawatr, T Berria, R Pratipanawatr, W Bajaj, M Mandarino, L DeFronzo, R Cusi, K TI A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; POLYCYSTIC OVARIAN SYNDROME; ORAL GLUCOSE-TOLERANCE; ADOLESCENT GIRLS; HEALTHY-SUBJECTS; SKELETAL-MUSCLE; DOSE-RESPONSE; CHAIN-LENGTH; RAT ISLETS; RESISTANCE AB Acute elevations in free fatty acids (FFAs) stimulate insulin secretion, but prolonged lipid exposure impairs beta-cell function in both in vitro studies and in vivo animal studies. In humans data are limited to short-term (less than or equal to48 h) lipid infusion studies and have led to conflicting results. We examined insulin secretion and action during a 4-day lipid infusion in healthy normal glucose tolerant subjects with (FH+ group, n = 13) and without (control subjects, n = 8) a family history of type 2 diabetes. Volunteers were admitted twice to the clinical research center and received, in random order, a lipid or saline infusion. On days 1 and 2, insulin and C-peptide concentration were measured as part of a metabolic profile after standardized mixed meals. Insulin secretion in response to glucose was assessed with a +125 mg/dl hyperglycemic clamp on day 3. On day 4, glucose turnover was measured with a euglycemic insulin clamp with [3-H-3]glucose. Day-long plasma FFA concentrations with lipid infusion were increased within the physiological range, to levels seen in type 2 diabetes (similar to500-800 mumol/l). Lipid infusion had strikingly opposite effects on insulin secretion in the two groups. After mixed meals, day-long plasma C-peptide levels increased with lipid infusion in control subjects but decreased in the FH+ group (+28 vs. -30%, respectively, P < 0.01). During the hyperglycemic clamp, lipid infusion enhanced the insulin secretion rate (ISR) in control subjects but decreased it in the FH+ group (first phase: +75 vs. -60%, P < 0.001; second phase: +25 vs. -35%, P < 0.04). When the ISR was adjusted for insulin resistance (ISRRd = ISR divided by [1/R-d] where R-d is the rate of insulin-stimulated glucose disposal), the inadequate P-cell response in the FH+ group was even more evident. Although ISRRd, was not different between the two groups before lipid infusion, in the FH+ group, lipid infusion reduced first- and second-phase ISRRd to 25 and 42% of that in control subjects, respectively (both P < 0.001 vs. control subjects). Lipid infusion in the FH+ group (but not in control subjects) also caused severe hepatic insulin resistance with an increase in basal endogenous glucose production (EGP), despite an elevation in fasting insulin levels, and impaired suppression of EGP to insulin. In summary, in individuals who are genetically predisposed to type 2 diabetes, a sustained physiological increase in plasma FFA impairs insulin secretion in response to mixed meals and to intravenous glucose, suggesting that in subjects at high risk of developing type 2 diabetes, beta-cell lipotoxicity may play an important role in the progression from normal glucose tolerance to overt hyperglycemia. C1 Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Cusi, K (reprint author), Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Med, Room 3-380S7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Bajaj, Mandeep/B-6060-2009; Gastaldelli, Amalia/H-3319-2014 OI Gastaldelli, Amalia/0000-0003-2594-1651 FU NCRR NIH HHS [M01-RR-01346]; NIDDK NIH HHS [R01 DK-24092] NR 62 TC 259 Z9 289 U1 2 U2 14 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2003 VL 52 IS 10 BP 2461 EP 2474 DI 10.2337/diabetes.52.10.2461 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 729AL UT WOS:000185748500002 PM 14514628 ER PT J AU Wang, CCL Gurevich, I Draznin, B AF Wang, CCL Gurevich, I Draznin, B TI Insulin affects vascular smooth muscle cell phenotype and migration via distinct signaling pathways SO DIABETES LA English DT Article ID CORONARY HEART-DISEASE; GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PLASMA-INSULIN; PROTEIN; KINASE; PROLIFERATION; WORTMANNIN AB Insulin maintains vascular smooth muscle cell (VSMC) quiescence yet can also promote VSMC migration. The mechanisms by which insulin exerts these contrasting effects were examined using alpha-smooth muscle actin (alpha-SMA) as a marker of VSMC phenotype because alpha-SMA is highly expressed in quiescent but not migratory VSMC. Insulin alone maintained VSMC quiescence and modestly stimulated VSMC migration. Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, decreased insulin-stimulated expression of a-SMA mRNA by 26% and protein by 48% but had no effect on VSMC migration. PD98059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, decreased insulin-induced VSMC migration by 52% but did not affect alpha-SMA levels. Platelet-derived growth factor (PDGF) promoted dedifferentiation of VSMC, and insulin counteracted this effect. Furthermore, insulin increased alpha-SMA mRNA and protein levels to 111 and 118%, respectively, after PDGF-induced dedifferentiation, an effect inhibited by wortmannin. In conclusion, insulin's ability to maintain VSMC quiescence and reverse the dedifferentiating influence of PDGF is mediated via the PI3K pathway, whereas insulin promotes VSMC migration via the MAPK pathway. Thus, with impaired PI3-kinase signaling and intact MAPK signaling, as seen in insulin resistance, insulin may lose its ability to maintain VSMC quiescence and instead promote VSMC migration. C1 Denver VA Med Ctr, Vet Affairs Res Serv, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Endocrinol Metab & Diabet, Denver, CO 80202 USA. RP Draznin, B (reprint author), ACOS Res Serv, 1055 Clemont St 151, Denver, CO 80220 USA. NR 42 TC 91 Z9 107 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2003 VL 52 IS 10 BP 2562 EP 2569 DI 10.2337/diabetes.52.10.2562 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 729AL UT WOS:000185748500015 PM 14514641 ER PT J AU Leonard, S AF Leonard, S TI Consequences of low levels of nicotinic acetylcholine receptors in schizophrenia for drug development SO DRUG DEVELOPMENT RESEARCH LA English DT Review DE nicotine; nicotinic receptor; smoking; schizophrenia; drug development; addiction ID BIND ALPHA-BUNGAROTOXIN; VENTRAL TEGMENTAL AREA; PURSUIT EYE-MOVEMENTS; INBRED MOUSE STRAINS; CIGARETTE-SMOKING; ALZHEIMERS-DISEASE; TREATMENT STRATEGY; PREFRONTAL CORTEX; POSTMORTEM BRAIN; RAT HIPPOCAMPUS AB The incidence of smoking in the mentally ill is much higher than in the general population and is inordinately high in schizophrenia. It has been suggested that this might be an attempt to self-medicate an underlying biological deficit. The receptors that mediate nicotinic responses are decreased in many regions of postmortem brain in schizophrenic smokers, compared to control smokers. Patients exhibit differential responses to nicotine in a number of behavioral, cognitive, and metabolic measures. As nicotine regulates the release of a large number of neurotransmitters, it is likely that differences in downstream neuroadaptation of other transmitter/receptor systems would result from the reduced level of nicotinic receptors in these patients. The disparate responses to nicotine have consequences for the development of cholinergic drug therapies in schizophrenia. (C) 2003 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Leonard, S (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, 4200 E 9th Ave,C268-71, Denver, CO 80262 USA. NR 103 TC 12 Z9 12 U1 3 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD OCT PY 2003 VL 60 IS 2 BP 127 EP 136 DI 10.1002/ddr.10292 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728BG UT WOS:000185694900007 ER PT J AU Merriam, GR Schwartz, RS Vitiello, MV AF Merriam, GR Schwartz, RS Vitiello, MV TI Growth hormone-releasing hormone and growth hormone secretagogues in normal aging SO ENDOCRINE LA English DT Article; Proceedings Paper CT 4th International Symposium on Growth Hormone Secretagogues CY NOV 07-10, 2002 CL CLEARWATER BEACH, FLORIDA DE aging; ghrelin; growth hormone (somatotropin); growth hormone-releasing hormone; growth hormone secretagogues; insulin-like growth factor-I ID HEALTHY OLDER MEN; FACTOR-I LEVELS; BODY-COMPOSITION; GH SECRETION; WOMEN; ADULTS; EXERCISE; PEPTIDE; GHRELIN; MK-677 AB Growth hormone (GH) secretion declines with aging, and parallels between normal aging and the signs and symptoms of adult GH deficiency have led to interest in the potential utility of replacing or stimulating GH to promote physical and psychological function and to prolong the capacity for independent living in older adults. The aging pituitary remains responsive to GH-releasing hormone (GHRH) and to ghrelin-mimetic GH secretagogues (GHS), and these agents have both theoretical and practical potential advantages as alternatives to the use of GH itself in this setting. Studies of the long duration and large scale needed to test the efficacy of GHRH or GHS on clinically important endpoints cannot be designed or conducted without first obtaining promising results in studies of smaller size focused on manageable intermediate endpoints, and all studies published to date have been of this latter type. GH RH and GHS both stimulate GH secretion, and, when given repeatedly, elevate IGF-I levels to within younger adult normal ranges. When GHRH treatment is continued for several months, these hormonal changes yield an increase in lean body (muscle) mass. GHRH, like GH, reduces body fat, but similar effects have not yet been shown with GHS. GH RH treatment has not yielded consistent improvements in physical function, although it may have a stabilizing effect. Chronic treatment with a short-acting GHRH did not improve sleep, possibly due to lack of sustained activity throughout the night. Compared to placebo, GHRH treatment improved certain tests of cognitive performance. These results, while encouraging, do not yet support the routine use of G H RH or GHS in normal aging. C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Colorado, Hlth Sci Ctr, Div Geriatr Med, Denver, CO 80202 USA. RP Merriam, GR (reprint author), VA Puget Sound Hlth Care Syst, Res A-151, Tacoma, WA 98493 USA. OI Vitiello, Michael/0000-0002-9776-0473 FU NCRR NIH HHS [M01 RR 00037]; NIA NIH HHS [R01 AG 10943]; NIMH NIH HHS [R01 MH 53575, K02 MH 01158] NR 49 TC 16 Z9 16 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD OCT PY 2003 VL 22 IS 1 BP 41 EP 48 DI 10.1385/ENDO:22:1:41 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738YF UT WOS:000186314900006 PM 14610297 ER PT J AU Straessle, A Loup, F Arabadzisz, D Ohning, GV Fritschy, JM AF Straessle, A Loup, F Arabadzisz, D Ohning, GV Fritschy, JM TI Rapid and long-term alterations of hippocampal GABA(B) receptors in a mouse model of temporal lobe epilepsy SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; kainic acid; metabotropic receptors; neurodegeneration; recurrent seizures; synaptic plasticity ID HUMAN EPILEPTOGENIC HIPPOCAMPUS; DENTATE GYRUS; RAT HIPPOCAMPUS; NEUROPEPTIDE-Y; SYNAPTIC REORGANIZATION; PYRAMIDAL CELLS; CELLULAR-DISTRIBUTION; EPILEPTIFORM ACTIVITY; RECURRENT SEIZURES; ANIMAL-MODELS AB Alterations of gamma-aminobutyric acid (GABA)(B) receptor expression have been reported in human temporal lobe epilepsy (TLE). Here, changes in regional and cellular expression of the GABA(B) receptor subunits R1 (GBR1) and R2 (GBR2) were investigated in a mouse model that replicates major functional and histopathological features of TLE. Adult mice received a single, unilateral injection of kainic acid (KA) into the dorsal hippocampus, and GABA(B) receptor immunoreactivity was analysed between 1 day and 3 months thereafter. In control mice, GBR1 and GBR2 were distributed uniformly across the dendritic layers of CA1-CA3 and dentate gyrus. In addition, some interneurons were labelled selectively for GBR1. At 1 day post-KA, staining for both GBR1 and GBR2 was profoundly reduced in CA1, CA3c and the hilus, and no interneurons were visible anymore. At later stages, the loss of GABA(B) receptors persisted in CA1 and CA3, whereas staining increased gradually in dentate gyrus granule cells, which become dispersed in this model. Most strikingly, a subpopulation of strongly labelled interneurons reappeared, mainly in the hilus and CA3 starting at 1 week post-KA. In double-staining experiments, these cells were selectively labelled for neuropeptide Y. The number of GBR1-positive interneurons also increased contralaterally in the hilus. The rapid KA-induced loss of GABA(B) receptors might contribute to epileptogenesis because of a reduction in both presynaptic control of transmitter release and postsynaptic inhibition. In turn, the long-term increase in GABA(B) receptors in granule cells and specific subtypes of interneurons may represent a compensatory response to recurrent seizures. C1 Univ Zurich, Inst Pharmacol & Toxicol, CH-8006 Zurich, Switzerland. VA GLAHS W Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Fritschy, JM (reprint author), Univ Zurich, Inst Pharmacol & Toxicol, CH-8006 Zurich, Switzerland. FU NIDDK NIH HHS [NIH DK4130] NR 68 TC 48 Z9 52 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2003 VL 18 IS 8 BP 2213 EP 2226 DI 10.1046/j.1460-9568.2003.02964.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 735ML UT WOS:000186119100012 PM 14622182 ER PT J AU Royall, DR Palmer, R Chiodo, LK Polk, MJ AF Royall, DR Palmer, R Chiodo, LK Polk, MJ TI Decline in learning ability best predicts future dementia type: The Freedom House Study SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID MILD COGNITIVE IMPAIRMENT; MINI-MENTAL-STATE; PROBABLE ALZHEIMERS-DISEASE; EXECUTIVE INTERVIEW; STRUCTURAL MODELS; DIAGNOSIS; PREVALENCE; FEATURES; RETIREES; CRITERIA AB The authors studied longitudinal change in learning efficiency as a predictor of future dementia type among healthy, well-educated, noninstitutionalized elderly retirees. Serial assessments of memory were obtained using the California Verbal Learning Test (CVLT). Latent growth (LG) models were developed from the slopes of the subjects' performance over the first five CVLT learning trials at each of three serial administrations (e.g., cohort inception [i.e., baseline] [CVLT1], 18 months [CVLT2] and 36 months [CVLT3]). The resulting growth curves were incorporated into a higher order LG model representing the dynamic change in learning efficiency over time (DeltaCVLT). DeltaCVLT was used to predict each subject's "dementia type'' (i.e., clinical state) at 36 months (e.g., no dementia, Type 1 [Alzheimer type] dementia or Type 2 [non-Alzheimer type] dementia), after adjusting for CVLT1, baseline age, and baseline dementia type. Nonlinear (logarithmic) LG models of CVLT1-CVLT3 and DeltaCVLT best fit the data. There was significant variability about both CVLT1 and DeltaCVLT, suggesting subgroups in the sample with significantly different baseline memory function, and different rates of deterioration in learning efficiency. Age, baseline dementia type, and DeltaCVLT made significant independent contributions to final dementia type. CVLT1 did not predict final dementia type independently of the other covariates. These data suggest that baseline memory performance in noninstitutionalized elderly retirees does not predict future dementia type independently of the dynamic rate of change in memory measures. Serial administrations of memory tests may help identify nondemented persons at greater or lesser risk for conversion to frank dementia in the near-term. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Psychiat, San Antonio, TX USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Med, San Antonio, TX USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Pharmacol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Family Practice, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Royall, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd curl Dr, San Antonio, TX 78284 USA. NR 70 TC 15 Z9 15 U1 4 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD OCT-DEC PY 2003 VL 29 IS 4 BP 385 EP 406 DI 10.1080/03610730390228303 PG 22 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 716FC UT WOS:000185017300001 PM 12959874 ER PT J AU Vaquero, EC Edderkaoui, M Nam, KJ Gukovsky, I Pandol, SJ Gukovskaya, AS AF Vaquero, EC Edderkaoui, M Nam, KJ Gukovsky, I Pandol, SJ Gukovskaya, AS TI Extracellular matrix proteins protect pancreatic cancer cells from death via mitochondrial and nonmitochondrial pathways SO GASTROENTEROLOGY LA English DT Article ID CYTOCHROME-C RELEASE; DEPENDENT CASPASE ACTIVATION; PERMEABILITY TRANSITION PORE; DETACHMENT-INDUCED APOPTOSIS; EPITHELIAL-CELLS; IN-VIVO; NECROSIS; INHIBITION; ANOIKIS; CARCINOMA AB Background & Aims: Pancreatic cancer is a very aggressive malignancy. Normal cells die through apoptosis when detached from extracellular matrix (ECM), but the role of ECM in cancer cell survival is poorly understood. Here, we determined the effects of ECM proteins on death responses and underlying signaling pathways in human pancreatic cancer cells. Methods: We measured apoptosis and necrosis, caspase activation, and mitochondrial dysfunction in MIA PaCa-2 and PANC-1 pancreatic carcinoma cells both detached and attached to ECM proteins. Results: Detachment of pancreatic cancer cells from ECM did not induce classic apoptosis, as it does in normal cells, but induced necrosis and apoptosis associated with secondary necrosis. It caused a pronounced mitochondrial depolarization and release of cytochrome c and Smac/DIABLO. However, as different from normal cells, cytochrome c release did not result in downstream caspase activation. Executioner caspases were activated in detached pancreatic cancer cells independent of cytochrome c. Laminin and fibronectin, but not collagen 1, markedly increased pancreatic cancer cell survival by inhibiting both mitochondrial dysfunction (leading to inhibition of necrosis) and caspase activity (leading to decreased apoptotic DNA fragmentation). Conclusions: ECM proteins greatly protect pancreatic cancer cells from death by mechanisms different from those operating in normal cells. The results suggest ECM proteins and their receptors as potential targets for treatment of pancreatic cancer. C1 W Los Angeles Healthcare Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Gukovskaya, AS (reprint author), W Los Angeles Healthcare Ctr, Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 57 TC 41 Z9 42 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2003 VL 125 IS 4 BP 1188 EP 1202 DI 10.1053/S0016-5085(03)01203-4 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 728TB UT WOS:000185731500023 PM 14517801 ER PT J AU Mistry, R Gokhman, I Jimenez, E Maxwell, A Rosansky, J Van Stone, W Jarvik, L AF Mistry, R Gokhman, I Jimenez, E Maxwell, A Rosansky, J Van Stone, W Jarvik, L TI Including acute medical conditions may not undermine usefulness of CIRS in measuring medical burden: Results of pilot study SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Charles R Drew Univ Med & Sci, Dept Psychiat, Los Angeles, CA 90059 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 246 EP 247 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078100690 ER PT J AU Kramer, B Finke, B Wang, M Harker, J AF Kramer, B Finke, B Wang, M Harker, J TI American Indian veterans' federal healthcare utilization: VA and IHS SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA GRECC, Sepulveda, CA USA. Indian Hlth Serv, Zuni, NM USA. VA HSR&D Ctr Excellence, Sepulveda, CA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 247 EP 247 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078100692 ER PT J AU Evans, W Lambert, C Bamman, M Quinn, L AF Evans, W Lambert, C Bamman, M Quinn, L TI Va grecc symposium: Exercise and aging molecular and whole body responses SO GERONTOLOGIST LA English DT Meeting Abstract C1 Cent Arkansas Vet Healhcare Syst, Ctr Geriatr Res Educ & Clin, Little Rock, AR 72205 USA. Birmingham VA Med Ctr, Muscle Res Lab, GRECC, Muscle Res Lab, Birmingham, AL USA. VA Puget Sound Healthcare Syst, Div Gerontol & Geriatr Med, Tacoma, WA 98493 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 274 EP 274 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078100773 ER PT J AU Benton, N Brighton, T Crane, M Espe, E Jenkins, K Parkison, T Setka, D AF Benton, N Brighton, T Crane, M Espe, E Jenkins, K Parkison, T Setka, D TI Innovations in home health care: Acute home care and the changing role of home care nurses SO GERONTOLOGIST LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 313 EP 313 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078100860 ER PT J AU Pawlowski, C Lee, M Kier, F Kendjelic, E AF Pawlowski, C Lee, M Kier, F Kendjelic, E TI Neuropsychological functioning and depressive symptoms in older veterans with cognitive impairment SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 410 EP 410 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078101116 ER PT J AU Evans, L Rubenstein, L Abrass, I AF Evans, L Rubenstein, L Abrass, I TI Joseph T. Freeman award lecture SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Seattle, WA USA. VA Greater Los Angeles Healthcare Ctr, GRECC 11E, Sepulveda, CA 91343 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 429 EP 429 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078101183 ER PT J AU Webber, A Alessi, C Harker, J Martin, J Josephson, K AF Webber, A Alessi, C Harker, J Martin, J Josephson, K TI Association between sedative medication use and actigraphic-scored sleep in long-stay nursing home residents SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, GRECC Sepulveda, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 490 EP 491 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078101352 ER PT J AU Liu, CF Sales, AE Sharp, ND Fishman, P Sloan, KL Todd-Stenberg, J Nichol, WP Rosen, AK Loveland, S AF Liu, CF Sales, AE Sharp, ND Fishman, P Sloan, KL Todd-Stenberg, J Nichol, WP Rosen, AK Loveland, S TI Case-mix adjusting performance measures in a veteran population: Pharmacy- and diagnosis-based approaches SO HEALTH SERVICES RESEARCH LA English DT Article DE case-mix adjustment; pharmacy data; profiling ID CHRONIC DISEASE SCORE; RISK ADJUSTMENT; AMBULATORY CARE; MODEL; AFFAIRS; HEALTH; COSTS; RECORDS; SYSTEM; RATES AB Objective. To compare the rankings for health care utilization performance measures at the facility level in a Veterans Health Administration (VHA) health care delivery network using pharmacy- and diagnosis-based case-mix adjustment measures. Data Sources/Study Setting. The study included veterans who used inpatient or outpatient services in Veterans Integrated Service Network (VISN) 26 during fiscal year 1998 (October 1997 to September 1998; N = 126,076). Utilization and pharmacy data were extracted from VHA national databases and the VISN 20 data warehouse. Study Design. We estimated concurrent regression models using pharmacy or diagnosis information in the base year (FY1998) to predict health service utilization in the same year. Utilization measures included bed days of care for inpatient care and provider visits for outpatient care. Principal Findings. Rankings of predicted utilization measures across facilities vary by case-mix adjustment measure. There is greater consistency within the diagnosis-based models than between the diagnosis- and pharmacy-based models. The eight facilities were ranked differently by the diagnosis- and pharmacy-based models. Conclusions. Choice of case-mix adjustment measure affects rankings of facilities on performance measures, raising concerns about the validity of profiling practices. Differences in rankings may reflect differences in comparability of data capture across facilities between pharmacy and diagnosis data sources, and unstable estimates due to small numbers of patients in a facility. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA USA. RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,HSR&D 152, Seattle, WA 98108 USA. OI Sales, Anne/0000-0001-9360-3334 NR 48 TC 21 Z9 21 U1 1 U2 5 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2003 VL 38 IS 5 BP 1319 EP 1337 DI 10.1111/1475-6773.00179 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 734JF UT WOS:000186051500008 PM 14596393 ER PT J AU Luo, B Tang, LP Zhang, JL Ling, YQ Fallon, MB AF Luo, B Tang, LP Zhang, JL Ling, YQ Fallon, MB TI Endothelin-1 in experimental hepatopulmonary syndrome: Evaluation in prehepatic portal hypertension, biliary and nonbiliary cirrhosis. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 90 BP 199A EP 199A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700091 ER PT J AU Smyk-Pearson, S Tester, I Sasaki, AW Rosen, HR AF Smyk-Pearson, S Tester, I Sasaki, AW Rosen, HR TI Comprehensive HCV genome-wide analysis of CD4+ and CD8+ T cells reveals hierarchy of immunodominance. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 383 BP 344A EP 344A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700384 ER PT J AU Tester, IA Pearson, SS Dean, S Rosen, HR AF Tester, IA Pearson, SS Dean, S Rosen, HR TI Acute hepatitis C infection following patellar tendon transplantation: Immunologic correlates of recovery. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 411 BP 358A EP 358A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700412 ER PT J AU Song, DS Ku, D Fallon, MB AF Song, DS Ku, D Fallon, MB TI Enhanced ETB receptor mediated vasodilatation in response to ET-1 in pulmonary artery segments from animals with prehepatic portal hypertension and experimental HPS. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 496 BP 398A EP 399A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700500 ER PT J AU Ling, YQ Zhang, JL Tang, LP Luo, B Fallon, MB AF Ling, YQ Zhang, JL Tang, LP Luo, B Fallon, MB TI Effects of selective endothelin receptor antagonists on the molecular and physiologic alterations in experimental HPS in vivo. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 544 BP 421A EP 421A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700548 ER PT J AU Sugimoto, K Kaplan, DE Ikeda, F Stadanlick, J Suh, G Aytaman, A Lucey, M Ray, S Nunes, F Reddy, KR Chang, KM AF Sugimoto, K Kaplan, DE Ikeda, F Stadanlick, J Suh, G Aytaman, A Lucey, M Ray, S Nunes, F Reddy, KR Chang, KM TI Host-virus interactions in acute hepatitis C. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Brooklyn VA Med Ctr, Brooklyn, NY USA. Univ Wisconsin, Madison, WI 53706 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Penn Hosp, Philadelphia, PA 19107 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 547 BP 422A EP 423A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700551 ER PT J AU Hu, KQ Cheung, RC Currie, S Bini, EJ Shen, H Anand, B Jeffers, LJ Ho, SB Brau, N Schmidt, WN McCracken, J Rossi, SJ Wright, TL AF Hu, KQ Cheung, RC Currie, S Bini, EJ Shen, H Anand, B Jeffers, LJ Ho, SB Brau, N Schmidt, WN McCracken, J Rossi, SJ Wright, TL TI Hepatic steatosis in patients with chronic hepatitis C: A multicenter study of US veterans. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Loma Linda Univ, Med Ctr, Loma Linda, CA 92350 USA. Loma Linda VA Med Ctr, Loma Linda, CA USA. Palo Alto VA Med Ctr, Palo Alto, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. New York Harbor VAMC, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Houston VA Med Ctr, Houston, TX USA. Miami VA Med Ctr, Miami, FL USA. Minneapolis VA Med Ctr, Minneapolis, MN USA. Bronx VAMC, Bronx, NY USA. Iowa VAMC, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 589 BP 445A EP 445A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700593 ER PT J AU Bini, EJ Brau, N Currie, S Shen, H Anand, B Hu, KQ Jeffers, L Ho, SB Johnson, D Schmidt, W King, P Cheung, R Morgan, T Awad, J Pedrosa, M Chang, KM Aytaman, A Simon, F Hagedorn, C Moseley, R Ahmad, J Mendenhall, C Rossi, S Wright, T AF Bini, EJ Brau, N Currie, S Shen, H Anand, B Hu, KQ Jeffers, L Ho, SB Johnson, D Schmidt, W King, P Cheung, R Morgan, T Awad, J Pedrosa, M Chang, KM Aytaman, A Simon, F Hagedorn, C Moseley, R Ahmad, J Mendenhall, C Rossi, S Wright, T TI Epidemiology of hepatitis C infection and eligibility for antiviral therapy among US veterans. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 VA Med Ctr, New York, NY USA. VA Med Ctr, Bronx, NY USA. VA Med Ctr, San Francisco, CA USA. VA Med Ctr, Houston, TX USA. VA Med Ctr, Loma Linda, CA USA. VA Med Ctr, Miami, FL USA. VA Med Ctr, Minneapolis, MN USA. VA Med Ctr, Bay Pines, FL USA. VA Med Ctr, Iowa City, IA USA. VA Med Ctr, Columbia, MO USA. VA Med Ctr, Palo Alto, CA USA. VA Med Ctr, Long Beach, CA USA. VA Med Ctr, Nashville, TN USA. VA Med Ctr, Boston, MA USA. VA Med Ctr, Philadelphia, PA USA. VA Med Ctr, Brooklyn, NY USA. VA Med Ctr, Denver, CO USA. VA Med Ctr, Atlanta, GA USA. VA Med Ctr, Ann Arbor, MI USA. VA Med Ctr, Pittsburgh, PA USA. VA Med Ctr, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 603 BP 452A EP 452A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700607 ER PT J AU Brau, N Bini, EJ Currie, S Shen, H Anand, BS Hu, KQ Ho, SB Johnson, D Schmidt, WN King, PD Cheung, RC Rossi, SJ Jeffers, LJ Wright, TL AF Brau, N Bini, EJ Currie, S Shen, H Anand, BS Hu, KQ Ho, SB Johnson, D Schmidt, WN King, PD Cheung, RC Rossi, SJ Jeffers, LJ Wright, TL TI Treatment of chronic hepatitis C with interferon alfa-2b and ribavirin in the community-based practice. A prospective study of 813 US veterans. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Vet Affairs Med Ctr, Bronx, NY USA. VA Med Ctr, New York, NY USA. VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Med Ctr, Houston, TX USA. VA Med Ctr, Loma Linda, CA USA. VA Med Ctr, Minneapolis, MN USA. VA Med Ctr, Bay Pines, FL USA. VA Med Ctr, Iowa City, IA USA. VA Med Ctr, Columbia, MO USA. VA Med Ctr, Palo Alto, CA USA. VA Med Ctr, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1009 BP 643A EP 643A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701009 ER PT J AU Kanwal, F Dulai, GS Gornbein, J Gralnek, IM AF Kanwal, F Dulai, GS Gornbein, J Gralnek, IM TI Recipient characteristics and post-liver tranplantation (LT) outcomes before and after MELD. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1112 BP 691A EP 691A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701111 ER PT J AU Kramer, JR Giordano, TP Souchek, J Richardson, P El-Serag, H AF Kramer, JR Giordano, TP Souchek, J Richardson, P El-Serag, H TI The effect of HIV co-infection on the risk of cirrhosis and hepatocellular carcinoma in HCV-infected patients. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Houston VA Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1118 BP 694A EP 694A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701117 ER PT J AU Wen, Y Marcus, EA Matrubutham, U Gleeson, MA Scott, DR Sachs, G AF Wen, Y Marcus, EA Matrubutham, U Gleeson, MA Scott, DR Sachs, G TI Acid-adaptive genes of Helicobacter pylori SO INFECTION AND IMMUNITY LA English DT Article ID UREASE APOPROTEIN COMPLEXES; ESCHERICHIA-COLI; GASTRIC-MUCOSA; LOW-PH; INTRACELLULAR PH; IN-VIVO; EXPRESSION; IDENTIFICATION; COLONIZATION; RESISTANCE AB Helicobacter pylori is the only neutralophile that has been able to colonize the human stomach by using a variety of acid-adaptive mechanisms. One of the adaptive mechanisms is increased buffering due to expression of an acid-activated inner membrane urea channel, UreI, and a neutral pH-optimum intrabacterial urease. To delineate other possible adaptive mechanisms, changes in gene expression in response to acid exposure were examined using genomic microarrays of H. pylori exposed to different levels of external pH (7.4, 6.2, 5.5, and 4.5) for 30 min in the absence and presence of 5 mM urea. Gene expression was correlated with intrabacterial pH measured using 2',7'-bis-(2-carboxyethyl)-5-carboxyfluorescein and compared to that observed with exposure to 42degreesC for 30 min. Microarrays containing the 1,534 open reading frames of H. pylori strain 26695 were hybridized with cDNAs from control (pH 7.4; labeled with Cy3) and acidic (labeled with Cy5) conditions. The intrabacterial pH was 8.1 at pH 7.4, fell to 5.3 at pH 4.5, and rose to 6.2 with urea. About 200 genes were up-regulated and similar to100 genes were down-regulated at pH 4.5 in the absence of urea, and about half that number changed in the presence of urea. These genes included pH-homeostatic, transcriptional regulatory, motility, cell envelope, and pathogenicity genes. The up-regulation of some pH-homeostatic genes was confirmed by real-time PCR. There was little overlap with the genes induced by temperature stress. These results suggest that H. pylori has evolved multifaceted acid-adaptive mechanisms enabling it to colonize the stomach that may be novel targets for eliminating infection. C1 Univ Calif Los Angeles, Membrane Biol Lab, Dept Physiol & Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Invitrogen Corp, Carlsbad, CA USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, Membrane Biol Lab, Dept Physiol & Med, 11301 Wilshire Blvd,Bldg 113,Room 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 41301, DK 17294, DK 46917, DK 534652, R01 DK046917] NR 57 TC 120 Z9 126 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2003 VL 71 IS 10 BP 5921 EP 5939 DI 10.1128/IAI.71.10.5921-5939.2003 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 725PH UT WOS:000185551200053 PM 14500513 ER PT J AU Hershman, JM Hassani, S Braunstein, GD Geola, F Brickman, A Seibel, MJ AF Hershman, JM Hassani, S Braunstein, GD Geola, F Brickman, A Seibel, MJ TI Bisphosphonate therapy in primary hyperparathyroidism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Letter ID ORAL ALENDRONATE; OSTEOPOROSIS C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Kaiser Med Ctr, Woodland Hills, CA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Sydney, Sydney, NSW 2006, Australia. RP Hershman, JM (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2003 VL 18 IS 10 BP 1889 EP 1889 DI 10.1359/jbmr.2003.18.10.1889 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 728LJ UT WOS:000185718400021 PM 14584900 ER PT J AU Frame, LH AF Frame, LH TI Responses to pacing depend on electrical and structural properties of the reentrant circuit SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material ID DOUBLE-WAVE REENTRY; VENTRICULAR-TACHYCARDIA; ATRIAL-FLUTTER; TERMINATION; MECHANISMS; ACCELERATION; PROPAGATION; STIMULATION; HEART; CONDUCTION C1 Philadelphia VA Med Ctr, Cardiol Sect 111C, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Cardiol, Philadelphia, PA 19104 USA. RP Frame, LH (reprint author), Philadelphia VA Med Ctr, Cardiol Sect 111C, 3900 Univ Ave, Philadelphia, PA 19104 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2003 VL 14 IS 10 BP 1075 EP 1076 DI 10.1046/k/1540-8167.2003.09999.x PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 741ZC UT WOS:000186489400008 PM 14521660 ER PT J AU Cao, GD Clark, RSB Pei, W Yin, W Zhang, F Sun, FY Graham, SH Chen, J AF Cao, GD Clark, RSB Pei, W Yin, W Zhang, F Sun, FY Graham, SH Chen, J TI Translocation of apoptosis-inducing factor in vulnerable neurons after transient cerebral ischemia and in neuronal cultures after oxygen-glucose deprivation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis-inducing factor; mitochondria; caspases; DNA fragmentation; Bcl; xL ID HIPPOCAMPAL CA1 NEURONS; CYTOCHROME-C RELEASE; CELL-DEATH; DNA FRAGMENTATION; SUPEROXIDE-DISMUTASE; FACTOR AIF; BCL-X; MITOCHONDRIAL RELEASE; GLOBAL-ISCHEMIA; NERVOUS-SYSTEM AB Loss of mitochondrial membrane integrity and the resulting release of apoptogenic factors may play a critical role in mediating hippocampal neurodegeneration after transient global ischemia. In the present study, the authors have cloned and characterized the rat cDNA encoding apoptosis-inducing factor (AIF), an intramitochondrial protein that promotes cell death in a caspase-independent manner upon release into non-mitochondrial compartments. In contrast to the expression patterns of a number of apoptosis-regulatory gene products during brain development, the expression of AIF protein increases gradually with brain maturation and peaks in adulthood. In a rat model of transient global ischemia, AIF was found to translocate from mitochondria to the nucleus in the hippocampal CA I neurons after ischemia and to manifest a DNA-degrading activity that mimicked the purified AIF protein and was inhibitable by AIF immunodepletion. The temporal profile of AIF translocation after ischemia (24 to 72 hours) coincided with the induction of large-scale DNA fragmentation at the size of 50 kbp, a well-characterized hallmark of AIF-like activity but preceded the formation of internucleosomal DNA fragmentation (72 hours), a DNA degradation associated with the terminal stage of cell death. Further, the nuclear translocation of AIF after ischemia was not blocked by inhibiting caspase-3/-7 activities, but, as shown in neuronal cultures that were challenged with transient oxygen-glucose deprivation, it can be prevented by intracellular delivery of the mitochondria-associated antiapoptotic protein Bcl-xL. The results presented here strongly suggest that mitochondrial release of AIF may be an important factor, in addition to the previously reported cytochrome c and Smac, which could contribute to the selective vulnerability of CA1 neurons to transient global ischemic injury. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA 15213 USA. Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [NS45048, NS38560, NS43802] NR 46 TC 125 Z9 133 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2003 VL 23 IS 10 BP 1137 EP 1150 DI 10.1097/01.WCB.0000087090.01171.E7 PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 729DD UT WOS:000185755500004 PM 14526224 ER PT J AU Xu, JM Moatamed, F Caldwell, JS Walker, JR Kraiem, Z Taki, K Brent, GA Hershman, JM AF Xu, JM Moatamed, F Caldwell, JS Walker, JR Kraiem, Z Taki, K Brent, GA Hershman, JM TI Enhanced expression of nicotinamide N-methyltransferase in human papillary thyroid carcinoma cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PARKINSONS-DISEASE; OLIGONUCLEOTIDE ARRAYS; GENE-EXPRESSION; LIVER CYTOSOL; CANCER; ACTIVATION; GROWTH; ESTABLISHMENT; REARRANGEMENT; HYBRIDIZATION AB To gain an understanding of the molecular pathogenesis of thyroid cancer, we used DNA microarray to study the expression profiles of 10 different human thyroid carcinoma cell lines. These included papillary lines BHP 2-7, BHP 7-13, BHP 10-3, BHP 18-21, NPA 87, and TPC1; anaplastic lines ARO 81-1 and DRO 90-1; follicular line WRO 82-1; and medullary line HRO 85-1. Among the genes with increased expression in the cancer cell lines, a gene coding for nicotinamide N-methyltransferase (NNMT) was identified for being highly expressed only in the papillary cell lines. NNMT catalyzes N-methylation of nicotinamide and other structurally related compounds and is highly expressed in the human liver. The results were further confirmed by semiquantitative RT-PCR and Northern blot analysis. NNMT catalytic activities were determined in all of the cells described above and in additional cell lines. Significantly higher NNMT enzyme activities were detected in eight of 10 of the papillary lines and three of six of the follicular cell lines tested. Normal thyroid tissue, thyroid primary cultures, anaplastic cancer cells, and medullary cancer cells showed no or low enzyme activity. Immunohistochemical staining for NNMT of human thyroid specimens showed strong and abundant cytoplasmic reactions in the sections of papillary carcinomas, and weak or scanty reaction in the normal thyroid tissues. These results indicate that NNMT is a potential biomarker for papillary thyroid carcinoma. C1 Univ Calif Los Angeles, Sch Med, Vet Affairs Med Ctr, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Vet Affairs Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. Novartis Genom Res Fdn, San Diego, CA 92121 USA. Carmel Hosp, Endocrine Res Unit, Haifa, Israel. RP Hershman, JM (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Endocrinol Div 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jhershmn@ucla.edu NR 45 TC 53 Z9 55 U1 0 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 OCT 1 PY 2003 VL 88 IS 10 BP 4990 EP 4996 DI 10.1210/jc.2002-021843 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 731VC UT WOS:000185906300070 PM 14557485 ER PT J AU Gopal, DV Corless, CL Rabkin, JM Olyaei, AJ Rosen, HR AF Gopal, DV Corless, CL Rabkin, JM Olyaei, AJ Rosen, HR TI Graft failure from severe recurrent primary sclerosing cholangitis following orthotopic liver transplantation SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE sclerosing cholangitis; recurrence of underlying liver disease; autoimmune; rejection ID BILIARY STRICTURES; COMPLICATIONS; ALLOGRAFTS; RECIPIENTS AB Speculation that primary sclerosing cholangitis (PSC) may recur in the transplanted liver is based on the relative increase in frequency of biliary abnormalities and histologic evidence of periportal fibrosis without other causes. A recent study demonstrated almost 9% of patients undergoing liver transplantation (OLT) for primary sclerosing cholangitis (PSC) develop recurrent sclerosing cholangitis although the patient and graft survival is not different from those in whom recurrence does not develop. Most reports of PSC recurrence post-OLT estimate rates of 1% to 14%, but to date, no center has reported rapidly progressive fibro-obliterative cholangitis leading to graft failure. Case Report: DV was a 39-year-old white man with ulcerative colitis, since age 2 1, who developed jaundice and pruritis in 1992. ERCP and liver biopsy were consistent with PSC, and he developed thrombocytopenia and bleeding esophageal varices. He underwent an uneventful OLT in May 1994 with an ABO-compatible organ and normal ischemic times. There was no evidence of postoperative cytomegalovirus infection, hepatic artery thrombosis, or rejection. In October 1994, mild abnormalities of liver function tests (LFTs) led to liver biopsy that revealed inflammatory infiltrate in triad with spill-over into lobules and mild periportal fibrosis. LFTs normalized without any treatment, but in February 1995 repeat liver biopsy for increased LFTs revealed moderate periportal fibrosis with inflammatory cells in triads and lobules. Viral shell and CMV titers were negative. No evidence of infectious etiology or rejection was noted. The patient was started on ursodeoxycholic acid at that time and percutaneous transhepatic cholangiogram (PTC) revealed marked narrowing of the intrahepatic ducts. Esophagogastroduodenoseopy (EGD) revealed esophageal varices. Hepatic arteriogram and Doppler ultrasound were negative. He developed progressive graft failure, and died at home while awaiting re-transplant. Conclusions: Although most series report mild recurrence of PSC following OLT, this case illustrates that early, severe recurrence of PSC may occur, leading to graft failure and need for re-transplantation. C1 Portland Vet Affairs Med Ctr, US Vet Hosp, Div Gastroenterol Hepatol, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Div Clin Pharmacol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Surg & Liver Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. Univ Wisconsin Hosp & Clin, Sect Gastroenterol & Hepatol, Madison, WI 53792 USA. RP Rosen, HR (reprint author), Portland Vet Affairs Med Ctr, US Vet Hosp, Div Gastroenterol Hepatol, 3710 SW,P3-G1, Portland, OR 97207 USA. NR 14 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD OCT PY 2003 VL 37 IS 4 BP 344 EP 347 DI 10.1097/00004836-200310000-00015 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 723YD UT WOS:000185458400015 PM 14506394 ER PT J AU Guo, SS Wu, X Shimoide, AT Wong, J Moatamed, F Sawicki, MP AF Guo, SS Wu, X Shimoide, AT Wong, J Moatamed, F Sawicki, MP TI Frequent overexpression of cyclin D1 in sporadic pancreatic endocrine tumours SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; SUPPRESSOR GENE; NEUROENDOCRINE TUMORS; PREDICTS PROGNOSIS; BREAST-CANCER; EXPRESSION; GASTRINOMAS; CARCINOMA; DELETION; KINASE AB Pancreatic endocrine tumours (PETS) occur sporadically or are inherited as part of the multiple endocrine neoplasia type-1 syndrome. Little is known about the molecular events leading to these tumours. Cyclin D1, a key regulator of the G1/S transition of the cell cycle, is overexpressed in a variety of human cancers as well as certain endocrine tumours. We hypothesized that similar to other endocrine tumours, cyclin D1 is overexpressed in human sporadic PETS. Cyclin D l protein overexpression was found in 20 of 31 PETS (65%) when compared with normal pancreatic tissue. Furthermore, Northern blot analysis suggests that cyclin D1 up-regulation occurs at the post-transcriptional level in some PETS. Because the key cell growth signalling pathways p42/p44/ERK (extracellular signal-regulated kinase), p38/MAPK (mitogen-activated protein kinase), and Akt/PKB (protein kinase B) can regulate cyclin D1 protein expression in other cell types, pancreatic endocrine tumours were analysed with phospho-specific antibodies against the active forms of these proteins to elucidate a tissue-specific regulatory mechanism of cyclin D1 in PETS. We found frequent activation of the p38/MAPK and Akt pathways, but down-regulation of the ERK pathway, in cyclin D1 overexpressing PETS. This study demonstrates that cyclin D1 overexpression is associated with human sporadic PET tumorigenesis, and suggests that this up-regulation may occur at the post-transcriptional level. These findings will direct future studies of PETS towards cell cycle dysregulation and the identification of key growth factor pathways involved in the formation of these tumours. C1 Univ Calif Los Angeles, Sch Med, Div Gen Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Pathol, Los Angeles, CA 90073 USA. RP Sawicki, MP (reprint author), Univ Calif Los Angeles, Sch Med, Div Gen Surg, Room 72-215,CHS10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 36 TC 34 Z9 35 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2003 VL 179 IS 1 BP 73 EP 79 DI 10.1677/joe.0.1790073 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 737JH UT WOS:000186226300008 PM 14529567 ER PT J AU Switzer, GE Halm, EA Chang, CCH Mittman, BS Walsh, MB Fine, MJ AF Switzer, GE Halm, EA Chang, CCH Mittman, BS Walsh, MB Fine, MJ TI Physician awareness and self-reported use of local and national guidelines for community-acquired pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE community-acquired pneumonia; medical practice guidelines ID CLINICAL-PRACTICE GUIDELINES; ANTIMICROBIAL THERAPY; MEDICAL OUTCOMES; HOSPITAL STAY; MANAGEMENT; ADULTS; CARE; IMPROVEMENT; DIAGNOSIS; ATTITUDES AB OBJECTIVES: To assess physician awareness and reported use of medical guidelines for community-acquired pneumonia (CAP), and to identify factors associated with variations in awareness and use of these guidelines. DESIGN: A questionnaire was administered during the preintervention phase of a randomized clinical trial of a pneumonia guideline implementation strategy. PARTICIPANTS: Three hundred and fifty-two physicians who managed CAP patients at 7 Pittsburgh, PA hospitals completed the questionnaire. Physician and practice setting characteristics, and physician awareness and reported use of national American Thoracic Society (ATS) and local (hospital-developed) guidelines for CAP were assessed. RESULTS: Overall, 48% reported being influenced by ATS guidelines and 20% reported using these guidelines; 48% were uncertain whether a local pneumonia guideline existed. Only 28% of physicians who knew a local guideline existed reported frequently using the guideline. Use of national ATS guidelines was independently associated with practice as an infectious disease or pulmonary medicine specialist, nonpatient care-related professional activities, and intellect personality score. Use of local guidelines was independently negatively associated with practice as an infectious disease or pulmonary medicine specialist, and positively associated with positive attitudes toward practice guidelines. CONCLUSIONS: Results indicate low levels of awareness and use of guidelines for the management of CAP. Key indicators (e.g., medical specialty, fewer clinical duties, and positive attitudes about guidelines) were associated with greater use of national and local guidelines. If replicated with data on actual physician management practices, more effective guideline implementation strategies will be necessary to encourage compliance with practice guidelines for the management of CAP. C1 Univ Pittsburgh, Med Ctr, Div Gen Internal Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. CUNY Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. CA RAND, Santa Monica, CA USA. RP Switzer, GE (reprint author), Univ Pittsburgh, Med Ctr, Div Gen Internal Med, Iroquois Bldg 502,3600 Forbes Ave, Pittsburgh, PA 15213 USA. FU AHRQ HHS [R01HS08282] NR 28 TC 31 Z9 32 U1 1 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2003 VL 18 IS 10 BP 816 EP 823 DI 10.1046/j.1525-1497.2003.20535.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 730HF UT WOS:000185823300007 PM 14521644 ER PT J AU Pabich, WL Fihn, SD Stamm, WE Scholes, D Boyko, EJ Gupta, K AF Pabich, WL Fihn, SD Stamm, WE Scholes, D Boyko, EJ Gupta, K TI Prevalence and determinants of vaginal flora alterations in postmenopausal women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID URINARY-TRACT INFECTIONS; BACTERIAL VAGINOSIS; RISK-FACTORS; H2O2-PRODUCING LACTOBACILLI; COLONIZATION; MICROFLORA; THERAPY AB The vaginal ecology of 463 community-dwelling postmenopausal women was characterized. Vaginal lactobacilli were present in 62% of the women and were significantly more prevalent among women receiving hormone replacement therapy during the previous year. Vaginal Escherichia coli and enterococci were each present in 39% of women and were significantly more frequent in women with a history of urinary tract infection. Heavy growth of lactobacilli was associated with a lower frequency of vaginal colonization with E. coli. Thus, postmenopausal women have a relative depletion of vaginal lactobacilli and an increase in vaginal E. coli compared with premenopausal women. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. VA Puget Sound, Epidemiol Res & Informat Ctr, Seattle, WA USA. VA Puget Sound, NW Hlth Serv, Res & Dev Program, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. RP Gupta, K (reprint author), 1959 NE Pacific St,BB1221,Box 356523, Seattle, WA 98195 USA. OI Boyko, Edward/0000-0002-3695-192X FU NIDDK NIH HHS [K23-DK-02660, P01-DK-53369, R01-DK-43134] NR 22 TC 47 Z9 56 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2003 VL 188 IS 7 BP 1054 EP 1058 DI 10.1086/378203 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726HV UT WOS:000185593900017 PM 14513427 ER PT J AU Chauhan, NB Siegel, GJ AF Chauhan, NB Siegel, GJ TI Intracerebroventricular passive immunization with anti-A beta antibody in Tg2576 SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Alzheimer's disease; immunotherapy; intracerebroventricular passive immunization; cerebral hemorrhage; inflammation ID AMYLOID PRECURSOR PROTEIN; ENDOSCOPIC 3RD VENTRICULOSTOMY; ALZHEIMERS-DISEASE MODEL; CENTRAL-NERVOUS-SYSTEM; TRANSGENIC MICE; MOUSE MODEL; CEREBRAL-HEMORRHAGE; PEPTIDE; VACCINATION; PATHOLOGY AB Current Alzheimer's disease (AD) research has established the fact that excessive genesis of Abeta derived from amyloidogenic processing of beta-amyloid (Abeta) precursor protein is fundamental to AD pathogenesis. There has been considerable interest in using immunization strategies for clearing excessive Abeta. Studies in animal models of AD have shown that active immunizations or systemic passive immunizations reduced cerebral plaque load and improved behavioral deficits. However, clinical translation of an active immunization strategy was interrupted because of evidence for meningoencephalitis produced in some patients who received Abeta vaccine. Studies in animal models have shown perimicrovascular hemorrhages and inflammation after sustained systemic immunizations in animals with vascular amyloid. In this light, our data showing the effects of a single intracerebroventricular (ICV) injection of anti-Abeta in the Alzheimer's Swedish mutant model Tg2576 are intriguing. We have previously demonstrated that a single ICV injection of anti-Abeta into the third ventricle of 10-month-old Tg2576 mice reduced cerebral plaques, reversed Abeta-induced depletion of presynaptic SNAP-25, and abolished astroglial activation as seen 1 month post-injection (Chauhan and Siegel [2002] J. Neurosci. Res. 69:10-23). The present report demonstrates that a single ICV injection of 10 mug anti-Abeta in 10-month-old Tg2576 mice reduced cerebral plaques, with decreased inflammation at this stage as evidenced by a reduced number of interleukin-1beta-positive microglia surrounding Congophilic plaques. Moreover, at this particular age, no microhemorrhage was discernible, as evidenced by the absence of hemosiderin deposition after a single ICV injection of anti-Abeta. This is the first report demonstrating absence of microhemorrhage and reduced inflammation after the ICV introduction of anti-Abeta in Tg2576 mice at 10 months of age. These facts indicate that, although invasive, ICV injection of anti-Abeta may be a safer method of vaccination in AD, possibly through reducing the vascular exposure to antibody. Further studies are warranted to determine the lasting effects of a single ICV anti-Abeta injection in animals with and without abundant plaque burden and at older ages. (C) 2003 Wiley-Liss, Inc. C1 W Side VA Med Ctr, Res & Dev 151, Chicago, IL 60612 USA. Univ Illinois, Dept Neuroanesthesiol, Chicago, IL USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. RP Chauhan, NB (reprint author), W Side VA Med Ctr, Res & Dev 151, 820 S Damen Ave, Chicago, IL 60612 USA. NR 39 TC 36 Z9 41 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 1 PY 2003 VL 74 IS 1 BP 142 EP 147 DI 10.1002/jnr.10721 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 725BA UT WOS:000185521700016 PM 13130516 ER PT J AU Wallis, RA Panizzon, KL AF Wallis, RA Panizzon, KL TI Treatment with BCl-2(20-34) protects against sustained injury susceptibility of CA1 and CA3 hippocampal neurons following controlled cortical impact SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 VA Greater Los Angeles Healthcare, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P117 BP 1057 EP 1057 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300030 ER PT J AU Long, Y Yuan, XQ Lu, H Yang, K AF Long, Y Yuan, XQ Lu, H Yang, K TI Effects of NGF gene transfer on profiles of gene expression in mouse hippocampus after traumatic brain injury. SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. VA Med Ctr, PADRECC, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P220 BP 1082 EP 1082 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300133 ER PT J AU Panizzon, KL Frautschy, SA Wallis, RA AF Panizzon, KL Frautschy, SA Wallis, RA TI Treatment with Bcl-2(20-34) preserves LTP and provides protection against loss of working memory following controlled cortical impact. SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare, Los Angeles, CA USA. RI yu, yan/C-2322-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P309 BP 1105 EP 1105 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300221 ER PT J AU Bennett, LAT Johnson, JM Stephens, DP Saad, AR Kellogg, DL AF Bennett, LAT Johnson, JM Stephens, DP Saad, AR Kellogg, DL TI Evidence for a role for vasoactive intestinal peptide in active vasodilatation in the cutaneous vasculature of humans SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID GLAND BLOOD-FLOW; LASER-DOPPLER FLOWMETRY; SWEAT GLANDS; COMPLEMENTARY ROLE; POLYPEPTIDE VIP; NITRIC-OXIDE; CYSTIC-FIBROSIS; SMOOTH-MUSCLE; HEAT-STRESS; HUMAN-SKIN AB Active vasodilatation (AVD) in human, non-glabrous skin depends on functional cholinergic fibres but not on acetylcholine (ACh). We tested whether AVD is a redundant system in which ACh and vasoactive intestinal polypeptide (VIP) are co-released from cholinergic nerves. (1) We administered VIP by intradermal microdialysis to four discrete areas of skin in the presence of different levels of the VIP receptor antagonist, VIP(10-28), also delivered by microdialysis. Skin blood flow (SkBF) was continuously monitored by laser Doppler flowmetry (LDF). Mean arterial pressure (MAP) was measured non-invasively and cutaneous vascular conductance (CVC) calculated as LDF/MAP. Subjects were supine and wore water-perfused suits to control whole-body skin temperature (T-sk) at 34degreesC. Concentrations of 54 mum, 107 mum, or 214 mum VIP(10-28) were perfused via intradermal. microdialysis at 2 mul min(-1) for approximately I h. Then 7.5 mum VIP was added to the perfusate containing VIP (10-28) at the three concentrations or Ringer solution and perfusion was continued for 45-60 min. At the control site, this level of VIP caused approximately the vasodilatation typical of heat stress. All VIP(10-28)-treated sites displayed an attenuated dilatation in response to the VIP. The greatest attenuation was observed at the site that received 214 mum VIP(10-28) (P < 0.01). (2) We used 214 mum VIP(10-28) alone and with the iontophoretically administered muscarinic receptor antagonist atropine (400 muA cm(-2), 45s, 10 mm) in heated subjects to test the roles of VIP and ACh in AVD. Ringer solution and 214 mum VIP(10-28) were each perfused at two sites, one of which in each case was pretreated with atropine. After I h of VIP(10-28) treatment, individuals underwent 45-60 min of whole-body heating (T-sk to 38.5degreesC). VIP(10-28), alone or in combination with atropine, attenuated the increase in CVC during heat stress, suggesting an important role for VIP in AVD. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78284 USA. RP Johnson, JM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL 59166, HL 65599, R01 HL059166, R01 HL065599] NR 47 TC 70 Z9 73 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 1 PY 2003 VL 552 IS 1 BP 223 EP 232 DI 10.1113/jphysiol.2003.042135 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 735EA UT WOS:000186098400018 PM 12847205 ER PT J AU Brodsky, MB McNeil, MR Doyle, PJ Fossett, TRD Timm, NH Park, GH AF Brodsky, MB McNeil, MR Doyle, PJ Fossett, TRD Timm, NH Park, GH TI Auditory serial position effects in story retelling for non-brain-injured participants and persons with aphasia SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE serial position effect; memory; aphasia; story retelling; discourse ID HEARING HANDICAP INVENTORY; SHORT-TERM-MEMORY; ELDERLY SUBJECTS; FREE-RECALL; INFORMATION; RELIABILITY; EXPLICIT; ADULTS; WORDS; SPAN AB Using story retelling as an index of language ability, it is difficult to disambiguate comprehension and memory deficits. Collecting data on the serial position effect (SPE), however, illuminates the memory component. This study examined the SPE of the percentage of information units (%IU) produced in the connected speech samples of adults with aphasia and age-matched, non-brain-injured (NBI) participants. The NBI participants produced significantly more direct and alternate IUs than participants with aphasia. Significant age and gender differences were found in subsamples of the NBI controls, with younger and female participants generating significantly more direct lUs than male and older NBI participants. Alternate IU productions did not generate an SPE from any group. There was a significant linear increase from the initial (primacy) to the final (recency) portion of the recalled alternate lUs for both the NBI group and the group of participants with aphasia. Results provide evidence that individuals with aphasia recall discourse length information using similar memory functions as the nonimpaired population, though at a reduced level of efficiency or quantity. A quadratic model is suggested for the recall of information directly recalled from discourse-length language material. C1 Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15260 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RP McNeil, MR (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. NR 49 TC 4 Z9 4 U1 1 U2 2 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT PY 2003 VL 46 IS 5 BP 1124 EP 1137 DI 10.1044/1092-4388(2003/088) PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 728HD UT WOS:000185711000008 PM 14575347 ER PT J AU Dorafshar, AH Angle, N Bryer-Ash, M Huang, DS Farooq, MM Gelabert, HA Freischlag, JA AF Dorafshar, AH Angle, N Bryer-Ash, M Huang, DS Farooq, MM Gelabert, HA Freischlag, JA TI Vascular endothelial growth factor inhibits mitogen-induced vascular smooth muscle cell proliferation SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-for-Academic-Surgery CY NOV 07-09, 2002 CL BOSTON, MASSACHUSETTS SP Assoc Acad Surg DE vascular endothelial growth factor; human aortic smooth muscle; neointimal hyperplasia ID FACTOR-LIKE PROTEIN; FACTOR-B-CHAIN; ARTERIAL INJURY; GENE-TRANSFER; IN-VITRO; THERAPEUTIC ANGIOGENESIS; BALLOON ANGIOPLASTY; INTIMAL HYPERPLASIA; EXPRESSION; RECEPTOR AB Introduction. Delivery of vascular endothelial growth factor (VEGF) protein or gene transfer has been shown to accelerate re-endothelialization and attenuate neointimal hyperplasia in various arterial injury models, including balloon injury, stent implantation, and vein grafts. In addition to stimulating re-endothelialization, we hypothesize that VEGF has further vascular protective functions to prevent neointimal hyperplasia by directly inhibiting mitogen-induced proliferation of vascular smooth muscle cells (VSMCs) via the mitogen-activated protein kinase pathway. Materials and methods. Human aortic VSMCs were seeded and serum starved for 24 h. The cells were then stimulated with a mitogen, recombinant human platelet derived growth factor at 20 ng/mL together with 0, 10, 20, 30, 40, 50 ng/mL recombinant human VEGF. A proliferation assay was used to quantitate bromodeoxyuridine uptake into newly synthesized DNA. Western immunoassay was used to quantify extracellular signal-regulated kinase (ERK) 2 protein and phosphorylation of retinoblastoma and ERK 1/2 protein. Results. VEGF inhibited bromodeoxyuridine incorporation into mitogen-induced VSMC in a dose-dependent manner, reaching statistical significance at concentrations of 30 (P < 0.05), 40 (P < 0.05), and 50 ng/mL (P < 0.01). Densitometry of western immunoblots revealed an inhibition of phosphorylation of retinoblastoma at VEGF concentrations of 40 and 50 ng/mL and ERK 1/2 phosphorylation at concentrations of 30, 40 and 50 ng/mL. Conclusion. In addition to stimulating re-endothelialization, VEGF appears to have a vascular protective function by directly inhibiting VSMC proliferation. This effect occurs in the absence of endothelial cells and via the mitogen-activated protein kinase pathway. VEGF may serve as an important modulator of mitogen-induced VSMC proliferation after vascular injury. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, UCLA Gonda Goldschmied Diabet Ctr, Div Vasc Surg, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, UCLA Gonda Goldschmied Diabet Ctr, Div Endocrinol Diabet & Hypertens, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. RP Angle, N (reprint author), Univ Calif San Diego, Vasc Surg Sect, 200 W Arbor Dr, San Diego, CA 92103 USA. NR 41 TC 23 Z9 28 U1 1 U2 4 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 OCT PY 2003 VL 114 IS 2 BP 179 EP 186 DI 10.1016/S0022-4804(03)00254-3 PG 8 WC Surgery SC Surgery GA 730LF UT WOS:000185831700012 PM 14559444 ER PT J AU Konrad-Martin, D Keefe, DH AF Konrad-Martin, D Keefe, DH TI Time-frequency analyses of transient-evoked stimulus-frequency and distortion-product otoacoustic emissions: Testing cochlear model predictions SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article; Proceedings Paper CT 143rd Annual Meeting of the Acoustical-Society-of-America CY JUN 03-07, 2002 CL PITTSBURGH, PA SP Acoust Soc Amer ID FINE-STRUCTURE; NORMAL EARS; SUPPRESSION; MECHANISMS; 2F(1)-F(2); LATENCY; DISTRIBUTIONS; REFLECTANCE; GENERATION; RESPONSES AB Time-frequency representations (TFRs) of otoacoustic emissions (OAEs) provide information simultaneously in time and frequency that may be obscured in waveform or spectral analyses. TFRs were applied to transient-evoked stimulus-frequency (SF) and distortion-product (DP) OAEs to test cochlear model predictions. SFOAEs and DPOAEs were elicited in 18 normal-hearing subjects using gated tones and tone pips. Synchronous spontaneous (SS) OAEs were measured to assess their contributions to SFOAEs and DPOAEs. A common form of TFR of measured OAEs was a collection of frequency-specific components often aligned with SSOAE sites, with each component characterized by one or more brief segments or a single long-duration segment. The spectral envelope of evoked OAEs differed from that of the evoking stimulus. Strong emission regions or cochlear "hot spots" were detected, and sometimes accounted for OAE energy observed outside the stimulus bandwidth. Contributions of hot spots and multiple internal reflections to the OAE, and differences between measured and predicted OAE spectra, increased as stimulus level decreased, consistent with level-dependent changes in the estimated cochlear reflectance. Suppression and frequency-pulling effects between components were observed. A recursive formulation was described for the linear coherent reflection emission theory [Zweig and Shera, J. Acoust. Soc. Am. 98, 2018-2047 (1995)] that is well suited for time-domain calculations. (C) 2003 Acoustical Society of America. C1 Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Autitory Res, Portland, OR 97239 USA. Rush Univ, Chicago, IL 60612 USA. Boys Town Natl Res Hosp, Omaha, NE 68131 USA. RP Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Autitory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM dawn.martin@med.va.gov FU NIDCD NIH HHS [T32 DC00013, R01 DC003784, R01 DC003784-07] NR 57 TC 24 Z9 24 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2003 VL 114 IS 4 BP 2021 EP 2043 DI 10.1121/1.1596170 PN 1 PG 23 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 733GU UT WOS:000185992200029 PM 14587602 ER PT J AU Rumsfeld, JS AF Rumsfeld, JS TI Valve surgery in the elderly - A question of quality (of life)? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID BYPASS GRAFT-SURGERY; OF-LIFE; YOUNGER PATIENTS; REPLACEMENT; MORTALITY; OCTOGENARIANS; PREDICTOR; DISEASE; OLDER; AGE C1 Univ Colorado, Ctr Hlth Sci, Vet Affairs Med Ctr, Denver, CO USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, 1055 Clemont St, Denver, CO 80220 USA. NR 25 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 1 PY 2003 VL 42 IS 7 BP 1215 EP 1217 DI 10.1016/S0735-1097(03)00950-1 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 726QU UT WOS:000185611200012 PM 14522483 ER PT J AU Friedlander, AH Freymiller, EG AF Friedlander, AH Freymiller, EG TI Detection of radiation-accelerated atherosclerosis of the carotid artery by panoramic radiography - A new opportunity for dentists SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID EXTERNAL CERVICAL IRRADIATION; INTIMA-MEDIA THICKNESS; NASOPHARYNGEAL CARCINOMA; NECK IRRADIATION; RISK FACTOR; STENOSIS; DISEASE; RADIOTHERAPY; HEAD; THERAPY AB Background. The authors review the pathophysiology, epidemiology, course of disease, dental findings and dental treatment of patients who developed atherosclerosis of the carotid artery after having received therapeutic radiation to the neck for squamous-cell carcinoma of the oral cavity, pharynx or larynx; salivary gland tumors; and lymphomas involving the cervical lymph nodes. Type of Studies Reviewed. The authors conducted a MEDLINE search for 1997 through 2002 using the key terms "radiation therapy," "carotid artery" atherosclerosis," "cancer" and "dentistry." The articles selected for further review included those published in English in peer-reviewed journals, with preference given to articles reporting randomized, controlled trials. Results. Recent advances in the delivery of radiation therapy to malignancies of the head and neck have resulted in the prolonged survival of increasing numbers of patients. However, the therapy has been implicated as causing atherosclerotic lesions in the cervical component of the carotid artery, which predisposes patients to an increased risk of developing stroke. Panoramic radiography can identify some of these lesions before they can cause a stroke. Radiation-induced atherosclerosis is Common, with approximately 40 percent of patients developing hemodynamically significant carotid artery plaques within 10 years of having received irradiation. Clinical Implications. Dentists treating patients who have received therapeutic radiation to the neck should examine the patients' panoramic radiographs for evidence of atheromalike calcifications, which appear 1.5 to 2.5 centimeters posterior and inferior to the angle of the mandible. Patients with evidence of such lesions should be referred to their physician for an ultrasound examination of their carotid arteries. C1 VA Greater Los Angeles Healthcare Syst, 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. Univ Calif Los Angeles, Med Ctr, Dent Serv, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 51 TC 18 Z9 21 U1 1 U2 1 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 OCT PY 2003 VL 134 IS 10 BP 1361 EP 1365 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 732ZJ UT WOS:000185975200023 PM 14620017 ER PT J AU Karlawish, JHT Casarett, DJ James, BD Tenhave, T Clark, CM Asch, DA AF Karlawish, JHT Casarett, DJ James, BD Tenhave, T Clark, CM Asch, DA TI Why would caregivers not want to treat their relative's Alzheimer's disease? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; treatment; decision-making ID DEMENTIA; CARE; SEVERITY; PREFERENCES; DEPRESSION; PATIENT; BURDEN; SCALE; ONSET AB OBJECTIVES: To determine family caregivers' willingness to use Alzheimer's disease (AD)-slowing medicines and to examine the relationships between this willingness, dementia severity, and caregiver characteristics. DESIGN: Cross-sectional survey. SETTING: In-home interviews of patients from the Memory Disorders Clinic of the University of Pennsylvania's Alzheimer's Disease Center. PARTICIPANTS: One hundred two caregivers of patients with mild to severe AD who were registered at an Alzheimer's disease center. MEASUREMENTS: Subjects participated in an in-home interview to assess their willingness to use a risk-free AD-slowing medicine and a medicine with 3% annual risk of gastrointestinal bleeding. RESULTS: Half of the patients had severe dementia (n = 52). Seventeen (17%) of the caregivers did not want their relative to take a risk-free medicine that could slow AD. Half (n = 52) did not want their relative to take an AD-slowing medicine that had a 3% annual risk of gastrointestinal bleeding. Caregivers who were more likely to forgo risk- free treatment of AD were older (odds ratio (OR) = 1.7, P = .04), were depressed (OR = 3.66, P = .03), had relatives living in a nursing home (OR = 3.6, P = .02), had relatives with more-severe dementia according to the Mini-Mental State Examination (MMSE) (OR = 2.29, P = .03) or Dementia Severity Rating Scale (DSRS) (OR = 2.55, P = .002), and rated their relatives' quality of life (QOL) poorly on a single-item global rating (OR = 0.25, P = .001) and the 13-item quality-of-life (QOL)-AD scale (OR = 0.38, P = .002). Caregivers who were more likely to forgo a risky treatment were nonwhite (OR = 6.53, P = .005), had financial burden (OR = 2.93, P = .02), and rated their relative's QOL poorly on a single-item global rating (OR = 0.61, P = .01) and the QOL-AD (OR = 0.56, P = .01). CONCLUSION: These results suggest that caregivers are generally willing to slow the progression of their relative's dementia even into the severe stage of the disease, especially if it can be done without risk to the patient. Clinical trials and practice guidelines should recognize that a caregiver's assessment of patient QOL and the factors that influence it affect a caregiver's willingness to use AD-slowing treatments. C1 Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Alzheimers Dis Ctr, Philadelphia, PA USA. RP Karlawish, JHT (reprint author), Univ Penn, Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. FU NIA NIH HHS [K01 AG-00931, P30-AG01024] NR 25 TC 20 Z9 20 U1 3 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2003 VL 51 IS 10 BP 1391 EP 1397 DI 10.1046/j.1532-5415.2003.51456.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 725GR UT WOS:000185535900007 PM 14511158 ER PT J AU Simmons, SF Garcia, ET Cadogan, MP Al-Samarrai, NR Levy-Storms, LF Osterweil, D Schnelle, JF AF Simmons, SF Garcia, ET Cadogan, MP Al-Samarrai, NR Levy-Storms, LF Osterweil, D Schnelle, JF TI The Minimum Data Set weight-loss quality indicator: Does it reflect differences in care processes related to weight loss? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Minimum Data Set; quality indicator; weight loss; nursing homes; nutrition ID NURSING-HOME RESIDENTS; FEEDING ASSISTANCE; VULNERABLE ELDERS; FOOD-INTAKE; STAFF AB OBJECTIVES: To determine whether nursing homes (NHs) that score differently on prevalence of weight loss, according to a Minimum Data Set (MDS) quality indicator, also provide different processes of care related to weight loss. DESIGN: Cross-sectional. SETTING: Sixteen skilled nursing facilities: 11 NHs in the lower (25th percentile-low prevalence) quartile and five NHs in the upper (75th percentile-high prevalence) quartile on the MDS weight-loss quality indicator. PARTICIPANTS: Four hundred long-term residents. MEASUREMENTS: Sixteen care processes related to weight loss were defined and operationalized into clinical indicators. Trained research staff conducted measurement of NH staff implementation of each care process during assessments on three consecutive 12-hour days (7 a.m. to 7 p.m.), which included direct observations during meals, resident interviews, and medical record abstraction using standardized protocols. RESULTS: The prevalence of weight loss was significantly higher in the participants in the upper quartile NHs than in participants in the lower quartile NHs based on MDS and monthly weight data documented in the medical record. NHs with a higher prevalence of weight loss had a significantly larger proportion of residents with risk factors for weight loss, namely low oral food and fluid intake. There were few significant differences on care process measures between low- and high-weight-loss NHs. Staff in low-weight-loss NHs consistently provided verbal prompting and social interaction during meals to a greater proportion of residents, including those most at risk for weight loss. CONCLUSION: The MDS weight-loss quality indicator reflects differences in the prevalence of weight loss between NHs. NHs with a lower prevalence of weight loss have fewer residents at risk for weight loss and staff who provide verbal prompting and social interaction to more residents during meals, but the adequacy and quality of feeding assistance care needs improvement in all NHs. C1 Univ Calif Los Angeles, Sch Med, Dept Geriatr, Borun Ctr Gerontol Res, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. Univ Calif Los Angeles, Borun Ctr Gerontol Res, Jewish Home Aging, Reseda, CA 91335 USA. RP Simmons, SF (reprint author), Univ Calif Los Angeles, Borun Ctr Gerontol Res, Jewish Home Aging, 7150 Tampa Ave, Reseda, CA 91335 USA. FU NIA NIH HHS [AG10415] NR 30 TC 45 Z9 46 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2003 VL 51 IS 10 BP 1410 EP 1418 DI 10.1046/j.1532-5415.2003.51459.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 725GR UT WOS:000185535900010 PM 14511161 ER PT J AU Seliger, SL Gillen, DL Tirschwell, D Wasse, H Kestenbaum, BR Stehman-Breen, CO AF Seliger, SL Gillen, DL Tirschwell, D Wasse, H Kestenbaum, BR Stehman-Breen, CO TI Risk factors for incident stroke among patients with end-stage renal disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID BLACK-WHITE DIFFERENCES; C-REACTIVE PROTEIN; NUTRITION EXAMINATION SURVEY; CORONARY HEART-DISEASE; HEMODIALYSIS-PATIENTS; BLOOD-PRESSURE; DIALYSIS PATIENTS; CEREBRAL INFARCTION; MAINTENANCE HEMODIALYSIS; ATHEROSCLEROSIS RISK AB Although patients with ESRD experience markedly higher rates of stroke, no studies in the US have identified risk factors associated with stroke in this population. It was hypothesized that black race, malnutrition, and elevated BP would be associated with the risk of stroke among patients with ESRD. Data from the United States Renal Data Systems were used. Adult Medicare-insured hemodialysis and peritoneal dialysis patients without a history of stroke or transient ischemic attack (TIA) were considered for analysis. The primary outcome was hospitalized or fatal stroke. Cox proportional hazards models were used to determine the associations between the primary predictor variables and stroke. The rate of incident stroke was 33/1,000 person-years in the study sample. After adjustment for age and other patient characteristics, three markers of malnutrition were associated with the risk of stroke-serum albumin (per I g/dl decrease, hazard ratio [HR] = 1.43), height-adjusted body weight (per 25% decrease, HR = 1.09), and a subjective assessment of undernourishment (HR = 1.27)-as was higher mean BP (per 10 mmHg, HR = 1.11). The association between black race varied by cardiac disease status, with blacks estimated to be at lower risk than whites among individuals with cardiac disease (HR = 0.74), but at higher risk among individuals without cardiac disease (HR 1.24). This study confirms the extraordinarily high rates of stroke in ESRD patients on dialysis and identifies high mean BP and malnutrition as potentially modifiable risk factors. The association between black race and stroke differs by cardiac disease status; the reasons for this differing effect of race deserve further investigation. C1 Univ Washington, Div Nephrol, Seattle, WA 98102 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98195 USA. RP Seliger, SL (reprint author), Univ Washington, Div Nephrol, Box 356521, Seattle, WA 98102 USA. RI Wasse, Haimanot/A-5726-2013 OI Wasse, Haimanot/0000-0001-5756-0242 FU NIDDK NIH HHS [DK63079-01, DK07721-6] NR 49 TC 94 Z9 100 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2003 VL 14 IS 10 BP 2623 EP 2631 DI 10.1097/01.ASN.0000088722.56342.A8 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 725JR UT WOS:000185540800025 PM 14514741 ER PT J AU Padow, M Lai, LL Deivanayagam, C DeLucas, LJ Weiss, RB Dunn, DM Wu, XY Kappes, JC AF Padow, M Lai, LL Deivanayagam, C DeLucas, LJ Weiss, RB Dunn, DM Wu, XY Kappes, JC TI Replication of chimeric human immunodeficiency virus type 1 (HIV-1) containing HIV-2 integrase (IN): Naturally selected mutations in IN augment DNA synthesis SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; REVERSE-TRANSCRIPTASE; CARBOXYL-TERMINUS; GENETIC-ANALYSIS; TY3 INTEGRASE; POL GENE; PROTEIN; INFECTION; MUTANTS; FUSION AB The human immunodeficiency virus type 1 (HIV-1) integrase (IN) protein augments the initiation of reverse transcription. Chimeric HIV-1 containing HIV-2 IN (SG3(IN2)) is severely impaired in virus infectivity and DNA synthesis. To analyze the nature of this defect, we infected T cells with the chimeric SG3(IN2) virus and by continuous passage in cell culture selected for virus with improved replication properties. Viruses from two different time points were chosen for further analysis, an early culture-adapted virus (CF-65) that exhibited an intermediate level of infectivity, and a later-passaged virus (CF-131) that was significantly more infectious. Sequence analysis of multiple clones derived from the CF-65 virus culture demonstrated a diversity of mutations in the reverse transcriptase (RT) and a common V204I IN mutation. Analysis of clones derived from the CF-131 virus indicated the selection of two additional IN mutations, Q96H and K127E, and a fixed V179I RT mutation. By cloning RT and/or IN sequences back into the original SG3IN2 chimeric virus, we demonstrated that mutations in both RT and IN contributed to the improvement in viral fitness. The effect of the HIV-2IN(IN2) mutations on virus DNA synthesis was analyzed by packaging IN2 mutants into HIV-1 as Vpr-IN2 fusion proteins. This analysis revealed that the Q96H, K127E and V204I mutations increased the infectivity of the chimeric virus by augmenting the initiation of viral cDNA synthesis in infected cells. The Q96H and K127E mutations are present in adjacent helical structures on the surface of the IN protein and together account for most of the increase observed in DNA synthesis. Our findings provide evidence that the IN protein augments the initiation of reverse transcription through specific interactions with other viral components comprising the initiation complex. Moreover, they implicate specific regions on the surface of IN that may help to elucidate mechanisms by which the HIV-1 IN protein augments the initiation of HIV-1 reverse transcription in vivo. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Ctr Biophys Sci & Engn, Birmingham, AL 35294 USA. Univ Utah, Dept Genet, Salt Lake City, UT 84112 USA. Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL 35233 USA. RP Kappes, JC (reprint author), Univ Alabama, Dept Microbiol, 701 19th St S, Birmingham, AL 35294 USA. FU NCI NIH HHS [CA73470]; NIAID NIH HHS [R01 AI047714, P30 AI027767, P30-AI-27767, AI47714] NR 41 TC 15 Z9 15 U1 0 U2 1 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 OCT PY 2003 VL 77 IS 20 BP 11050 EP 11059 DI 10.1128/JVI.77.20.11050-11059.2003 PG 10 WC Virology SC Virology GA 727XL UT WOS:000185686100031 PM 14512553 ER PT J AU Hickman, DL Wasson, K Ehrhart, EJ AF Hickman, DL Wasson, K Ehrhart, EJ TI What is your diagnosis? Subclinical hypovitaminosis C SO LAB ANIMAL LA English DT Article ID ASCORBIC-ACID DEFICIENCY; GUINEA-PIGS; COLLAGEN-SYNTHESIS; VITAMIN-C; SCURVY C1 Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. Colorado State Univ, Ft Collins, CO 80523 USA. RP Hickman, DL (reprint author), Portland VA Med Ctr, Res & Dev Serv, 3710 SW US Vet Hosp Rd,R&D 36, Portland, OR 97239 USA. RI Hickman, Debra/D-3289-2009 NR 16 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD OCT PY 2003 VL 32 IS 9 BP 23 EP 25 DI 10.1038/laban1003-23 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 727NH UT WOS:000185664600007 PM 15235658 ER PT J AU Brochmann, EJ Duarte, ME Zaidi, HA Murray, SS AF Brochmann, EJ Duarte, ME Zaidi, HA Murray, SS TI Effects of dietary restriction on total body, femoral, and vertebral bone in SENCAR, C57BL/6, and DBA/2 mice SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res ID INBRED MOUSE STRAINS; SKIN TUMOR PROMOTION; HIGH-FAT DIETS; CALORIE RESTRICTION; EPIDERMAL HYPERPLASIA; ALTERED EXPRESSION; CALCIUM-REPLETE; INDUCED OBESE; B6C3F1 MICE; DNA DAMAGE AB Dietary restriction (DR) increases the life span and retards aging, in part, by limiting free radical generation and oxidative damage. DR also reduces body mass, a major determinant of bone mass across the life span. We tested the hypothesis that DR has its most beneficial effects on bone in mouse strains with high free radical generation (sensitive to carcinogenesis [SENCAR] > C57 > DBA) versus the hypothesis that bone mass at weight-bearing sites is determined by body mass in DR and ad libitum (AL)-fed mice. Male mice of each strain were killed at 10 weeks of age (t(0)) or randomized to an AL-fed or 30% DR feeding regimen for 6 months. Food consumption by AL-fed mice was measured daily, and DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. Body fat (%) and bone mineral density (BMD) and content (BMC) were determined by PIXImus densitometry. There were strain-dependent effects on body mass, crown-to-rump length, percent body fat, and total body, femoral, and vertebral BMD and BMC under all conditions. SENCAR mice were heavier, longer, had larger bones, and generally exhibited higher total body, femoral, and vertebral BMC and BMD than C57 and DBA mice. DR had beneficial effects on BMD and BMC in the vertebrae of the SENCAR mouse model of high free radical generation and in the obese, diabetes-prone C57 mouse model of high end-stage protein glycation. DR DBA and SENCAR mice had lower femoral BMDs and BMCs than their respective AL-fed controls. Regression analysis confirmed linear relationships between total and lean body mass and total body and femoral BMDs and BMCs, suggesting that physiologic adaptation to a lower body mass accounts for the lower femoral bone mineral values observed in DR versus AL-fed mice. Thus, both hypotheses are, at least, partially valid. DR is beneficial in the trabeculae-rich vertebrae of animal models of high oxidant stress, and total/lean body mass determines BMD and BMC in the weight-bearing femur in DR and AL-fed mice. (C) 2003 Elsevier Inc. All rights reserved. C1 Sepulveda Ambulat Care Ctr & Nursing Home, VA Greater Los Angeles Healthcare Syst, 11E GRECC, Sepulveda, CA 91343 USA. Fed Univ Rio De Janeiro, Dept Histol & Embryol, Rio De Janeiro, Brazil. Fed Univ Rio De Janeiro, PABCAM, HUCFF, Rio De Janeiro, Brazil. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Murray, SS (reprint author), Sepulveda Ambulat Care Ctr & Nursing Home, VA Greater Los Angeles Healthcare Syst, GRECC 11E, 16111 Plummer St, Sepulveda, CA 91343 USA. RI Biguzzi, Felipe/E-4724-2015 NR 50 TC 30 Z9 30 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 2003 VL 52 IS 10 BP 1265 EP 1273 DI 10.1016/S0026-0495(03)00194-0 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 731YH UT WOS:000185913700007 PM 14564677 ER PT J AU Tyler, KL AF Tyler, KL TI Origins and early descriptions of "Duchenne muscular dystrophy" SO MUSCLE & NERVE LA English DT Article DE Becker muscular dystrophy; Duchenne muscular dystrophy; Gowers' sign; historical aspects; muscular dystrophy; pseudohypertrophic muscular dystrophy ID HISTORY AB One of the seminal events in the history of neurology was the identification of primary diseases of muscle and their separation from diseases in which muscle weakness was secondary to injury involving the anterior horns of the spinal cord ("progressive muscular atrophy"). Not surprisingly, one of the first groups of primary muscle diseases to be satisfactorily characterized belonged to what would today be classified as muscular dystrophies. Pride of place in this group belongs to Duchenne muscular dystrophy (DMD). DMD's primacy as the first well-characterized muscular dystrophy was due both to the fact that it is relatively common, as well as to the clinically striking feature, apparent in many cases, of apparent paradoxical enlargement of severely weakened muscles ("pseudo-hypertrophy"). This review traces the historical roots of DMD in the 19th century, from the early papers by Conte, Bell, Partridge, and Meryon through the classic monographs by Duchenne and Gowers. In addition, the first American contributions to DMID are reviewed, including those by Pepper, Hammond, and S. Weir Mitchell. Many of the original papers describing this disease are now unavailable outside of major medical libraries, and several important contributions, excepting those of Duchenne, which are recognized eponymously, are now virtually forgotten. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Univ Colorado, Neurol Serv, Dept Neurol B 182, Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, Denver Vet Affairs Med Ctr, 4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 63 TC 31 Z9 32 U1 1 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2003 VL 28 IS 4 BP 402 EP 422 DI 10.1002/mus.10435 PG 21 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 726RN UT WOS:000185613200002 PM 14506712 ER PT J AU Chan, EM Young, EJ Ianzano, L Munteanu, I Zhao, XC Christopoulos, CC Avanzini, G Elia, M Ackerley, CA Jovic, NJ Bohlega, S Andermann, E Rouleau, GA Delgado-Escueta, AV Minassian, BA Scherer, SW AF Chan, EM Young, EJ Ianzano, L Munteanu, I Zhao, XC Christopoulos, CC Avanzini, G Elia, M Ackerley, CA Jovic, NJ Bohlega, S Andermann, E Rouleau, GA Delgado-Escueta, AV Minassian, BA Scherer, SW TI Mutations in NHLRC1 cause progressive myoclonus epilepsy SO NATURE GENETICS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; LAFORIN; FAMILY; BODIES AB Lafora progressive myoclonus epilepsy is characterized by pathognomonic endoplasmic reticulum (ER)-associated polyglucosan accumulations. We previously discovered that mutations in EPM2A cause Lafora disease. Here, we identify a second gene associated with this disease, NHLRC1 ( also called EPM2B), which encodes malin, a putative E3 ubiquitin ligase with a RING finger domain and six NHL motifs. Laforin and malin colocalize to the ER, suggesting they operate in a related pathway protecting against polyglucosan accumulation and epilepsy. C1 Hosp Sick Children, Res Inst, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1X8, Canada. Inst Nazl Neurol, I-20133 Milan, Italy. Oasi Inst Res Mental Retardat & Brain Aging, Dept Neurol, I-94018 Troina, Italy. Hosp Sick Children, Dept Pathol & Lab Med, Toronto, ON M5G 1X8, Canada. Clin Neurol & Psychiat Children & Youth, YU-11000 Belgrade, Serbia Monteneg, Yugoslavia. King Faisal Specialist Hosp & Res Ctr, Dept Neurosci, Riyadh 11211, Saudi Arabia. McGill Univ, Montreal Neurol Inst, Neurogenet Unit, Montreal, PQ H3A 2B4, Canada. McGill Univ, Montreal Gen Hosp, Ctr Hlth, Res Inst Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada. Univ Calif Los Angeles, Sch Med, W Los Angeles DVA Med Ctr, Dept Neurol,Comprehens Epilepsy Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles DVA Med Ctr, Brain Res Inst, Los Angeles, CA 90073 USA. Hosp Sick Children, Dept Pediat, Div Neurol, Toronto, ON M5G 1X8, Canada. RP Minassian, BA (reprint author), Hosp Sick Children, Res Inst, Program Genet & Genom Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999; Delgado-Escueta, Antonio V./0000-0002-1581-6999; Elia, Maurizio/0000-0002-0414-1359 FU Telethon [GFP01003] NR 15 TC 143 Z9 148 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2003 VL 35 IS 2 BP 125 EP 127 DI 10.1038/ng1238 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 726WV UT WOS:000185625300007 PM 12958597 ER PT J AU Thongboonkerd, V Klein, JB Arthur, JM AF Thongboonkerd, V Klein, JB Arthur, JM TI Proteomic identification of a large complement of rat urinary proteins SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE proteomics; proteome; kidney; biomarker; L-myc; ezrin; GAP-43; 2-D PAGE; 2-D Western blot; posttranslational modifications ID OXIDATIVELY MODIFIED PROTEINS; ALZHEIMERS-DISEASE BRAIN; 2-DIMENSIONAL ELECTROPHORESIS; MASS-SPECTROMETRY; L-MYC; EXPRESSION; BINDING; KINASE; PRECIPITATION; GROWTH AB The characterization of urinary proteins is an important tool to identify disease-related biomarkers and to better understand renal physiology. Expression of urinary proteins has been previously studied by Western blotting and other immunological methods. The scope of such studies, however, is limited to previously identified proteins for which specific antibodies are existed. We used proteomic analysis to identify proteins and to construct a proteome map for Sprague-Dawley (SD) rat urine isolated by ultracentrifugation. Urinary proteins were separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and visualized by silver staining. Proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), followed by peptide mass fingerprinting using the NCBI protein database. A total of 350 protein spots were visualized. From 250 excised spots, 111 protein components were identified including transporters, transport regulators, chaperones, enzymes, signaling proteins, cytoskeletal proteins, pheromone-binding proteins, receptors, and novel gene products. The presence of a number of these identified proteins was unexpected and had not previously been identified in the urine. 2-D Western blot analyses for randomly selected proteins (ezrin, HSP70, beta- and gamma-actin, Rho-GDI, and I-myc) clearly confirmed the proteomic identification. Several potential posttranslational modifications were predicted by bioinformatic analyses. These data indicate that a large complement of expected and unexpected urinary proteins can be simultaneously studied by proteomic analysis. This approach may lead to better understanding of renal physiology and pathophysiology, and to biomarker discovery. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ Louisville, Kidney Dis Program, Core Proteom Lab, Dept Med, Louisville, KY 40202 USA. Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40202 USA. Vet Adm, Louisville, KY USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Thongboonkerd, V (reprint author), Univ Louisville, Kidney Dis Program, Core Proteom Lab, Dept Med, 570 S Preston St,Suite 102, Louisville, KY 40202 USA. RI THONGBOONKERD, VISITH /C-6920-2009; Klein, Jon/B-9833-2013 FU NHLBI NIH HHS [R01 HL66358-01]; NIDDK NIH HHS [R21 DK62086-01] NR 28 TC 29 Z9 32 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PD OCT PY 2003 VL 95 IS 2 BP E69 EP E78 DI 10.1159/000073674 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 742VH UT WOS:000186538400004 PM 14610326 ER PT J AU Hohler, AD Ransom, BR Chun, MR Troster, AI Samii, A AF Hohler, AD Ransom, BR Chun, MR Troster, AI Samii, A TI The youngest reported case of corticobasal degeneration SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE corticobasal ganglionic degeneration; corticobasal degeneration; Parkinson's disease; Parkinson Plus syndrome; young onset ID PROGRESSIVE SUPRANUCLEAR PALSY; BASAL GANGLIONIC DEGENERATION; MULTIPLE SYSTEM ATROPHY; ALZHEIMERS-DISEASE; DIAGNOSIS AB Corticobasal degeneration (CBD) is a movement disorder characterized by early apraxia and asymmetric parkinsonism that responds poorly to anti-Parkinson medications. There are clinical manifestations reflecting dysfunction in both the cerebral cortex and the basal ganglia. Patients typically present between the sixth and seventh decades. Previously, the youngest clinically diagnosed individual was 40 years old. Here we describe a 34-year-old woman who meets the clinical diagnostic criteria for CBD with onset of symptoms at age 28. In this patient, the first symptom was an 'uncooperative' right hand. This was soon followed by right hand dystonia. Symptoms progressed rapidly, and she developed generalized bradykinesia, rigidity, and corticospinal tract signs with preservation of the initial asymmetry. Her symptoms did not respond to a daily dose of 1200 mg of immediate release levodopa. Extensive laboratory workup and brain imaging were normal. Neuropsychological evaluation revealed mild deficits consistent with frontal-subcortical dysfunction. The chronic, progressive course, asymmetric limb rigidity, apraxia, focal dystonia, and lack of response to levodopa suggest CBD. To our knowledge, this is the youngest reported case of clinically probable CBD. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98108 USA. Madigan Army Med Ctr, Dept Neurol, Tacoma, WA 98431 USA. Everett Neurol Ctr, Everett, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Samii, A (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Neurol, 1660 S Columbian Way,Mailstop 127, Seattle, WA 98108 USA. OI Ransom, Bruce R./0000-0002-9658-0294; Hohler, Anna/0000-0003-3134-1708 NR 18 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD OCT PY 2003 VL 10 IS 1 BP 47 EP 50 DI 10.1016/S1353-8020(03)00046-4 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 737UB UT WOS:000186249200009 ER PT J AU Mendez, MF AF Mendez, MF TI Surveying a blank field with the attentional spotlight SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article ID VISUAL-SPATIAL ATTENTION; SELECTIVE ATTENTION; FEATURE-INTEGRATION; EXOGENOUS CUE; MOVEMENT; SHIFTS; VISION; TASKS; FOCUS AB Spatial localization is a unique aspect of selective attention that precedes and facilitates other aspects of sensory processing. A common model of spatial attention is an attentional spotlight that enlarges to fit attentional demands. It is unclear if this attentional spotlight expands to survey a blank field or to scan the spatial environment with a smaller attentional spotlight. Two tachistoscopic experiments with young adults investigated how attention is surveyed in a blank field. Exp. 1 consisted of single letters at two concentric regions and under different conditions of attentional demand. Reaction times were proportionally slower for stimuli occurring in a combination of the two regions located at different distances from the fixation point than for stimuli occurring in each region alone. This finding is not consistent with attentional spread to encompass the entire attentional field. The addition of more stimulus locations within each single region yielded significantly slower reaction times. Together these findings suggest that a small attentional spotlight serially monitors different regions of the visual field when there are anticipated locations to be attended. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol,Neurobehav Unit 116AF, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat,Neurobehav Unit 116AF, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol,Neurobehav Unit 116AF, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 PU PERCEPTUAL MOTOR SKILLS PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807 USA SN 0031-5125 J9 PERCEPT MOTOR SKILL JI Percept. Mot. Skills PD OCT PY 2003 VL 97 IS 2 BP 560 EP 568 PG 9 WC Psychology, Experimental SC Psychology GA 736GW UT WOS:000186163900030 PM 14620245 ER PT J AU Pisegna, JR AF Pisegna, JR TI Treating patients with acute gastrointestinal bleeding or rebleeding SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Spring Practice and Research Forum of the American College of Clinical Pharmacy CY APR 02, 2000 CL MONTEREY, CALIFORNIA SP Amer Coll Clin Pharmacy ID ZOLLINGER-ELLISON-SYNDROME; GASTRIC-ACID HYPERSECRETION; PROTON PUMP INHIBITORS; PEPTIC-ULCER; INTRAVENOUS PANTOPRAZOLE; INTRAGASTRIC PH; ECL CELLS; NONVARICEAL; SUPPRESSION; SECRETION AB Despite advances in medical management, gastrointestinal bleeding remains a substantial cause of morbidity and mortality. At risk are patients with history of the event, those taking nonsteroidal antiinflammatory agents, and those with active peptic ulcer disease. Endoscopy may be performed for diagnosis and treatment. Antisecretory therapy may be employed to control gastric acid secretion, treat active peptic ulcer disease, and control symptoms such as diarrhea and abdominal pain. Options for antisecretory therapy include histamine(2)-receptor antagonists (H2RAs) that target the histamine pathway, and proton pump inhibitors (PPIs) that target the final step in acid secretion. The H2RAs generally are ineffective at reaching a target pH of 6 in patients with gastrointestinal bleeding because of tachyphylaxis. The PPIs are more effective and do not lead to tachyphylaxis. With the availability of an intravenous PPI, pantoprazole, options for managing hospitalized patients with gastrointestinal bleeding are expanding. C1 VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 23 TC 2 Z9 3 U1 0 U2 0 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 OCT PY 2003 VL 23 IS 10 SU S BP 81S EP 86S DI 10.1592/phco.23.13.81S.31930 PN 2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 730JZ UT WOS:000185828800006 PM 14587962 ER PT J AU Worrall, TJ Simpson, KN Jenrette, DE Johnson, RH AF Worrall, TJ Simpson, KN Jenrette, DE Johnson, RH TI Appropriate treatment of systolic heart failure in the primary care clinics. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2003 VL 23 IS 10 BP 1332 EP 1332 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200035 ER PT J AU Lumpkin, AR Hamm, JW Herndon, KC AF Lumpkin, AR Hamm, JW Herndon, KC TI Evaluation of lipid management following coronary artery bypass graft surgery. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Pfizer Inc, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2003 VL 23 IS 10 BP 1333 EP 1333 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200037 ER PT J AU McMaster, NL Jung, SA Erwin, TC Linn, WD AF McMaster, NL Jung, SA Erwin, TC Linn, WD TI Acute coronary syndromes: quality of care in an academic VA medical center. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2003 VL 23 IS 10 BP 1333 EP 1333 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200036 ER PT J AU Marceille, JR Goins, J Soni, R Biery, J Lee, TA AF Marceille, JR Goins, J Soni, R Biery, J Lee, TA TI Incidence of congestive heart failure-related interventions in patients receiving rosiglitazone and insulin. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2003 VL 23 IS 10 BP 1337 EP 1337 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200055 ER PT J AU Benge, CD Greene, RS AF Benge, CD Greene, RS TI Comprehensive diabetes management: a clinical pharmacy practitioner as a means to improve the health care report card. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Austin, TX 78712 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Texas Tech Hlth Sci Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2003 VL 23 IS 10 BP 1372 EP 1372 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200209 ER PT J AU Kushner, M Weissman, E AF Kushner, M Weissman, E TI A VA health care system two years after September 11, 2001 SO PSYCHIATRIC SERVICES LA English DT News Item C1 Bronx Vet Adm Med Ctr, OOMH, Mental Illness Res Educ & Clin Ctr, VISN 3 Bronx, Bronx, NY 10468 USA. RP Weissman, E (reprint author), Bronx Vet Adm Med Ctr, OOMH, Mental Illness Res Educ & Clin Ctr, VISN 3 Bronx, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ellen.weissman@med.va.gov NR 0 TC 0 Z9 0 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 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2003 VL 54 IS 10 BP 1410 EP 1411 DI 10.1176/appi.ps.54.10.1410 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BS UT WOS:000222758900019 PM 14557531 ER PT J AU Young, AJ Ofori-Boateng, T Rodriguez, KL Plowman, JL AF Young, AJ Ofori-Boateng, T Rodriguez, KL Plowman, JL TI Meaning and agency in discussing end-of-life care: A study of elderly veterans' values and interpretations SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE end-of-life care; communication; geriatrics; veterans ID INCORPORATING PALLIATIVE CARE; ADVANCE DIRECTIVES; DYING PATIENTS; TREATMENT PREFERENCES; PATIENT; EDUCATION; PREDICTIONS; EXPERIENCE; KNOWLEDGE; BARRIERS AB The authors of this exploratory study used textual analysis of transcribed interviews to examine the mental constructs that individuals form around advance care terminology and to learn how elderly veterans conceptualize the language used in the Veterans Administration advance directive. They found that respondents often negotiated meaning by drawing on rigid schemas, specific mental constructs already in place: The Lord's Will, Machine Talk, Being a Burden, and Being Productive. The authors also examined the transcripts for agency. In addition to assigning external agency for end-of-life care decisions, respondents often expressed a complex interaction of ''self'' and "other" agency. These results challenge us to develop communication methods that allow patients to claim agency and participate fully in decisions regarding their health care, especially at the end of life. C1 VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. Metrohlth Med Ctr, Cleveland, OH USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Young, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. NR 66 TC 9 Z9 9 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD OCT PY 2003 VL 13 IS 8 BP 1039 EP 1062 DI 10.1177/1049732303256554 PG 24 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 722BY UT WOS:000185356500002 PM 14556418 ER PT J AU Peng, CC Aspinall, SL Good, CB Atwood, CW Chang, CCH AF Peng, CC Aspinall, SL Good, CB Atwood, CW Chang, CCH TI Equal effectiveness of older traditional antibiotics and newer broad-spectrum antibiotics in treating patients with acute exacerbations of chronic bronchitis SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID 30-CENTER NATIONAL SURVEILLANCE; OBSTRUCTIVE PULMONARY-DISEASE; UNITED-STATES; ANTIMICROBIAL RESISTANCE; OUTPATIENTS; UPDATE AB Background: Choice of antibiotic therapy for acute exacerbations of chronic bronchitis (AECB) is important because of cost and concerns about development of resistance. Methods: A retrospective cohort study was conducted in outpatients with chronic obstructive pulmonary disease and documented AECB treated with antibiotics. Results: We compared outcomes and costs of AECB treated with first-line antibiotics having partial coverage against organisms associated with AECB (eg, amoxicillin), first-line antibiotics with full coverage against organisms associated with AECB (eg, sulfamethoxazole-trimethoprim), and newer broad-spectrum antibiotics (eg, azithromycin). There were no significant differences among the three antibiotic groups in failure rate, hospitalization rate, or time until subsequent AECB. Pharmacy costs were significantly less with first-line antibiotics ($3.18 +/- 0.64, $3.00 +/- 0.48, and $36.70 +/- 16.29, respectively; P < 0.0001), but there was no significant difference among all three groups with regard to total costs. Conclusion: We found no difference in outcome between older traditional antibiotics with adequate coverage against organisms associated with AECB and newer broad-spectrum antibiotics. C1 VA Pittsburgh Healthcare Syst, Pharm Serv 132 MU, Pittsburgh, PA 15240 USA. RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, Pharm Serv 132 MU, Univ Dr C, Pittsburgh, PA 15240 USA. EM sherrie.aspinall@med.va.gov NR 16 TC 9 Z9 9 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 OCT PY 2003 VL 96 IS 10 BP 986 EP 991 DI 10.1097/01.SMJ.0000054536.50460.F1 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 831CP UT WOS:000222170800007 PM 14570342 ER PT J AU Black, S Roman, GC Geldmacher, DS Salloway, S Hecker, J Burns, A Perdomo, C Kumar, D Pratt, R AF Black, S Roman, GC Geldmacher, DS Salloway, S Hecker, J Burns, A Perdomo, C Kumar, D Pratt, R CA Donepezil 307 Vascular Dementia St TI Efficacy and tolerability of donepezil in vascular dementia - Positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial SO STROKE LA English DT Article DE dementia; donepezil; randomized controlled trials ID ALZHEIMERS-DISEASE; DOUBLE-BLIND; MODERATE; GALANTAMINE; POPULATIONS; DIAGNOSIS; 1-YEAR AB Background and Purpose - Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD. Methods - Patients (n = 603; mean age, 73.9 years; 55.2% men) with probable (70.5%) or possible (29.5%) VaD, according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), were randomized to 24 weeks of treatment with donepezil 5 mg/d ( n = 198), donepezil 10 mg/d ( 5 mg/d for first 28 days; n = 206), or placebo ( n = 199). Analyses were based on the intent-to-treat population. Results - At week 24, both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer's Disease Assessment Scale - cognitive subscale ( mean change from baseline score effect size: donepezil 5 mg/ d, - 1.90; P = 0.001; donepezil 10 mg/ d, - 2.33; P < 0.001). Significant improvements in patients' global function were seen versus placebo at week 24 ( observed cases), on the Clinician's Interview- Based Impression of Change - Plus version only for patients on donepezil 5 mg/ d ( P = 0.014), and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/ d ( P = 0.007). Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer's Disease Functional Assessment and Change Scale ( mean change from baseline score effect size at week 24: donepezil 5 mg/ d, - 1.31, P = 0.02; donepezil 10 mg/ d, - 1.31, P = 0.02). Donepezil was well tolerated. Withdrawal rates due to adverse events were relatively low ( placebo, 11.1%; donepezil 5 mg/ d, 11.1%; donepezil 10 mg/ d, 21.8%; P = 0.005 versus placebo). Conclusions - These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition. C1 Eisai Inc, Glenpointe Ctr W, Teaneck, NJ 07666 USA. Univ Toronto, Dept Med, Div Neurol, Sunnybrook & Womens Coll Hlth Sci Ctr, Toronto, ON, Canada. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Vet Adm Hosp, San Antonio, TX USA. Univ Virginia, Dept Neurol, Memory Disorders Program, Charlottesville, VA USA. Butler Hosp, Brown Med Sch, Providence, RI 02906 USA. Repatriat Gen Hosp, Dept Rehabil & Aged Care, Daw Pk, SA, Australia. Univ Manchester, Manchester, Lancs, England. Wythenshawe Hosp, Manchester M23 9LT, Lancs, England. RP Pratt, R (reprint author), Eisai Inc, Glenpointe Ctr W, Teaneck, NJ 07666 USA. OI Burns, Alistair/0000-0002-9837-0645; Black, Sandra/0000-0001-7093-8289 NR 30 TC 168 Z9 193 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2003 VL 34 IS 10 BP 2323 EP 2330 DI 10.1161/01.STR.0000091396.95360.E1 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 727UK UT WOS:000185679100019 PM 12970516 ER PT J AU Eid, GM Prince, JM Mattar, SG Hamad, G Ikrammudin, S Schauer, PR AF Eid, GM Prince, JM Mattar, SG Hamad, G Ikrammudin, S Schauer, PR TI Medium-term follow-up confirms the safety and durability of laparoscopic ventral hernia repair with PTFE SO SURGERY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Central-Surgical-Association CY MAR 20-22, 2003 CL TORONTO, CANADA SP Central Surg Assoc ID INCISIONAL HERNIA; MESH; HERNIORRHAPHY; RECURRENCE; GROIN; RISK AB Background. Ventral abdominal wall hernias are common lesions and may be associated with life-threatening complications. The application of laparoscopic principles to the treatment of ventral hernias has reduced recurrence rates from a range of 25 % to 52 % to a range of 3.4 % to 9 %. In this study, we review our experience and assess the clinical outcome of patients who have undergone laparoscopic repair of ventral hernias. Methods. We reviewed the outcome of 79 patients with more than 1 year of follow-up who underwent laparoscopic ventral hernia repair between March 1996 and December 2001. Patient demographics, hernia characteristics, operative parameters, and clinical outcomes were evaluated. Results. Of the 79 patients, 37 were males. Mean age was 55.8 years (range 28-81). Sixty-eight patients had incisional hernias, including 17 with recurrent hernias. Eleven patients had primary ventral hernias. The mean defect size was 103 cm(2) (range 4-510); incarceration was present in 22 patients (27.8 %), and multiple (Swiss-cheese) defects in 20 (25.3 %). Laparoscopic expanded polytetrafluoroethylene mesh repair by the modified Rives-Stoppa technique was completed in 78 (98.7 %). One conversion occurred because of bowel injury. The mean operating time was 110 minutes (range 45-210) and mean hospital stay was 1.7 days (range 0-20), with 46 patients (58.2 %) being discharged within 24 hours of surgery. Complications included seroma formation (3), chronic pain (3), prolonged dens (1), hematoma formation (1), and missed bowel injury (1)for a complication rate of (11.4 %). There were no deaths. After a follow-up of up to 6 years (a mean of 34 months), there were 4 recurrences (5 %). Conclusion. The laparoscopic repair of ventral hernias is safe, effective, and durable with minimal morbidity. It is particularly successful in patients with recurrent lesions. The laparoscopic approach to ventral hernia repair should be considered the standard of care. C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Minnesota, Minneapolis, MN USA. RP Schauer, PR (reprint author), Magee Womens Hosp, Suite 5500,300 Halket St, Pittsburgh, PA 15213 USA. NR 19 TC 66 Z9 66 U1 0 U2 2 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 OCT PY 2003 VL 134 IS 4 BP 599 EP 603 DI 10.1016/S0039-6060(03)00273-6 PG 5 WC Surgery SC Surgery GA 741KT UT WOS:000186457800022 PM 14605620 ER PT J AU Hunskaar, S Burgio, K Diokno, A Herzog, AR Hjalmas, K Lapitan, MC AF Hunskaar, S Burgio, K Diokno, A Herzog, AR Hjalmas, K Lapitan, MC TI Epidemiology and natural history of urinary incontinence in women SO UROLOGY LA English DT Article; Proceedings Paper CT 26th International-Urogynecological-Association Meeting CY AUG, 2002 CL PRAGUE, CZECH REPUBLIC SP Int Urogynecolog Assoc ID OLDER-PEOPLE; RISK-FACTORS; SEVERITY INDEX; FECAL INCONTINENCE; NURSING-HOMES; PREVALENCE; FEMALE; POPULATION; COMMUNITY; SYMPTOMS AB Understanding the epidemiology (distribution and determinants) of urinary incontinence (UI), as well as its natural history is a very important issue. In this article, we discuss prevalence, incidence, natural history, and the variations that may be related to race and ethnicity. We focus on epidemiologic population comprising community-dwelling women who are not institutionalized. Our review clearly shows that there is a lack of advanced epidemiologic analyses. Variables that better characterize UI include frequency measure, quantity of urine loss, duration, type, and severity. These factors should be incorporated into basic study design so that more advanced and informative analyses may be conducted. (C) 2003 Elsevier Inc. C1 Univ Bergen, Sect Gen Practice, Dept Publ Hlth & Primary Hlth Care, N-5009 Bergen, Norway. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. Univ Gothenburg, Dept Paediat Surg, Gothenburg, Sweden. Philippine Gen Hosp, Div Urol, Manila, Philippines. RP Hunskaar, S (reprint author), Univ Bergen, Sect Gen Practice, Dept Publ Hlth & Primary Hlth Care, Ulriksdal 8C, N-5009 Bergen, Norway. NR 62 TC 136 Z9 141 U1 0 U2 5 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 OCT PY 2003 VL 62 IS 4A SU S BP 16 EP 23 DI 10.1016/S0090-4295(03)00755-6 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 731QZ UT WOS:000185899100004 PM 14550833 ER PT J AU Zhong, XB Reynolds, R Kidd, JR Kidd, KK Jenison, R Marlar, RA Ward, DC AF Zhong, XB Reynolds, R Kidd, JR Kidd, KK Jenison, R Marlar, RA Ward, DC TI Single-nucleotide polymorphism genotyping on optical thin-film biosensor chips SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROLLING-CIRCLE AMPLIFICATION; DISPLACEMENT AMPLIFICATION; DISCRIMINATION; SEQUENCE; SILICON; PROBES; ASSAY; RISK AB Single-nucleotide polymorphisms (SNPs) constitute the bulk of human genetic variation and provide excellent markers to identify genetic factors contributing to complex disease susceptibility. A rapid, sensitive, and inexpensive assay is important for large-scale SNIP scoring. Here we report the development of a multiplex SNIP detection system using silicon chips coated to create a thin-film optical biosensor. Allele-discriminating, aldehyde-labeled oligonucleotides are arrayed and covalently attached to a hydrazine-derivatized chip surface. Target sequences (e.g., PCR amplicons) then are hybridized in the presence of a mixture of biotinylated detector probes, one for each SNIP, and a thermostable DNA ligase. After a stringent wash (0.01 M NaOH), ligation of biotinylated detector probes to perfectly matched capture oligomers is visualized as a color change on the chip surface (gold to blue/purple) after brief incubations with an anti-biotin IgG-horseradish peroxidase conjugate and a precipitable horseradish peroxidase substrate. Testing of PCIR fragments is completed in 30-40 min. Up to several hundred SNPs can be assayed on a 36-mm(2) chip, and SNIP scoring can be done by eye or with a simple digital-camera system. This assay is extremely robust, exhibits high sensitivity and specificity, and is format-flexible and economical. In studies of mutations associated with risk for venous thrombosis and genotyping/ haplotyping of African-American samples, we document high-fidelity analysis with 0 misassignments in 500 assays performed in duplicate. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. ThermoBioStar Inc, Louisville, CO 80027 USA. Oklahoma City Vet Affairs Med Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Ward, DC (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06510 USA. FU NIGMS NIH HHS [P01 GM057672, P01GM57672] NR 26 TC 75 Z9 82 U1 2 U2 13 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 SEP 30 PY 2003 VL 100 IS 20 BP 11559 EP 11564 DI 10.1073/pnas.1934783100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 727XG UT WOS:000185685700070 PM 12975525 ER PT J AU Horner, RD Kamins, KG Feussner, JR Grambow, SC Hoff-Lindquist, J Harati, Y Mitsumoto, H Pascuzzi, R Spencer, PS Tim, R Howard, D Smith, TC Ryan, MAK Coffman, CJ Kasarskis, EJ AF Horner, RD Kamins, KG Feussner, JR Grambow, SC Hoff-Lindquist, J Harati, Y Mitsumoto, H Pascuzzi, R Spencer, PS Tim, R Howard, D Smith, TC Ryan, MAK Coffman, CJ Kasarskis, EJ TI Occurrence of amyotrophic lateral sclerosis among Gulf War veterans SO NEUROLOGY LA English DT Article ID US VETERANS; EPIDEMIOLOGY; MORTALITY; TRAUMA AB Background: In response to Gulf War veterans' concerns of high rates of ALS, this investigation sought to determine if Gulf War veterans have an elevated rate of ALS. Methods: A nationwide epidemiologic case ascertainment study design was used to ascertain all occurrences of ALS for the 10-year period since August 1990 among active duty military and mobilized Reserves, including National Guard, who served during the Gulf War (August 2, 1990, through July 31, 1991). The diagnosis of ALS was confirmed by medical record review. Risk was assessed by the age-adjusted, average, annual 10-year cumulative incidence rate. Results: Among approximately 2.5 million eligible military personnel, 107 confirmed cases of ALS were identified for an overall occurrence of 0.43 per 100,000 persons per year. A significant elevated risk of ALS occurred among all deployed personnel (RR = 1.92; 95% CL = 1.29, 2.84), deployed active duty military (RR = 2.15, 95% CL = 1.38, 3.36), deployed Air Force (RR = 2.68, 95% CL = 1.24, 5.78), and deployed Army (RR = 2;04; 95% CL = 1.10, 3.77) personnel. Elevated, but nonsignificant, risks were observed for deployed Reserves and National Guard (RR = 2.50; 95% CL = 0.88, 7.07), deployed Navy (RR = 1.48, 95% CL = 0.62, 3.57), and deployed Marine Corps (RR = 1.13; 95% CL = 0.27, 4.79) personnel. Overall, the attributable risk associated with deployment was 18% (95% CL = 4.9%, 29.4%). Conclusions: Military personnel who were deployed to the Gulf Region during the Gulf War period experienced a greater post-war risk of ALS than those who were deployed to the Gulf. C1 NINDS, Rockville, MD 20852 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. VA Epidemiol Res & Informat Ctr, Durham, NC 27705 USA. VA Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27705 USA. Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Oregon Hlth & Sci Univ, Portland, OR USA. Durham VA Med Ctr, Durham, NC 27705 USA. USN, Hlth Res Ctr, San Diego, CA 92152 USA. Lexington VA Med Ctr, Lexington, KY 40511 USA. Univ Kentucky, Lexington, KY 40536 USA. RP Horner, RD (reprint author), NINDS, NSC Bldg,Room 2149,6001 Execut Blvd, Rockville, MD 20852 USA. RI Grambow, Steven/E-1422-2015 OI Grambow, Steven/0000-0001-6037-3253 NR 23 TC 141 Z9 143 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 23 PY 2003 VL 61 IS 6 BP 742 EP 749 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 723ZC UT WOS:000185460600006 PM 14504315 ER PT J AU Million, M Grigoriadis, DE Sullivan, S Crowe, PD McRoberts, JA Zhou, HP Saunders, PR Maillot, C Mayer, EA Tache, Y AF Million, M Grigoriadis, DE Sullivan, S Crowe, PD McRoberts, JA Zhou, HP Saunders, PR Maillot, C Mayer, EA Tache, Y TI A novel water-soluble selective CRF1 receptor antagonist, NBI 35965, blunts stress-induced visceral hyperalgesia and colonic motor function in rats SO BRAIN RESEARCH LA English DT Article DE non-peptide receptor antagonist; CRF1 receptor; colonic transit; colorectal distention; visceral pain ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; GASTROINTESTINAL-TRACT; AVOIDANCE STRESS; BINDING-PROTEIN; FOS EXPRESSION; UROCORTIN-II; BRAIN; RESPONSES; SUBTYPE-1 AB The stress response involves the activation of two corticotropin-releasing factor (CRF) receptor subtypes. We investigated the role of CRF, in stress-related visceral responses. A novel water-soluble tricyclic CRF, antagonist, NBI 35965 was developed that displayed a high affinity for CRF1 (K(i)similar to4 nM) while having no binding affinity to CRF2. This antagonist also inhibited the stimulation of cAMP induced by sauvagine in CRF1 transfected cells. NBI 35965 administered per orally (p.o.) in rats (1, 3, 10 or 30 mg/kg) inhibited dose-dependently [I-125] sauvagine binding selectively at brain sites of CRF, distribution as shown by ex vivo receptor autoradiography. At the highest doses, NBI 35965 completely prevented [I-125]sauvagine labeling in the cortex. NBI 35965 (10 mg/kg) administered p.o. or subcutaneously (sc) 1 h before intravenous CRF completely blocked the 81% shortening of distal colonic transit time induced by CRF. NBI 35965 (20 mg/kg s.c.) significantly reduced the defecation in response to water avoidance stress but not that induced by s.c. carbachol. In adult male Long-Evans rats that had undergone maternal separation, acute water avoidance stress significantly increased the visceromotor response to colorectal distention (20-80 mmHg) by 42+/-19% compared with the response before stress. Stress-induced visceral hyperalgesia was abolished by NBI 35965 (20 mg/kg, s.c.). The data show that NBI 35965 is a novel water-soluble selective CRF, antagonist with bioavailability to the brain upon peripheral administration and that CRF1 receptor signaling pathways are involved in water avoidance stress-induced hyperalgesia to colorectal distention and stimulation of colonic transit. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis,Dept Med, Los Angeles, CA 90073 USA. Neurocrine Biosci Inc, San Diego, CA 92121 USA. RP Million, M (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [R01 DK58173, R43 DK61863, DK 57238-01A1S1, DK-57238, R01 DK-33061] NR 53 TC 78 Z9 82 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 19 PY 2003 VL 985 IS 1 BP 32 EP 42 DI 10.1016/S0006-8993(03)03027-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 723TB UT WOS:000185446700004 PM 12957366 ER PT J AU Paul, K Keith, DJ Johnson, SW AF Paul, K Keith, DJ Johnson, SW TI Modulation of calcium-activated potassium small conductance (SK) current in rat dopamine neurons of the ventral tegmental area SO NEUROSCIENCE LETTERS LA English DT Article DE Ca2+ dependent potassium SK channel; bicuculline methiodide; apamin; brain slice; dopamine; ventral tegmental area ID BEHAVIORAL REACTIONS; FIRING PROPERTIES; MIDBRAIN; RESPONSES; INVITRO; BICUCULLINE; STIMULI; PATTERN AB Block of calcium-sensitive potassium SK current (gKCa([SK])) by apamin or bicuculline methiodide potentiates burst firing in dopamine neurons in the presence of N-methyl-D-aspartate (NMDA). The purpose of this study was to test the hypothesis that calcium entry through NMDA-gated channels can potentiate gKCa([SK]) in dopamine neurons in the ventral tegmental area. We used microelectrodes to record an outward tail current that was evoked by membrane depolarization under single-electrode voltage-clamp. Using bicuculline methiodide (50 muM) as a reversible inhibitor of gKCa([SK]), we found that NMDA (15 muM) reduced the peak amplitude of the outward tail current by 39%. Contrary to expectations, our results suggest that stimulation of NMDA receptors reduces the calcium-activated potassium gKCa([SK]), an effect that could facilitate NMDA-dependent burst firing. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97207 USA. RP Paul, K (reprint author), SUNY Stony Brook, Dept Neurobiol & Behav, Rm 550,Life Sci Bldg, Stony Brook, NY 11794 USA. FU NIMH NIH HHS [MH40416] NR 19 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 18 PY 2003 VL 348 IS 3 BP 180 EP 184 DI 10.1016/S0304-3940(03)00747-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA 715KZ UT WOS:000184972200014 PM 12932823 ER PT J AU Moliterno, DJ Hermiller, JB Kereiakes, DJ Yow, E Applegate, RJ Braden, GA Dippel, EJ Furman, MI Grines, CL Kleiman, NS Levien, GN Mann, T Nair, RN Stine, RA Yacubov, SJ Tcheng, JE AF Moliterno, DJ Hermiller, JB Kereiakes, DJ Yow, E Applegate, RJ Braden, GA Dippel, EJ Furman, MI Grines, CL Kleiman, NS Levien, GN Mann, T Nair, RN Stine, RA Yacubov, SJ Tcheng, JE CA ELECT Inv TI A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention - Results of the evaluating enoxaparin clotting times (ELECT) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID MOLECULAR-WEIGHT HEPARIN; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; TRIAL; THERAPY; SAFETY AB OBJECTIVES The aim of this study was to discern a target range of anticoagulation for enoxaparin during percutaneous coronary intervention (PCI) as measured by the Rapidpoint ENOX (Pharmanetics Inc., Morrisville, North Carolina), a new point-of-care test. BACKGROUND In the U.S., enoxaparin has been used in only a small proportion of PCI procedures, partly because a rapid enoxaparin-specific assay was unavailable. METHODS We analyzed data from 445 enrolled patients receiving subcutaneous or intravenous enoxaparin in a prospective, multicenter study. Serial anticoagulation measurements and clinical outcomes were recorded. RESULTS The in-hospital composite occurrence of death, myocardial infarction, and urgent target vessel revascularization was 5.4%, and Thrombolysis In Myocardial Infarction (TIMI) major bleeding, minor bleeding, and any reported bleeding occurred in 0.2%, 1.3%, and 7.9% of patients, respectively. No significant association between procedural ENOX times and ischemic events was observed (p = 0.222), although the event rate was 4.0% among those with ENOX times between 250 to 450 s versus 7.2% for those outside this range (p = 0.134). Increasing ENOX time at sheath removal was correlated with any bleeding (p = 0.010) with a 1% increase for every similar to30-s rise. CONCLUSIONS Ischemic events were infrequent, and the rate appeared lowest in the mid-range of ENOX times. Bleeding events increased with increasing ENOX times. These observations, combined with a suggested procedural anti-Xa level of 0.8 to 1.8 IU/ml, translate into a recommended ENOX time range of 250 to 450 s for PCI and <200 to 250 s for sheath removal. (C) 2003 by the American College of Cardiology Foundation. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. St Vincent Hosp, Indianapolis, IN USA. Linder Ctr, Ohio Heart Hlth Ctr, Cincinnati, OH USA. Duke Clin Res Inst, Durham, NC USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Forsythe Med Ctr, Winston Salem, NC USA. Genesis Med Ctr, Davenport, IA USA. Univ Massachusetts, Worcester, MA 01605 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Baylor Coll Med, Houston, TX 77030 USA. Methodist DeBakey Heart Ctr, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Wake Med Ctr, Raleigh, NC USA. Case Western Reserve Univ Hosp, Cleveland, OH 44106 USA. Sentara Norfolk Gen, Norfolk, VA USA. Riverside Methodist Hosp, Columbus, OH 43214 USA. RP Moliterno, DJ (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, 9500 Euclid Ave,F-25, Cleveland, OH 44195 USA. OI Dippel, Eric/0000-0003-1085-1178 NR 20 TC 28 Z9 29 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 SEP 17 PY 2003 VL 42 IS 6 BP 1132 EP 1139 DI 10.1016/S0735-1097(03)01053-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 721YK UT WOS:000185345900030 PM 13678943 ER PT J AU Washington, DL Shekelle, PG Stevens, CD AF Washington, DL Shekelle, PG Stevens, CD TI Deferred care for emergency department users with nonacute conditions - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID HOSPITAL EMERGENCY C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Washington, DL (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 5 TC 0 Z9 0 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 SEP 16 PY 2003 VL 139 IS 6 BP 528 EP 528 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 721PE UT WOS:000185324100014 ER PT J AU Gehi, AK Rumsfeld, JS Liu, HY Schiller, NB Whooley, MA AF Gehi, AK Rumsfeld, JS Liu, HY Schiller, NB Whooley, MA TI Relation of self-reported angina pectoris to inducible myocardial ischemia in patients with known coronary artery disease: The Heart and Soul Study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CLINICAL-DIAGNOSIS; PROBABILITY; LIKELIHOOD; RISK AB To determine whether self-reported angina pectoris is associated with objective evidence of myocardial ischemia, we assessed angina symptoms, using the Seattle Angina Questionnaire, and measured ischemia using stress echocardiography in 933 patients with known coronary artery disease. We observed no association between self-reported angina pectoris and objective evidence of inducible ischemia. (C) 2003 by Excerpta Medica, Inc. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Denver VA Med Ctr, Denver, CO USA. Vet Adm Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. RP Whooley, MA (reprint author), Vet Adm Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [R01 HL079235-01A1, R01 HL079235] NR 10 TC 14 Z9 14 U1 0 U2 1 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 SEP 15 PY 2003 VL 92 IS 6 BP 705 EP 707 DI 10.1016/S0002-9149(03)00831-2 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 721RR UT WOS:000185330800013 PM 12972112 ER PT J AU Levine, S Nguyen, T Kaiser, LR Rubinstein, NA Maislin, G Gregory, C Rome, LC Dudley, GA Sieck, GC Shrager, JB AF Levine, S Nguyen, T Kaiser, LR Rubinstein, NA Maislin, G Gregory, C Rome, LC Dudley, GA Sieck, GC Shrager, JB TI Human diaphragm remodeling associated with chronic obstructive pulmonary disease - Clinical implications SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; fiber type transformations; single fiber physiology; specific force; within-fiber type adaptations ID VOLUME REDUCTION SURGERY; MUSCLE-FIBERS; FATIGUE RESISTANCE; SDH ACTIVITY; NORMAL MEN; CONTRACTION; FREQUENCY; DEPENDENCE; ADAPTATION; EMPHYSEMA AB Diaphragm remodeling associated with chronic obstructive pulmonary-disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsieson 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPID on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type 11 fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations. C1 Univ Penn, Sch Med, Surg & Res Serv, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Surg & Res Serv, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Surg & Res Serv, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Surg & Res Serv, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Arts & Sci, Dept Biol, Philadelphia, PA 19104 USA. Mayo Med Sch Clin & Fdn, Dept Physiol & Biophys, Rochester, MN USA. Mayo Med Sch Clin & Fdn, Dept Anesthesiol, Rochester, MN USA. Univ Georgia, Dept Exercise Sci, Athens, GA 30602 USA. RP Levine, S (reprint author), 1345 Bobarn Dr, Narberth, PA 19072 USA. NR 33 TC 76 Z9 80 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 15 PY 2003 VL 168 IS 6 BP 706 EP 713 DI 10.1164/rccm.200209-1070OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 721PK UT WOS:000185324600016 PM 12857719 ER PT J AU Feng, SJ Resendiz, JC Lu, X Kroll, MH AF Feng, SJ Resendiz, JC Lu, X Kroll, MH TI Filamin A binding to the cytoplasmic tail of glycoprotein Ib alpha regulates von Willebrand factor-induced platelet activation SO BLOOD LA English DT Article ID IX-V COMPLEX; INTEGRIN ALPHA(IIB)BETA(3); SHEAR-STRESS; INSIDE-OUT; PHOSPHOINOSITIDE 3-KINASE; CALCIUM SIGNALS; MEMBRANE; PROTEIN; PHOSPHORYLATION; ADHESION AB We examined the hypothesis that filamin A binding to the cytoplasmic tail of platelet glycoprotein lbalpha (Gplbalpha) is regulated by pathologic shear stress and modulates von Willebrand factor (VWF)-induced platelet activation. To begin, we examined filamin binding to Gplbalpha in Chinese hamster ovary cells coexpressing mutant human Gplb-IX and wild-type human filamin A. We observed that many different deletions and truncations N-terminal to Gplbalpha's cytoplasmic domain residue 594 disrupted filamin A binding, but that binding was unaffected by 14 different point mutations in hydrophilic residues between amino acids 557 and 593. To try to narrow Gplbalpha's filamin A-binding domain, we next measured the effect of several cytoplasmic domain peptides on human filamin A binding to a GST-Gplbalpha cytoplasmic domain fusion protein. One peptide (residues 557-575; designated "A4 peptide") inhibited filamin A binding to the GST-Gplbalpha cytoplasmic domain fusion protein and competed with Gplbalpha for binding to filamin A. When the A4 peptide was delivered to intact human platelets using a carrier peptide, we observed the dose-dependent inhibition of VWF-induced platelet aggregation in response to both ristocetin and shear stress. The effect of the A4 peptide on shear-induced platelet aggregation was accompanied by the attenuation of shear-induced filamin A binding to Gplbalpha and diminished shear-dependent protein tyrosine phosphorylation. These results suggest that shear-dependent VWF-induced platelet activation affects filamin A binding to Gplb-IX-V, and that filamin A binding to the cytoplasmic tail of Gplbalpha regulates proaggregatory tyrosine kinase signaling. (C) 2003 by The American Society of Hematology. C1 VA Med Ctr, Thrombosis Res Sect 151, Houston, TX 77030 USA. Rice Univ, Dept Biomed Engn, Houston, TX 77251 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Wihuri Res Inst, SF-00140 Helsinki, Finland. RP Kroll, MH (reprint author), VA Med Ctr, Thrombosis Res Sect 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL 65967] NR 41 TC 51 Z9 54 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2003 VL 102 IS 6 BP 2122 EP 2129 DI 10.1182/blood-2002-12-3805 PG 8 WC Hematology SC Hematology GA 721NQ UT WOS:000185322800036 PM 12791664 ER PT J AU Beer, TM Garzotto, M Henner, WD Eilers, KM Wersinger, EM AF Beer, TM Garzotto, M Henner, WD Eilers, KM Wersinger, EM TI Intermittent chemotherapy in metastatic androgen-independent prostate cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE docetaxel; calcitriol; vitamin D; prostate cancer; chemotherapy ID QUALITY-OF-LIFE; CLINICAL-TRIALS; PHASE-II; MITOXANTRONE; MEN; HYDROCORTISONE; SUPPRESSION; PREDNISONE; DOCETAXEL; QLQ-C30 AB Intermittent use of chemotherapy for androgen-independent prostate cancer ( AIPC) instead of treatment until disease progression may reduce toxicity. We prospectively tested this approach in eight AIPC patients responding to calcitriol plus docetaxel who reached a serum prostate-specific antigen (PSA) <4 ng ml(-1). Chemotherapy was suspended until a rise in PSA &GE;50% and 1 ng ml(-1). The median duration of treatment holiday was 20 weeks (13 - 43+ weeks) and all patients retained sensitivity to re-treatment. Chemotherapy holiday was associated with an improvement of fatigue ( P = 0.05). Intermittent chemotherapy for AIPC is feasible and deserves further study. C1 Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. Portland VA Med Ctr, Div Urol, Portland, OR 97207 USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Mail Code L586,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. FU NCRR NIH HHS [M01 RR000334, 3M01RR00334-33S2] NR 12 TC 37 Z9 37 U1 0 U2 0 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 SEP 15 PY 2003 VL 89 IS 6 BP 968 EP 970 DI 10.1038/sj.bjc.6601232 PG 3 WC Oncology SC Oncology GA 721LY UT WOS:000185318900004 PM 12966410 ER PT J AU Polnaszek, N Kwabi-Addo, B Peterson, LE Ozen, M Greenberg, NM Ortega, S Basilico, C Ittmann, M AF Polnaszek, N Kwabi-Addo, B Peterson, LE Ozen, M Greenberg, NM Ortega, S Basilico, C Ittmann, M TI Fibroblast growth factor 2 promotes tumor progression in an autochthonous mouse model of prostate cancer SO CANCER RESEARCH LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; INTRAEPITHELIAL NEOPLASIA; FACTOR EXPRESSION; TRANSGENIC MOUSE; EPITHELIAL-CELLS; GENE-EXPRESSION; FGF RECEPTORS; MESSENGER-RNA; ANGIOGENESIS; MICE AB Fibroblast growth factor (FGF) 2 (or basic FGF) is expressed at increased levels in human prostate cancer. FGF2 can promote cell motility and proliferation, increase tumor angiogenesis, and inhibit apoptosis, all of which play an important role in tumor progression. To determine whether FGF2 plays a critical role in prostate cancer progression, we have used the transgenic adenocarcinoma of the mouse prostate (TRAMP) model system. A high percentage of TRAMP mice develop metastatic prostate cancer, and thus the TRAMP model is useful for evaluating cancer progression. TRAMP mice were crossed with FGF2 knockout (FGF2(-/-)) mice, and tumor progression in TRAMP mice that were either hemi- or homozygous for inactivation of the FGF2 allele was compared with progression in wild-type TRAMP mice. Inactivation of even one FGF2 allele resulted in increased survival, a decrease in metastasis, and inhibition of progression to the poorly differentiated phenotype in primary prostatic tumors. When compared with wild-type mice, poorly differentiated tumors arising in FGF(+/-) and FGF(-/-) mice expressed higher levels of vascular endothelial growth factor and, in some cases, increased levels of acidic FGF intracellular binding protein, a nuclear FGF1-binding protein. These findings suggest that both FGF2-mediated angiogenesis and intranuclear FGF2 activities may promote tumor progression and support the hypothesis that FGF2 plays a significant role in prostate cancer progression in vivo. C1 Houston Vet Affairs Med Ctr, Res Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. RP Ittmann, M (reprint author), Houston Vet Affairs Med Ctr, Res Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Kwabi-Addo, Bernard/A-6993-2016 OI Kwabi-Addo, Bernard/0000-0003-3692-6350; Peterson, Leif/0000-0002-1187-0883 FU NCI NIH HHS [CA058204, CA84926] NR 41 TC 89 Z9 95 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2003 VL 63 IS 18 BP 5754 EP 5760 PG 7 WC Oncology SC Oncology GA 727RN UT WOS:000185672600018 PM 14522896 ER PT J AU Cruz, F Rubin, BP Wilson, D Town, A Schroeder, A Haley, A Bainbridge, T Heinrich, MC Corless, CL AF Cruz, F Rubin, BP Wilson, D Town, A Schroeder, A Haley, A Bainbridge, T Heinrich, MC Corless, CL TI Absence of BRAF and NRAS mutations in uveal melanoma SO CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; CUTANEOUS MALIGNANT-MELANOMA; N-RAS; FAMILIAL MELANOMA; IMATINIB MESYLATE; S-100 PROTEIN; CELL-LINES; EXPRESSION; P53; GENE AB Uveal melanoma (UM) and cutaneous melanoma (CM) differ significantly in their epidemiological, clinical, immunophenotypical, and cytogenetic features, but the molecular basis for these differences has not been delineated. CMs frequently harbor an activating mutation in either NRAS or the RAS-regulated kinase BRAF, suggesting that either of these oncogenes may increase signaling through the mitogen-activated protein (MAP) kinase pathway and promote melanoma development. The aim of this study was to examine BPAF and NPAS gene mutations in UM. Genomic DNA from CM and UM was screened for mutations in BRAF exons 11 and 15 and NPAS exons I and 2 using a combination of denaturing high-performance liquid chromatography and direct sequencing. Mutations in BRAF exon 15 were detected in 16 (36.4%) of 44 CMs and 0 (0%) of 62 UMs. The most common mutation in CM was V599E, but a novel point mutation (L596Q) was identified in two cases and an in-frame deletion/insertion (VKSRWK599-604D) was discovered in one case. No BRAF exon 11 mutations were observed among seven CMs and nine UMs that were wild-type for exon 15. Mutation of NRAS exon 2 was rare in CM [1 (3.7%) of 27] and absent in UM [0 (0%) of 47]. No NPAS exon I mutations were detected in either type of melanoma. We conclude that UMs arise independent of oncogenic BRAF and NPAS mutations, an observation that may have implications for therapies targeted to the NRAS-BRAF pathway. C1 Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Hematol & Oncol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Univ Washington, Med Ctr, Dept Anat Pathol, Seattle, WA 98195 USA. RP Corless, CL (reprint author), Oregon Hlth Sci Univ, Dept Pathol, L471,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. NR 57 TC 133 Z9 137 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2003 VL 63 IS 18 BP 5761 EP 5766 PG 6 WC Oncology SC Oncology GA 727RN UT WOS:000185672600019 PM 14522897 ER PT J AU Cabelof, DC Guo, ZM Raffoul, JJ Sobol, RW Wilson, SH Richardson, A Heydari, AR AF Cabelof, DC Guo, ZM Raffoul, JJ Sobol, RW Wilson, SH Richardson, A Heydari, AR TI Base excision repair deficiency caused by polymerase beta haploinsufficiency: Accelerated DNA damage and increased mutational response to carcinogens SO CANCER RESEARCH LA English DT Article ID HEPATOCARCINOGEN 2-NITROPROPANE; OXIDATIVE STRESS; NUCLEAR-DNA; POLY(ADP-RIBOSE) POLYMERASE; IN-VIVO; LESIONS; CELLS; MICE; XRCC1; METHYLATION AB The base excision repair pathway (BER) is believed to maintain genomic integrity by repairing DNA damage arising spontaneously or induced by oxidizing and alkylating agents. To establish the role of DNA polymerase beta (beta-pol) in BER and beta-pol-dependent BER in maintaining genomic stability, we have measured the impact of a gene-targeted disruption in the beta-pol gene on DNA repair capacity and on in vivo sensitivity to carcinogens. We have extensively phenotyped the DNA beta-pol heterozygous (beta-pol(+/-)) mouse as expressing similar to50% less beta-pol mRNA and protein and as exhibiting an equivalent reduction in the specific activity of beta-pol. We measured BER activity by in vitro G:U mismatch and (8-OH)G:C repair and find that there is a significant reduction in the ability of extracts from beta-pol(+/-) mice to repair these types of DNA damage. In vivo, the beta-pol(+/-) mice sustain higher levels of DNA single-strand breaks as well as increased chromosomal aberrations as compared with beta-pol(+/+) littermates. Additionally, we show that reduction in beta-pol expression and BER activity results in increased mutagenicity of dimethyl sulfate as evidenced by a 2-fold increase in LacI mutation frequency. Importantly, the beta-pol(+/-) mice do not exhibit increased sensitivity to DNA damage induced by N-nitroso-N-ethylurea, ionizing radiation, or UV radiation, which induce damage processed by alternative repair pathways, demonstrating that this model is specifically a BER-deficient model. C1 Wayne State Univ, Dept Nutr & Food Sci, Detroit, MI 48202 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. RP Heydari, AR (reprint author), Wayne State Univ, Dept Nutr & Food Sci, 3009 Sci Hall, Detroit, MI 48202 USA. RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 FU NIA NIH HHS [1P01-AG14674, 1P30-AG13319, P01-AG19316]; NIDDK NIH HHS [1R21-DK62256] NR 50 TC 71 Z9 75 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2003 VL 63 IS 18 BP 5799 EP 5807 PG 9 WC Oncology SC Oncology GA 727RN UT WOS:000185672600024 PM 14522902 ER PT J AU Chaiyakunapruk, N Veenstra, DL Lipsky, BA Sullivan, SD Saint, S AF Chaiyakunapruk, N Veenstra, DL Lipsky, BA Sullivan, SD Saint, S TI Vascular catheter site care: The clinical and economic benefits of chlorhexidine gluconate compared with povidone iodine SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CRITICALLY-ILL PATIENTS; CENTRAL VENOUS CATHETERS; BLOOD-STREAM INFECTION; PROSPECTIVE RANDOMIZED TRIAL; ATTRIBUTABLE MORTALITY; NOSOCOMIAL INFECTIONS; PREVENTION; COHORT; SEPSIS; CONSEQUENCES AB The use of chlorhexidine gluconate solution for vascular catheter insertion site care reduces the risk of catheter-related bloodstream infection by one-half, compared with povidone iodine. Our objective was to evaluate the cost-effectiveness of chlorhexidine gluconate versus povidone iodine. We used data from randomized, controlled trials, meta-analyses, and epidemiologic studies to construct a decision analysis model. We estimated that use of chlorhexidine, rather than povidone, for central catheter site care resulted in a 1.6% decrease in the incidence of catheter-related bloodstream infection, a 0.23% decrease in the incidence of death, and savings of $113 per catheter used. For peripheral catheter site care, the results were similar, although the differences were smaller. The results were found to be robust on multivariate sensitivity analyses. Use of chlorhexidine gluconate in place of the current standard solution for vascular catheter site care is a simple and cost-effective method of improving patient safety in the hospital setting. C1 Univ Washington, Dept Pharm, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan Hlth Syst, Patient Safety Enhancement Program, Ann Arbor, MI USA. Naresuan Univ, Dept Pharm Practice, Pitsanuloak, Thailand. RP Veenstra, DL (reprint author), Univ Washington, Dept Pharm, Pharmaceut Outcomes Res & Policy Program, Box 357630, Seattle, WA 98195 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 FU AHRQ HHS [P20-HS11540] NR 46 TC 42 Z9 46 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 15 PY 2003 VL 37 IS 6 BP 764 EP 771 DI 10.1086/377265 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 718EA UT WOS:000185131100004 PM 12955636 ER PT J AU Chan, SE Rosen, HR AF Chan, SE Rosen, HR TI Outcome and management of hepatitis C in liver transplant recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTERFERON-ALPHA; ANTIVIRAL THERAPY; VIRUS-INFECTION; GRAFT CIRRHOSIS; RIBAVIRIN; COMBINATION; RECURRENCE; EFFICACY; SURVIVAL; RETRANSPLANTATION AB Hepatitis C virus (HCV)- related cirrhosis is the leading indication for liver transplantation. Reinfection of the allograft with HCV is universal in all patients with pretransplantation viremia, and leads to histologically proven hepatitis in 50% - 80% of these patients. Recent data have demonstrated significantly higher mortality among HCV-positive liver transplant recipients. For this subgroup of patients, retransplantation remains highly controversial. As current antiviral therapy is limited in efficacy and tolerability, an improved understanding of those patients at greatest risk of developing serious HCV-induced graft injury is necessary to optimize treatment. C1 Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. RP Rosen, HR (reprint author), Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, 371 0 SW US Vet Hosp,P3-GI, Portland, OR 97207 USA. NR 37 TC 13 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 15 PY 2003 VL 37 IS 6 BP 807 EP 812 DI 10.1086/377605 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 718EA UT WOS:000185131100011 PM 12955642 ER PT J AU Littner, M Hirshkowitz, M Kramer, M Kapen, S Anderson, WM Bailey, D Berry, RB Davila, D Johnson, S Kushida, C Loube, DI Wise, M Woodson, T AF Littner, M Hirshkowitz, M Kramer, M Kapen, S Anderson, WM Bailey, D Berry, RB Davila, D Johnson, S Kushida, C Loube, DI Wise, M Woodson, T TI Practice parameters for using polysomnography to evaluate insomnia: An update SO SLEEP LA English DT Article ID ALPHA-DELTA SLEEP; PANIC DISORDER; ELECTROENCEPHALOGRAPHIC SLEEP; DIFFERENTIAL-DIAGNOSIS; NONDEPRESSED PATIENTS; ALZHEIMER-TYPE; EEG; COMPLAINTS; DISTURBANCES; CONTINUITY AB Insomnia is a common and clinically important problem. It may arise directly from a sleep-wake regulatory dysfunction and/or indirectly result from comorbid psychiatric, behavioral, medical, or neurological conditions. As an important public-health problem, insomnia requires accurate diagnosis and effective treatment. Insomnia is primarily diagnosed clinically with a detailed medical, psychiatric, and sleep history. Polysomnography is indicated when a sleep-related breathing disorder or periodic limb movement disorder is suspected, initial diagnosis is uncertain, treatment fails, or precipitous arousals occur with violent or injurious behavior. However, polysomnography is not indicated for the routine evaluation of transient insomnia, chronic insomnia, or insomnia associated with psychiatric disorders. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Sepulveda, CA USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Maimonides Hosp, Dept Psychiat, Brooklyn, NY 11219 USA. NYU, Sch Med, New York, NY USA. VA Med Ctr, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Univ S Florida, Coll Med, Tampa, FL USA. Englewood, Colorado Springs, CO USA. Univ Florida, Hlth Sci Ctr, Gainesville, FL USA. Baptist Med Ctr, Little Rock, AR USA. St Patricks Hosp, Sleep Ctr, Missoula, MT USA. Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA 94305 USA. Swedish Med Ctr, Sleep Med Inst, Seattle, WA USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Milwaukee, WI 53226 USA. RP Littner, M (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 61 TC 115 Z9 118 U1 0 U2 7 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 SEP 15 PY 2003 VL 26 IS 6 BP 754 EP 760 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 724DQ UT WOS:000185472200020 PM 14572131 ER PT J AU Loeb, HS AF Loeb, HS TI Use of angiography in the Veterans Affairs health care system and Medicare SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Loeb, HS (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 SEP 11 PY 2003 VL 349 IS 11 BP 1093 EP 1093 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 719UH UT WOS:000185223100026 PM 12968101 ER PT J AU Reusch, JEB Klemm, DJ AF Reusch, JEB Klemm, DJ TI Cyclic AMP response element-binding protein in the vessel wall - Good or bad? SO CIRCULATION LA English DT Article DE editorials; protein, DNA-binding, cyclic AMP-responsive; atherosclerosis; restenosis; cells, smooth muscle, vascular ID MUSCLE CELL-PROLIFERATION; EXPRESSION; MIGRATION/; INJURY C1 Denver VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. RP Reusch, JEB (reprint author), Denver VA Med Ctr, Endo 111-H,1055 Clermont St, Denver, CO 80220 USA. FU NHLBI NIH HHS [P01 HL 14985]; NIDDK NIH HHS [R01DK53969] NR 15 TC 17 Z9 17 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 SEP 9 PY 2003 VL 108 IS 10 BP 1164 EP 1166 DI 10.1161/01.CIR.0000084296.45158.50 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 719DF UT WOS:000185187800001 PM 12963681 ER PT J AU Johnson, KR Johnson, KY Becker, KP Bielawski, J Mao, CG Obeid, LM AF Johnson, KR Johnson, KY Becker, KP Bielawski, J Mao, CG Obeid, LM TI Role of human sphingosine-1-phosphate phosphatase 1 in the regulation of intra- and extracellular sphingosine-1-phosphate levels and cell viability SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SPHINGOSINE KINASE; SPHINGOLIPID METABOLISM; STRESS-RESPONSE; HEAT-STRESS; PHOSPHOHYDROLASE; 1-PHOSPHATE; IDENTIFICATION; DEATH; ACTIVATION AB Sphingosine-1-phosphate (S1P) is a highly bioactive lipid that exerts numerous biological effects both intracellularly as a second messenger and extracellularly by binding to its G-protein-coupled receptors of the endothelial differentiation gene family (S1P receptors-(1-5)). Intracellularly, at least two enzymes, sphingosine kinase and S1P phosphatase, regulate the activity of S1P by governing the phosphorylation status of S1P. To study the regulation of S1P levels, we cloned the human isoform of S1P phosphatase 1 (hSPPase1). The hSPPase1 has 78% homology to the mouse SPPase at the amino acid level with 6-8 possible transmembrane domains. Confocal microscopy revealed green fluorescent protein-tagged hSPPase1, expressed in either MCF7 or HEK293 cells, co-localized to endoplasmic reticulum with calreticulin. According to Northern blot analysis, hSPPase1 is expressed in most tissues, with the strongest levels found in the highly vascular tissues of placenta and kidney. Transient overexpression of hSPPase1 exhibited a 2-fold increase in phosphatase activity against S1P and dihydro-S1P, indicating that the expressed protein was functional. Small interfering RNA (siRNA) knockdown of endogenous hSPPase1 drastically reduced hSPPase1 mRNA levels, as confirmed by reverse transcription PCR, and resulted in an overall 25% reduction of in vitro phosphatase activity in the membrane fractions. Sphingolipid mass measurements in hSPPase1 siRNA knockdown cells revealed a 2-fold increase of S1P levels and concomitant decrease in sphingosine. In vivo labeling of hSPPase1 siRNA-treated cells showed accumulation of S1P within cells, as well as significantly increased secretion of S1P into the media, indicating that hSPPase1 regulates secreted S1P. In addition, siRNA-induced knockdown of hSPPase1 endowed resistance to tumor necrosis factor-alpha and the chemotherapeutic agent daunorubicin. Collectively, these data suggest that regulation of hSPPase1 with the resultant changes in cellular and secreted S1P could have important implications to cell proliferation, angiogenesis, and apoptosis. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Hosp, Div Gen Internal Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Citadel, Dept Biol, Charleston, SC 29409 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NCRR NIH HHS [1P20RR17677]; NHLBI NIH HHS [HL 07260]; NIGMS NIH HHS [GM62287] NR 25 TC 100 Z9 102 U1 0 U2 3 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 SEP 5 PY 2003 VL 278 IS 36 BP 34541 EP 34547 DI 10.1074/jbc.M301741200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 716UK UT WOS:000185047500115 PM 12815058 ER PT J AU Samaha, FF Stern, L Iqbal, N AF Samaha, FF Stern, L Iqbal, N TI Low-carbohydrate diets as compared with low-fat diets - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID LIFE-STYLE C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Samaha, FF (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 SEP 4 PY 2003 VL 349 IS 10 BP 1001 EP 1002 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 717HJ UT WOS:000185081400021 ER PT J AU Grande, D Volpp, K AF Grande, D Volpp, K TI Cost and quality of industry-sponsored meals for medical residents SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PHYSICIANS C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Grande, D (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 3 PY 2003 VL 290 IS 9 BP 1150 EP 1151 DI 10.1001/jama.290.9.1150-c PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 717LK UT WOS:000185090400006 PM 12952992 ER PT J AU Mann, DL Reid, MB AF Mann, DL Reid, MB TI Exercise training and skeletal muscle inflammation in chronic heart failure: Feeling better about fatigue SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; FACTOR-ALPHA; REACTIVE OXYGEN; DIAPHRAGM CONTRACTILITY; OXIDATIVE STRESS; PROTEIN LOSS; CACHEXIA; APOPTOSIS; DYSFUNCTION C1 Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Cardiol Sect, Houston, TX 77030 USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Sect Pulm Med, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX USA. RP Mann, DL (reprint author), Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Cardiol Sect, MS 524,6565 Fannin, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 NR 38 TC 26 Z9 26 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 SEP 3 PY 2003 VL 42 IS 5 BP 869 EP 872 DI 10.1016/S0735-1097(03)00847-7 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 716RH UT WOS:000185029200016 PM 12957434 ER PT J AU Bent, S Tiedt, TN Shlipak, MG AF Bent, S Tiedt, TN Shlipak, MG TI The relative safety of ephedra compared with other herbal products - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 Univ Calif San Francisco, San Francisco, CA 94121 USA. Med Tox Grp, Longboat Key, FL 34228 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Bent, S (reprint author), Univ Calif San Francisco, San Francisco, CA 94121 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 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 SEP 2 PY 2003 VL 139 IS 5 BP 386 EP 386 PN 1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 716PL UT WOS:000185037500015 ER PT J AU Landefeld, CS AF Landefeld, CS TI Improving health care for older persons SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 8th Regenstrief Conference CY SEP 30-OCT 02, 2002 CL MARSHALL, INDIANA ID COMPREHENSIVE GERIATRIC ASSESSMENT; FUNCTIONAL DECLINE; RANDOMIZED-TRIAL; MULTICOMPONENT INTERVENTION; HOSPITALIZED-PATIENTS; PROSTATE-CANCER; OUTCOMES; HOME; ADMISSION; PROGRAM AB Health care of the highest quality promotes successful aging. This paper examines the efforts that have been taken to improve the quality of health care, especially hospital care. Most of these efforts have evaluated conventional treatments of specific diseases; they are critical but underfunded and underused, and many practices persist without much evidence of efficacy. Fewer efforts have attempted to improve care for groups of persons in specific settings, such as the hospital. Three complementary approaches to improving comprehensive outcomes for hospitalized older persons-Geriatric Evaluation and Management, Acute Care for Elders, and the Elder Life Program-demonstrate what has been learned about improving care for older persons by redesigning microsystems of care. A research agenda for advancing successful aging should include specific actions to improve the quality of health care. C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, Div Geriatr, Box 1265, San Francisco, CA 94143 USA. FU NIA NIH HHS [K07 AG00912] NR 19 TC 31 Z9 31 U1 0 U2 3 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 SEP 2 PY 2003 VL 139 IS 5 SU S BP 421 EP 424 PN 2 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 718FE UT WOS:000185133800008 PM 12965969 ER PT J AU Jha, AK Varosy, PD Kanaya, AM Hunninghake, DB Hlatky, MA Waters, DD Furberg, CD Shlipak, MG AF Jha, AK Varosy, PD Kanaya, AM Hunninghake, DB Hlatky, MA Waters, DD Furberg, CD Shlipak, MG TI Differences in medical care and disease outcomes among black and white women with heart disease SO CIRCULATION LA English DT Article DE women; epidemiology; prevention ID ACUTE MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; RACIAL VARIATION; RISK-FACTORS; RACE; SEX; MORTALITY; MEN AB Background-The risk of cardiovascular mortality is higher among black women than white women, and the reasons for this disparity are largely unexplored. We sought to evaluate differences in medical care and clinical outcomes among black and white women with established coronary artery disease. Methods and Results-Among the 2699 women enrolled in the Heart and Estrogen/progestin Replacement Study (HERS), we used Cox proportional hazards models to determine the association of race with risk of coronary heart disease (CHD) events independent of major cardiovascular risk factors or medical therapies. During an average of 4.1 years of follow-up, CHD events were twice as likely in black compared with white women (6.4 versus 3.1 per 100 person-years, hazard ratio, 2.1; 95% confidence interval, 1.5 to 2.8; P<0.001). Black women had higher rates of hypertension, diabetes, and hypercholesterolemia, yet were less likely to receive aspirin or statins. Black women less often had optimal blood pressure (56% versus 63%; P=0.01) and LDL cholesterol (30% versus 38%; P=0.04) control at baseline and during follow-up. After adjusting for these and other differences, black women still had >50% higher CHD event risk (hazard ratio, 1.52; 95% confidence interval, 1.1 to 2.1; P=0.03). Conclusions-In a large cohort of women with heart disease, black women less often received appropriate preventive therapy and adequate risk factor control despite a greater CHD event risk. Interventions to improve appropriate therapy and risk factor control in all women, and especially black women, are needed. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Div Gen Med, San Francisco, CA 94143 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Wake Forest Sch Med, Winston Salem, NC USA. RP Jha, AK (reprint author), Brigham & Womens Hosp, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. NR 18 TC 85 Z9 85 U1 1 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 SEP 2 PY 2003 VL 108 IS 9 BP 1089 EP 1094 DI 10.1161/01.CIR.0000085994.38132.E5 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 717KN UT WOS:000185087800013 PM 12939228 ER PT J AU Bonner, LT AF Bonner, LT TI Merging academic medicine with community activism: An academic psychiatrist chronicles her day SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Bonner, LT (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD FAL PY 2003 VL 27 IS 3 BP 209 EP 210 DI 10.1176/appi.ap.27.3.209 PG 2 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 723ND UT WOS:000185437700026 PM 12969857 ER PT J AU Kearney, DJ Liu, CF Crump, C Brousal, A AF Kearney, DJ Liu, CF Crump, C Brousal, A TI The effect of a Helicobacter pylori treatment strategy on health care expenditures in patients with peptic ulcer disease and dyspepsia SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; DUODENAL-ULCER; DOUBLE-BLIND; FOLLOW-UP; MAINTENANCE ORGANIZATION; CAMPYLOBACTER-PYLORI; NONULCER DYSPEPSIA; GENERAL-PRACTICE AB OBJECTIVE: The aim of this study was to determine whether treatment for Helicobacter pylori (H. pylori) for patients with dyspepsia or a history of peptic ulcer decreases hospital expenditures. METHODS: Patients receiving acid suppressive medications were interviewed. Those with a documented ulcer, a self-reported ulcer, or dyspepsia were tested for H. pylori and treated with antibiotics if seropositive. Acid suppressive medications were stopped on completion of H. pylori therapy unless there was a history of gastroesophageal reflux disease (GERD) or Barrett's esophagus, and were started again at the discretion of primary care providers. Total hospital costs and GI medication costs in the 12 months before H. pylori treatment were compared to costs 12 months after H. pylori treatment. RESULTS: A total of 432 consecutive patients were treated for H. pylori. Of the patients, 125 (29%) had dyspepsia, 45 (10%) documented peptic ulcer, and 262 (61%) self-reported peptic ulcer. Total costs (mean $327 +/- 349 vs $291 +/- 362, p = 0.06) and medication costs (mean $207 +/- 237 vs $224 +/- 277, p = 0.38) were not significantly different after treatment versus before treatment. A significant decrease in expenditures was limited to patients chronically on acid suppressive medications who had documented peptic ulcers and no history of GERD or Barrett's esophagus (mean $482 +/- 274 vs $282 +/- 218, p = 0.03). CONCLUSIONS: Treatment of H. pylori for patients with chronic dyspepsia or self-reported peptic ulcer does not reduce expenditures over 1 yr of follow up. H. pylori treatment for patients chronically receiving acid suppressive treatment with a prior documented ulcer significantly reduces expenditures if GERD and Barrett's esophagus are absent. (C) 2003 by Am. Coll. of Gastroenterology. C1 VA Puget Sound Health Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Serv Pharm, Seattle, WA USA. RP Kearney, DJ (reprint author), VAMC, 111G1,1660 S Columbian Way, Seattle, WA 98108 USA. NR 40 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2003 VL 98 IS 9 BP 1952 EP 1962 DI 10.1016/S0002-9270(03)00433-7 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 726CR UT WOS:000185581000009 PM 14499771 ER PT J AU Ioannou, GN Chapko, MK Dominitz, JA AF Ioannou, GN Chapko, MK Dominitz, JA TI Predictors of colorectal cancer screening participation in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID FECAL OCCULT-BLOOD; SERVICES TASK-FORCE; COST-EFFECTIVENESS; ASYMPTOMATIC ADULTS; SOCIETY GUIDELINES; PROSTATE-CANCER; AVERAGE-RISK; SURVEILLANCE; MORTALITY; CARE AB OBJECTIVE: Our aim was to identify predictors of colorectal cancer screening in the United States and subgroups with particularly low rates of screening. METHODS: The responses to a telephone-administered questionnaire of a nationally representative sample of 61,068 persons aged greater than or equal to50 yr were analyzed. Current screening was defined as either sigmoidoscopy/colonoscopy in the preceding 5 years or fecal occult blood testing (FOBT) in the preceding year, or both. RESULTS: Overall, current colorectal cancer screening was reported by 43.4% (sigmoidoscopy/colonoscopy by 22.8%, FOBT by 9.9%, and both by 10.7%). The lowest rates of screening were reported by the following subgroups: those aged 50-54 yr (31.2%), Hispanics (31.2%), Asian/Pacific Islanders (34.8%), those with education less than the ninth grade (34.4%), no health care coverage (20.4%), or coverage by Medicaid (29.2%), those who had no routine doctor's visit in the last year (20.3%), and every-day smokers (32.1%). The most important modifiable predictors of current colorectal cancer screening were health care coverage (OR = 1.7, 95% Cl = 1.5-1.9) and a routine doctor's visit in the last year (OR = 3.5, 95% Cl = 3.2-3.8). FOBT was more common in women than in men (OR = 1.8, 95% Cl = 1.6-2.0); sigmoidoscopy/colonoscopy was more common in Hispanics (OR = 1.4, 95% CI 1.1-1.7) and Asian/Pacific Islanders (OR = 2.4, 95% Cl 1.5-3.9) relative to whites, in persons without routine doctor's visits in the preceding year (OR = 3.3, 95% CI = 2.8-4), and in persons with poor self-reported health (OR = 1.3, 95% CI = 1.2-1.5). CONCLUSIONS: Interventions should be developed to improve screening for the subgroups who reported the lowest screening rates. Such interventions may incorporate individual screening strategy preferences. (C) 2003 by Am. Coll. of Gastroenterology. C1 Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, Seattle, WA 98108 USA. Univ Washington, Div Gastroenterol, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, MS 152,Room 422,1660 S Columbian Way, Seattle, WA 98108 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 49 TC 177 Z9 178 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2003 VL 98 IS 9 BP 2082 EP 2091 DI 10.1016/S0002-9270(03)00423-4 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 726CR UT WOS:000185581000030 PM 14499792 ER PT J AU Basile, AN AF Basile, AN TI Optimizing antihypertensive treatment in clinical practice SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article; Proceedings Paper CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NY SP Amer Soc Hypertens DE hypertension; diabetes; ischemic heart disease; antihypertensive therapy; beta-blockers ID HIGH BLOOD-PRESSURE; ACUTE MYOCARDIAL-INFARCTION; CHRONIC HEART-FAILURE; RANDOMIZED-TRIAL; HYPERTENSIVE PATIENTS; PRIMARY PREVENTION; METOPROLOL; MORTALITY; MAPHY; PREVALENCE AB Hypertension affects approximately 50 million individuals in the United States (US) and approximately I billion individuals worldwide. Blood pressure (BP) reduction significantly lowers the risk of cardiovascular (CV) disease the most common cause of death in the US-yet only approximately one third of Americans with hypertension have their disease controlled to the minimum recommended level of <140/90 mm. Hg. Clinical trials such as the Hypertension Optimal Treatment (HOT) study, and Treatment of Mild Hypertension Study (TOMHS) have shown that control of BP to targets of less than or equal to140/90 mm Hg reduces the likelihood of CV disease and improves quality of life. This appears to be true even in patients at high risk, such as those with diabetes. Furthermore, it has become increasingly recognized that multiple BP-lowering agents are usually necessary to achieve BP control (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease). In fact, current hypertension guidelines clearly state that most hypertensive patients will require two or more agents, and recommend initiating treatment with two antihypertensive medications if the BP is >20/10 mm Hg above goal BP. A valuable class of drug in the management of hypertension, beta-blockers (betaB) play an important role-whether as initial agents or as add-on therapy. They are especially useful in hypertensive patients with certain comorbidities such as diabetes or heart failure, in patients post-myocardial infarction, or in those generally at high risk for coronary disease. This article explores the cardioprotective role of how OB may be used to optimize antihypertensive treatment. (C) 2003 American Journal of Hypertension, Ltd. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Med, Div Gen Internal Med Geriatr, Charleston, SC 29401 USA. RP Basile, AN (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Med, Div Gen Internal Med Geriatr, 109 Bee St, Charleston, SC 29401 USA. EM Jan.Basile@med.va.gov NR 25 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD SEP PY 2003 VL 16 IS 9 SU S BP 13S EP 17S DI 10.1016/S0895-7061(03)00967-1 PN 2 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 726MN UT WOS:000185603000004 ER PT J AU Broberg, CS Giraud, GD Schultz, JM Thornburg, KL Hohimer, AR Davis, LE AF Broberg, CS Giraud, GD Schultz, JM Thornburg, KL Hohimer, AR Davis, LE TI Fetal anemia leads to augmented contractile response to hypoxic stress in adulthood SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE phlebotomy; end-systolic elastance ID PRESSURE-OVERLOAD HYPERTROPHY; CANINE LEFT-VENTRICLE; CARDIOVASCULAR-DISEASE; SHEEP; FLOW; DYSFUNCTION; RESERVE; GROWTH; RATIO; LIFE AB In response to chronic fetal anemia, coronary blood flow, maximal coronary conductance, and coronary reserve increase. We sought to determine whether chronic fetal anemia alters left ventricular (LV) function in adulthood. We studied adult sheep that had been made anemic for 20 days in utero by phlebotomy. They were transfused just before birth. At 7 mo of age, LV function was measured by pressure-volume loops at rest and during hypoxic stress. The in utero anemia group (n = 8) did not differ from controls (n = 5) with respect to hematocrit, heart and body weight, or baseline hemodynamic parameters. However, the effect of hypoxia ( relative to baseline) on multiple indexes of systolic function was different between the two groups. End-systolic elastance increased in the in utero anemia group ( baseline to hypoxia) by 4.15 +/- 3.47 mmHg/ml (mean +/- SD) but changed little in controls (0.24 +/- 0.45), which shows that the response to hypoxia was significantly different (P < 0.01) between groups. Similarly, the maximum derivative of LV pressure with respect to time increased in the in utero anemia group (486 &PLUSMN; 340 mmHg/s,) but on average fell in the controls (-503 &PLUSMN; 211 mmHg/s) with the response again being significantly different ( P < 0.03). We conclude that in sheep, perinatal anemia can alter cardiac responses to hypoxic stress in the adult long after restoration of normocythemia. C1 Oregon Hlth Sci Univ, Dept Med, Div Cardiol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Cardiol, Portland, OR 97201 USA. RP Davis, LE (reprint author), Div Maternal Fetal Med, Med Res Bldg,L-458,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Thornburg, Kent/0000-0002-5561-4785 FU NICHD NIH HHS [P02 HD-34430]; PHS HHS [LH-45043] NR 23 TC 22 Z9 23 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2003 VL 285 IS 3 BP R649 EP R655 DI 10.1152/ajpregu.00656.2002 PG 7 WC Physiology SC Physiology GA 710KV UT WOS:000184680100022 PM 12775557 ER PT J AU Hazlett, EA Levine, J Buchsbaum, MS Silverman, JM New, A Sevin, EM Maldari, LA Siever, LJ AF Hazlett, EA Levine, J Buchsbaum, MS Silverman, JM New, A Sevin, EM Maldari, LA Siever, LJ TI Deficient attentional modulation of the startle response in patients with schizotypal personality disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID EYEBLINK MODIFICATION; SCHIZOPHRENIA; REFLEX; SYMPTOMS AB Objective: Attentional deficits have been identified as an abnormality that individuals with schizotypal personality disorder share with schizophrenia patients. The purpose of this study was to examine automatic sensorimotor gating and controlled attentional modulation of the startle eye blink response in unmedicated subjects with schizotypal personality disorder. Method: Eighteen unmedicated patients with schizotypal personality disorder and 16 healthy individuals were assessed in an acoustic attention-to-prepulse paradigm. The participants performed a selective attention task involving the presentation of attended, ignored, and novel tones that served as prepulse tones. Acoustic startle probes were presented at short and long lead intervals after the onset of tones and occasionally during the intertone interval. Results: The comparison subjects showed greater prepulse inhibition and prepulse facilitation during the attended than the ignored prepulses, demonstrating early and later attentional modulation of startle eye blink response. In contrast, the subjects with schizotypal personality disorder failed to show this pattern. Conclusions: Subjects with schizotypal personality disorder have deficits in controlled attentional processing, as indexed by modification of the startle eye blink response, that are similar to those observed in patients with schizophrenia. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. RP Hazlett, EA (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505, New York, NY 10029 USA. FU NCRR NIH HHS [RR 0071]; NIMH NIH HHS [MH 58673] NR 23 TC 20 Z9 21 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2003 VL 160 IS 9 BP 1621 EP 1626 DI 10.1176/appi.ajp.160.9.1621 PG 6 WC Psychiatry SC Psychiatry GA 718PV UT WOS:000185156400012 PM 12944337 ER PT J AU Kao, WHL Kammerer, CM Schneider, JL Bauer, RL Mitchell, BD AF Kao, WHL Kammerer, CM Schneider, JL Bauer, RL Mitchell, BD TI Type 2 diabetes is associated with increased bone mineral density in Mexican-American women SO ARCHIVES OF MEDICAL RESEARCH LA English DT Article DE osteoporosis; diabetes; Mexican-Americans; insulin ID GROWTH FACTOR-I; HORMONE-BINDING GLOBULIN; X-RAY ABSORPTIOMETRY; SARCOMA CELL-LINE; HIP FRACTURE; POSTMENOPAUSAL WOMEN; RISK-FACTORS; ESTROGEN REPLACEMENT; PREMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY AB Background. Our purpose was to determine whether type 2 diabetes is associated with altered bone mineral density (BMD) and whether fasting serum insulin levels are correlated with BMD. Methods. In a population-based family study of Mexican-Americans, we obtained measurements of BMD, diabetes status (by 2-h oral glucose tolerance test), obesity, and serum insulin concentrations in 600 subjects from 34 families. Analyses were stratified by sex and conditioned on the pedigree structure to account for residual correlations among related individuals. Results. Women with diabetes had significantly higher BMD at hip than women without diabetes (p = 0.03) even after adjustment for age, body mass index (BMI), and menopause status. BMD at spine was also higher in diabetic women than in nondiabetic women, although the association was no longer statistically significant after adjustment for BMI. Diabetes was not associated with BMD in men. In nondiabetic men and women, insulin levels were significantly correlated with BMD after adjustment for age and other lifestyle covariates, but correlations were diminished and were no longer statistically significant after further adjustment for body mass index. Conclusions. These results suggest that Mexican-American women with type 2 diabetes have hi-her BMD compared to their nondiabetic counterparts, with the association independent of obesity at hip, although not at spine or forearm. Increased BMD was also correlated with serum insulin levels, although this association was not independent of obesity. Longitudinal studies may be required to better define the mechanisms underlying the observed association between BMD and diabetes. (C) 2003 IMSS. Published by Elsevier Inc. C1 Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. Univ Pittsburgh, Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15260 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. RP Mitchell, BD (reprint author), Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, 660 W Redwood St,Room 492, Baltimore, MD 21201 USA. OI Mitchell, Braxton/0000-0003-4920-4744 FU NCRR NIH HHS [M01-RR-01346]; NHLBI NIH HHS [P01-HL45522]; NIAMS NIH HHS [R01-AR43351] NR 58 TC 30 Z9 35 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0188-4409 J9 ARCH MED RES JI Arch. Med. Res. PD SEP-OCT PY 2003 VL 34 IS 5 BP 399 EP 406 DI 10.1016/j.rcmed.2002.07.001 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 743YT UT WOS:000186601700009 PM 14602507 ER PT J AU Kelly, JA Sestak, AL Kilpatrick, J Frank, S Hutchings, D Garriott, CP Weese, J Cooney, C Aberle, TJ Namjou, B Gray-McGuire, C Bruner, GR Kaufman, KM Guthridge, JM James, JA Harley, JB AF Kelly, JA Sestak, AL Kilpatrick, J Frank, S Hutchings, D Garriott, CP Weese, J Cooney, C Aberle, TJ Namjou, B Gray-McGuire, C Bruner, GR Kaufman, KM Guthridge, JM James, JA Harley, JB TI Confirmation of susceptibility loci at 1q22-23, 4p16-15 and 11p13 in pedigrees multiplex for systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Univ Oklahoma, US Dept Vet Affairs, Med Ctr, OMRF,Hlth Sci Ctr, Oklahoma City, OK USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 496 BP S225 EP S225 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432800540 ER PT J AU Kovac, SH Patino, F Saag, KG Mikuls, TR AF Kovac, SH Patino, F Saag, KG Mikuls, TR TI The association of race and residence on HRQoL for self-reported arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. Univ Nebraska, Ctr Med, Omaha VA Med Ctr, Omaha, NE 68198 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 561 BP S249 EP S249 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432800605 ER PT J AU Morehead, K Chan, OTM Daikh, DI AF Morehead, K Chan, OTM Daikh, DI TI Magnetic resonance imaging of central nervous system disease in a murine model of systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Hawaii, Sch Med, Honolulu, HI 96822 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 422 BP S198 EP S198 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432800466 ER PT J AU Aikawa, K Retzlaff, B Fish, B Walden, C Kahn, S Knopp, R AF Aikawa, K Retzlaff, B Fish, B Walden, C Kahn, S Knopp, R TI Dyslipidemia of insulin resistance and obesity: Gender differences SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 13th International Symposium on Atherosclerosis CY SEP 28-OCT 02, 2003 CL KYOTO, JAPAN C1 Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Univ Washington, NW Lipid Res Clin, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD SEP PY 2003 VL 4 IS 2 BP 260 EP 260 DI 10.1016/S1567-5688(03)91120-2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 749NH UT WOS:000186926501117 ER PT J AU Lu, S Chen, GL Ren, CX Kwabi-Addo, B Epner, DE AF Lu, S Chen, GL Ren, CX Kwabi-Addo, B Epner, DE TI Methionine restriction selectively targets thymidylate synthase in prostate cancer cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE methionine; folate; thymidylate synthase; prostate neoplasms ID LEUKEMIC HEMATOPOIETIC-CELLS; TOTAL PARENTERAL-NUTRITION; BRAIN-TUMOR XENOGRAFTS; HUMAN GASTRIC-CANCER; IN-VIVO; RECOMBINANT METHIONINASE; URACIL MISINCORPORATION; ANTICANCER EFFICACY; METABOLIC DEFECT; CLINICAL-TRIAL AB Tumor cells are more sensitive to methionine restriction than normal tissues, a phenomenon known as methionine auxotrophy. Previous studies showed that 5-fluorouracil and methionine restriction act synergistically against a variety of tumors. The purpose of the current studies was to determine the molecular mechanism(s) underlying this synergy. 5-Fluorouracil is known to inhibit thymidylate synthase (TS), a key enzyme that transfers a methyl group from 5,10-methylene-tetrahydrofolate to dUMP during nucleotide biosynthesis. We found that methionine restriction reduced 5, 10-methylene-tetrahydrofolate levels by 75% and selectively inhibited TS activity in PC-3 human prostate cancer cells within 24 hr, whereas it did not in normal prostate epithelial cells. The observed fall in TS activity was accompanied by a commensurate reduction in TS protein levels as determined by western blot analysis. In contrast, 5-fluorouracil inhibited TS activity by >90% but increased TS protein levels. This increase was abrogated by methionine restriction. Surprisingly, methionine restriction increased H-3-leucine incorporation in PC-3 cells over the first 24 hr, suggesting that reduction of TS levels was not simply due to global protein synthesis inhibition. Methionine restriction also significantly reduced the ratio of dUMP to dTTP in PC-3 cells, creating an imbalanced nucleotide pool. These results suggest that synergy between methionine restriction and 5-fluorouracil is attributable to multiple factors, including depletion of reduced folates, selective inhibition of TS, and creation of an imbalanced nucleotide pool. Dietary and/or enzymatic methionine restriction combined with 5-fluoruracil has great promise as a novel treatment for advanced cancer. (C) 2003 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, VA Med Ctr, Dept Med, Med Serv 111H, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Dept Pathol, Houston, TX 77030 USA. RP Epner, DE (reprint author), Baylor Coll Med, VA Med Ctr, Dept Med, Med Serv 111H, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Kwabi-Addo, Bernard/A-6993-2016 OI Kwabi-Addo, Bernard/0000-0003-3692-6350 NR 48 TC 7 Z9 8 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 2003 VL 66 IS 5 BP 791 EP 800 DI 10.1016/S0006-2952(03)00406-4 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 721NT UT WOS:000185323000012 PM 12948860 ER PT J AU Dallalio, G Fleury, T Means, RT AF Dallalio, G Fleury, T Means, RT TI Serum hepcidin in clinical specimens SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE anaemia; anaemia of chronic disease; hepcidin; iron absorption; iron deficiency ID CHRONIC DISEASE; RHEUMATOID-ARTHRITIS; IRON OVERLOAD; ANEMIA; INFLAMMATION; PEPTIDE; LIVER; PATHOGENESIS; EXPRESSION; MECHANISM AB The hepatic antimicrobial protein, hepcidin, is implicated in duodenal iron absorption and mobilization. Overexpression of the hepcidin gene is associated with a hypoferraemic, microcytic, iron-refractory anaemia. On the basis of these observations, it has been proposed that hepcidin is a mediator of the common clinical syndrome, anaemia of chronic disease (ACD), and recent findings evaluating urinary hepcidin production in patients support this hypothesis. In the present report, serum hepcidin concentrations were measured in 55 specimens submitted for ferritin determination, and in 37 specimens collected from anaemic patients undergoing diagnostic bone marrow examination. The serum hepcidin concentration exhibited a statistically significant correlation with serum ferritin concentrations in both patient subsets. No statistically significant correlations were observed between serum hepcidin and other laboratory markers of iron status or anaemia diagnosis. Serum hepcidin does not appear to correlate as well with clinical diagnosis as urinary hepcidin, suggesting that a better understanding of the clearance and metabolism of this protein is required to understand fully its potential contribution to the pathogenesis of ACD. C1 Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Div Hematol Oncol, Dept Med, Charleston, SC USA. RP Means, RT (reprint author), Med Univ S Carolina, Div Hematol Oncol, 903 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 FU NHLBI NIH HHS [HL69418-01] NR 19 TC 73 Z9 77 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2003 VL 122 IS 6 BP 996 EP 1000 DI 10.1046/j.1365-2141.2003.04516.x PG 5 WC Hematology SC Hematology GA 719HC UT WOS:000185196700015 PM 12956771 ER PT J AU Chopra, V Marmur, JD Cavusoglu, E AF Chopra, V Marmur, JD Cavusoglu, E TI The role of clopidogrel in the management of patients with ischemic heart disease SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Review DE atherosclerosis; thrombosis; ischemic heart disease; clopidogrel; aspirin; thienopyridine ID ACUTE CORONARY SYNDROMES; IN-STENT RESTENOSIS; INTRACORONARY GAMMA-RADIATION; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; ARTERY DISEASE; INTRAVASCULAR ULTRASOUND; NEOINTIMAL PROLIFERATION; CARDIOVASCULAR-DISEASE AB Antiplatelet therapy plays a pivotal role in the treatment of patients across the entire spectrum of coronary artery disease. Platelets are believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. While aspirin remains the traditional antiplatelet agent in patients with CAD, adverse vascular events continue to occur in patients on aspirin therapy. Clopidogrel is a relatively new antiplatelet agent and is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. As a member of the class of drugs known as the thienopyridines, clopidogrel irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate ( ADP) receptors on its surface. The findings of a number of seminal clinical trials have expanded the indications for the use of clopidogrel in patients with coronary artery disease. When used in conjunction with aspirin, these studies have demonstrated an incremental benefit of clopidogrel above and beyond that of aspirin alone. This article reviews the data supporting the use of clopidogrel in patients with atherosclerotic heart disease, and makes recommendations for its use based on the available evidence. C1 SUNY Hlth Sci Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. Bronx Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. RP Cavusoglu, E (reprint author), SUNY Hlth Sci Ctr, Dept Med, Div Cardiol, 450 Clarkson Ave, Brooklyn, NY 11203 USA. EM ecavusoglu@aol.com NR 54 TC 13 Z9 13 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD SEP-NOV PY 2003 VL 17 IS 5-6 BP 467 EP 477 DI 10.1023/B:CARD.0000015862.62649.c8 PG 11 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 773KJ UT WOS:000188922700010 PM 15107602 ER PT J AU Tahir, SA Ren, CZ Timme, TL Gdor, Y Hoogeveen, R Morrisett, JD Frolov, A Ayala, G Wheeler, TM Thompson, TC AF Tahir, SA Ren, CZ Timme, TL Gdor, Y Hoogeveen, R Morrisett, JD Frolov, A Ayala, G Wheeler, TM Thompson, TC TI Development of an immunoassay for serum caveolin-1: A novel biomarker for prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SURVIVAL/CLONAL GROWTH; RADICAL PROSTATECTOMY; CLINICAL STAGE; ANTIGEN; EXPRESSION; CELLS; METASTASIS AB Purpose: Caveolin-1 (cav-1), the major protein component of caveolae, plays an important role in multiple signaling pathways, molecular transport, and cellular proliferation and differentiation. The specific functions of cav-1/ caveolae are highly cell and context dependent. We have previously shown that cav-1 expression is increased in metastatic human prostate cancer and that cav-1 cellular protein expression is predictive of recurrence of the disease after radical prostatectomy. Recently, we reported that cav-1 is secreted by androgen-insensitive prostate cancer cells, and we detected, by Western blotting, cav-1 in the high-density lipoprotein, fraction of serum specimens from patients with prostate cancer. Experimental Design: Using rabbit polyclonal antibodies with specificity for cav-1, we developed a direct sandwich inummoassay for the determination of cav-1 in serum. A recombinant human cav-1 fusion protein was overexpressed and purified from 293 PE cells and used as a calibrator. Results: The assay was highly specific and had a minimum detection limit of 0.017 ng/ml (mean + 3 SD of zero calibrator) and measuring range of up to 200 ng/ml. Intra-assay coefficient of variation was 2.29-6.74% and inter-assay coefficient of variation was 2.81-6.43% over the serum concentration tested 0.04-31.89 ng/ml. The recovery limit of cav-1 by the assay was 89.55-100.28%. The median serum cav-1 level in 102 prostate cancer patients with clinically localized disease (0.463 ng/ml) was significantly higher than 81 healthy control men (0.324 ng/ml; P = 0.0446, Mann-Whitney test) or 107 men with benign prostatic hyperplasia (0.172 ng/ml; P = 0.0317, Mann-Whitney test). Conclusions: Our results indicate that serum cav-1 has the power to differentiate between prostate cancer and benign prostatic hyperplasia patients and the potential to be an important biomarker for prostate cancer. Additional studies to test the potential of serum cav-1 as a diagnostic and/or prognostic marker in prostate cancer are warranted. C1 Scott Dept Urol, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. RP Thompson, TC (reprint author), Scott Dept Urol, 6560 Fannin St,Suite 2100, Houston, TX 77030 USA. FU NCI NIH HHS [CA 50588, CA 68814] NR 22 TC 59 Z9 64 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2003 VL 9 IS 10 BP 3653 EP 3659 PN 1 PG 7 WC Oncology SC Oncology GA 725NB UT WOS:000185548300019 PM 14506154 ER PT J AU Inadomi, JM Sonnenberg, A AF Inadomi, John M. Sonnenberg, Amnon TI An evidence-based medicine approach to economic studies: assessing the cost-effectiveness of competing strategies for colorectal cancer screening SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article AB Cost-effectiveness analysis aims to quantitatively compare the expected outcomes of competing management strategies in environments with limited economic resources. A valid economic study models all relevant strategies from an appropriate perspective. The model must use costs that are accurately measured and strategies that have established clinical effectiveness, and appropriately integrate these data. The results should include the incremental cost-effectiveness ratio, which quantifies the resources required to achieve greater benefit with one strategy compared to another. A sensitivity analysis is required to determine whether uncertainty in assumptions alters the conclusions. Final interpretation of a cost-effectiveness analysis relies on whether costs and outcomes in the study can be realized in one's own health care environment. C1 [Inadomi, John M.] Vet Adm Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. [Inadomi, John M.] Univ Michigan, Dept Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. RP Inadomi, JM (reprint author), VA Med Ctr, 111-D,2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM jinadomi@umich.edu RI Inadomi, John/A-6221-2014 OI Inadomi, John/0000-0001-6776-8661 NR 44 TC 3 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2003 VL 1 IS 5 BP 404 EP 413 DI 10.1053/S1542-3565(03)00181-2 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KK UT WOS:000208071100011 PM 15017661 ER PT J AU Pappas, PG Rex, JH Lee, J Hamill, RJ Larsen, RA Powderly, W Kauffman, CA Hyslop, N Mangino, JE Chapman, S Horowitz, HW Edwards, JE Dismukes, WE AF Pappas, PG Rex, JH Lee, J Hamill, RJ Larsen, RA Powderly, W Kauffman, CA Hyslop, N Mangino, JE Chapman, S Horowitz, HW Edwards, JE Dismukes, WE CA NIAID Mycoses Study Grp TI A prospective observational study of candidemia: Epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTENSIVE-CARE UNIT; BLOOD-STREAM INFECTIONS; RISK-FACTORS; AMPHOTERICIN-B; PARAPSILOSIS FUNGEMIA; ACQUIRED CANDIDEMIA; CANCER-PATIENTS; ATTRIBUTABLE MORTALITY; NOSOCOMIAL CANDIDEMIA; RANDOMIZED TRIAL AB We conducted a prospective, multicenter observational study of adults (n = 1447) and children (n = 144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P < .001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P < .001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials. C1 Univ Alabama, Div Infect Dis, Birmingham, AL 35294 USA. Univ Texas, Houston, TX USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Washington Univ, St Louis, MO USA. Univ Michigan, Ann Arbor, MI 48109 USA. Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. Tulane Univ, New Orleans, LA 70118 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. New York Med Coll, Westchester Cty Med Ctr, Valhalla, NY 10595 USA. Univ Calif Los Angeles, Harbor Med Ctr, Los Angeles, CA 90024 USA. Univ So Calif, Los Angeles, CA USA. RP Pappas, PG (reprint author), Univ Alabama, Div Infect Dis, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. FU PHS HHS [N01-AL-65296] NR 52 TC 482 Z9 512 U1 4 U2 18 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2003 VL 37 IS 5 BP 634 EP 643 DI 10.1086/376906 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 715YK UT WOS:000185001900003 PM 12942393 ER PT J AU Faulconbridge, LF Cummings, DE Kaplan, JM Grill, HJ AF Faulconbridge, LF Cummings, DE Kaplan, JM Grill, HJ TI Hyperphagic effects of brainstem ghrelin administration SO DIABETES LA English DT Article ID GROWTH-HORMONE SECRETAGOGUE; FOOD-INTAKE; MESSENGER-RNA; SOLITARY TRACT; ACYLATED PEPTIDE; NEUROPEPTIDE-Y; BLOOD-GLUCOSE; NUCLEUS; RAT; RECEPTOR AB The role of ghrelin in feeding control has been addressed from a largely hypothalamic perspective, with little attention directed at ingestive consequences of stimulation of the peptide's receptor, the growth hormone secretagogue receptor (GHS-R), in the caudal brainstem. Here, we demonstrate a hyperphagic response to stimulation of GHS-R in the caudal brainstem. Ghrelin (150 pmol) delivered to the third and fourth ventricles significantly and comparably increased cumulative food intake, with maximal response similar to3 It after injection. The meal patterning effects underlying this hyperphagia were also similar for the two placements (i.e., significant reduction in the time between injection and first-meal onset, an increase in the number of meals taken shortly after the injection, and a trend toward an increase in the average size of the first meals that approached but did not achieve statistical significance). In a separate experiment, ghrelin microinjected unilaterally into the dorsal vagal complex (DVC) significantly increased food intake measured 1.5 and 3 h after treatment. The response was obtained with a 10-pmol dose, establishing the DVC as a site of action with at least comparable sensitivity to that reported for the arcuate nucleus. Taken together, the results affirm a caudal brainstem site of action and recommend further investigation into multisite interactions underlying the modulation of ingestive behavior by ghrelin. C1 Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Faulconbridge, LF (reprint author), Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. FU NIDDK NIH HHS [DK21397, DK42284] NR 25 TC 172 Z9 174 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 SEP PY 2003 VL 52 IS 9 BP 2260 EP 2265 DI 10.2337/diabetes.52.9.2260 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 716KP UT WOS:000185027600009 PM 12941764 ER PT J AU Badger, TM Ronis, MJJ Frank, SJ Chen, Y He, L AF Badger, TM Ronis, MJJ Frank, SJ Chen, Y He, L TI Effects of chronic ethanol on hepatic and renal CYP2C11 in the male rat: Interactions with the Janus-Kinase 2-signal transducer and activators of transcription proteins 5b pathway SO ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE-RECEPTOR; CHRONIC ALCOHOL-CONSUMPTION; GENE-EXPRESSION; BINDING-PROTEIN; LIVER; CELLS; CYTOCHROME-P450; PROLACTIN; STAT5B; DEHYDROGENASE AB Chronic alcohol intake in male rats results in: 1) demasculinization of the GH pulse pattern; 2) reduced serum testosterone concentrations; and 3) decreased expression hepatic CYP2C11. Hepatic CYP2C11 expression is regulated by the male pattern of GH through the Janus-kinase/signal transducer and activators of transcription proteins (JAK/STAT) signal transduction pathway in the male rat. Renal CYP2C11 is regulated by testosterone, not GH. The involvement of the JAK/STAT5b signal transduction pathway in renal CYP2C11 signaling has not been studied. We tested the hypothesis that ethanol reduces CYP2C11 levels by interfering with the JAK/STAT5b pathway. Using a total enteral nutrition (TEN) model to feed rats a well-balanced diet, we have studied the effects of chronic ethanol intake (21 d) on hepatic and renal JAK/STAT pathway of adult male rats (8-10/group). We found decreased hepatic and renal expression of CYP2C11 in ethanol-fed rats with concomitant decreases in STAT5b and phospho-STAT5b, decreased in vitro hepatic STAT5b binding to a CYP2C11 promoter element and no effects on hepatic GHR levels. Ethanol caused tissue specific effects in phospho-JAK2 and JAK2, with increased levels in the liver, but decreased JAK2 expression in the kidney. We conclude that ethanol suppression of CYP2C11 expression is clearly associated with reductions in STAT5b levels, but not necessarily in reductions of JAK2 levels. The mechanisms underlying ethanol-induced suppression of STAT5b is yet to be determined, as is the question of whether this is secondary to hormonal effects or a direct ethanol effect. C1 Univ Arkansas Med Sci Hosp, Arkansas Childrens Nutr Ctr, Little Rock, AR 72202 USA. Univ Arkansas Med Sci Hosp, Dept Physiol Biophys, Little Rock, AR 72202 USA. Univ Arkansas Med Sci Hosp, Dept Pharmacol Toxicol, Little Rock, AR 72202 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Med Serv, Birmingham, AL 35294 USA. RP Badger, TM (reprint author), Univ Arkansas Med Sci Hosp, Arkansas Childrens Nutr Ctr, 1120 Marshall St, Little Rock, AR 72202 USA. FU NIAAA NIH HHS [AA008645]; NIDDK NIH HHS [DK46395] NR 31 TC 10 Z9 10 U1 1 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP 1 PY 2003 VL 144 IS 9 BP 3969 EP 3976 DI 10.1210/en.2002-0163 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 713XN UT WOS:000184883400033 PM 12933671 ER PT J AU Krahl, SE Senanayake, SS Handforth, A AF Krahl, SE Senanayake, SS Handforth, A TI Right-sided vagus nerve stimulation reduces generalized seizure severity in rats as effectively as left-sided SO EPILEPSY RESEARCH LA English DT Article DE VNS; pentylenetetrazole; anticonvulsant; epilepsy; vagus nerve ID C-FIBERS; SUPPRESSION; REFLEX; HEART AB As currently utilized, vagus nerve stimulation (VNS) is applied to the cervical trunk of the left vagus nerve to suppress seizures clinically. Demonstration that VNS can also reduce seizure severity when electrodes are placed on the right cervical vagus nerve in rats would provide empirical evidence that the antiepileptic effects of VNS are not an exclusive property of the left vagus nerve. Rats were implanted with a custom cuff electrode on either the left or right cervical vagus nerve. Two days later, continuous VNS was begun in half the rats with left-sided and half with right-sided electrodes. The remaining rats were connected to the stimulator, but did not receive VNS. After 30 s, pentylenetetrazole (PTZ) was administered systemically and seizures were rated by a blinded observer. The PTZ test was repeated two days later, with VNS administered to the previously unstimulated rats, while the others received no stimulation. VNS significantly reduced the severity of PTZ-induced seizures in rats regardless of the side of stimulation as compared to their no-VNS (control condition) seizure severity. No significant differences in efficacy existed based on the side of stimulation. These results indicate that right-sided VNS in rats is just as effective as left-sided VNS, suggesting that fibers necessary for seizure suppression are not unique to the left vagus nerve. Published by Elsevier B.V. C1 VA Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Neurosurg, Los Angeles, CA 90095 USA. RP Krahl, SE (reprint author), VA Greater Los Angeles Healthcare Syst, Neurol Serv, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 10 TC 23 Z9 25 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 2003 VL 56 IS 1 BP 1 EP 4 DI 10.1016/S0920-1211(03)00122-0 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 732MZ UT WOS:000185951300001 PM 14529948 ER PT J AU Singh, BN AF Singh, BN TI Increased heart rate as a risk factor for cardiovascular disease SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article DE agents that exclusively reduce heart rate; beta-blockade; cardiovascular mortality; hypertension; increased heart rate; myocardial infarction; sudden death ID ACUTE MYOCARDIAL-INFARCTION; CORONARY ATHEROSCLEROSIS; VAGAL-STIMULATION; FOLLOW-UP; MORTALITY; AGE; MEN; HYPERTENSION; ISCHEMIA; SEVERITY AB Heart rate is a major determinant of oxygen consumption in patients with ischaemic heart disease. Its pharmacological modulation is increasingly the focus of therapeutic approaches to alleviate symptoms and prolong survival. It is the simplest cardiovascular variable to measure accurately and reproducibly. Many long-term follow-up studies suggest that elevated heart rate increases all-cause mortality, cardiovascular disease and sudden death in patients with known or suspected coronary heart disease, survivors of myocardial infarction and patients with hypertension. These links hold for men and women, and are unrelated to ethnic origin. The effect on sudden death or total mortality increases as a function of heart rate such that an increase in heart rate by more than 40 beats/min doubles total mortality. Conversely, tow heart rate reduces risk for coronary artery disease and sudden death. Primary and secondary prevention studies in myocardial infarction indicated that elevated heart rate in susceptible patients predicts risk for developing myocardial infarction and death. Prophylactic beta-blockers attenuate risks for reinfarction, sudden death and total mortality; these effects correlate with reduced heart rate, thus providing a compelling basis for developing agents that reduce heart rate exclusively as antianginal agents for the therapy of myocardial ischaemia with broader therapeutic implications. (C) 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Dept Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Singh, BN (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Cardiol, 1301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 29 TC 12 Z9 17 U1 1 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD SEP PY 2003 VL 5 IS G BP G3 EP G9 DI 10.1016/S1520-765X(03)90001-0 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 733ZQ UT WOS:000186031100002 ER PT J AU Gardner, B Zhu, LX Sharma, S Tashkin, DP Dubinett, SM AF Gardner, B Zhu, LX Sharma, S Tashkin, DP Dubinett, SM TI Methanandamide increases COX-2 expression and tumor growth in murine lung cancer SO FASEB JOURNAL LA English DT Article DE cannabinoid; PGE(2); MAPK ID MESSENGER-RNA EXPRESSION; CYCLOOXYGENASE-2 EXPRESSION; CANNABINOID RECEPTOR; ENDOGENOUS CANNABINOIDS; IN-VIVO; PROGNOSTIC-SIGNIFICANCE; SIGNALING PATHWAYS; ANTITUMOR IMMUNITY; EPITHELIAL-CELLS; GASTRIC-CANCER AB Increased COX-2 expression and elevated PGE(2) have been associated with a poor prognosis in lung cancer. Cannabinoids have been known to exert some of their biological effects via modulation of prostaglandin production. We evaluated the impact of methanandamide on COX-2 expression, PGE(2) production, and tumor growth in murine lung cancer. Methanandamide administration (5 mg/kg, four times/wk i.p.) resulted in an increased rate of tumor growth (P<0.01 compared with diluent treated controls). The CB1 and CB2 receptor antagonists, SR141716 and SR144528, did not block the methanandamide-mediated increase in tumor growth. In vivo, methanandamide treatment increased the production of PGE(2) at the tumor site as well as in splenocytes. Consistent with these results, methanandamide increased PGE(2) and COX-2 levels in murine lung cancer cells in vitro via a cannabinoid receptor-independent mechanism. The COX-2-specific inhibitor, SC58236, abrogated methanandamide induction of PGE2 production in vitro and blocked methanandamide-enhanced tumor growth in vivo. Furthermore, the p38/MAPK inhibitor, SB203528, and the p42/44 inhibitor, PD98059, blocked methanandamide-mediated induction of PGE(2) and COX-2. These results suggest that methanandamide augments tumor growth by a cannabinoid receptor-independent pathway that is associated with the up-regulation of COX-2. C1 Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Lung Canc Res Program,Ctr Hlth Sci 37 131, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Lung Canc Res Program,Ctr Hlth Sci 37 131, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu NR 56 TC 28 Z9 30 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD SEP PY 2003 VL 17 IS 12 BP 2157 EP + DI 10.1096/fj.03-0254fje PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 732DG UT WOS:000185925100017 PM 12958151 ER PT J AU Smith, DG Assal, M Reiber, GE Vath, C LeMaster, J Wallace, C AF Smith, DG Assal, M Reiber, GE Vath, C LeMaster, J Wallace, C TI Minor environmental trauma and lower extremity amputation in high-risk patients with diabetes: Incidence, pivotal events, etiology, and amputation level in a prospectively followed cohort SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE diabetes mellitus; amputation; foot injuries; shoes ID PREVENTION; MEDICARE AB This study determined the incidence, pivotal events, etiology, and levels of amputation in a prospectively followed cohort of 400 people with diabetes and a prior healed foot ulcer who participated in a randomized footwear trial. Participants were seen every 17 weeks for 2 years. Subjects with foot lesions were referred to their healthcare provider for treatment. In this cohort, 11 participants required lower limb amputation (rate 13.8 per 1000 person-years). Pivotal event analysis revealed that only one amputation was related to footwear, six amputations were due to non-footwear-related minor environmental trauma, two were due to progression of vascular disease (dry gangrene from critical ischemia), one was due to a self-care injury while cutting the toenails, and one was due to a decubitus ulcer. Previously proposed strategies to reduce the amputation rates in individuals with diabetes have focused heavily on footwear and education. However, even with this emphasis, amputation rates in the United States are still high. This study suggests that the prevention of minor environmental trauma, including household accidents, merits additional attention. We believe that further efforts to reduce amputation rates for individuals with diabetes will need to emphasize the prevention of minor trauma, especially in those already compromised with neuropathy and vascular disease. C1 Univ Washington, Harborview Med Ctr, Dept Orthopaed, Seattle, WA 98104 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. Univ Washington, Dept Family Med, Seattle, WA 98104 USA. Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Smith, DG (reprint author), Univ Washington, Harborview Med Ctr, Dept Orthopaed, 325 9Th Ave, Seattle, WA 98104 USA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD SEP PY 2003 VL 24 IS 9 BP 690 EP 695 PG 6 WC Orthopedics SC Orthopedics GA 721GB UT WOS:000185307700006 PM 14524519 ER PT J AU Lopes-Virella, MF Virella, G AF Lopes-Virella, MF Virella, G TI The role of immune and inflammatory processes in the development of macrovascular disease in diabetes SO FRONTIERS IN BIOSCIENCE LA English DT Review DE diabetes; macrovascular disease; inflammation; autoimmunity; atherosclerosis; modified LDL antibodies; LDL autoantibodies; LDL immune complexes; autoimmunity; atherosclerosis; review ID LOW-DENSITY-LIPOPROTEIN; C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; HUMAN ATHEROSCLEROTIC PLAQUES; HUMAN-ENDOTHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; ACUTE MYOCARDIAL-INFARCTION; MONOCYTE-DERIVED MACROPHAGES; HUMAN VASCULAR ENDOTHELIUM; COLONY-STIMULATING FACTOR AB Diabetes is associated with a high incidence of cardiovascular disease, which is the major cause of morbidity and mortality in this disease. There is considerable interest in defining factors responsible for the accelerated development of atherosclerosis in diabetes. There is no evidence to suggest that the inflammatory process in diabetic patients is different from those in nondiabetic individuals. The main difference may lie on factors able to trigger the inflammatory process. Diabetes is a major predisposing factor for the generation of modified proteins though advanced glycation and oxidation, two intimately interrelated processes. Advanced glycation end-products modified low density lipoprotein (AGE-LDL) and other AGE-modified proteins as well as oxidized LDL (oxLDL) are able to interact with a variety of cells and induce cell dysfunction and the release of pro-inflammatory mediators. But AGE-LDL and oxLDL are also immunogenic. Activated T lymphocytes reacting with peptides derived from oxidized LDL have been detected in atheromatous lesions. Their pro-inflammatory potential is directly linked to the release of interferon-gamma and other cytokines able to activate macrophages, smooth muscle cells, and endothelial cells. On the other hand, antibodies to oxidized and AGE-modified LDL have been isolated from diabetic patients and shown to belong predominantly to the IgG isotype, subclasses 1 and 3, which have well-defined proinflammatory properties. These autoantibodies to modified lipoproteins have sufficient affinity to form stable antigen-antibody complexes, which have been also shown to have pro-atheromatous and pro-inflammatory properties. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Vet Affairs, Charleston, SC 29403 USA. RP Lopes-Virella, MF (reprint author), Ralph H Johnson VA Med Ctr, Strom Thurmond Res Bldg,114 Doughty St,Room 529, Charleston, SC 29425 USA. NR 245 TC 32 Z9 34 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP PY 2003 VL 8 BP S750 EP S768 DI 10.2741/1141 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 719VX UT WOS:000185226700022 PM 12957881 ER PT J AU McGinty, D Szymusiak, R AF McGinty, D Szymusiak, R TI Hypothalamic regulation of sleep and arousal SO FRONTIERS IN BIOSCIENCE LA English DT Review DE sleep; arousal; hypothalamus; preoptic area; median preoptic nucleus; thermoregulation; monoamines; gaba; galanin; hypocretin; orexin; review ID MEDIAN PREOPTIC NUCLEUS; EYE-MOVEMENT SLEEP; WAKING DISCHARGE PATTERNS; POSTERIOR LATERAL HYPOTHALAMUS; DORSAL RAPHE NUCLEUS; C-FOS PROTEIN; BASAL FOREBRAIN; LOCUS-COERULEUS; AMBIENT-TEMPERATURES; RETICULAR-FORMATION AB The hypnogenic function of the rostral hypothalamic region, particularly the preoptic area (POA) was established previously on the basis of lesion, neuronal unit recording, and neurochemical and thermal stimulation studies. Recent studies have mapped the locations of putative sleep-promoting neurons in the POA using c-Fos immunostaining techniques and confirmed these findings with electrophysiological methods. Segregated groups of sleep-active neurons have been localized in the ventrolateral POA (vlPOA) and median preoptic nucleus (MnPN). MnPN and vlPOA sleep-active neurons express the inhibitory transmitter, GABA. In vlPOA neurons, GABA is co-localized with a second inhibitory transmitter, galanin. Descending projections from these sites terminate in putative arousal-promoting cell groups, including histaminergic, serotonergic, orexinergic, noradrenergic, and cholinergic neurons. These findings suggest the hypothesis that non-REM sleep occurs as a consequence of GABAergic and galaninergic inhibition of arousal-promoting neurons resulting from activation of vlPOA and MnPN sleep-promoting neurons. In support of this hypothesis, it was shown that putative sleep-promoting and arousal-promoting neurons exhibit reciprocal changes in discharge across the sleep-wake cycle and that GABA release in wake-promoting sites increases during nonREM sleep. In addition, some POA sleep-active neurons are warm-sensitive. Local POA warming inhibits discharge of multiple arousal-promoting neuronal groups. POA warming, unit recording, and lesion studies also show that POA regulates the amount of delta EEG activity within nonREM sleep, and index of the depth of sleep. Finally, there is evidence that arousal systems inhibit vlPOA and MnPN neurons and the POA hypnogenic mechanism. Mutually-inhibitory interactions between sleep-promoting and arousal-promoting systems are hypothesized to form a functional sleep-wake switch. C1 VA Greater Los Angeles Healthcare Syst, Neurophysiol Res 151A3, Res Serv, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP McGinty, D (reprint author), VA Greater Los Angeles Healthcare Syst, Neurophysiol Res 151A3, Res Serv, 16111 Plummer St, North Hills, CA 91343 USA. FU NHLBI NIH HHS [HL60296]; NIMH NIH HHS [MH63323, MH47480] NR 105 TC 29 Z9 30 U1 1 U2 9 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP PY 2003 VL 8 BP S1074 EP S1083 DI 10.2741/1159 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 719VX UT WOS:000185226700048 PM 12957869 ER PT J AU Wilt, SG Masuda, M Yiannoulos, G Dugger, NV Hoffman, PM AF Wilt, SG Masuda, M Yiannoulos, G Dugger, NV Hoffman, PM TI Role of oxidative injury in a retroviral induced neurodegenerative disease SO GLIA LA English DT Meeting Abstract CT 6th European Meeting on Glial Cell Function in Health and Disease CY SEP 03-06, 2003 CL BERLIN, GERMANY C1 Bronx Vet Adm Med Ctr, Res & Dev Program, Bronx, NY USA. Dokkyo Univ, Sch Med, Dept Microbiol, Mibu, Tochigi, Japan. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. VA Maryland Healthcare Syst, Res Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD SEP PY 2003 SU 2 BP 34 EP 34 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 714XB UT WOS:000184938300144 ER PT J AU McQuillen, AD Licht, MH Licht, BG AF McQuillen, AD Licht, MH Licht, BG TI Contributions of disease severity and perceptions of primary and secondary control to the prediction of psychosocial adjustment to Parkinson's disease SO HEALTH PSYCHOLOGY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Gerontological-Society-of-America CY NOV 19-23, 1999 CL SAN FRANCISCO, CALIFORNIA SP Gerontol Soc Amer DE Parkinson's disease; perceived control; primary control; secondary control; psychosocial adjustment; control beliefs; locus of control ID MINI-MENTAL-STATE; QUALITY-OF-LIFE; PERCEIVED CONTROL; DEPRESSION; ILLNESS; AGE AB Seventy-four people with Parkinson's disease (PD) completed questionnaires and were interviewed to determine the degree to which the severity of PD and perceptions of primary and secondary control over PD predicted psychosocial adjustment. Significant unique contributions to PD-related participation restrictions were made by disease severity (positive relationship) and perceived internal secondary control (negative relationship). Also, participation restrictions had a significant direct effect, and disease severity and perceived internal secondary control significant indirect effects, on both depressive symptomatology and life satisfaction. Results are consistent with theories that suggest the importance of enhancing internal secondary control processes in situations in which actual control over objective circumstances is limited, such as with chronic and progressive diseases like PD. C1 Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. Audie L Murphy Mem Vet Adm Med Ctr, Dept Psychol, San Antonio, TX 78284 USA. RP Licht, MH (reprint author), Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. NR 39 TC 21 Z9 21 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2003 VL 22 IS 5 BP 504 EP 512 DI 10.1037/0278-6133.22.5.504 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 730KJ UT WOS:000185829700008 PM 14570534 ER PT J AU El-Zimaity, HMT Ramchatesingh, J Clarridge, JE Abudayyeh, S Osato, MS Graham, DY AF El-Zimaity, HMT Ramchatesingh, J Clarridge, JE Abudayyeh, S Osato, MS Graham, DY TI Enterococcus gastritis SO HUMAN PATHOLOGY LA English DT Article DE Helicobacter pylori; gastritis; Enterococcus ID VANCOMYCIN-RESISTANT; FLORA AB Helicobacter pylori infection is the most common cause of gastritis with its associated sequelae. Gastritis secondary to other bacteria is rare. This report describes Enterococcus-associated gastritis in a 59-year-old diabetic man. Nine months after receiving treatment for H. pylori-associated gastritis, he underwent endoscopy to confirm H. pylori eradication and to evaluate the status of previously seen ulcers. Mucosal biopsy specimens revealed severe active but focal gastritis adjacent to gram-positive coccobacilli in short to long chains with no H. pylori. Culture grew an Enterococcus similar to E. hirae and E. durans. No treatment was given, and endoscopy done 2 months later showed complete resolution of the gastritis and absence of H. pylori or enterococci. Our patient's gastritis represents a previously undescribed manifestation of Enterococcus infection. It is possible that the presence of NSAID gastric mucosal injury and diabetes predisposed this individual to the development of transient Enterococcus gastritis. (C) 2003 Elsevier Inc. All rights reserved. C1 VA Med Ctr, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Zimaity, HMT (reprint author), VA Med Ctr, Dept Med, 111-D,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2003 VL 34 IS 9 BP 944 EP 945 DI 10.1016/S0046-8177(03)00287-9 PG 2 WC Pathology SC Pathology GA 726UB UT WOS:000185617500017 PM 14562292 ER PT J AU Krishnan, B AF Krishnan, B TI Renal epithelial neoplasms: The diagnostic implications of electron microscopy study in 55 cases - Reply SO HUMAN PATHOLOGY LA English DT Letter C1 VA Med Ctr, Houston, TX USA. RP Krishnan, B (reprint author), VA Med Ctr, Houston, TX USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2003 VL 34 IS 9 BP 959 EP 959 DI 10.1016/S0046-8177(03)00095-9 PG 1 WC Pathology SC Pathology GA 726UB UT WOS:000185617500023 ER PT J AU Goodfriend, TL Ball, DL Egan, BM Campbell, WB Nithipatikom, K AF Goodfriend, TL Ball, DL Egan, BM Campbell, WB Nithipatikom, K TI Epoxy-keto-linoleic acid (EKODE) stimulates aldosterone secretion by rat adrenal cells, and its levels in human blood correlate with those of aldosterone SO HYPERTENSION LA English DT Meeting Abstract CT 57th Annual Fall Conference of the Council-for-High-Blood-Pressure-Research CY SEP 23-26, 2003 CL WASHINGTON, D.C. SP Council High Blood Pressure Res, Amer Heart Assoc, Council Nutrit, Phys Activ & Metabolism C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Med Univ S Carolina, Charleston, SC 29425 USA. Med Coll Wisconsin, Milwaukee, WI 53226 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2003 VL 42 IS 3 MA 82 BP 403 EP 403 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 718FY UT WOS:000185135500114 ER PT J AU Tofovic, SP Maddy, H Jackson, EK AF Tofovic, SP Maddy, H Jackson, EK TI Estradiol metabolites attenuate renal and cardiovascular injury induced by chronic angiotensin II administration SO HYPERTENSION LA English DT Meeting Abstract CT 57th Annual Fall Conference of the Council-for-High-Blood-Pressure-Research CY SEP 23-26, 2003 CL WASHINGTON, D.C. SP Council High Blood Pressure Res, Amer Heart Assoc, Council Nutrit, Phys Activ & Metabolism C1 Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Ctr Clin Pharmacol, Pittsburgh, PA 15261 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2003 VL 42 IS 3 MA P52 BP 414 EP 414 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 718FY UT WOS:000185135500170 ER PT J AU Tofovic, SP Mady, H Salah, E Jackson, EK Melhem, M AF Tofovic, SP Mady, H Salah, E Jackson, EK Melhem, M TI Estradiol metabolites retard the progression of pulmonary hypertension preclinical evidence for clinical development SO HYPERTENSION LA English DT Meeting Abstract CT 57th Annual Fall Conference of the Council-for-High-Blood-Pressure-Research CY SEP 23-26, 2003 CL WASHINGTON, D.C. SP Council High Blood Pressure Res, Amer Heart Assoc, Council Nutrit, Phys Activ & Metabolism C1 Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Ctr Clin Pharmacol, Pittsburgh, PA 15261 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2003 VL 42 IS 3 MA P62 BP 416 EP 416 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 718FY UT WOS:000185135500180 ER PT J AU DiGiovine, CP Cooper, RA Fitzgerald, SG Boninger, ML Wolf, EJ Guo, SF AF DiGiovine, CP Cooper, RA Fitzgerald, SG Boninger, ML Wolf, EJ Guo, SF TI Whole-body vibration during manual wheelchair propulsion with selected seat cushions and back supports SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE back supports; individual with a disability; manual wheelchair propulsion; seat cushions; seating systems; shock; vibration; wheelchairs; whole-body vibration (WBV) ID VERTICAL VIBRATION; SUSPENSION DESIGN; APPARENT MASS; PAIN; TRANSMISSION; POSTURE; HEAD; DISCOMFORT; EXPOSURE; SUBJECT AB Although the exposure to whole-body vibrations (WBV) has been shown to be detrimental to seated humans, the effects of wheelchairs and seating systems on the transmission of vibration to an individual have not been thoroughly examined. The purpose of this study was to determine if the selected wheelchair seat cushions and back supports minimize the transmission of vibrations. Thirty-two wheelchair users traversed an activities of daily living course three times using 16 randomly selected seating systems as well as their own. Vibrations were measured using triaxial accelerometers at the seat and participant's head. The weighted fore-to-aft (T-x), vertical (T-z), and resultant (T-r) transmissibility based on the vibrational-dose-value (VDV) were used to determine if differences existed among the four seat cushions and back supports. The obstacles that seem to have the largest effect on the transmission of WBV are the single event shocks and the repeated event shocks. Comparisons between the individuals own seating system and the tested seating systems suggest that the individuals are not using the most appropriate seating system in terms of the reduction of vibration transmission. C1 Assist Technol Unit, Chicago, IL 60608 USA. Univ Illinois, Dept Disabil & Human Dev, Chicago, IL 60608 USA. Univ Illinois, Dept Bioengn, Chicago, IL 60608 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R 1, Ctr Excellence Wheelchairs & Related Technol, Dept Vet Affairs,VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. RP DiGiovine, CP (reprint author), Assist Technol Unit, Chicago, IL 60608 USA. RI DiGiovine, Carmen/E-2982-2011 OI Wolf, Erik/0000-0002-6353-7978; Boninger, Michael/0000-0001-6966-919X NR 51 TC 8 Z9 8 U1 0 U2 1 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 SEP PY 2003 VL 11 IS 3 BP 311 EP 322 DI 10.1109/TNSRE.2003.816872 PG 12 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 723ED UT WOS:000185418700014 PM 14518796 ER PT J AU Craig, WA AF Craig, WA TI Basic pharmacodynamics of antibacterials with clinical applications to the use of beta-lactams, glycopeptides, and linezolid SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID ACUTE OTITIS-MEDIA; RESPIRATORY-TRACT INFECTIONS; GRAM-POSITIVE INFECTIONS; MOUSE PERITONITIS MODEL; CRITICALLY ILL PATIENTS; STAPHYLOCOCCUS-AUREUS; STREPTOCOCCUS-PNEUMONIAE; CONTINUOUS-INFUSION; IN-VIVO; PHARMACOKINETIC PARAMETERS AB Pharmacodynamics (PDs) deals with the relationship between measures of drug exposure and the antimicrobial effect. Although different antimicrobials have been shown to vary in both their killing pattern and the presence and duration of persistent effects, drugs can still be divided into three major groups. The first group includes antibacterials that induce concentration-dependent killing and produce moderate to prolonged persistent effects. The second group is virtually the opposite of first group in that these drugs exhibit primarily time-dependent killing and produce minimal or no persistent effects with most organisms. The third and last group includes drugs that also have time-dependent killing but differ from the second group in that they produce moderate to prolonged persistent effects. This article focuses on the pharmacodynamics for beta-lactams, glycopeptides, and linezolid. C1 Univ Wisconsin, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Craig, WA (reprint author), Univ Wisconsin, 2500 Overlook Terrace,Room D-2221, Madison, WI 53705 USA. NR 101 TC 273 Z9 284 U1 1 U2 29 PU W B SAUNDERS CO 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 SEP PY 2003 VL 17 IS 3 BP 479 EP + DI 10.1016/S0891-5520(03)00065-5 PG 24 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 755YM UT WOS:000187439100001 PM 14711073 ER PT J AU Hoffelt, SC Marshall, LM Garzotto, M Hung, A Holland, J Beer, TM AF Hoffelt, SC Marshall, LM Garzotto, M Hung, A Holland, J Beer, TM TI A comparison of CT scan to transrectal ultrasound-measured prostate volume in untreated prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; prostate volume; CT; ultrasonography ID 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; INTEROBSERVER VARIABILITY; RADIATION-THERAPY; LOCALIZATION; APEX; MRI; IMPLANTATION; DOSIMETRY; ACCURACY; IMPACT AB (P) under bar(u) under bar(r) under bar(p) under bar(o) under bar(s) under bar(e) under bar To compare CT and transrectal ultrasound (TRUS)-measured prostate volumes in patients with untreated prostate cancer. (M) under bar(e) under bar(t) under bar(h) under bar(o) under bar(d) under bar(s) under bar (a) under bar(n) under bar(d) under bar (M) under bar(a) under bar(t) under bar(e) under bar(r) under bar(i) under bar(a) under bar(l) under bar(s) under bar: Between 1995 and 1999, 48 consecutive patients at the Portland Veterans Affairs Medical Center were treated with external beam radiotherapy. In 36 of these patients, TRUS and CT measurements of the prostate volume were obtained before treatment and <6 months apart. The TRUS volume was calculated using the prolate ellipsoid formula. The CT volume was calculated from the contours of the prostate drawn by one physician, who was unaware of the TRUS volume calculation, on axial CT images. (R) under bar(e) under bar(s) under bar(u) under bar(l) under bar(t) under bar(s) under bar: The TRUS and CT prostate volume measurements correlated strongly (Pearson's correlation coefficient = 0.925, 95% confidence interval 0.856-0.961, p < 0.0001). The CT volume was consistently larger than the TRUS volume by a factor of approximately 1.5. In men with a TRUS prostate volume less than the median (<28 cm(3)), the CT/TRUS volume ratio was 1.7, and it was 1.4 for men whose volume was greater than the median. The CT volumes were correlated similarly with the TRUS volumes regardless of the CT slice interval. (C) under bar(o) under bar(n) under bar(c) under bar(l) under bar(u) under bar(s) under bar(i) under bar(o) under bar(n) under bar: A strong correlation was found between CT scan and TRUS measurement of the prostate volume; however, CT consistently overestimated the prostate volume by approximately 50% compared with TRUS. (C) 2003 Elsevier Inc. C1 Oregon Hlth Sci Univ, Dept Radiat Oncol & Div, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Urol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Hematol & Med Oncol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Div Urol, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd,Mial Code L586, Portland, OR 97239 USA. FU NCRR NIH HHS [3 M01RR00334-33S2] NR 22 TC 51 Z9 51 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2003 VL 57 IS 1 BP 29 EP 32 DI 10.1016/S0360-3016(03)00509-1 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 710JB UT WOS:000184676100009 PM 12909212 ER PT J AU Dahiya, MC Redding, SW Dahiya, RS Eng, TY Kirkpatrick, WR Coco, BJ Sadkowski, LC Fothergill, AW Waite, A Rinaldi, MG Patterson, TF Thomas, CR AF Dahiya, MC Redding, SW Dahiya, RS Eng, TY Kirkpatrick, WR Coco, BJ Sadkowski, LC Fothergill, AW Waite, A Rinaldi, MG Patterson, TF Thomas, CR TI Oropharyngeal candidiasis caused by non-albicans yeast in patients receiving external beam radiotherapy for head-and-neck cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE non-albicans Candida; oropharyngeal candidiasis; head-and-neck cancer; radiotherapy; chromogenic medium ID VIRUS-INFECTED PATIENTS; ORAL CANDIDIASIS; FLUCONAZOLE SUSCEPTIBILITY; RADIATION; DUBLINIENSIS; COLONIZATION; RESISTANCE; AIDS AB Purpose: To characterize non-albicans Candida oral infections in patients with head-and-neck cancer receiving external beam radiotherapy (EBRT) with or without concurrent chemotherapy. Methods and Materials: Thirty-seven patients with head-and-neck cancer received EBRT in 2.0-Gy daily fractions to a median dose of 60.4 Gy (range 38-82.8, mean 64.6). They were followed for oropharyngeal candidiasis (OPC) confirmed by positive examination, positive KOH smear, and/or positive swab or swish culture. Samples were identified and plated on chromogenic media to identify non-albicans yeasts. Colonies were plated on Sabouraud dextrose slants for microdilution antifungal susceptibility testing to fluconazole. DNA typing, including karyotyping, restriction fragment length polymorphism analysis, and Southern blot hybridization with the moderately repetitive Ca3 probe, was performed on selected isolates to confirm individual species. Results: Of the 37 patients, 10 (27%) developed OPC, and 26 (70.3%) displayed Candida carriage state. The median EBRT dose at time of positive culture was 22.5 Gy and at time of OPC was 28.6 Gy. Of the 6 patients receiving chemotherapy and EBRT, 4 (66%) developed OPC at median dose of 27.6 Gy. Three (8%) of 37 patients were infected with non-albicans Candida, and 3 (30%) of all 10 infections were caused by these organisms. Conclusion: Non-albicans Candida is emerging as a relatively common cause of OPC in head-and-neck cancer patients. Chromogenic media are helpful to screen these infections. Our data also suggest a greater likelihood of developing OPC in patients receiving concomitant chemotherapy and EBRT. (C) 2003 Elsevier Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Gen Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Dept Pathol, San Antonio, TX USA. RP Dahiya, MC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 19 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2003 VL 57 IS 1 BP 79 EP 83 DI 10.1016/S0360-3016(03)00415-2 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 710JB UT WOS:000184676100015 PM 12909218 ER PT J AU Wagner, B Galey, WR AF Wagner, B Galey, WR TI Kinetic analysis of hexose transport to determine the mechanism of amygdalin and prunasin absorption in the intestine SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE amygdalin; prunasin/D-mandelonitrile beta-D-glucoside; phloridzin; rat; monosaccharide transport; everted sac; glycoside transport; small intestine; absorption; D-[C-14]-glucose ID ACTIVE-TRANSPORT; RAT INTESTINE; DOSAGE FORMS; LAETRILE; INVITRO; METABOLISM; TOXICITY; SYSTEM; MEXICO; CANCER AB Evidence is accumulating that glucose-conjugated compounds may be carried across the gut mucosa via the epithelial sodium-dependent monosaccharide transporter SGLT1. A modification of the everted intestinal sac technique was utilized to study the transport of the cyanogenic glycoside amygdalin (D-mandelonitrile beta-D-gentiobioside) and its metabolite D-mandelontrile P-D-glucoside (prunasin). Everted sacs of rat jejunum and ileum were bathed in isotonic oxygenated sodium chloride-potassium phosphate buffer containing 2.8 muCi D-[H-3]-mannose and 0.187 muCi D-[C-14]-glucose. For treatment groups, buffers contained phloridzin, galactose, amygdalin or prunasin. The rate constant (k) for the transport process was calculated. Compared with the control (n = 33), phloridzin (n = 25) significantly reduced the rate constants of both D-[C-14]-glucose and D-[H-3]-mannose. Substitution of sodium with choline and incremental galactose treatments similarly reduced D-[C-14]-glucose influx, indicating that a fraction of the transport is carrier-mediated. Treatment with amygdalin did not significantly affect the rate constants Of D- [C-14]-glucose or D- [H-3]-mannose transport. However, treatment with 1 mM prunasin (a = 16) did reduce the influx of D-[C-14]-glucose without affecting D-[H-3]-mannose values. This is consistent with the reports finding that glycoside absorption may be mediated by SGLT1. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol,S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Howard Hughes Med Inst, HHMI NIH Med Scholars Program, Chevy Chase, MD 20815 USA. RP Wagner, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol,S Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr,MC 7882, San Antonio, TX 78229 USA. OI Wagner, Brent/0000-0002-7063-0142 NR 38 TC 4 Z9 4 U1 1 U2 9 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD SEP-OCT PY 2003 VL 23 IS 5 BP 371 EP 375 DI 10.1002/jat.934 PG 5 WC Toxicology SC Toxicology GA 724LX UT WOS:000185490000010 PM 12975776 ER PT J AU Bischoff, DS Jia, S Yamaguchi, DT AF Bischoff, DS Jia, S Yamaguchi, DT TI Analysis of protein secretion profiles in undifferentiated and ATRA-differentiated C3H10T1/2 cells upon TGFB stimulation using the Ciphergen ProteinChip System. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Ciphergen Biosyst Inc, Fremont, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S331 EP S331 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501333 ER PT J AU Hansen, KE Vallarta-Ast, N Krueger, D Drezner, M Binkley, N AF Hansen, KE Vallarta-Ast, N Krueger, D Drezner, M Binkley, N TI A comparison of lumbar vertebral T-scores by three methods: Average L1-L4 BMD, lumbar BMD by ISCD criteria, and lowest vertebral body T-score. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 Univ Wisconsin, Osteoprososis Clin Ctr, Madison, WI 53706 USA. Univ Wisconsin, Res Program, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S117 EP S117 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500457 ER PT J AU Huang, W Rudkin, GH Sukkarieh, M Ishida, K Yamaguchi, DT Miller, TA AF Huang, W Rudkin, GH Sukkarieh, M Ishida, K Yamaguchi, DT Miller, TA TI Differentiation of MC3T3-E1 pre-osteoblastic cells on two-dimensional poly(lactide-co-glycolide) (PLGA) films and three-dimensional PLGA scaffolds - A real-time RT-PCR study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 VA Greater LA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S342 EP S343 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501383 ER PT J AU Vallarta-Ast, NL Krueger, D Binkley, N AF Vallarta-Ast, NL Krueger, D Binkley, N TI Does radius bone density measurement over-diagnosis osteoporosis in men? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Osteoporosis Clin Ctr, Madison, WI 53706 USA. Univ Wisconsin, Res Program, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S116 EP S117 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500456 ER PT J AU Wiren, K Zhang, XW Toombs, A Harada, S Jepsen, K AF Wiren, K Zhang, XW Toombs, A Harada, S Jepsen, K TI Targeted overexpression of androgen receptor in osteoblasts results in complex skeletal phenotype in growing animals. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 OHSU, Portland VA Med Ctr, Portland, OR USA. Merck Res Labs, W Point, PA USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S293 EP S293 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080501173 ER PT J AU Wiren, K Toombs, A Zhang, XW AF Wiren, K Toombs, A Zhang, XW TI Inhibition of MEK-ERK-Elk signaling by androgens may influence osteoblast apoptosis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 19-23, 2003 CL MINNEAPOLIS, MINNESOTA SP Amer Soc Bone Mineral Res C1 OHSU, Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2003 VL 18 SU 2 BP S138 EP S138 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 734WG UT WOS:000186080500537 ER PT J AU Binkley, N Krueger, D Vallarta-Ast, N AF Binkley, N Krueger, D Vallarta-Ast, N TI An overlying femur bone fat panniculus affects mass measurement SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE bone density; obesity; DXA; femur ID X-RAY ABSORPTIOMETRY; MINERAL DENSITY; LUMBAR SPINE; SOFT-TISSUE; OSTEOPOROSIS; IMPACT; WEIGHT; ERRORS; HIP AB Dual-energy X-ray absorptiometry (DXA) is currently the gold standard technique for osteoporosis diagnosis. However, DXA has limitations, including artifacts, such as degenerative disease or metallic foreign bodies, that may confound bone mineral density (BMD) results. Because fat folds overlying the proximal femur may alter soft-tissue density in a nonuniform manner, this may be a currently unappreciated confounder of proximal femur BMD measurement. This possibility was evaluated in 127 patients (52 women/75 men) referred for routine BMD measurement who were identified as having a fat panniculus overlying their proximal femur scan area. Presence of a fat panniculus within the scan field was confirmed by visual assessment of images obtained utilizing a GE Lunar Expert-XL. Subsequently, these individuals were rescanned while retracting their fat panniculus away from the femur scan area without other repositioning between scans. In 49% of the men, and 56% of the women, either the femoral neck, trochanter, or total femur BNID differed by more than the least significant change at our facility. No pattern was observed to predict whether BMD would increase or decrease upon fat retraction. Subsequently, 30 patients were scanned using the standard and retracted technique twice, with repositioning between scans to establish precision. Retracted and standard precision was similar. In conclusion, an overlying fat panniculus may alter proximal femur BMD measurement, which would be expected to impair the ability to accurately diagnose low bone mass and monitor osteoporosis therapy. When a fat panniculus overlays the proximal femur scan area, its retraction should be part of routine densitometric practice. C1 Univ Wisconsin, Inst Aging, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Radiol, Madison, WI 53705 USA. RP Binkley, N (reprint author), Univ Wisconsin, Inst Aging, 1300 Univ Ave,2245 MSC, Madison, WI 53706 USA. NR 17 TC 37 Z9 37 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1094-6950 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD FAL PY 2003 VL 6 IS 3 BP 199 EP 204 DI 10.1385/JCD:6:3:199 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 726QX UT WOS:000185611500001 PM 14514987 ER PT J AU Hardee, JT Breth, GF El-Serag, HB AF Hardee, JT Breth, GF El-Serag, HB TI Hepatocellular carcinoma associated with autoimmune hepatitis SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Letter ID CHRONIC ACTIVE HEPATITIS; LUPOID HEPATITIS C1 Kaiser Permanente, Dept Internal Med, Denver, CO 80231 USA. Kaiser Permanente, Dept Rheumatol, Denver, CO USA. Baylor Coll Med, Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Hardee, JT (reprint author), Kaiser Permanente, Dept Internal Med, Denver, CO 80231 USA. NR 10 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD SEP PY 2003 VL 37 IS 3 BP 271 EP 272 DI 10.1097/00004836-200309000-00017 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 712ZT UT WOS:000184830000017 PM 12960731 ER PT J AU Wu, XB Li, YN Schneider, A Yu, WQ Rajendren, G Iqbal, J Yamamoto, M Alam, M Brunet, LJ Blair, HC Zaidi, M Abe, E AF Wu, XB Li, YN Schneider, A Yu, WQ Rajendren, G Iqbal, J Yamamoto, M Alam, M Brunet, LJ Blair, HC Zaidi, M Abe, E TI Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FACTOR-KAPPA-B; MORPHOGENETIC PROTEIN-4; SPEMANN ORGANIZER; GENE-EXPRESSION; SMAD-BINDING; MARROW; MOUSE; OSTEOCLAST; PROMOTER; ELEMENT AB We describe the effects of the overexpression of noggin, a bone morphogenetic protein (BMP) inhibitor, on osteoblast differentiation and bone formation. Cells of the osteoblast and chondrocyte lineages, as well as bone marrow macrophages, showed intense beta-gal histo- or cytostaining in adult noggin(+/-) mice that had a LacZ transgene inserted at the site of noggin deletion. Despite identical BMP levels, however, osteoblasts of 20-month-old C57BL/6J and 4-month-old senescence-accelerated mice (SAM-P6 mice) had noggin expression levels that were approximately fourfold higher than those of 4-month-old C57BL/6J and SAM-R1 (control) mice, respectively. U-33 preosteoblastic cells overexpressing the noggin gene showed defective maturation and, in parallel, a decreased expression of Runx-2, bone sialoprotein, osteocalcin, and RANK-L. Noggin did not inhibit the ligandless signaling and prodifferentiation action of the constitutively activated BMP receptor type 1A, ca-ALK-3. Transgenic mice overexpressing noggin in mature osteocalcin-positive osteoblasts showed dramatic decreases in bone mineral density and bone formation rates with histological evidence of decreased trabecular bone and CFU-osteoblast colonies at 4 and 8 months. Together, the results provide compelling evidence that noggin, expressed in mature osteoblasts, inhibits osteoblast differentiation and bone formation. Thus, the overproduction of noggin during biological aging may result in impaired osteoblast formation and function and hence, net bone loss. C1 Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, Mt Sinai Bone Program, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, New York, NY USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Vet Adm Med Ctr, Pittsburgh, PA USA. Univ Arkansas Med Sci, Div Endocrinol & Metab, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. Univ Calif Berkeley, Div Biochem & Mol Biol, Berkeley, CA 94720 USA. RP Abe, E (reprint author), Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, Mt Sinai Bone Program, 1 Gustave L Levy Pl,Box 1055, New York, NY 10029 USA. FU NIA NIH HHS [AG-14197-08] NR 42 TC 126 Z9 142 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2003 VL 112 IS 6 BP 924 EP 934 DI 10.1172/JCI200315543 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 722LN UT WOS:000185376400016 PM 12975477 ER PT J AU Lin, AL Johnson, DA Stephan, KT Yeh, CK AF Lin, AL Johnson, DA Stephan, KT Yeh, CK TI Alteration in salivary function in early HIV infection SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE HIV; xerostomia; saliva; salivary glands ID CANDIDA-ALBICANS; PAROTID-SALIVA; FLOW-RATES; AIDS; XEROSTOMIA; PROTEINS; DISEASE AB The etiology of salivary gland hypofunction in HIV(+) patients is unclear. This study was designed to determine the effect of early-stage HIV(+) infection (CD4(+) > 200 cells/muL; n = 139) on salivary gland function and the relationship of this dysfunction to the taking of xerostomic medications. Salivary flow rates and the content of electrolytes and antimicrobial proteins in stimulated parotid and submandibular/sublingual saliva were determined. Compared with healthy controls (n = 50), the HIV(+) group showed significant reductions in flow rates of unstimulated whole (35%),. stimulated parotid (47%), unstimulated submandibular/sublingual (23%), and stimulated submandibular/sublingual (39%) saliva. The flow rates for the HIV(+) patients taking xerostomic medications did not differ from those of patients who did not. Concentrations of some salivary gland components were altered in the HIV(+) group. Analysis of these data suggests that salivary gland function is adversely affected early in HIV infection and that these changes do not appear to be compounded by the taking of xerostomic medications. C1 Univ Texas, Ctr Hlth Sci, Dept Dent Diagnost Sci, San Antonio, TX USA. Univ Texas, Ctr Hlth Sci, Dept Community Dent, San Antonio, TX USA. Wilford Hall USAF Med Ctr, HIV Unit, Dept Infect Dis, Lackland AFB, TX 78236 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Res Serv, San Antonio, TX 78229 USA. RP Yeh, CK (reprint author), Univ Texas, Ctr Hlth Sci, Dept Dent Diagnost Sci, San Antonio, TX USA. FU NIDCR NIH HHS [DE12188] NR 21 TC 22 Z9 25 U1 1 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2003 VL 82 IS 9 BP 719 EP 724 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 716JF UT WOS:000185024500012 PM 12939357 ER PT J AU Landefeld, CS AF Landefeld, CS TI Training in the care of older adults - Opportunity knocks for general internal medicine SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID DELIRIUM C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Aging, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2003 VL 18 IS 9 BP 770 EP 771 DI 10.1046/j.1525-1497.2003.30703.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 719EA UT WOS:000185189600014 PM 12950488 ER PT J AU Peskind, ER Bonner, LT Hoff, DJ Raskind, MA AF Peskind, ER Bonner, LT Hoff, DJ Raskind, MA TI Prazosin reduces trauma-related nightmares in older men with chronic posttraumatic stress disorder SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE PTSD; prazosin; nightmares; veterans; Holocaust ID CORTICOTROPIN-RELEASING-FACTOR; COMBAT VETERANS; ALZHEIMERS-DISEASE; MILITARY VETERANS; HORMONE-LEVELS; PTSD; NOREPINEPHRINE; SYMPTOMS; SLEEP; SERTRALINE AB Trauma-related nightmares in posttraumatic stress disorder (PTSD) rarely respond. to pharmacologic treatment. Neurobiologic data suggest that enhanced brain responsiveness to adrenergic stimulation may contribute to the pathophysiology of trauma-related nightmares in PTSD. Nine older men with chronic PTSD secondary to military or Holocaust trauma were prescribed the lipophilic alpha-1 adrenergic antagonist prazosin for treatment-resistant trauma-related nightmares. Prazosin 2 mg to 4 mg 1 hour before bedtime substantially reduced nightmares and moderately or markedly reduced overall PTSD severity in 8 of 9 subjects. Prazosin was well tolerated. These open-label results are consistent with demonstrated therapeutic efficacy of prazosin for PTSD nightmares and sleep disturbance in a recent placebo-controlled trial in Vietnam veterans. C1 NW Network Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Peskind, ER (reprint author), VA Puget Sound Hlth Care Syst, S-116,1660 S Columbian Way, Seattle, WA 98108 USA. EM murray.raskind@med.va.gov FU NIA NIH HHS [R01 AG18644] NR 44 TC 65 Z9 67 U1 3 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2003 VL 16 IS 3 BP 165 EP 171 DI 10.1177/0891988703256050 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 847GJ UT WOS:000223380400007 PM 12967060 ER PT J AU Weintraub, D Moberg, PJ Duda, JE Katz, IR Stern, MB AF Weintraub, D Moberg, PJ Duda, JE Katz, IR Stern, MB TI Recognition and treatment of depression in Parkinson's disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Parkinson's disease; depression; diagnosis; treatment; response; antidepressant ID CONTROLLED-TRIAL; INCREASED RISK; PRIMARY-CARE; SYMPTOMS; SCALE; CITALOPRAM; PREVALENCE; PAROXETINE; DISORDER; VALIDITY AB Depression in Parkinson's disease (PD) is common, but little is known about its recognition and treatment. The authors report the antidepressant experience (N = 100) and outcome of depression assessment (n = 77) of a convenience sample of patients at a PD center. Subjects were assessed with a psychiatric and neurological battery, and information was gathered on depression treatment. One third (34%) of subjects met criteria for a depressive disorder, and two thirds (65%) of them were not currently receiving antidepressant treatment. Approximately one quarter (23%) of subjects were taking an antidepressant, but almost half (47%) of them still met criteria for a depressive disorder. Few antidepressant users with persistent depression had received either antidepressant treatment at dosages within the highest recommended range (11%) or more than 1 antidepressant trial (33%). Most depressed patients are untreated, and half of antidepressant users remain depressed, suggesting that even when delivered, treatment is often inadequate or ineffective. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. RP Weintraub, D (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu NR 44 TC 94 Z9 95 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2003 VL 16 IS 3 BP 178 EP 183 DI 10.1177/0891988703256053 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 847GJ UT WOS:000223380400009 PM 12967062 ER PT J AU Chan, EM Bulman, DE Paterson, AD Turnbull, J Andermann, E Andermann, F Rouleau, GA Delgado-Escueta, AV Scherer, SW Minassian, BA AF Chan, EM Bulman, DE Paterson, AD Turnbull, J Andermann, E Andermann, F Rouleau, GA Delgado-Escueta, AV Scherer, SW Minassian, BA TI Genetic mapping of a new Lafora progressive myoclonus epilepsy locus (EPM2B) on 6p22 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; LINKAGE ANALYSIS; CORPORA-AMYLACEA; BODIES; IDENTIFICATION; DISEASE AB Background: Lafora disease is a progressive myoclonus epilepsy with polyglucosan accumulations and a peculiar neurodegeneration with generalised organellar disintegration. It causes severe seizures, leading to dementia and eventually death in early adulthood. Methods: One Lafora disease gene, EPM2A, has been identified on chromosome 6q24. Locus heterogeneity led us to search for a second gene using a genome wide linkage scan in French-Canadian families. Results: We mapped a second Lafora disease locus, EPM2B, to a 2.2 Mb region at 6p22, a region known to code for several proteins, including kinesins. Kinesins are microtubule dependent motor proteins that are involved in transporting cellular components. In neurones, they play a major role in axonal and dendritic transport. Conclusion: Analysis of the present locus in other non-EPM2A families will reveal whether there is further locus heterogeneity. Identification of the disease gene will be of major importance towards our understanding of the pathogenesis of Lafora disease. C1 Hosp Sick Children, Dept Pediat, Div Neurol, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1X8, Canada. Ottawa Gen Hosp, Ottawa Hlth Res Inst, Div Neurol, Ottawa, ON K1H 8L6, Canada. McGill Univ, Montreal Neurol Hosp & Inst, Dept Neurol & Neurosurg, Neurogenet Unit, Montreal, PQ H3A 2B4, Canada. McGill Univ, Montreal Neurol Hosp & Inst, Dept Human Genet, Neurogenet Unit, Montreal, PQ H3A 2B4, Canada. McGill Univ, Montreal Neurol Hosp & Inst, Epilepsy Serv, Montreal, PQ H3A 2B4, Canada. McGill Univ, Dept Paediat, Montreal, PQ H3A 2B4, Canada. McGill Univ, Montreal Gen Hosp, Ctr Hlth, Res Inst,Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada. Univ Calif Los Angeles, Sch Med, W Los Angeles DVA Med Ctr, Dept Neurol,Comprehens Epilepsy Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles DVA Med Ctr, Brain Res Inst, Los Angeles, CA 90073 USA. RP Minassian, BA (reprint author), Hosp Sick Children, Dept Pediat, Div Neurol, Program Genet & Genom Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; Paterson, Andrew/A-4088-2011 OI Scherer, Stephen /0000-0002-8326-1999; Paterson, Andrew/0000-0002-9169-118X FU NINDS NIH HHS [R01 NS042376] NR 25 TC 32 Z9 33 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP 1 PY 2003 VL 40 IS 9 BP 671 EP 675 DI 10.1136/jmg.40.9.671 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 718ZP UT WOS:000185177700005 PM 12960212 ER PT J AU Ozcan, C Bienengraeber, M Hodgson, DM Mann, DL Terzic, A AF Ozcan, C Bienengraeber, M Hodgson, DM Mann, DL Terzic, A TI Mitochondrial tolerance to stress impaired in failing heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE mitochondria; oxidative stress; calcium; heart failure; TNF alpha; energy metabolism ID TUMOR-NECROSIS-FACTOR; CARDIAC MITOCHONDRIA; HUMAN MYOCARDIUM; TRANSGENIC MICE; FAILURE; OVEREXPRESSION; ATP; CREATINE; DISEASE; DOGS AB Mitochondrial integrity is critical in the maintenance of bioenergetic homeostasis of the myocardium, with oxidative or metabolic challenge to mitochondria precipitating cell injury. In heart failure, where cardiac cell, are exposed to elevated stress, mitochondrial vulnerability could contribute to the disease state. However, the mitochondrial response to stress is yet to be established in heart failure. Here, mitochondrial function and structure was evaluated prior and following stress using a transgenic (TG) model of heart failure, generated by cardiac overexpression of the cytokine TNFalpha. Compared to the wild type, mitochondria from TG failing hearts demonstrated impaired oxidative phosphorylation, mitochondrial DNA damage, reduced mitochondrial creatine kinase activity, abnormal calcium handling, and altered ultrastructure. Under anoxia/reoxygenation or calcium stress, mitochondria from failing hearts suffered exacerbated energetic failure with pronounced cytochrome c release. Thus, mitochondria from TNFalpha-TG failing hearts demonstrate structural and functional abnormalities, with reduced tolerance to stress manifested by impaired bioenergetics and increased susceptibility to injury. This abnormal vulnerability to stress underscores the impact of mitochondrial dysfunction in the pathobiology of heart failure. (C) 2003 Elsevier Ltd. All rights reserved. C1 Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Dept Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Dept Mol Pharmacol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Dept Expt Therapeut, Rochester, MN 55905 USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX 77030 USA. RP Terzic, A (reprint author), Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Dept Med, Guggenheim 7F, Rochester, MN 55905 USA. EM terzic.andre@mayo.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [HL 64822, HL 07111] NR 22 TC 12 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2003 VL 35 IS 9 BP 1161 EP 1166 DI 10.1016/S0022-2828(03)00204-9 PG 6 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 724NZ UT WOS:000185494800020 PM 12967639 ER PT J AU Haq, E Giri, S Singh, I Singh, AK AF Haq, E Giri, S Singh, I Singh, AK TI Molecular mechanism of psychosine-induced cell death in human oligodendrocyte cell line SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoplosis; beta-galactosidase; oligodendroglial cells; psychosine; redox ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; MEDIATED APOPTOSIS; TWITCHER MOUSE; TNF-ALPHA; C-MYC; JNK ACTIVATION; CYTOCHROME-C; MURINE MODEL; MICE LACKING AB This study delineates the molecular mechanism underlying psychosine-induced oligodendroglial cell death. An immortalized human oligodendroglial cell line, MO3.13, was treated with exogenous psychosine (P-galactosylsphingosine), a toxic metabolite that accumulates in the tissues of patients with Krabbe's disease. The mode of cell death induced by psychosine was found to be apoptotic, as revealed by different apoptotic markers viz., TUNEL, DNA fragmentation and caspase cleavage/activation. The action of psychosine was redox sensitive, as measured by changes in mitochondrial membrane potential ( A), and this effect of psychosine could be reversed by pre-treatment with the antioxidant molecules N-acetyl-L-cysteine or pro-cysteine. Psychosine directly affects the mitochondria as revealed by the activation of caspase 9 but not caspase 8. Up-regulation of the c-jun/c-jun N-terminal kinase pathway by psychosine leads to the induction of AP-1 and, at the same time, psychosine also down-regulates the lipopolysaccharide-induced NF-kappaB transactivation. These observations indicate that the mechanism of action of psychosine is, through the up-regulation of AP-1, a pro-apoptotic pathway as well as, through the down-regulation of the NF-kappaB pathway, an antiapoptotic pathway. C1 Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. EM singha@musc.edu OI Haq, Ehtishamul/0000-0002-4195-0606 FU NINDS NIH HHS [NS-40810, NS 37766, NS-22576, NS-34741] NR 57 TC 63 Z9 65 U1 1 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2003 VL 86 IS 6 BP 1428 EP 1440 DI 10.1046/j.1471-4159.2003.01941.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 764ZQ UT WOS:000188241400011 PM 12950451 ER PT J AU Matejuk, A Hopke, C Dwyer, J Subramanian, S Jones, RE Bourdette, DN Vandenbark, AA Offner, H AF Matejuk, A Hopke, C Dwyer, J Subramanian, S Jones, RE Bourdette, DN Vandenbark, AA Offner, H TI CNS gene expression pattern associated with spontaneous experimental autoimmune encephalomyelitis SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE spontaneous EAE; microarray; spinal cord ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS LESIONS; CEREBROSPINAL-FLUID; TRANSGENIC MICE; NERVOUS-SYSTEM; T-CELLS; PROTEIN; RECEPTOR; IDENTIFICATION; TRANSCRIPTION AB Transgenic mice with T-cell receptor (TCR) specific for myelin basic protein (MBP)-Ac1-11 peptide and homozygous for the RAG-1 mutation (T/R-mice) spontaneously develop acute progressive experimental autoimmune encephalomyelitis (Sp-EAE) mediated by CD4+ T cells. Microarray analysis of spinal cord tissue obtained from symptomatic versus non-symptomatic T/R- mice revealed strongly upregulated transcripts for genes involved in antigen presentation and processing, signal transduction, transcription regulation, metabolism, development, cell cycle, and many other processes involved in the induction of clinical and pathological signs of Sp-EAE. Several highly expressed genes were related directly to inflammation, including cytokines/receptors, chemokines/receptors, acute phase, complement molecules, and others. Many CNS-specific genes were also upregulated in sick mice. Abundance of message for the Tg TCR BV8S2 gene as well as several monocyte/ macrophage-associated genes would suggest that both components play a crucial role in the pathogenesis of Sp-EAE. The profile of transcriptional changes found during the development of Sp-EAE provides the first description of the encephalitogenic process in the absence of purposeful immunization with myelin peptides and immune-enhancing adjuvants. This unique approach is the first to implicate molecules and pathways that contribute naturally to onset of paralysis and demyelination, and thus may provide unique insights and novel treatment strategies for human diseases such as multiple sclerosis. (C) 2003 Wiley-Liss, Inc. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp, Portland, OR 97239 USA. FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23444, NS23221] NR 44 TC 18 Z9 20 U1 0 U2 1 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 SEP 1 PY 2003 VL 73 IS 5 BP 667 EP 678 DI 10.1002/jnr.10689 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 719RL UT WOS:000185218100009 PM 12929134 ER PT J AU Studer, RK Decker, K Melhem, S Georgescu, H AF Studer, RK Decker, K Melhem, S Georgescu, H TI Nitric oxide inhibition of IGF-1 stimulated proteoglycan synthesis: role of cGMP SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE nitric oxide; cartilage; chondrocytes; cGMP dependent kinase; arthritis ID DEPENDENT PROTEIN-KINASE; ARTICULAR CHONDROCYTES; CYCLIC-GMP; NOS2-DEFICIENT MICE; I ISOFORMS; EXPRESSION; METABOLISM; ARTHRITIS; SYNTHASE; CELLS AB Insulin-like growth factor (IGF-1) is critical for normal development and maintenance of cartilage, however arthritic cartilage responds poorly to IGF-1; part of this insensitivity is mediated by nitric oxide (NO). These studies test if cGMP is responsible for NO dependent insensitivity to IGF-1 in chondrocytes in situ in organ culture and in monolayer culture. Lapine cartilage and chondrocytes in monolayer culture and cartilage from osteoarthritic human knees were used. Tissues were exposed to NO from iNOS induced by IL-1, and proteoglycan synthesis in response to IGF-1 was evaluated in the presence and absence of cGMP dependent protein kinase (PKG) inhibitors. PKG activators inhibited IGF-1 responses in cartilage but not chondrocytes in monolayer. IL-1 stimulated cGMP synthesis in both monolayer and organ cultures. However, PKG inhibitors in cartilage slices but not in monolayer cultures restored response to IGF-1. PKG activity was detected in both fresh and monolayer chondrocytes, confirming this part of the cGMP signal cascade is intact in both of the preparations evaluated. Arthritic cartilage response to IGF-1 was restored by both N-G-monomethyl-(L)-arginine inhibition of NO synthesis and PKG inhibitors. The data suggests that cGMP mediated effects are critical to NO actions on chondrocytes in situ in the cartilage matrix and supports a role for cGMP in the pathophysiologic effects of NO in osteoarthritis. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Ferguson Lab,Dept Orthopaed Surg,MSRC, Pittsburgh, PA 15240 USA. RP Studer, RK (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Ferguson Lab,Dept Orthopaed Surg,MSRC, Univ Dr C,151U VA Med Ctr, Pittsburgh, PA 15240 USA. NR 29 TC 12 Z9 12 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 2003 VL 21 IS 5 BP 914 EP 921 DI 10.1016/S0736-0266(03)00029-9 PG 8 WC Orthopedics SC Orthopedics GA 717HC UT WOS:000185080600022 PM 12919881 ER PT J AU Mericq, V Cassorla, F Bowers, CY Avila, A Gonen, B Merriam, GR AF Mericq, V Cassorla, F Bowers, CY Avila, A Gonen, B Merriam, GR TI Changes in appetite and body weight in response to long-term oral administration of the ghrelin agonist GHRP-2 in growth hormone deficient children SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE ghrelin; appetite; growth hormone deficiency; children ID ACYLATED PEPTIDE; SECRETAGOGUE; RECEPTOR; HUMANS; ACTIVATION; OBESITY AB GHRP-2 (GPA-748, Wyeth-Ayerst) is an orally active peptide growth hormone (GH) secretagogue which acts through a G-protein coupled receptor for which the natural ligand an acylated 28 amino acid peptide, ghrelin - was recently isolated. Ghrelin and its analogs have potent GH-releasing activities, but in animal studies ghrelin also causes weight gain. As part of a study examining the effect of GHRP-2 on GH secretory dynamics and growth, we evaluated its effects on appetite and body weight. Ten prepubertal children with GH deficiency (growth velocity less than or equal to4 cm/year in association with a GH response to two provocative stimuli <10 ng/ml) were included in the study. At the beginning of the study their age was 10.4 +/- 2 years (mean SD), with a height of -3.8 +/- 0.1 SDS. Body mass index (BMI) was 17.9 +/- 3.6 kg/m(2), and the BMI Z score 0.21 +/- 1.51 SDS. GHRP-2 was administered orally at a dose of 900 mug/kg b.i.d. for 12 months. Seven out of ten patients reported a significant increase in appetite during the first 6 months of the study. There was a tendency for the BMI SDS to increase during the study, but this increase did not reach statistical significance (0.21 +/- 1.5 vs 0.25 +/- 1.5 SDS). These results suggest that at a dose of 900 mug/kg b.i.d., GHRP-2 appears to have a transient stimulatory effect on appetite, but does not have a chronic clinically significant effect on BMI in children with GH deficiency. C1 Univ Chile, Inst Invest Materno Infantil, Santiago, Chile. Wyeth Ayerst Res, Philadelphia, PA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound HCS, Seattle, WA 98195 USA. RP Mericq, V (reprint author), Univ Chile, Inst Invest Materno Infantil, Casilla 226-3, Santiago, Chile. EM vmericq@machi.med.uchile.cl RI Mericq, Veronica/F-3927-2010 NR 20 TC 16 Z9 16 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD SEP PY 2003 VL 16 IS 7 BP 981 EP 985 PG 5 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 721XD UT WOS:000185343000005 PM 14513874 ER PT J AU LaFranchi, SH Snyder, DB Sesser, DE Skeels, MR Singh, N Brent, GA Nelson, JC AF LaFranchi, SH Snyder, DB Sesser, DE Skeels, MR Singh, N Brent, GA Nelson, JC TI Follow-up of newborns with elevated screening T4 concentrations SO JOURNAL OF PEDIATRICS LA English DT Article ID MCCUNE-ALBRIGHT SYNDROME; THYROTROPIN-RECEPTOR GENE; THYROID-HORMONE; CONGENITAL HYPERTHYROIDISM; DYSALBUMINEMIC HYPERTHYROXINEMIA; NEONATAL HYPERTHYROIDISM; GENERALIZED RESISTANCE; BETA GENE; MUTATION; ABNORMALITIES AB Objective To determine the type and incidence of hyperthyroxinemic disorders detected by follow-up of infants with elevated screening total T4 (TT4) values. Study design Infants born in Oregon with a screening TT4 measurement >3 SD above the mean were offered enrollment. Serum TT4, free T4, total T3, free T3, and thyroid-stimulating hormone concentrations were measured in. study infants and their mothers. Results Over a 20-month period, 101 infants (51 boys) and their mothers enrolled in the study (of 241 eligible infants), from a total screening population of 80,884; 17 infants were identified with persistent hyperthyroxinemia (TT4 >16 mug/dL). Ten had thyroxine-binding globulin excess (1:8088), 5 had evidence for increased T4 binding but not thyroxine-binding globulin excess (1:16,177), and 2 had findings compatible with thyroid hormone resistance (1:40,442); the other 84 infants had transient hyperthyroxinemia. Sequence analysis revealed a point mutation in the thyroid hormone receptor-beta gene in one infant with thyroid hormone resistance; no mutation was identified in the other infant. Conclusions Although neonatal Graves' disease occurs in approximately 1 in 25,000 newborn infants, we did not detect any case among 80, 84 infants, most likely because their mothers were receiving antithyroid drugs. Although the other hyperthyroxinemic disorders in the aggregate occur frequently (1:4758) and may benefit from detection, in general they do not require treatment. C1 Legacy Emanuel Childrens Hosp, Portland, OR USA. Oregon State Publ Hlth Lab, Portland, OR USA. Univ Calif Los Angeles, VA Greater Los Angeles Hlth Care Syst, Dept Med, Sch Med, Los Angeles, CA USA. Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. Loma Linda Univ, Med Ctr, Dept Internal Med, Loma Linda, CA USA. Loma Linda Univ, Med Ctr, Dept Pathol, Loma Linda, CA USA. RP LaFranchi, SH (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, 707 SW Gaines Rd, Portland, OR 97239 USA. EM lafrancs@ohsu.edu NR 27 TC 50 Z9 58 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2003 VL 143 IS 3 BP 296 EP 301 DI 10.1067/S0022-3476(03)00184-7 PG 6 WC Pediatrics SC Pediatrics GA 728GV UT WOS:000185710200007 PM 14517508 ER PT J AU LeMarbre, G Stauber, S Khayat, RN Puleo, DS Skatrud, JB Morgan, BJ AF LeMarbre, G Stauber, S Khayat, RN Puleo, DS Skatrud, JB Morgan, BJ TI Baroreflex-induced sympathetic activation does not alter cerebrovascular CO2 responsiveness in humans SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CEREBRAL BLOOD-FLOW; BODY NEGATIVE-PRESSURE; TRANSCRANIAL DOPPLER; ORTHOSTATIC STRESS; CARBON-DIOXIDE; NERVE ACTIVITY; UPRIGHT TILT; RESPONSES; BARORECEPTOR; CIRCULATION AB We investigated the effect of baroreflex-induced sympathetic activation, produced by lower body negative pressure (LBNP) at -40 mmHg, on cerebrovascular responsiveness to hyper- and hypocapnia in healthy humans. Transcranial Doppler ultrasound was used to measure blood flow velocity (CFV) in the middle cerebral artery during variations in end-tidal carbon dioxide pressure (PIT,11,)of +10, +5,0,-5, and -10 mmHg relative to eupnoea. The slopes of the linear relationships between PET,CO, and CFV were computed separately for hyper- and hypocapnia during the LBNP and no-LBNP conditions. LBNP decreased pulse pressure, but did not change mean arterial pressure. LBNP evoked an increase in ventilation that resulted in a 9 2 mmHg decrease in P-ET,P-CO2, which was corrected by CO2 supplementation of the inspired air. LBNP did not affect cerebrovascular CO2 response slopes during steady-state hypercapnia (3.14 +/- 0.24 vs. 2.96 +/- 0.26 cm s(-1) mmHg(-1)) or hypocapnia (1.31 +/- 0.18 vs. 1.32 +/- 0.19 cm s(-1) mmHg(-1)), or the CFV responses to voluntary apnoea (+51 +/- 19 vs. +50 +/- 18 %). Thus, cerebrovascular CO2 responsiveness was not altered by baroreflex-induced sympathetic activation. Our data challenge the concept that sympathetic activation restrains cerebrovascular responses to alterations in CO2 pressure. C1 Univ Wisconsin, Dept Orthopaed & Rehabil, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Middleton Vet Adm Hosp, Madison, WI 53705 USA. RP Morgan, BJ (reprint author), Univ Wisconsin, Dept Orthopaed & Rehabil, 1300 Univ Ave,5173 MSC, Madison, WI 53706 USA. RI Khayat, Rami/E-3380-2011 NR 52 TC 43 Z9 43 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2003 VL 551 IS 2 BP 609 EP 616 DI 10.1113/jphysiol.2003.046987 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 727XK UT WOS:000185686000022 PM 12844511 ER PT J AU Sherman, SE Lanto, AB Nield, M Yano, EM AF Sherman, SE Lanto, AB Nield, M Yano, EM TI Smoking cessation care received by veterans with chronic obstructive pulmonary disease SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE chronic obstructive pulmonary disease; counseling; smoking cessation ID LUNG HEALTH; INTERVENTION; HABITS; BURDEN AB Smoking is the main cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the only effective intervention to slow its progression. We examined whether smokers with COPD received more cessation services than smokers without COPD. Current smokers from 18 Veterans Health Administration primary care clinics completed baseline and 12 month follow-up surveys (baseline n = 1,941; 12 month n = 1,080), composed of validated questions on smoking habits, history, and attitudes; health/functional status; and sociodemographics. Both at baseline and 12 month follow-up, smokers with COPD were more likely to report that they had been advised to quit, prescribed nicotine patches, or referred to a smoking cessation program within the last year. However, the rate of quitting smoking was the same for smokers with COPD and smokers without COPD. The increase in cessation services received by smokers with COPD was noted primarily among smokers not interested in quitting. New approaches may be required, particularly to help smokers not interested in quitting. C1 VA Greater Los Angles Healthcare Syst, Ctr Excellence Study Healthcare Provider Behavior, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Div Pulm & Crit Care, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Sherman, SE (reprint author), VA Greater Los Angles Healthcare Syst, Ctr Excellence Study Healthcare Provider Behavior, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 31 TC 13 Z9 14 U1 2 U2 4 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 SEP-OCT PY 2003 VL 40 IS 5 SU 2 BP 1 EP 12 PG 12 WC Rehabilitation SC Rehabilitation GA 737MC UT WOS:000186235500002 PM 15074449 ER PT J AU Rentschler, AJ Cooper, RA Blasch, B Boninger, ML AF Rentschler, AJ Cooper, RA Blasch, B Boninger, ML TI Intelligent walkers for the elderly: Performance and safety testing of VA-PAMAID robotic walker SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE engineering test; navigational assistance; obstacle avoidance; robotic walker; visual impairment ID FALLS AB A walker that could help navigate and avoid collisions with obstacles could help reduce health costs and increase the quality of care and independence of thousands of people. This study evaluated the safety and performance of the Veterans Affairs Personal Adaptive Mobility Aid (VA-PAMAID). We performed engineering tests on the VA-PAMAID to determine safety factors, including stability, energy consumption, fatigue life, and sensor and control malfunctions. The VA-PAMAID traveled 10.9 km on a full charge and avoided obstacles while traveling at a speed of up to 1.2 m/s. No failures occurred during static stability, climatic, or fatigue testing. Some problems were encountered during obstacle climbing and sensor and control testing. The VA-PAMAID has good range, has adequate reaction time, and is structurally sound. Clinical trials are planned to compare the device to other low-technical adaptive mobility devices. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Va Rehabil Res & Dev, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil & Bioengn, Pittsburgh, PA USA. Atlanta VA Med Ctr, VA Rehabil Res & Dev Ctr, Decatur, GA USA. RP VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Va Rehabil Res & Dev, 151-R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 19 TC 48 Z9 52 U1 2 U2 4 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 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD SEP-OCT PY 2003 VL 40 IS 5 BP 423 EP 431 PG 9 WC Rehabilitation SC Rehabilitation GA 736RH UT WOS:000186186600008 PM 15080227 ER PT J AU Evans, CT Legro, MW Weaver, FM Goldstein, B AF Evans, CT Legro, MW Weaver, FM Goldstein, B TI Influenza vaccination among veterans with Spinal Cord Injury: Part 1. A survey of attitudes and behavior SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE spinal cord injuries; influenza; vaccination; immunization; veterans; health promotion; preventive medicine; paraplegia; tetraplegia; rehabilitation ID POPULATION; ADULTS; DEATH AB Background/Objective: Persons with spinal cord injury and disorders (SCID) are at increased risk of developing influenza, pneumonia, and ensuing complications. Influenza vaccine has been shown to be effective, yet vaccination rates have been low in this population. To improve these rates, barriers and facilitators to receiving influenza vaccine in this population were identified. Methods: A cross-sectional telephone survey was conducted with a convenience sample of patients at 13 Department of Veterans Affairs (VA) Spinal Cord Injury (SCI) Centers between September and November 2000. Survey questions assessed perceptions regarding the influenza vaccine. Results: Participants interviewed (N = 377) had a mean age of 58.6 years and were predominantly male and white. Most had had received the influenza vaccine at some time in the past; however, 35% had not received it in the previous year. The most common reason reported for not being vaccinated was the belief that it was not important. Those who knew the best time to be vaccinated were more likely to have been vaccinated the previous year (OR = 3.57, 95%, Cl: 2.12-6.01). Other predictors of vaccination included being married, being aged 65 and older, and being aware that the vaccine was a good way to prevent some pulmonary problems that can result from influenza. Conclusions: Barriers to vaccination include poor understanding of the seriousness of influenza and of the vulnerability of someone with SCID to respiratory complications. Availability of the influenza vaccine at VA facilities and knowledge of when to be vaccinated were facilitators. Providers should use every opportunity to vaccinate patients and provide education about the value of influenza vaccination and when to be vaccinated. C1 Edward J Hines Jr VA Hosp, Midw Ctr Hlth Serv & Policy Res, Dept Vet Affairs, Hines, IL 60141 USA. VA Puget Sound Hlth Care Syst, Spinal Cord Injury Qual Enhancement Res Initiat, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Spinal Cord Injury & Disorders Strateg Healthcare, Dept Vet Affairs, Seattle, WA USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Chicago, IL 60611 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Evans, CT (reprint author), Edward J Hines Jr VA Hosp, Midw Ctr Hlth Serv & Policy Res, Dept Vet Affairs, 151H,5th & Roosevelt Rd,POB 5000, Hines, IL 60141 USA. NR 16 TC 6 Z9 6 U1 1 U2 3 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FAL PY 2003 VL 26 IS 3 BP 204 EP 209 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 739PJ UT WOS:000186355400004 PM 14997958 ER PT J AU Weaver, FM Goldstein, B Evans, CT Legro, MW LaVela, S Smith, B Miskevics, S Hammond, MC AF Weaver, FM Goldstein, B Evans, CT Legro, MW LaVela, S Smith, B Miskevics, S Hammond, MC TI Influenza vaccination among veterans with spinal cord injury: Part 2. Increasing vaccination rates SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE spinal cord injuries; influenza; vaccination; immunization; veterans; health promotion; preventive medicine; paraplegia; tetraplegia; rehabilitation ID RANDOMIZED CONTROLLED-TRIAL; MEDICAL OPINION LEADERS; IMMUNIZATION RATES; REMINDERS; PERFORMANCE; MORTALITY; DEATH; CARE; QUESTIONNAIRE; GUIDELINES AB Background/Objective: Respiratory complications are the leading cause of morbidity and mortality among individuals with spinal cord injury (SCI). Influenza vaccination is effective in reducing the likelihood of contracting influenza and of subsequent respiratory complications, hospitalizations, and deaths. Historically, vaccination rates for veterans with SCI treated in Veterans Affairs (VA) facilities have been low. The objective of this study was to increase vaccination rates in this population using a multipronged strategy. Methods: A quasi-experimental design involving 2,284 veterans treated at 8 VA SCI Centers was used. Patients at 4 centers received reminder letters and educational materials tailored to SCI. Provider education included mailed reminders and posters in SCI clinical areas. Clinical champions were identified at each site. Four other centers, matched to the study sites in program size and prior vaccination rates, served as comparison sites providing usual care. Vaccination rates were assessed using mailed surveys with telephone follow-up. Results: The influenza vaccination rate was significantly higher in the intervention group than in the comparison group (60.5% vs 54.3%; P = 0.01). Vaccine recipients were older than nonrecipients (mean age 60.8 vs 53.1 years; P < 0.0001). Reasons for not receiving a vaccination included refusal, feeling that being vaccinated was not worth the trouble, and not believing that the vaccine would prevent influenza. Conclusions: Use of low-cost mailed reminders and educational materials resulted in significantly higher vaccination rates. Further efforts to reach targeted subgroups of nonrecipients, such as patients who are younger or from an ethnic minority, are warranted. C1 Edward Hines Jr VA Hosp, Midw Ctr Hlth Serv & Policy Res 151H, Dept Vet Affairs, Hines, IL 60141 USA. Edward Hines Jr VA Hosp, SCI QUERI, Dept Vet Affairs, Hines, IL 60141 USA. Northwestern Univ, ISHRPS, Chicago, IL 60611 USA. VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Spinal Cord Injury & Disorders Strateg Healthcare, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Vet Affairs, SCI QUERI, Seattle, WA USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Weaver, FM (reprint author), Edward Hines Jr VA Hosp, Midw Ctr Hlth Serv & Policy Res 151H, Dept Vet Affairs, 5th & Roosevelt Rd,POB 5000, Hines, IL 60141 USA. NR 43 TC 21 Z9 21 U1 0 U2 1 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FAL PY 2003 VL 26 IS 3 BP 210 EP 218 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 739PJ UT WOS:000186355400005 PM 14997959 ER PT J AU Goldstein, B Hammond, MC AF Goldstein, B Hammond, MC TI Commentary - The importance of influenza vaccinations in persons with spinal cord injury and disease SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, SCI Hlth Care Grp, Seattle, WA USA. RP Goldstein, B (reprint author), VA Puget Sound Hlth Care Syst, SCI Hlth Care Grp, Seattle, WA USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FAL PY 2003 VL 26 IS 3 BP 219 EP 220 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 739PJ UT WOS:000186355400006 PM 14997960 ER PT J AU Helkowski, WM Ditunno, JF Boninger, M AF Helkowski, WM Ditunno, JF Boninger, M TI Autonomic dysreflexia: Incidence in persons with neurologically complete and incomplete tetraplegia SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE autonomic dysreflexia; tetraplegia; spinal cord injuries; hypertension; rehabilitation ID SPINAL-CORD INJURY; HYPERREFLEXIA AB Background: Autonomic dysreflexia (AD) is a common problem in patients with spinal cord injury (SCI) above the T6 neurologic level and may cause serious medical complications if untreated. Previous studies have focused on patients with complete SCI. Design: Prospective analysis of a historic cohort. A retrospective review of a subset of the cohort also was performed. Objectives: To examine the percentage of persons with complete and incomplete tetraplegia who developed AD and determine whether patients with incomplete injuries were at risk for developing AD; and to study the onset of AD and determine the time period that patients are at risk for developing AD. Methods: Data were collected prospectively on 332 patients with tetraplegia to determine American Spinal Injury Association (ASIA) impairment score, neurologic level, presence of AD, and length of hospital stay. The charts of 34 patients who developed AD were then reviewed retrospectively for further data such as onset and contributing factors of AD. Also obtained were data from the National SCI Statistical Center database for comparison of percentage of patients with complete and incomplete injuries who developed AD. Results: Patients with motor-complete SCI (ASIA A or ASIA 13) had a higher percentage of AD (P = 0.001) during their initial hospitalization than did patients with motor-incomplete SCI. However, patients with motor-incomplete injuries also were at risk for developing AD. The onset of AD occurred between I and 6 months after injury. Conclusion: Patients with incomplete tetraplegia are at risk for developing AD. As hospital lengths of stay decrease, patients may be discharged before onset of symptoms. Patient and family education about AD is, therefore, increasingly important for all patients with tetraplegia. C1 Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Thomas Jefferson Univ Hosp, Dept Rehabil Med, Philadelphia, PA 19107 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. RP Helkowski, WM (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, 3471 5th Ave,201 Kaufman Bldg, Pittsburgh, PA 15260 USA. OI Boninger, Michael/0000-0001-6966-919X NR 12 TC 28 Z9 29 U1 0 U2 1 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FAL PY 2003 VL 26 IS 3 BP 244 EP 247 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 739PJ UT WOS:000186355400012 PM 14997966 ER PT J AU Westbrook, SD Paunovich, ED Freytes, CO AF Westbrook, SD Paunovich, ED Freytes, CO TI Adult hemopoietic stem cell transplantation SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; ORAL COMPLICATIONS; INFECTIONS; MANAGEMENT; MUCOSITIS; PATIENT; IMMUNOTHERAPY; CHEMOTHERAPY; MALIGNANCIES; RECIPIENTS AB Background. Hemopoietic stem cell transplantation, or HSCT, is an important tool in modern cancer treatment. Refinement of transplantation techniques and supportive care has resulted in increased posttranslation survival rates. Dental care is a key supportive element in both pretransplantation and posttransplantation care of this patient population. Methods. The authors provide an overview of HSCT transplantation, emphasizing the oral complications and required supportive dental care. Conclusions. It is critical that transplantation candidates undergo dental screenings and be treated adequately before transplantation, that their care be closely managed during the transplantation process, and that they be given dental support as soon as their recovery permits. Dentists should consult with the patient's oncologist or primary health provider to identify the appropriate timing and intensity of dental support. Clinical Implications. Because of improved transplantation survival rates, more patients may seek supportive outpatient dental care after transplantation, which requires special management considerations. Dental professionals need to be knowledgeable about modern HSCT. C1 S Texas Vet Hlth Care Syst, Clin Oral Hlth Care Program Geriatr & Extended Ca, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Adult Bone Marrow Transplant Program, San Antonio, TX USA. RP Westbrook, SD (reprint author), 13614 Inwood Pk, San Antonio, TX 78216 USA. NR 37 TC 1 Z9 3 U1 0 U2 1 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 SEP PY 2003 VL 134 IS 9 BP 1224 EP 1231 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 722XY UT WOS:000185404400022 PM 14528994 ER PT J AU Bates-Jensen, BM Cadogan, M Jorge, J Schnelle, JE AF Bates-Jensen, BM Cadogan, M Jorge, J Schnelle, JE TI Standardized quality-assessment ulcer care in the nursing home SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pressure ulcer care; quality indicators; quality assessment ID PRESSURE ULCERS; RISK AB OBJECTIVES: To demonstrate reliability and feasibility of a standardized protocol to assess and score quality indicators relevant to pressure ulcer (PU) care processes in nursing homes (NHs). DESIGN: Descriptive. SETTING: Eight NHs. PARTICIPANTS: One hundred ninety-one NH residents for whom the PU Resident Assessment Protocol of the Minimum Data Set was initiated. MEASUREMENTS: Nine quality indicators (two related to screening and prevention of PU, two focused on assessment, and five addressing management) were scored using medical record data, direct human observation, and wireless thigh monitor observation data. Feasibility and reliability of medical record, observation, and thigh monitor protocols were determined. RESULTS: The percentage of participants who passed each of the indicators, indicating care consistent with practice guidelines, ranged from 0% to 98% across all indicators. In general, participants in NHs passed fewer indicators and had more problems with medical record accuracy before a PU was detected (screening/prevention indicators) than they did once an ulcer was documented (assessment and management indicators). Reliability of the medical record protocol showed kappa statistics ranging from 0.689 to 1.00 and percentage agreement from 80% to 100%. Direct observation protocols yielded kappa statistics of 0.979 and 0.928. Thigh monitor protocols showed kappa statistics ranging from 0.609 to 0.842. Training was variable, with the observation protocol requiring 1 to 2 hours, medical records requiring joint review of 20 charts with average time to complete the review of 20 minutes, and the thigh monitor data requiring 1 week for training in data preparation and interpretation. CONCLUSION: The standardized quality assessment system generated scores for nine PU quality indicators with good reliability and provided explicit scoring rules that permit reproducible conclusions about PU care. The focus of the indicators on care processes that are under the control of NH staff made the protocol useful for external survey and internal quality improvement purposes, and the thigh monitor observational technology provided a method for monitoring repositioning care processes that were otherwise difficult to monitor and manage. C1 Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA USA. Borun Ctr Gerontol Res & Jewish Home Aging, Reseda, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Sepulveda Geriatr Res Educ & Clin Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda, CA USA. RP Bates-Jensen, BM (reprint author), Univ Calif Los Angeles, Jewish Home Borun Ctr, 7150 Tampa Ave, Reseda, CA 91335 USA. NR 16 TC 13 Z9 13 U1 1 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2003 VL 51 IS 9 BP 1195 EP 1202 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 721NF UT WOS:000185321900001 ER PT J AU Bates-Jensen, BM Cadogan, M Osterweil, D Levy-Storms, L Jorge, J Al-Samarrai, N Grbic, V Schnelle, JF AF Bates-Jensen, BM Cadogan, M Osterweil, D Levy-Storms, L Jorge, J Al-Samarrai, N Grbic, V Schnelle, JF TI The minimum data set pressure ulcer indicator: Does it reflect differences in care processes related to pressure ulcer prevention and treatment in nursing homes? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Minimum Data Set; pressure ulcer care; quality indicators ID VULNERABLE ELDERS; QUALITY AB OBJECTIVES: To determine whether nursing homes (NHs) that score in the extreme quartiles of pressure ulcer (PU) prevalence as reported on the Minimum Data Set (MDS) PU quality indicator provide different PU care. DESIGN: Descriptive, cohort. SETTING: Sixteen NHs. PARTICIPANTS: Three hundred twenty-nine NH residents at risk for PU development as determined by the PU Resident Assessment Protocol of the MDS. MEASUREMENTS: Sixteen care process quality indicators (10 specific to PU care processes, five related to nutrition, and one related to incontinence management) were scored using medical record data, direct human observation, interviews, and data from wireless thigh movement monitors. RESULTS: There were no differences between homes with low- and high-PU prevalence rates reported on the MDS PU quality indicator on most care processes. NHs with high PU prevalence rates used pressure-reduction surfaces more frequently and were better at documentation of four wound characteristics when PUs were present. No measure of PU care processes was better in low-PU NHs. Neither low- nor high-PU prevalence NHs routinely repositioned residents every 2 hours, even though 2-hour repositioning was documented in the medical record for nearly all residents. CONCLUSION: The assumption that homes with fewer PUs and thus low PU prevalence according to the MDS quality indicator are providing better PU care was not supported in this sample. NHs that scored low on the MDS PU quality indicator did not provide significantly better care than NHs that scored high. All NHs could improve PU prevention, as evidenced by the poor performance on prevention care processes by low- and high-PU NHs. The MDS PU quality indicator is not a useful measure of the quality of PU care in NHs and can be misleading if not presented with an explanation of the meaning of the indicator. C1 Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Borun Ctr Gerontol Res, Reseda, CA USA. Univ Calif Los Angeles, Los Angeles Jewish Home Aging, Reseda, CA USA. Sepulveda Geriatr Res Educ & Clin Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda, CA USA. RP Bates-Jensen, BM (reprint author), Univ Calif Los Angeles, Jewish Home Borun Ctr, 7150 Tampa Ave, Reseda, CA 91335 USA. NR 19 TC 64 Z9 64 U1 3 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2003 VL 51 IS 9 BP 1203 EP 1212 DI 10.1046/j.1532-5415.2003.51403.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 721NF UT WOS:000185321900002 PM 12919231 ER PT J AU Volicer, L Ganzini, L AF Volicer, L Ganzini, L TI Health professionals' views on standards for decision-making capacity regarding refusal of medical treatment in mild Alzheimer's disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE decision-making capacity; dementia; ethical standards ID INFORMED CONSENT; ASSESSMENT-TOOL; LEGAL STANDARD; COMPETENCE; CONSISTENCY; JUDGMENTS; PATIENT AB This study was designed to determine which elements professionals consider important for evaluation of decision-making capacity. Survey with a vignette case report of an individual with mild dementia was mailed to four groups of individuals: 1. members of the Academy of Psychosomatic Medicine, 2. chairs of Veterans Affairs (VA) Ethics Advisory Committees (EACs), 3. randomly selected geriatricians who were members of the Gerontological Society of America (GSA), and 4. randomly selected psychologists who were members of the GSA. Two hundred thirty-seven psychiatrists, 95 VA EAC chairs, 103 geriatricians, and 46 psychologists responded to this survey. The majority of the respondents endorsed all five basic elements as necessary for determination of decision-making capacity in the presented vignette, but only a minority of respondents endorsed all five basic elements, and a small proportion of respondents endorsed only one or two elements. The results indicate that physicians do not use uniform standards for assessment of decision-making capacity. C1 EN Rogers Mem Hosp, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Volicer, L (reprint author), Edith Nourse Rogers Mem Vet Hosp, GRECC 182B, 200 Springs Rd, Bedford, MA 01730 USA. NR 17 TC 14 Z9 14 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2003 VL 51 IS 9 BP 1270 EP 1274 DI 10.1046/j.1532-5415.2003.51412.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 721NF UT WOS:000185321900011 PM 12919240 ER PT J AU Stehman-Breen, CO Gillen, D Steffes, M Jacobs, DR Lewis, CE Kiefe, CI Siscovick, D AF Stehman-Breen, CO Gillen, D Steffes, M Jacobs, DR Lewis, CE Kiefe, CI Siscovick, D TI Racial differences in early-onset renal disease among young adults: The Coronary Artery Risk Development in Young Adults (CARDIA) Study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION RATE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; DIABETES-MELLITUS; SERUM CREATININE; QUALITY-CONTROL; CHOLESTEROL; RECRUITMENT; SEGREGATION; EXCRETION AB Although 11 million people in the United States have chronic renal insufficiency, little is known about ethnic/racial disparities for early-onset renal impairment. This study sought to determine whether there is an independent association between race/ethnicity and early-onset renal impairment and to identify other risk factors that might account for observed disparities. All Coronary Artery Risk Development in Young Adults subjects in which serum creatinine was measured at the year 15 examination were identified (n = 3554), excluding those who were pregnant at year 15, Potential risk factors at study entry (ages 18 to 30 yr, 1985 to 1986) included age, weight, gender, race/ethnicity, glucose, uric acid, and systolic BP. Renal impairment was defined as creatinine greater than or equal to1.5 mg/dl for men and greater than or equal to1.2 mg/dl for women at year 15 (ages 33 to 45 yr). Fifty-two (2.7%) women and 39 (2.4%) men had renal impairment at the year 15 examination. In bivariate analyses, the odds of renal impairment among black women was estimated to be 2.4-fold that of white women, and among black men, the odds of renal impairment were 9.0-fold that of white men. In multivariate analysis, the odds of an elevated creatinine among black women compared with white women reduced to a nonsignificant 1.5-fold, whereas among men, the odds of an elevated creatinine among blacks was 11.4-fold that of whites. Although adjustment for baseline glucose levels accounted for much of the association between ethnicity and elevated creatinine among women, adjustment for weight, systolic BP, uric acid, glucose, and socioeconomic status did not account for the association between ethnicity and renal impairment among men. The data suggest that there are ethnic differences in the development of early-onset renal dysfunction. Among women, these differences are modest and largely accounted for by differences in glucose levels early in adult life. Differences in race/ethnicity related risk of early-onset renal impairment are particularly large among men and are not accounted for by the metabolic or socioeconomic factors evaluated. C1 Seattle VA Med Ctr, Dept Med, Seattle, WA 98108 USA. Seattle VA Med Ctr, Dept Epidemiol, Seattle, WA 98108 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Publ Hlth, Dept Epidemiol, Minneapolis, MN 55455 USA. Univ Oslo, Inst Nutr Res, N-0316 Oslo, Norway. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. RP Stehman-Breen, CO (reprint author), Seattle VA Med Ctr, Dept Med, 1660 S Columbian Way,MS 111A, Seattle, WA 98108 USA. NR 30 TC 22 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2003 VL 14 IS 9 BP 2352 EP 2357 DI 10.1097/01.ASN.0000083392.11042.14 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 716JR UT WOS:000185025500017 PM 12937313 ER PT J AU Menke, TJ Giordano, TP Rabeneck, L AF Menke, TJ Giordano, TP Rabeneck, L TI Utilization of health care resources by HIV-infected white, African-American, and Hispanic men in the era before highly active antiretroviral therapy SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE HIV disease/AIDS; race; ethnic groups; health services; utilization; cohort studies ID UNITED-STATES; RACIAL-DIFFERENCES; DISEASE; ACCESS; ZIDOVUDINE; SERVICES; ADULTS; QUESTIONNAIRE; MEDICATIONS; VETERANS AB In the highly active antiretroviral therapy (HAART) era, U.S. African-American and Hispanic patients with HIV use HAART less, but emergency and inpatient services more, than white patients. We evaluated whether these patterns existed in the pre-HAART era. Data from prospective cohort studies of 462 male Veterans Affairs patients and 1,309 male patients from the AIDS Costs and Services Utilization Survey were combined. Resource utilization of white, African-American, and Hispanic men was compared. Compared to whites, African Americans were more likely to visit the emergency department and less likely to have mental health, home health, and dental visits; had fewer outpatient and substance abuse treatment visits; and had more inpatient nights. Hispanics were less likely to have mental health and home health visits, and had more inpatient nights. Whites used prescription drugs more than African Americans or Hispanics, but antiretrovirals were equally used. Lower access to HAART for African-American and Hispanic patients is a new phenomenon, not a continuation of pre-HAART patterns, while the undesirable patterns of emergency and outpatient provider resource utilization in the HAART era are a continuation of pre-HAART patterns. Undesirable resource utilization patterns by African-American and Hispanic populations need urgent attention. C1 Houston VA Med Ctr, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. RP Giordano, TP (reprint author), Houston VA Med Ctr, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU NIAID NIH HHS [T32AI07456]; NIDDK NIH HHS [K24DK59318]; NIMH NIH HHS [K23MH67505] NR 37 TC 13 Z9 13 U1 0 U2 0 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 SEP PY 2003 VL 95 IS 9 BP 853 EP 861 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 836IH UT WOS:000222548600009 PM 14527053 ER PT J AU Webber, AP AF Webber, AP TI Recurrent cardiac failure of environmental origin SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Editorial Material ID CARBON-MONOXIDE C1 Univ Calif Los Angeles, Sch Med, Sepulveda, CA USA. GRECC, VA Greater Los Angeles, Sepulveda, CA USA. RP Webber, AP (reprint author), 10982 Roebling Ave,341 Westwood, Los Angeles, CA 90024 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD SEP PY 2003 VL 96 IS 9 BP 458 EP 459 DI 10.1258/jrsm.96.9.458 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 720RQ UT WOS:000185274100011 PM 12949204 ER PT J AU Cooperberg, MR Lubeck, DP Penson, DF Mehta, SS Carroll, PR Kane, CJ AF Cooperberg, MR Lubeck, DP Penson, DF Mehta, SS Carroll, PR Kane, CJ TI Sociodemographic and clinical risk characteristics of patients with prostate cancer within the veterans affairs health care system: Data from capsure SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; United States Department of Veterans Affairs; ethnicity ID RADICAL PROSTATECTOMY; SOCIOECONOMIC-STATUS; RACE AB Purpose: Veterans Affairs (VA) health care system investigators perform large clinical trials in prostate cancer treatment but potential differences between VA and other patient cohorts have not been explored systematically. Materials and Methods: Cancer of the Prostate Strategic Urologic Research Endeavor is an ongoing observational database of men with prostate cancer, comprising 7,202 patients treated at 35 sites across the United States. Three sites that together contribute 241 patients are VA medical centers. Demographic and clinical characteristics were compared between all VA and nonVA patients in the database and a multivariate model was used to explore the interactions between ethnicity and VA status for predicting clinical characteristics. Results: VA patients were 4 times as likely as nonVA patients to be black. They had lower income, less education and more co-morbidity at presentation (all comparisons p <0.0001). VA patients had higher risk disease. Mean serum prostate specific antigen at diagnosis was 20.1 vs 15.3 ng/ml for nonVA patients (p = 0.003). Mean Gleason score was 6.4 for VA patients vs 6.0 for nonVA patients (p <0.0001). Differing ethnic distributions explained the differences in prostate specific antigen between VA and nonVA patients. However, VA status, socioeconomic level and ethnicity independently predicted Gleason score. VA patients were more likely to undergo watchful waiting or primary hormonal therapy and less likely to receive definitive local treatment (p <0.0001). Conclusions: Significant sociodemographic and clinical differences exist between VA and nonVA patients, which should be borne in mind when extrapolating the results of VA clinical trials to the general population. These observations require validation in larger patient cohorts. C1 Univ Calif San Francisco, Dept Urol, Program Urol Oncol, Urol Outcomes Res Grp,Mt Zion Comprehens Canc Ctr, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Kane, CJ (reprint author), Box 0738,400 Parnassus Ave, San Francisco, CA 94143 USA. RI Cooperberg, Matthew/B-3867-2008; Cooperberg, Matthew/G-6249-2017 OI Cooperberg, Matthew/0000-0003-4339-6685 FU PHS HHS [1P50 C 89520] NR 15 TC 35 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2003 VL 170 IS 3 BP 905 EP 908 DI 10.1097/01.ju.0000081200.63275.0b PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 712TN UT WOS:000184813400054 PM 12913727 ER PT J AU Flaherty, JH Stalvey, B Rubenstein, L AF Flaherty, JH Stalvey, B Rubenstein, L TI A consensus statement on nonemergent medical transportation services for older persons SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID CARE; HEALTH; DRIVERS; HOSPITALIZATION; INTERVENTION; COMMUNITY; FRAILTY; PROGRAM; ADULTS; MODEL C1 St Louis Univ, Med Ctr, Div Geriatr Med, St Louis, MO 63104 USA. St Louis VA Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO USA. Texas Dept Aging, Off Aging Policy & Informat, Austin, TX USA. Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Univ Calif Los Angeles, Multicampus Geriatr Program, Sepulveda, CA USA. RP Flaherty, JH (reprint author), St Louis Univ, Med Ctr, Div Geriatr Med, 1402 S Grand, St Louis, MO 63104 USA. NR 37 TC 2 Z9 2 U1 1 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2003 VL 58 IS 9 BP 826 EP 831 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 729UL UT WOS:000185793100011 ER PT J AU Jenkins, AJ Lyons, TJ Zheng, DY Otvos, JD Lackland, DT McGee, D Garvey, WT Klein, RL AF Jenkins, AJ Lyons, TJ Zheng, DY Otvos, JD Lackland, DT McGee, D Garvey, WT Klein, RL CA DCCT EDIC Res Grp TI Lipoproteins in the DCCT/EDIC cohort: Associations with diabetic nephropathy SO KIDNEY INTERNATIONAL LA English DT Article DE diabetes mellitus; nephropathy; lipoproteins; NMR ID LOW-DENSITY-LIPOPROTEIN; IN-VITRO OXIDATION; RENAL-DISEASE; COMPLICATIONS TRIAL; IDDM PATIENTS; APOLIPOPROTEIN-B; BLOOD-PRESSURE; FOLLOW-UP; LDL; MICROALBUMINURIA AB Background. Lipoproteins may contribute to diabetic nephropathy. Nuclear magnetic resonance (NMR) can quantify subclasses and mean particle size of very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL), and LDL particle concentration. The relationship between detailed lipoprotein analyses and diabetic nephropathy is of interest. Methods. In a cross-sectional study, lipoproteins from 428 women and 540 men from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort were characterized by conventional lipid enzymology, NMR, apolipoprotein levels, and LDL oxidizibility. Linear regression was performed for each lipoprotein parameter versus log albumin excretion rate (AER), with and without covariates for age, diabetes duration, HbA(1c) , hypertension, body mass index, waist-hip ratio, and DCCT treatment group. Significance was taken at P < 0.05. Results. By multivariate analysis, conventional profile, total triglycerides, total- and LDL cholesterol, but not HDL cholesterol, were associated with AER. NMR-determined large, medium, and small VLDL were associated with AER in both genders (except large VLDL in women), and intermediate density lipoprotein (IDL) was associated with AER (men only). LDL particle concentration and ApoB were positively associated with AER (in men and in the total cohort), and there was a borderline inverse association between LDL diameter and AER in men. Small HDL was positively associated with AER and a borderline negative association was found for large HDL. No associations were found with ApoA1, Lp(a), or LDL oxidizibility. Conclusion. Potentially atherogenic lipoprotein profiles are associated with renal dysfunction in type 1 diabetes and further details are gained from NMR analysis. Longitudinal studies are needed to determine if dyslipoproteinemia can predict patients at risk of nephropathy, or if lipoprotein-related interventions retard nephropathy. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Biometry, Charleston, SC 29401 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. N Carolina State Univ, Raleigh, NC 27695 USA. RP Klein, RL (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, POB 250766,114 Doughty St, Charleston, SC 29401 USA. EM kleinrl@musc.edu FU NHLBI NIH HHS [P01 HL55782] NR 47 TC 107 Z9 112 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2003 VL 64 IS 3 BP 817 EP 828 DI 10.1046/j.1523-1755.2003.00164.x PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 711GY UT WOS:000184732300006 PM 12911531 ER PT J AU Breitner, JCS AF Breitner, JCS TI NSAIDs and Alzheimer's disease: how far to generalise from trials? SO LANCET NEUROLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; CACHE COUNTY; PLACEBO; WOMEN C1 VA Puget Sound Hlth Care Syst, GRECC S182, Seattle, WA 98108 USA. RP Breitner, JCS (reprint author), VA Puget Sound Hlth Care Syst, GRECC S182, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 7 TC 20 Z9 27 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD SEP PY 2003 VL 2 IS 9 BP 527 EP 527 DI 10.1016/S1474-4422(03)00498-8 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 717VT UT WOS:000185112000013 PM 12941571 ER PT J AU Beach, MC Asch, DA Jepson, C Hershey, JC Mohr, T McMorrow, S Ubel, PA AF Beach, MC Asch, DA Jepson, C Hershey, JC Mohr, T McMorrow, S Ubel, PA TI Public response to cost-quality tradeoffs in clinical decisions SO MEDICAL DECISION MAKING LA English DT Article DE decision making; public opinion; cost-benefit analysis; health care rationing ID MANAGED CARE; HEALTH-CARE; PHYSICIAN; CONTAINMENT; JUSTICE; LOYALTIES; MEDICINE; BEDSIDE; DUTIES; ETHICS AB Purpose. To explore public attitudes toward the incorporation of cost-effectiveness analysis into clinical decisions. Methods. The authors presented 781 jurors with a survey describing 1 of 6 clinical encounters in which a physician has to choose between cancer screening tests. They provided cost-effectiveness data for all tests, and in each scenario, the most effective test was more expensive. They instructed respondents to imagine that he or she was the physician in the scenario and asked them to choose which test to recommend and then explain their choice in an open-ended manner. The authors then qualitatively analyzed the responses by identifying themes and developed a coding scheme. Two authors separately coded the statements with high overall agreement (kappa = 0.76). Categories were not mutually exclusive. Results. Overall, 410 respondents (55%) chose the most expensive option, and 332 respondents (45%) choose a less expensive option. Explanatory comments were given by 82% respondents. Respondents who chose the most expensive test focused on the increased benefit (without directly acknowledging the additional cost) (39%), a general belief that life is more important than money (22%), the significance of cancer risk for the patient in the scenario (20%), the belief that the benefit of the test was worth the additional cost (8%), and personal anecdotes/preferences (6%). Of the respondents who chose the less expensive test, 40% indicated that they did not believe that the patient in the scenario was of significant risk for cancer, 13% indicated that they thought the less expensive test was adequate or not meaningfully different from the more expensive test, 12% thought the cost of the test was not worth the additional benefit, 9% indicated that the test was too expensive (without mention of additional benefit), and 7% responded that resources were limited. Conclusions. Public response to cost-quality tradeoffs is mixed. Although some respondents justified their decision based on the cost-effectiveness information provided, many focused instead on specific features of the scenario or on general beliefs about whether cost should be incorporated into clinical decisions. C1 Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21205 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Philadelphia Hlth Management Corp, Philadelphia, PA USA. Urban Inst, Ctr Hlth Policy, Washington, DC 20037 USA. VA Ann Arbor Healthcare Syst, VA Hlth Serv, Res & Dev Ctr Excellence, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Program Improving Heath Care Decis Making, Ann Arbor, MI USA. RP Beach, MC (reprint author), Johns Hopkins Univ, Sch Med, Div Gen Internal Med, 1830 E Monument St,Room 8016, Baltimore, MD 21205 USA. OI Asch, David/0000-0002-7970-286X FU NCI NIH HHS [R01-CA78052-01]; NIMHD NIH HHS [L60 MD000303-02, L60 MD000303-01, L60 MD000303] NR 28 TC 5 Z9 5 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2003 VL 23 IS 5 BP 369 EP 378 DI 10.1177/0272989X03256882 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 724RK UT WOS:000185500400002 PM 14570295 ER PT J AU Baron, J Asch, DA Fagerlin, A Jepson, C Loewenstein, G Riis, J Stineman, MG Ubel, PA AF Baron, J Asch, DA Fagerlin, A Jepson, C Loewenstein, G Riis, J Stineman, MG Ubel, PA TI Effect of assessment method on the discrepancy between judgments of health disorders people have and do not have: A Web study SO MEDICAL DECISION MAKING LA English DT Article DE adaptation; utility assessment; response shift; focusing illusion ID QUALITY-OF-LIFE; RESPONSE SHIFT; PREFERENCES; UTILITY; CHEMOTHERAPY; EXPERIENCE; PERCEPTION; VALUATION; STATES; CANCER AB Three experiments on the World Wide Web asked subjects to rate the severity of common health disorders such as acne or arthritis. People who had a disorder ("Haves") tended to rate it as less severe than people who did not have it ("Not-haves"). Two explanations of this Have versus Not-have discrepancy were rejected. By one account, people change their reference point when they rate a disorder that they have. More precise reference points would, on this account, reduce the discrepancy, but, if anything, the discrepancy was larger. By another account, people who do not have the disorder focus on attributes that are most affected by it, and the discrepancy should decrease when people make ratings on several attributes. Again, if anything, the discrepancy increased when ratings were on separate attributes (combined by a weighted average). The discrepancy varied in size and direction across disorders. Subjects also thought that they would be less affected than others. C1 Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Rehabil Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Vet Affairs Ann Arbor Healthcare Syst, Vet Adm Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Program Improving Hlth Care Decis, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. RP Baron, J (reprint author), Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X FU NIA NIH HHS [AG16258] NR 26 TC 33 Z9 33 U1 4 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2003 VL 23 IS 5 BP 422 EP 434 DI 10.1177/0272989X03257277 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 724RK UT WOS:000185500400007 PM 14570300 ER PT J AU Hao, SL Mata, M Wolfe, D Huang, SH Glorioso, JC Fink, DJ AF Hao, SL Mata, M Wolfe, D Huang, SH Glorioso, JC Fink, DJ TI HSV-mediated gene transfer of the glial cell-derived neurotrophic factor provides an antiallodynic effect on neuropathic pain SO MOLECULAR THERAPY LA English DT Article DE gene therapy; pain; HSV; GDNF ID FOS-LIKE IMMUNOREACTIVITY; NERVE GROWTH-FACTOR; SPINAL-CORD NEURONS; DORSAL-HORN; SENSORY NEURONS; SCIATIC-NERVE; DRG NEURONS; PERIPHERAL NEUROPATHIES; FACTOR GDNF; RAT AB Neuropathic pain is a difficult clinical problem that is often refractory to medical management. Glial-derived neurotrophic factor (GDNF) administered intrathecally has been shown to prevent or reduce pain in an animal model of neuropathic pain, but cannot be delivered in the required doses to treat human pain. We have previously demonstrated that peripheral subcutaneous inoculation of a replication-incompetent herpes simplex virus (HSV)-based vector can be used to transduce neurons of the dorsal root ganglion. To examine whether HSV-mediated expression of GDNF could be used to ameliorate neuropathic pain, we constructed a replication-incompetent HSV vector expressing GDNF. Subcutaneous inoculation of the vector I week after spinal nerve ligation resulted in a continuous antiallodynic effect that was maintained for 3-4 weeks. Reinoculation of the vector reestablished the antiallodynic effect with a magnitude that was at least equivalent to the initial effect. Vector-mediated GDNF expression blocked the nonnoxious touch-induced increase in c-fos expression in dorsal horn characteristic of the painful state. Gene transfer to produce a trophic factor offers a novel approach to the treatment of neuropathic pain that may be appropriate for human therapy. C1 VA Pittsburgh Healthcare Syst, Dept Neurol, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15260 USA. RP Fink, DJ (reprint author), VA Pittsburgh Healthcare Syst, Dept Neurol, S-520 BST200 Lothrop St, Pittsburgh, PA 15213 USA. NR 59 TC 60 Z9 68 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2003 VL 8 IS 3 BP 367 EP 375 DI 10.1016/S1525-0016(03)00185-0 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 719HG UT WOS:000185197100005 PM 12946309 ER PT J AU Siegle, GJ Steinhauer, SR Stenger, VA Konecky, R Carter, CS AF Siegle, GJ Steinhauer, SR Stenger, VA Konecky, R Carter, CS TI Use of concurrent pupil dilation assessment to inform interpretation and analysis of fMRI data SO NEUROIMAGE LA English DT Article ID PREFRONTAL CORTEX INVOLVEMENT; WORKING-MEMORY; EMOTIONAL INFORMATION; BRAIN ACTIVATION; TASK; LOAD; RESPONSES; MAINTENANCE; PERFORMANCE; COMPONENTS AB Potential contributions of concurrently acquired pupil dilation data to functional magnetic resonance imaging (fMRI) experiments were examined. Sixteen healthy participants completed a working memory task (digit sorting) during measurement of pupil dilation outside the fMRI environment and during concurrent 3T fMRI assessment. Pupil dilation increased parametrically with task difficulty inside and outside the scanner, on a similar time course, suggesting that task demand was similar in both environments. The time course of pupil dilation during digit sorting was similar to the time course of the fMRI signal in the middle frontal gyrus, suggesting that middle-frontal gyrus activity indexed the engagement working memory processes. Incorporating individual differences in pupil dilation improved the sensitivity and specificity of general linear modeling analyses of activity in the middle frontal gyrus, above and beyond standard analytic techniques. Results suggest concurrent pupil dilation during fMRI assessment can help to (1) specify whether task demand is the same inside and outside the fMRI environment, (2) resolve the extent to which fMRI signals reflect different aspects of event-related designs, and (3) explain variation in fMRI data due to individual differences in information processing. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Siegle, GJ (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH55762, MH60473, MH64159-01] NR 35 TC 84 Z9 85 U1 2 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2003 VL 20 IS 1 BP 114 EP 124 DI 10.1016/S1053-8119(03)00298-2 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 728ZN UT WOS:000185746400010 PM 14527574 ER PT J AU Raskind, MA AF Raskind, MA TI Update on Alzheimer drugs (galantamine) SO NEUROLOGIST LA English DT Article DE cholinesterase inhibitor; galantamine; Alzheimer disease ID NICOTINIC ACETYLCHOLINE-RECEPTORS; PLACEBO-CONTROLLED TRIAL; VASCULAR DEMENTIA; HEALTH ECONOMICS; BINDING-SITES; DISEASE; GALANTHAMINE; INHIBITION; MODULATION; TACRINE AB Background: Deficient cholinergic function contributes to the cognitive and behavioral signs and symptoms of Alzheimer disease (AD). A successful treatment approach in AD has been the enhancement of cholinergic function by cholinesterase inhibitors. Review Summary: Galantamine is a cholinesterase inhibitor and allosteric modulating ligand at nicotinic cholinergic receptors. Galantamine 24 mg/d has been demonstrated consistently effective compared with placebo for the cognitive, functional, and behavioral aspects of Alzheimer's disease in large multicenter trials. Cognition and function on average are preserved for 12 months in Alzheimer disease patients receiving galantamine. It is safe and very well tolerated when dosage is escalated gradually. Conclusions: Galantamine is a valuable addition to agents available for the pharmacologic treatment of AD. C1 Univ Washington, Alzheimers Dis Res Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst Mental Illness Res, 116MI-RECC,1660 S Columbia Way, Seattle, WA 98108 USA. NR 42 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD SEP PY 2003 VL 9 IS 5 BP 235 EP 240 DI 10.1097/01.nrl.0000087722.46430.c4 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 726ZJ UT WOS:000185631200004 PM 12971834 ER PT J AU Gould, GG Pardon, MC Morilak, DA Frazer, A AF Gould, GG Pardon, MC Morilak, DA Frazer, A TI Regulatory effects of reboxetine treatment alone, or following paroxetine treatment, on brain noradrenergic and serotonergic systems SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE antidepressants; reboxetine; norepinephrine transporter; quantitative autoradiography; serotonin transporter; paroxetine ID MESSENGER-RNA EXPRESSION; TYROSINE-HYDROXYLASE; LOCUS-COERULEUS; RAT-BRAIN; EXTRACELLULAR NORADRENALINE; QUANTITATIVE AUTORADIOGRAPHY; ANTIDEPRESSANT TREATMENTS; REUPTAKE INHIBITORS; BETA-ADRENOCEPTORS; MAJOR DEPRESSION AB When patients do not respond to an initial antidepressant, one clinical approach is to switch to an agent in a different pharmacological class. However, few studies have examined the neurochemical consequences of this practice. To study this, we examined changes in binding sites in rat brain for norepinephrine (NET) and serotonin transporters (SERT), alpha(1), alpha(2), and beta(1) adrenergic receptors after chronic administration of paroxetine (PRX), reboxetine (RBX), or PRX followed by RBX. We also examined the effects of these treatments on mRNA expression for tyrosine hydroxylase (TH). RBX treatment for 3 weeks reduced NET binding significantly, by similar to40% in terminal field areas, and 6 weeks of RBX reduced it even more, by similar to60%. RBX treatment for 3 and 6 weeks reduced beta(1) adrenergic receptor-binding sites equally, by 50-60%. At no time did RBX treatment reduce SERT-binding sites. PRX treatment had no effect on beta(1) adrenergic or NET-binding sites, but reduced SERT-binding sites by 75-80%. Neither treatment altered mRNA for TH, alpha(1), or alpha(2) adrenergic receptor-binding sites. When 3 weeks of RBX treatment followed 3 weeks of PRX treatment, NET-binding sites were reduced to the same extent as measured after 6 weeks of RBX treatment alone, indicating that PRX pretreatment may have 'primed' the subsequent regulatory effect of RBX on the NET. Thus, pretreatment of rats with PRX actually enhanced at least one regulatory effect of RBX treatment on the noradrenergic system, and did not interfere with any other pharmacological effect caused by RBX treatment. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 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, MC 7764,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. OI Pardon, Marie-Christine/0000-0003-4737-9479; Gould, Georgianna/0000-0002-5470-8763 FU NIMH NIH HHS [MH57001] NR 39 TC 25 Z9 25 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2003 VL 28 IS 9 BP 1633 EP 1641 DI 10.1038/sj.npp.1300236 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 717HX UT WOS:000185083900010 PM 12825093 ER PT J AU Piraino, B Bernardini, J Florio, T Fried, L AF Piraino, B Bernardini, J Florio, T Fried, L TI Staphylococcus aureus prophylaxis and trends in gram-negative infections in peritoneal dialysis patients SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article; Proceedings Paper CT 22nd Annual Conference on Dialysis CY MAR 04-06, 2002 CL TAMPA, FLORIDA DE Staphylococcus aureus; Pseudomonas aeruginosa; peritonitis; exit-site infection; mupirocin; gram-negative infection; prophylaxis ID EXIT-SITE INFECTION; MUPIROCIN OINTMENT; NASAL CARRIAGE; CAPD AB Objective: To examine gram-negative exit-site infection and peritonitis rates before and after the implementation of Staphylococcus aureus prophylaxis in peritoneal dialysis (PD) patients. Design: Prospective data collection with periodic implementation of protocols to decrease infection rates in two PD programs. Patients: 663 incident patients on PD. Interventions: Implementation of S. aureus prophylaxis, beginning in 1990. Main Outcome Measures: Rates of S. aureus, gram-negative, and Pseudomonas aeruginosa exit-site infections and peritonitis. Results: Staphylococcus aureus exit-site infection and peritonitis rates fluctuated without significant trends during the first decade (without prophylaxis), then began to decline during the 1990s subsequent to implementation of prophylaxis, reaching levels of 0.02/year at risk and zero in the year 2000. Gram-negative infections fell toward the end of the 1980s, due probably to the implementation of better connectology. However, there have been no significant changes for the past 6 years. There was little change in P. aeruginosa infections over the entire time period. Pseudomonas aeruginosa is now the most common cause of catheter infection and catheter-related peritonitis. Conclusions: Prophylaxis against S. aureus is highly effective in reducing the rate of S. aureus infections but has no effect on gram-negative infections. Pseudomonas aeruginosa is now the most serious cause of catheter-related peritonitis. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Piraino, B (reprint author), Suite 200,3504 5th Ave, Pittsburgh, PA 15213 USA. OI Piraino, Beth/0000-0001-5061-0841 NR 17 TC 43 Z9 44 U1 0 U2 0 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD SEP-OCT PY 2003 VL 23 IS 5 BP 456 EP 459 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 735NQ UT WOS:000186121800009 PM 14604197 ER PT J AU Murthy, S Marcelli, M Weigel, NL AF Murthy, S Marcelli, M Weigel, NL TI Stable expression of full length human androgen receptor in PC-3 prostate cancer cells enhances sensitivity to retinoic acid but not to I alpha,25-dihydroxyvitamin D-3 SO PROSTATE LA English DT Article DE prostate cancer; vitamin D; androgen receptor; PC-3 cells; retinoids ID VITAMIN-D; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; 1,25-DIHYDROXYVITAMIN D-3; 9-CIS-RETINOIC ACID; LNCAP CELLS; 24-HYDROXYLASE ACTIVITY; GROWTH-INHIBITION; LINE LNCAP; IN-VITRO; PROLIFERATION AB BACKGROUND. PC-3 prostate cancer cell growth is inhibited by 1alpha,25-dihydroxyvitamin D-3 (1,25 D) and retinoids, but not to the same extent as the androgen receptor (AR) positive LNCaP prostate cancer cells. Previous reports suggest a role for AR in growth inhibition of LNCaP cells by 1,25 D and retinoids. PC-3 cells do not express AR. We therefore asked whether re-expression of AR would enhance the response of PC-3 cells to 1,25 D and retinoids. METHODS. PC-3 cells were stably transfected with wild type human AR cDNA. Pooled cells expressing AR protein at levels comparable to LNCaP cells were used to analyze response to 1,25 D, retinoids, androgens, and anti-androgens. RESULTS. AR re-expression in PC-3 cells restored response to androgens and anti-androgens, but growth inhibition by 1,25 D was not significantly altered. However, cells were sensitized to low levels of retinoids, and, in contrast to the parental PC-3 cells, sub-optimal levels of 1,25 D and retinoids caused additive growth inhibition. CONCLUSIONS. Restoring AR expression and activity in PC-3 cells results in enhanced sensitivity to low levels of retinoids while the response to 1,25 D remains unaltered. Thus, the involvement of AR in prostate cancer growth inhibition by 1,25 D appears to be cell line specific. Prostate 56: 293-304, 2003. (C) 2003 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. RP Weigel, NL (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NCI NIH HHS [R01 CA 75337] NR 40 TC 10 Z9 10 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD SEP PY 2003 VL 56 IS 4 BP 293 EP 304 DI 10.1002/pros.10261 PG 12 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 711LJ UT WOS:000184741800008 PM 12858358 ER PT J AU Crowley, JJ Oslin, DW Patkar, AA Gottheil, E DeMaria, PA O'Brien, CP Berrettini, WH Grice, DE AF Crowley, JJ Oslin, DW Patkar, AA Gottheil, E DeMaria, PA O'Brien, CP Berrettini, WH Grice, DE TI A genetic association study of the mu opioid receptor and severe opioid dependence SO PSYCHIATRIC GENETICS LA English DT Article DE opioid dependence; substance dependence; genetics; mu opioid receptor gene; OPRM1; single nucleotide polymorphism; association study; heroin ID CONTROLLING MORPHINE PREFERENCE; SINGLE-NUCLEOTIDE POLYMORPHISM; SUBSTANCE DEPENDENCE; ALCOHOL DEPENDENCE; ABUSE; ADDICTION; WITHDRAWAL; VARIANTS; BINDING; OPIATES AB Objectives Twin, family and adoption studies have suggested that vulnerability to opioid dependence may be a partially inherited trait (Cadoret et al., 1986; Merikangas et al., 1998; Tsuang et al., 1998, 2001). Studies using animal models also support a role for genetic factors in opioid dependence, and point to a locus of major effect on mouse chromosome 10 (Berrettini et al., 1994; Alexander et al., 1996), which harbors the mu opioid receptor gene (Mor1) (Kozak et aL, 1994). The gene encoding the human mu opioid receptor (OPRM1) is thus an obvious candidate gene for contributing to opioid dependence. A recent report (Hoehe et al., 2000) found a significant association between a specific combination of OPRM1 single nucleotide polymorphisms (SNPs) and substance dependence. Methods In the current study, we genotyped 213 subjects with severe opioid dependence (89 African-Americans, 124 European-Americans) and 196 carefully screened 'super-control' subjects (96 African-Americans, 100 European-Americans) at five SNPs residing in the OPRM1 gene. The polymorphisms include three in the promoter region (T(-1793)A, T-1699 insertion and A(-1320)G) and two in exon 1 (C+17T [Ala6Val] and A(+118)G [Asp40Asn]). Results Statistical analysis of the allele frequency differences between opioid-dependent and control subjects for each of the polymorphisms studied yielded P values in the range of 0.444-1.000. Haplotype analysis failed to identify any specific combination of SNPs associated with the phenotype. Conclusions Despite reasonable statistical power we found no evidence of association between the five mu opioid receptor polymorphisms studied and severe opioid dependence in our sample. There were, however, significant allele frequency differences between African-Americans and European-Americans for all five polymorphisms, irrespective of drug-dependent status. Linkage disequilibrium analysis of the African-American genotypes indicated linkage disequilibrium (P<0.0001) across the five-polymorphism, 1911 base pair region. In addition, only four haplotypes of these five polymorphisms are predicted to exist in African-Americans. (C) 2003 Lippincott Williams Wilkins. C1 Univ Penn, Dept Pharmacol, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Psychiat & Human Behav, Philadelphia, PA 19107 USA. MIRECC, Vet Affairs Med Ctr, Philadelphia, PA USA. OI Crowley, James/0000-0001-9051-1557 FU NIDA NIH HHS [K12 DA 00357, K08 DA 00340, K12 DA000357, P60 DA 05186-16, R01 DA 11835]; NIGMS NIH HHS [T32 GM 008076-17] NR 30 TC 83 Z9 87 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD SEP PY 2003 VL 13 IS 3 BP 169 EP 173 DI 10.1097/01.ypg.0000071762.90004.45 PG 5 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 718MH UT WOS:000185150200006 PM 12960749 ER PT J AU Cook, JM Ruzek, JI Cassidy, E AF Cook, JM Ruzek, JI Cassidy, E TI Possible association of posttraumatic stress disorder with cognitive impairment among older adults SO PSYCHIATRIC SERVICES LA English DT Editorial Material ID MENTAL-HEALTH-SERVICES; DEMENTIA; SURVIVORS; SYMPTOMS; VETERANS; MEMORY; SERIES C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Palo Alto Hlth Care Syst Natl Ctr PTSD, Dept Vet Affairs, Palo Alto, CA USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Cook, JM (reprint author), Univ Penn, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM cook_j@mail.trc.upenn.edu NR 20 TC 7 Z9 7 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2003 VL 54 IS 9 BP 1223 EP 1225 DI 10.1176/appi.ps.54.9.1223 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BQ UT WOS:000222758700007 PM 12954937 ER PT J AU Shaner, A Eckman, L Roberts, LJ Fuller, T AF Shaner, A Eckman, L Roberts, LJ Fuller, T TI Feasibility of a skills training approach to reduce substance dependence among individuals with schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article AB A novel treatment for persons who have both schizophrenia and substance abuse was evaluated by incorporating cognitive-behavioral drug relapse prevention strategies, into a skills training method originally developed to teach social and independent living skills to patients with schizophrenia. Thirty-four of 56 patients completed treatment and a three-month follow-up assessment. Participants learned substance abuse management skills and reported that they found the treatment relevant, useful, and satisfying, and their drug use decreased. Improvements were noted in medication adherence, Psychiatric symptoms, and quality of life. This manual-driven therapy may play an important role in the treatment of substance abuse among patients with schizophrenia. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Dept Vet Affairs Puget Sound Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Shaner, A (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,116A, Los Angeles, CA 90073 USA. EM andrew.shaner@med.va.gov FU NIDA NIH HHS [R01 DA 09436] NR 10 TC 19 Z9 19 U1 1 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2003 VL 54 IS 9 BP 1287 EP 1289 DI 10.1176/appi.ps.54.9.1287 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BQ UT WOS:000222758700018 PM 12954948 ER PT J AU Rull, M Clayburne, G Sieck, M Schumacher, HR AF Rull, M Clayburne, G Sieck, M Schumacher, HR TI Intra-articular corticosteroid preparations: different characteristics and their effect during inflammation induced by monosodium urate crystals in the rat subcutaneous air pouch SO RHEUMATOLOGY LA English DT Article DE corticosteroids; betamethasone; prednisolone; triamcinolone; rat air pouch; monosodium urate crystals; inflammation; tophi ID TRIAMCINOLONE HEXACETONIDE; SYNOVIAL-FLUID; INJECTION; OSTEOARTHRITIS; HYDROCORTISONE; OSTEONECROSIS; INVIVO; KNEE AB Objective. To examine the effects of three commonly used intra-articular depot corticosteroid preparations tested in a rat air pouch model and their effect against monosodium urate (MSU) crystal-induced inflammation. Rheumatologists use intra-articular corticosteroid preparations to relieve pain and inflammation of acute monoarthritis without really knowing their effects on the synovial fluid and membrane or the differences between distinct preparations. This work compares the effect of three commonly used corticosteroid preparations in vivo, showing that they behave differently. Methods. A subcutaneous air pouch was formed in male Sprague-Dawley rats. A first group of 6-day-old air pouches were injected with 10 ml of 6 mg/ml normal saline solution, 6 mg/ml betamethasone containing both depot betamethasone acetate and soluble betamethasone phosphate (Celestone) in 9 ml of normal saline solution, 20 mg/ml of prednisolone tebutate (Hydeltra) in 9 ml of normal saline solution or 20 mg/ml of triamcinolone hexacetonide (Aristospan) in 9 ml of normal saline solution. A second group (group 2) of air pouches were injected with 15 mg of synthetic MSU crystals and 24 h later they were reinjected with 1 ml of the same three corticosteroid suspensions. For each condition four rats were killed at 6, 24, 48 h and 7 days. Pouch fluid and tissue were analysed. Results. In the first 6 h after normal saline solution or corticosteroid injection into the air pouch there were mildly increased leucocyte counts in the air pouch fluid. Betamethasone-injected pouches showed no cells in the fluid after 6 h and no crystals after 24 h, triamcinolone-injected pouches still showed rare cells at 7 days. Both triamcinolone and prednisolone crystals persisted in higher numbers and lasted longer in the fluid than did betamethasone (P<0.05). In group 2 MSU crystal phagocytosis in the fluid was decreased in the betamethasone- (P<0.01), prednisolone- (P<0.003) and triamcinolone- (P<0.006) injected pouches when compared with the MSU crystal-injected pouches alone. Pouches injected with MSU crystals alone showed the most intense tissue inflammation at all times. After MSU, betamethasone-injected pouches had a rapid but mild decrease in the number of lining cells and inflammation. In contrast, triamcinolone- and prednisolone-injected pouches showed a very thin tissue with few or no vessels and almost no inflammation at 7 days. The pouches injected with MSU crystals and any of the corticoid preparations had three times more tophus-like structures and persistent crystals identified than the ones injected with MSU crystals alone. Conclusion. Each of the corticosteroid preparations by themselves produced very mild transient inflammation. The betamethasone preparation with a soluble steroid component had a quicker but milder anti-inflammatory effect on MSU crystal-induced inflammation. In contrast to the doses used, prednisolone tebutate and triamcinolone hexacetonide preparations dramatically suppressed urate crystal-induced inflammation at 7 days, but both produced atrophy and necrosis of the membrane, yielding a very thin membrane with almost no vessels. When used for MSU crystal-induced inflammation these corticosteroid preparations suppressed some aspects of inflammation but may actually promote the persistence of MSU crystals and the formation of tophi. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), VAMC Arthrit Res 151K, Univ & Woodland & Ave, Philadelphia, PA 19104 USA. NR 24 TC 18 Z9 22 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD SEP PY 2003 VL 42 IS 9 BP 1093 EP 1100 DI 10.1093/rheumatology/keg305 PG 8 WC Rheumatology SC Rheumatology GA 714QA UT WOS:000184923900013 PM 12777646 ER PT J AU Conde, FA Aronson, WJ AF Conde, FA Aronson, WJ TI Risk factors for male osteoporosis SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE androgen deprivation therapy; prostate cancer; osteoporosis; orchiectomy; gonadotropin-releasing hormone agonists ID ANDROGEN DEPRIVATION THERAPY; BONE-MINERAL DENSITY; PROSTATE-CANCER; ELDERLY-MEN; HORMONE AGONISTS; HIP FRACTURE; WOMEN; CARCINOMA; DETERMINANTS; ORCHIECTOMY AB Hypogonadism from long-term androgen deprivation therapy (ADT), either by bilateral orchiectomy or administration of gonadotropin-releasing hormone (GnRH) agonists, causes significant and accelerated bone loss that may increase the risk of bone fractures in men with prostate cancer. Recent reports, as well as new data from our institution, have shown a high prevalence of pre-existing osteopenia and osteoporosis in men with prostate cancer before receiving ADT, and this is of great concern because of the risk of further bone loss during ADT. Data from these studies suggest the urgent need for clinical guidelines for screening, prevention, and treatment of these cases. This article reviews the prevalence and risk factors associated with osteoporosis in men and addresses risk factors in men with prostate cancer not receiving ADT. Considerations for the patient selection and timing of bone densitometry will also be discussed. (C) 2003 Elsevier Inc. All rights reserved. C1 W Los Angeles VA Healthcare Ctr, Dept Nursing, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. RP Aronson, WJ (reprint author), W Los Angeles VA Healthcare Ctr, Dept Nursing, Los Angeles, CA USA. NR 39 TC 17 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN O I JI Urol. Oncol.-Semin. Orig. Investig. PD SEP-OCT PY 2003 VL 21 IS 5 BP 380 EP 383 DI 10.1016/S1078-1439(03)00109-1 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 755UT UT WOS:000187430400013 PM 14670549 ER PT J AU Rosen, T AF Rosen, T TI Update on genital lesions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID EXTRAMAMMARY PAGETS-DISEASE; CLINICAL-DIAGNOSIS; ANOGENITAL WARTS; LICHEN-SCLEROSUS; EARLY SYPHILIS; ULCER DISEASE; VITILIGO; HERPES; CREAM; VIRUS C1 Baylor Coll Med, Houston Vet Adm Med Ctr, Dermatol Serv, Houston, TX 77005 USA. RP Rosen, T (reprint author), Baylor Coll Med, Houston Vet Adm Med Ctr, Dermatol Serv, 2815 Plumb, Houston, TX 77005 USA. OI Rosen, Ted/0000-0002-5946-5529 NR 33 TC 10 Z9 10 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 27 PY 2003 VL 290 IS 8 BP 1001 EP 1005 DI 10.1001/jama.290.8.1001 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 715FA UT WOS:000184958900002 PM 12941660 ER PT J AU Chen, EW Canto, JG Parsons, LS Peterson, ED Littrell, KA Every, NR Gibson, CM Hochman, JS Ohman, EM Cheeks, M Barron, HV AF Chen, EW Canto, JG Parsons, LS Peterson, ED Littrell, KA Every, NR Gibson, CM Hochman, JS Ohman, EM Cheeks, M Barron, HV CA Investigators Natl Registry Myocar TI Relation between hospital intra-aortic balloon counterpulsation volume and mortality in acute myocardial infarction complicated by cardiogenic shock SO CIRCULATION LA English DT Article DE mortality; balloon; myocardial infarction; shock; epidemiology ID PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; ONE-YEAR SURVIVAL; GUSTO-I TRIAL; CORONARY ANGIOPLASTY; EARLY REVASCULARIZATION; AORTIC COUNTERPULSATION; ACC/AHA GUIDELINES; CLINICAL OUTCOMES; NATIONAL REGISTRY AB Background - Increasing evidence suggests an inverse relationship between outcome and the total number of invasive cardiac procedures performed at a given hospital. The purpose of the present study was to determine if a similar relationship exists between the number of intra-aortic balloon counterpulsation ( IABP) procedures performed at a given hospital per year and the in-hospital mortality rate of patients with acute myocardial infarction complicated by cardiogenic shock. Methods and Results - We analyzed data of 12 730 patients at 750 hospitals enrolled in the National Registry of Myocardial Infarction 2 from 1994 to 1998. The hospitals were divided into tertiles ( low -, intermediate -, and high - IABP volume hospitals) according to the number of IABPs performed at the given hospital per year. The median number of IABPs performed per hospital per year was 3.4, 12.7, and 37.4 IABPs at low-, intermediate-, and high-volume hospitals, respectively. Of those patients who underwent IABP, there were only minor differences in baseline patient characteristics between the 3 groups. Crude mortality rate decreased with increasing IABP volume: 65.4%, lowest volume tertile; 54.1%, intermediate volume tertile; and 50.6%, highest volume tertile ( P for trend < 0.001). This mortality difference represented 150 fewer deaths per 1000 patients treated at the high IABP hospitals. In the multivariate analysis, high hospital IABP volume for patients with acute myocardial infarction was associated with lower mortality ( OR = 0.71, 95% CI = 0.56 to 0.90), independent of baseline patient characteristics, hospital factors, treatment, and procedures such as PTCA. Conclusions - Among the myocardial infarction patients with cardiogenic shock who underwent IABP placement, mortality rate was significantly lower at high - IABP volume hospitals compared with low - IABP volume hospitals. C1 Permanente Med Grp Inc, Dept Med, Div Cardiol, Richmond, CA 94801 USA. Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. Univ Alabama, Chest Pain Ctr, Birmingham, AL USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. Ovat Res Grp, Seattle, WA USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Genentech Inc, Dept Med Affairs, San Francisco, CA 94080 USA. VA Puget Sound Healthcare Syst, NW HSR&D Field Program, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NYU, Sch Med, Div Cardiol, New York, NY USA. Univ N Carolina, Dept Med, Div Cardiol, Chapel Hill, NC USA. RP Chen, EW (reprint author), Permanente Med Grp Inc, Dept Med, Div Cardiol, 901 Nevin Ave, Richmond, CA 94801 USA. NR 30 TC 74 Z9 91 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 AUG 26 PY 2003 VL 108 IS 8 BP 951 EP 957 DI 10.1161/01.CIR.000008508.59734.E4 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 715DH UT WOS:000184954900011 PM 12912817 ER PT J AU Silbert, LC Quinn, JF Moore, MM Corbridge, E Ball, MJ Murdoch, G Sexton, G Kaye, JA AF Silbert, LC Quinn, JF Moore, MM Corbridge, E Ball, MJ Murdoch, G Sexton, G Kaye, JA TI Changes in premorbid brain volume predict Alzheimer's disease pathology SO NEUROLOGY LA English DT Article ID HIPPOCAMPAL-FORMATION; TEMPORAL-LOBE; OLDEST-OLD; NEUROPATHOLOGY; DEMENTIA; SEVERITY; DURATION AB Objective: To assess whether changes in antemortem MRI brain volume measurements are valid predictors of subsequent Alzheimer disease (AD) pathology. Methods: Thirty-nine subjects, 15 nondemented and 24 with cognitive impairment, were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to cross-sectional and longitudinal volumetric measurements obtained from antemortem MRI. Results: Total brain volume change over time was related to the accumulation of cortical NFT. The rate of ventricular CSF volume increase was related to both cortical NFT and SP. The last hippocampal volume prior to death was related to hippocampal NFT burden; the rate of hippocampal volume atrophy was not related to hippocampal NFT pathology. These significant relationships continue to exist when all nondemented subjects are excluded from analysis. In subjects with cognitive impairment, the best predictor of cortical NFT and SP is the rate of ventricular volume increase. Excluding subjects with long duration between MRI and death did not appreciably alter results. Conclusions: MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology. C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Med & Preventat Med, Portland, OR USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Silbert, LC (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, CR-131,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NCRR NIH HHS [M01 RR00334]; NIA NIH HHS [AG 08073] NR 27 TC 145 Z9 147 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 26 PY 2003 VL 61 IS 4 BP 487 EP 492 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 715CX UT WOS:000184953900012 PM 12939422 ER PT J AU Won, JS Im, YB Key, L Singh, I Singh, AK AF Won, JS Im, YB Key, L Singh, I Singh, AK TI The involvement of glucose metabolism in the regulation of inducible nitric oxide synthase gene expression in glial cells: possible role of glucose-6-phosphate dehydrogenase and CCAAT/enhancing binding protein SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C/EBP; astrocytes; glucose; G6PD; iNOS; NADPH; NF-kappa B; nitric oxide ID SMOOTH-MUSCLE-CELLS; COLONIC ADENOCARCINOMA CELLS; TRANSIENT FOCAL ISCHEMIA; FACTOR-KAPPA-B; CEREBRAL INFARCTION; MESANGIAL CELLS; BRAIN INJURY; RAT; INHIBITION; DEHYDROEPIANDROSTERONE AB In rat glial cells the lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) gene expression was enhanced by extracellular glucose concentration in a dose-dependent manner. On the other hand, 2-deoxy-D-glucose decreased the LPS-induced iNOS gene expression even in the presence of glucose (6 gm/l), suggesting that glucose metabolism is linked to the regulation of iNOS gene expression. The intracellular NADPH/NADP(+) directly correlated with the extracellular glucose concentration, and the reduction of NADPH generation via a block of glucose-6-phosphate dehydrogenase (G6PD) by treatment with dehydroepiandrosterone or the antisense DNA oligomer of G6PD mRNA resulted in the inhibition of iNOS gene expression. Gel shift assays showed that CAAT/enhancing binding protein (C/EBP), rather than AP-1 or NF-kappaB, correlated better with a glucose-dependent increase in iNOS gene expression. The induction of C/EBP DNA binding activity by LPS and glucose was attributable mainly to the increase in C/EBP-delta protein. The cotransfection with wild-type C/EBP-delta increased the iNOS promoter activity to the level achieved with a higher glucose concentration in the presence of LPS. Therefore, our results suggest that C/EBP-delta may be a critical mediator in glucose-mediated regulation of iNOS gene expression. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Lab Med Serv, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pediat, Clin Sci Bldg,Room 316,171 Ashley Ave, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40810] NR 44 TC 32 Z9 32 U1 0 U2 0 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 AUG 20 PY 2003 VL 23 IS 20 BP 7470 EP 7478 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 713HX UT WOS:000184852600003 PM 12930785 ER PT J AU Kerlikowske, K Smith-Bindman, R Ljung, BM Grady, D AF Kerlikowske, K Smith-Bindman, R Ljung, BM Grady, D TI Evaluation of abnormal mammography results and palpable breast abnormalities SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID FINE-NEEDLE ASPIRATION; PROBABLY BENIGN LESIONS; FOLLOW-UP MAMMOGRAPHY; MULTICENTER CLINICAL-TRIAL; SCREENING MAMMOGRAPHY; CORE-NEEDLE; DIAGNOSTIC-ACCURACY; PHYSICAL-EXAMINATION; HISTOPATHOLOGIC CORRELATION; CYTOLOGIC EXAMINATION AB Background: Because approximately 1 in 10 women with a breast lump or abnormal mammography result will have breast cancer, a series of decisions must be taken by a primary care practitioner to exclude or establish a diagnosis of breast cancer among these women. Purpose: To determine the most accurate and least invasive means to evaluate an abnormal mammography result and a palpable breast abnormality. Data Source: MEDLINE search (January 1966 to March 2003) for articles and reviews describing the accuracy of clinical examination, biopsy procedures, and radiographic examination for patients with abnormal mammography results or palpable breast abnormalities. Study Selection: The authors reviewed abstracts and selected articles that provided relevant primary data. Studies were included if 1) mammography, fine-needle aspiration biopsy, or core-needle biopsy was performed before a definitive diagnosis was obtained; 2) the study sample included 100 or more women; and 3) breast cancer status was determined from histopathology review of excisional biopsy specimens, from linkage with a state cancer registry or the Surveillance, Epidemiology, and End Results program, or from clinical follow-up of 95% or more of the study sample. Data Extraction: One investigator abstracted results. Methods were evaluated for major potential biases, but methodologic scoring was not performed. Data Synthesis: Likelihood ratios for first screening mammography were 0.1 for the Breast Imaging Reporting and Data System (BI-RADS) assessment category "negative or benign finding," 1.2 for "probably benign finding," 7 for "need additional imaging evaluation," 125 for "suspicious abnormality," and 2200 for "highly suggestive of malignancy." For fine-needle aspiration biopsy of a palpable lump performed by formally trained physicians, the likelihood ratio was infinity for an assessment of "malignant," 2.6 for "atypical/suspicious," and 0.02 for "benign." When diagnostic mammography was used to evaluate a palpable lump or nonpalpable breast abnormality, the positive likelihood ratios were 5.6 and 9.4, and the negative likelihood ratios were 0.15 and 0.19, respectively. Conclusions: Women whose screening mammography results are interpreted as "suspicious abnormality" or "highly suggestive of malignancy" have a high risk for breast cancer and should undergo core-needle biopsy or needle localization with surgical biopsy. Women whose screening mammography results are interpreted as "need additional imaging evaluation" have a moderate risk for breast cancer and should undergo diagnostic mammography or ultrasonography to decide whether a nonpalpable breast lesion should be biopsied. Women whose screening mammography results are interpreted as "probably benign finding" have a low risk for breast cancer and can undergo follow-up mammography in 6 months. Either fine-needle aspiration biopsy or ultrasonography is recommended as the first diagnostic test of a palpable breast abnormality to distinguish simple cysts from solid masses. Fine-needle aspiration biopsy also allows characterization of a solid mass. Diagnostic mammography does not help determine whether a palpable breast mass should be biopsied and should not affect the decision to perform a biopsy. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kerlikowske, K (reprint author), San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NCI NIH HHS [P50 CA58207, U01CA63740] NR 96 TC 69 Z9 74 U1 0 U2 3 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 AUG 19 PY 2003 VL 139 IS 4 BP 274 EP 284 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 712JY UT WOS:000184795600006 PM 12965983 ER PT J AU Jensen, DM Geffen, D AF Jensen, DM Geffen, D TI Treatment of patients at high risk for recurrent bleeding from a peptic ulcer SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID UPPER GASTROINTESTINAL HEMORRHAGE; ENDOSCOPIC TREATMENT; THERAPY; COAGULATION C1 Vet Affairs Greater Los Angeles Healthcare Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, CURE, Los Angeles, CA 90073 USA. RP Jensen, DM (reprint author), Vet Affairs Greater Los Angeles Healthcare Ctr, CURE, 11301 Wilshire Blvd,Bldg 115,Room 318, Los Angeles, CA 90073 USA. NR 15 TC 9 Z9 10 U1 0 U2 0 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 AUG 19 PY 2003 VL 139 IS 4 BP 294 EP 295 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 712JY UT WOS:000184795600008 PM 12965985 ER PT J AU Kraemer, BC Zhang, B Leverenz, JB Thomas, JH Trojanowski, JQ Schellenberg, GD AF Kraemer, BC Zhang, B Leverenz, JB Thomas, JH Trojanowski, JQ Schellenberg, GD TI Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MULTIPLE SYSTEM TAUOPATHY; TAU TRANSGENIC MICE; C-ELEGANS; FRONTOTEMPORAL DEMENTIA; NEUROFIBRILLARY TANGLES; PRESENILE-DEMENTIA; NERVOUS-SYSTEM; PROTEIN; MUTANTS; MUTATIONS AB Frontotemporal dementia with parkinsonism chromosome 17 type (FTDP-17) is caused by mutations in MAPT, the gene encoding tau. FTDP-17 begins with executive function deficits and other abnormal behaviors, which progress to dementia. Neurodegenerative changes include accumulation of aggregated tau as neuronal and glial fibrillary tangles. Aggregated tau is seen in numerous other neurodegenerative diseases, including Alzheimer's disease (AD). We expressed normal and FTDP-17 mutant human tau (mutations (P)301(L) and (V)337(M)) in Caenorhabditis elegans to model tauopathy disorders. Tau pan-neuronal expression caused progressive uncoordinated locomotion (Unc), characteristic of nervous system defects in worms. Subsequently, insoluble tau accumulates and both soluble and insoluble tau is phosphorylated at many of the sites hyperphosphorylated in FTDP-17, AD, and other tauopathies. Substantial neurodegeneration, seen as bulges and gaps in nerve cords followed by loss of neurons, occurs after insoluble tau begins to accumulate. Axons show vacuoles, membranous infoldings, and whorls with associated amorphous tau accumulations and abnormal tau-positive aggregates. FTDP-17 mutation lines had a more severe Unc phenotype, accumulated more insoluble tau at a younger age, were more resistant to cholinergic inhibitors, and had more severe axonal degeneration when compared with lines expressing normal tau. The Unc phenotype is caused by a presynaptic defect. Postsynaptic transmission is intact. This transgenic model will enable mechanistic dissection of tau-induced neurodegeneration and identification of genes and compounds that inhibit pathological tau formation. C1 Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness & Parkinson Dis Res Educ & Clin Ct, Seattle, WA 98108 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Div Neurogenet, Dept Neurol, Seattle, WA 98195 USA. Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Schellenberg, GD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. FU NIA NIH HHS [AG 17583]; NIGMS NIH HHS [GM 48700, R01 GM048700] NR 37 TC 166 Z9 180 U1 2 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 AUG 19 PY 2003 VL 100 IS 17 BP 9980 EP 9985 DI 10.1073/pnas.1533448100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714QY UT WOS:000184926000065 PM 12872001 ER PT J AU El-Serag, HB Talley, NJ AF El-Serag, HB Talley, NJ TI Systematic review: health-related quality of life in functional dyspepsia SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID REFLUX DISEASE; DUODENAL-ULCER; IMPACT; DISORDERS; ENDOSCOPY; QUESTIONNAIRE; VALIDATION; INDEX AB Background: We performed a systematic review of the literature to compare the health-related quality of life (HRQOL) of patients with functional dyspepsia with either healthy controls or those with other diseases. Methods: Full-length published manuscripts during 1980-2002 were included if (a) patients had functional dyspepsia, but not uninvestigated dyspepsia; and (b) HRQOL was measured using a validated generic or dyspepsia-specific instruments, but not global assessment alone. Results: Twelve studies were reviewed; six fulfilled the selection criteria. None examined HRQOL among samples of the general population. None used dyspepsia-specific HRQOL instruments. Three studies contained four comparisons of HRQOL between functional dyspepsia patients and controls; two studies examined HRQOL changes in response to therapy. Two studies demonstrated a significant reduction at least in some domains of HRQOL among patients with functional dyspepsia compared to controls, while one study was negative. In general, studies that reported a decline in HRQOL Short Form-36 (SF-36) showed that changes in the physical domain were similar to those on mental domain of the SF-36. Conclusions: There is some evidence for a decrease in HRQOL in patients with moderate to severe functional dyspepsia who seek care for their symptoms; however, more studies are needed. A therapeutic response in functional dyspepsia-related pain or discomfort might result in a corresponding improvement in HRQOL. C1 Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. Mayo Clin, Ctr Enter Neurosci & Translat Epidemiol Res, Rochester, MN USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Gastroenterol Sect, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. RI Talley, nicholas/D-5399-2013 OI Talley, nicholas/0000-0003-2537-3092 NR 27 TC 77 Z9 83 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD AUG 15 PY 2003 VL 18 IS 4 BP 387 EP 393 DI 10.1046/j.0269-2813.2003.01706.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 717RF UT WOS:000185103200003 PM 12940923 ER PT J AU Ofman, JJ Maclean, CH Straus, WL Morton, SC Berger, ML Roth, EA Shekelle, PG AF Ofman, JJ Maclean, CH Straus, WL Morton, SC Berger, ML Roth, EA Shekelle, PG TI Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Review DE NSAIDs; dyspepsia; meta-analysis; adverse events ID DOUBLE-BLIND MULTICENTER; PLACEBO-CONTROLLED TRIAL; DEGENERATIVE JOINT DISEASE; TIAPROFENIC ACID SURGAM; ANTI-INFLAMMATORY DRUG; RANDOMIZED CONTROLLED TRIAL; COMPARATIVE CLINICAL-TRIAL; PEPTIC-ULCER DISEASE; LOW-BACK-PAIN; RHEUMATOID-ARTHRITIS AB Objective. Nonsteroidal antiinflammatory drug (NSAID) use is a known risk factor for gastrointestinal (GI) perforations, ulcers, and bleeds, but there are limited data on its association with the very common symptom of dyspepsia. Using published and unpublished data sources, we sought to determine estimates of the risks of dyspepsia associated with NSAIDs. Methods. We searched computerized databases (1966-1998) for primary studies of NSAIDs reporting on GI complications. We also obtained Food and Drug Administration (FDA) new drug application reviews for the 5 most common NSAIDs. We included studies reporting defined upper GI outcomes among subjects (> 17 years old) who used oral NSAIDs for more than 4 days. Two reviewers evaluated 4,881 published titles, identifying 55 NSAID versus placebo randomized controlled trials (RCTs), 37 unpublished (FDA data) placebo-controlled RCTs; 86 NSAID versus NSAID RCTs (sample size 2:50); and 103 observational studies. Results. The majority of clinical trials were of good quality. Meta-regression identified an increased risk of dyspepsia for users of specific NSAIDs (adjusted odds ratio [OR] of indomethacin, meclofenamate, piroxicam = 2.8), and for high dosages of other NSAIDs (OR = 3.1), but not for other NSAIDs regardless of dosage (OR = 1.1). Dyspepsia was not reported as an outcome in the case control or cohort studies. Conclusions. Clinical trial data indicate that high dosages of any NSAID along with any dosage of indomethacin, meclofenamate, or piroxicam increase the risk of dyspepsia by about 3-fold. Other NSAIDs at lower dosages were not associated with an increased risk of dyspepsia. C1 Cedars Sinai Hlth Syst, Los Angeles, CA USA. Zynx Hlth Inc, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Merck & Co Inc, W Point, PA USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Ofman, JJ (reprint author), Cedars Sinai, Zynx Hlth, 9100 Wilshire Blvd,Suite 655E, Beverly Hills, CA 90212 USA. NR 185 TC 52 Z9 52 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD AUG 15 PY 2003 VL 49 IS 4 BP 508 EP 518 DI 10.1002/art.11192 PG 11 WC Rheumatology SC Rheumatology GA 709KL UT WOS:000184624300006 PM 12910557 ER PT J AU Zhang, L Sharma, S Zhu, LX Kogai, T Hershman, JM Brent, GA Dubinett, SM Huang, M AF Zhang, L Sharma, S Zhu, LX Kogai, T Hershman, JM Brent, GA Dubinett, SM Huang, M TI Nonradioactive iodide effectively induces apoptosis in genetically modified lung cancer cells SO CANCER RESEARCH LA English DT Article ID SODIUM/IODIDE SYMPORTER GENE; THYROID PEROXIDASE; OXIDATIVE STRESS; BREAST-CANCER; RADIOIODIDE UPTAKE; DNA-DAMAGE; EXPRESSION; THERAPY; P21; INHIBITOR AB We assessed a nonradioactive approach to induce apoptosis in non-small cell lung cancer by a novel iodide uptake and retention mechanism. To enhance tumor apoptosis, we transduced non-small cell lung cancer cells with retroviral vectors containing the sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes. Expression of NIS and TPO facilitated concentration of iodide in tumors. As a consequence of the marked increase in intracellular levels of iodide, apoptosis was seen in >95% of NIS/TPO-modified lung cancer cells. Intraperitoneal injection of potassium iodide resulted in significant tumor volume reduction in NIS/TPO-modified tumor xenografts without apparent adverse effects in SCID mice. Iodide induced an increase in the level of reactive oxygen species. Iodide-induced apoptosis is sensitive to N-acetylcysteine inhibition, suggesting an important role by reactive oxygen species in this apoptotic process. In addition, iodide-induced apoptosis is associated with overexpression of CDKN1A (p21/Waf1) and down-regulation of survivin at both mRNA and protein levels. This is the first report demonstrating that a therapeutic dose of nonradioactive iodide has potent efficacy and high selectivity against lung cancer when used in combination with genetic modification of cancer cells to express the NIS/TPO genes. C1 Univ Calif Los Angeles, W Los Angeles VA, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Endocrinol & Metab, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, W Los Angeles VA, Div Pulm & Crit Care Med, Bldg 114,Room 103, Los Angeles, CA 90073 USA. FU NCI NIH HHS [R01 CA085686, P50 CA90388] NR 62 TC 28 Z9 29 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2003 VL 63 IS 16 BP 5065 EP 5072 PG 8 WC Oncology SC Oncology GA 715AM UT WOS:000184948400048 PM 12941836 ER PT J AU Mao, CG Xu, RJ Szulc, ZM Bielawski, J Becker, KP Bielawska, A Galadari, SH Hu, W Obeid, LM AF Mao, CG Xu, RJ Szulc, ZM Bielawski, J Becker, KP Bielawska, A Galadari, SH Hu, W Obeid, LM TI Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase - An enzyme that preferentially regulates metabolism of very long chain ceramides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ACID CERAMIDASE; MOLECULAR-CLONING; NEUTRAL CERAMIDASE; SACCHAROMYCES-CEREVISIAE; PSEUDOMONAS-AERUGINOSA; PURIFICATION; SYNTHASE; DISEASE; SPHINGOMYELINASE; NEUTRAL/ALKALINE AB Ceramidases deacylate ceramides, important intermediates in the metabolic pathway of sphingolipids. In this study, we report the cloning and characterization of a novel mouse alkaline ceramidase (maCER1) with a highly restricted substrate specificity. maCER1 consists of 287 amino acids, and it has a 28 and 32% identity to the Saccharomyces alkaline ceramidases (YPC1p and YDC1p) and the human alkaline phytoceramidase, respectively. Reverse transcriptase-PCR analysis demonstrated that maCER1 was predominantly expressed in skin. maCER1 was localized to the endoplasmic reticulum as revealed by immunocytochemistry. In vitro biochemical characterization determined that maCER1 hydrolyzed D-erythro-ceramide exclusively but not D-erythro-dihydroceramide or D-ribo-phytoceramide. Similar to other alkaline ceramidases, maCER1 had an alkaline pH optimum of 8.0, and it was activated by Ca2+ but inhibited by Zn2+, Cu2+, and Mn2+. maCER1 was also inhibited by sphingosine, one of its products. Metabolic labeling studies showed that overexpression of maCER1 caused a decrease in the incorporation of radiolabeled dihydrosphingosine into ceramide and complex sphingolipids but led to a concomitant increase in sphingosine-1-P (S1P) in HeLa cells. Mass measurement showed that overexpression of maCER1 selectively lowered the cellular levels of D-erythro-C-24:1-ceramide, but not other ceramide species and caused an increase in the levels of S1P. Taken together, these data suggest that maCER1 is a novel alkaline ceramidase with a stringent substrate specificity and that maCER1 is selectively expressed in skin and may have a role in regulating the levels of bioactive lipids ceramide and S1P, as well as complex sphingolipids. C1 Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. United Arab Emirates Univ, Dept Biochem, Fac Med & Hlth Sci, Al Ain, U Arab Emirates. RP Mao, CG (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, 114 Doughty St,Rm 605 STB,POB 250779, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NCRR NIH HHS [1P20RR017677-01]; NIGMS NIH HHS [GM62887-01] NR 30 TC 59 Z9 61 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 15 PY 2003 VL 278 IS 33 BP 31184 EP 31191 DI 10.1074/jbc.M303875200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 710AN UT WOS:000184658800096 PM 12783875 ER PT J AU Clark, JI Atkins, MB Urba, WJ Creech, S Figlin, RA Dutcher, JP Flaherty, L Sosman, JA Logan, TF White, R Weiss, GR Redman, BG Tretter, CPG McDermott, D Smith, JW Gordon, MS Margolin, KA AF Clark, JI Atkins, MB Urba, WJ Creech, S Figlin, RA Dutcher, JP Flaherty, L Sosman, JA Logan, TF White, R Weiss, GR Redman, BG Tretter, CPG McDermott, D Smith, JW Gordon, MS Margolin, KA TI Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: A cytokine working group randomized trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01, 2003 CL CHICAGO, ILLINOIS SP Amer Soc Clin Oncol ID PHASE-II TRIAL; GROUP EXPERIENCE 1986-2001; RECOMBINANT INTERLEUKIN-2; RADICAL NEPHRECTOMY; INTERFERON-ALPHA; CLINICAL-TRIALS; KIDNEY CANCER; STAGE-II; IMMUNOTHERAPY; MANAGEMENT AB Purpose : This prospective, randomized, controlled phase III trial assessed high-dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC). Patients and Methods: Eligibility requirements were resected locally advanced (LA, T3b-4 or N1-3) or metastatic (M1) RCC, no prior systemic therapy, and excellent organ function. Randomized assignment was to one course of IL-2 (600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [maximum 28 doses]) or observation. The study was designed and powered to show an improvement in predicted 2-year disease-free survival (DFS) from 400% for the observation group to 70% for the treatment group. The accrual goal was 68 patients with LA disease, with 34 patients per treatment arm. Metastasectomy patients were to be analyzed separately because of their unpredictable natural history. Results : Sixty-nine patients were enrolled onto the study (44 LA and 25 M1 patients). Toxic effects of IL-2 were as anticipated; no unexpected serious adverse events or treatment-related deaths occurred. Early closure occurred when an interim analysis determined that the 30% improvement in 2-year DFS could not be achieved despite full accrual. Sixteen of 21 LA patients receiving IL-2 experienced relapse, compared with 15 of 23 patients in the observation arm (P =.73); in the LA group, three deaths occurred in the IL-2 arm, and five deaths occurred in the observation arm (P =.38). Analysis including metastasectomy patients made no difference in DFS or overall survival. Conclusion: One course of high-dose bolus IL-2, though feasible, did not produce the ambitious clinically meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC. C1 Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR USA. Univ Calif Los Angeles, Los Angeles, CA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Our Lady Mercy Comprehens Canc Ctr, New York, NY USA. Wayne State Univ, Detroit, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Vanderbilt Univ, Nashville, TN USA. Indiana Univ, Indianapolis, IN 46204 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Univ Texas, S Texas Vet Hlth Care Syst, San Antonio, TX 78285 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Arizona Hlth Sci Ctr, Phoenix, AZ USA. RP Clark, JI (reprint author), Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 30 TC 144 Z9 154 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 AUG 15 PY 2003 VL 21 IS 16 BP 3133 EP 3140 DI 10.1200/JCO.2003.02.014 PG 8 WC Oncology SC Oncology GA 712CZ UT WOS:000184780300021 PM 12810695 ER PT J AU Jackson, LA Neuzil, KM Thompson, WW AF Jackson, LA Neuzil, KM Thompson, WW TI Pneumococcal vaccination in older adults - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Grp Hlth Cooperat Puget Sound, Seattle, WA 98101 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RP Jackson, LA (reprint author), Grp Hlth Cooperat Puget Sound, Seattle, WA 98101 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 14 PY 2003 VL 349 IS 7 BP 713 EP 714 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 711FL UT WOS:000184728900029 ER PT J AU Berkowitz, GS Wolff, MS Janevic, TM Holzman, IR Yehuda, R Landrigan, PJ AF Berkowitz, GS Wolff, MS Janevic, TM Holzman, IR Yehuda, R Landrigan, PJ TI The World Trade Center disaster and intrauterine growth restriction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID AIR-POLLUTION; FETAL GROWTH; BIRTH C1 CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. RP Berkowitz, GS (reprint author), CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. FU NIEHS NIH HHS [P42 ES07384-07S1] NR 6 TC 82 Z9 83 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 6 PY 2003 VL 290 IS 5 BP 595 EP 596 DI 10.1001/jama.290.5.595-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 708GH UT WOS:000184558500010 PM 12902358 ER PT J AU Flesch, M Hoper, A Dell'Italia, L Evans, K Bond, R Peshock, R Diwan, A Brinsa, TA Wei, CC Sivasubramanian, N Spinale, FG Mann, DL AF Flesch, M Hoper, A Dell'Italia, L Evans, K Bond, R Peshock, R Diwan, A Brinsa, TA Wei, CC Sivasubramanian, N Spinale, FG Mann, DL TI Activation and functional significance of the renin- angiotensin system in mice with cardiac restricted overexpression of tumor necrosis factor SO CIRCULATION LA English DT Article DE hypertrophy; genes; heart failure; remodeling; apoptosis ID FACTOR-ALPHA; TRANSGENIC MICE; GENE-EXPRESSION; CONVERTING ENZYME; DOWN-REGULATION; MOUSE; HEART; RATS; CARDIOMYOPATHY; DYSFUNCTION AB Background-The functional significance of cross-regulation between the renin-angiotensin system (RAS) and tumor necrosis factor (TNF) has been established in nonmyocyte cell types; however, the degree and functional significance of the interaction between RAS and TNF has not been characterized in the heart. Methods and Results-We examined the expression of components of the RAS in a line of transgenic mice (MHCsTNF) with cardiac restricted overexpression of TNF. When examined at 4, 8, and 12 weeks of age, the MHCsTNF mice had increased activation of myocardial RAS, as shown by an increase in ACE mRNA level and ACE activity and increased angiotensin II peptide levels. Furthermore, myocardial angiotensin receptor mRNA and protein levels were reduced in the MHCsTNF mice, consistent with homologous desensitization of the receptors. However, expression of renin and angiotensinogen was not increased in MHCsTNF mice compared with littermate controls. To determine the functional significance of RAS activation in the MHCsTNF mice, we treated the mice with an angiotensin type I receptor antagonist, losartan (30 mg/kg), or diluent from 4 to 8 weeks of age. Analysis of cardiac structure with MRI showed that treatment with losartan normalized left ventricular mass and wall thickness. Furthermore, treatment with losartan reduced myocardial collagen content and reduced the incidence of myocyte apoptosis. Conclusions-Taken together, these results show that there are functionally significant interactions between RAS and TNF in the heart and that these interactions play an important role in the development and progression of left ventricular remodeling. C1 Houston VAMC, Winters Ctr Heart Failure Res, Cardiol Sect, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77030 USA. Texas SW Univ, Dept Radiol, Dallas, TX USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. RP Mann, DL (reprint author), Houston VAMC, Winters Ctr Heart Failure Res, Cardiol Sect, Dept Med, 6565 Fannin,MS 524, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [R01-HL-58081-01, HL-42250-10/10, R01-HL-61543-01, P50-HL-O6H] NR 24 TC 44 Z9 54 U1 1 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 AUG 5 PY 2003 VL 108 IS 5 BP 598 EP 604 DI 10.1161/01.CIR.0000081768.13378.BF PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 708CH UT WOS:000184549200018 PM 12874189 ER PT J AU Pastore, Y Jedlickova, K Guan, YL Liu, EL Fahner, J Hasle, H Prchal, JF Prchal, JT AF Pastore, Y Jedlickova, K Guan, YL Liu, EL Fahner, J Hasle, H Prchal, JF Prchal, JT TI Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID REGULATE HIF; VHL GENE; DISEASE; PROTEIN; HYDROXYLATION; COMPLEX; CANCER; DEFINE; ALPHA AB The von Hippel-Lindau (pVHL) protein plays an important role in hypoxia sensing. It binds to the hydroxylated hypoxia-inducible factor 1alpha (HIF-1alpha) and serves as a recognition component of an E3-ubiquitin ligase complex. In hypoxia or secondary to a mutated VHL gene, the nondegraded HIF-1alpha forms a heterodimer with HIF-beta and leads to increased transcription of hypoxia-inducible genes, including erythropoietin (EPO). The autosomal dominant cancer-predisposition von Hippel-Lindau (VHL) syndrome is due to inheritance of a single mutated allele of VHL. In contrast, we recently showed that homozygous germline 598C-->T VHL mutation leads to Chuvash polycythemia (CP). We subsequently found VHL mutations in three unrelated individuals unaffected with CP, one of whom was compound heterozygous for the 598C-->T mutation and another VHL mutation. We now report seven additional polycythemic patients with VHL mutations in both alleles. Two Danish siblings and another American boy were homozygous for the VHL 598C-->T mutation. Three unrelated white Americans were compound heterozygotes for 598C-->T and another VHL mutation, 562C-->G in two and 574C-->T in the third. Additionally, a Croatian boy was homozygous for a 571C-->G VHL mutation, the first example of homozygous VHL germline mutation causing polycythemia, other than the VHL 598C-->T mutation. We have not observed VHL syndrome - associated tumors in polycythemic subjects or their heterozygous relatives; however, this will need to be evaluated by longitudinal studies. Over all, we found that up to half of the consecutive patients with apparent congenital polycythemia and increased serum Epo we have examined have mutations of both VHL alleles. Those findings, along with reports of CP, underscore that VHL mutations are the most frequent cause of congenital polycythemia and define a new class of polycythemic disorder, polycythemias due to augmented hypoxia sensing. C1 Baylor Coll Med, Houston, TX 77030 USA. Texas Childrens Canc Ctr & Hematol Serv, Houston, TX USA. Vet Adm Hosp, Houston, TX USA. DeVos Childrens Hosp, Grand Rapids, MI USA. Viborg Hosp, Dept Pediat, Viborg, Denmark. McGill Univ, Dept Hematol Oncol, Montreal, PQ, Canada. RP Prchal, JT (reprint author), Baylor Coll Med, 1 Baylor Plaza,Suite 802E, Houston, TX 77030 USA. FU NHLBI NIH HHS [R01HL66333-01, R01HL5007-08, R01 HL066333] NR 28 TC 76 Z9 79 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 2003 VL 73 IS 2 BP 412 EP 419 DI 10.1086/377108 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 702KW UT WOS:000184223900018 PM 12844285 ER PT J AU Taylor, JGC Zwillich, CW Kaehny, WD Levi, M Popovtzer, MM AF Taylor, JGC Zwillich, CW Kaehny, WD Levi, M Popovtzer, MM TI Hyperkalemia with concomitant watery diarrhea: An unusual association SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE herkalemia; diarrhea; angiotensin-converting enzyme (ACE) inhibitor ID HYPOKALEMIA; ABSORPTION; SECRETION AB Four patients presented to the emergency room with life-threatening hyperkalemia and concomitant watery diarrhea. Hypovolemia, acidosis, and renal insufficiency were present in all 4 cases. In 2 patients, hyperkalemia followed initiation of angiotensin-converting enzyme (ACE) inhibitor therapy, whereas 1 patient experienced hyperkalemia after a dose increase of an ACE inhibitor, and the fourth patient was on continuous ACE-inhibitor therapy at the time of the hyperkalemia episode. Two of the 3 patients with functioning kidneys required hemodialysis to correct the hyperkalemia, whereas the other patient was on long-term hemodialysis therapy. In the 2 patients in whom transtubular potassium (K+) gradients were available, their values ranged far below normal, indicating tubular failure to secrete K+. This abnormality was attributed to decreased distal delivery of sodium and water and to renin/angiotensin II/aldosterone blockade. It has been proposed that aldosterone blockade impairs the capacity of the colonic epithelial cells to secrete K+. In all 4 patients the watery diarrhea ceased in parallel with the correction of serum K+ to normal values. It is suggested that hyperkalemia, most likely by stimulating intestinal motility, induced the watery diarrhea in all 4 patients. The watery diarrhea, however, failed to compensate for the renal tubular failure to secrete K+. C1 Denver VA Med Ctr, Renal Sect 111C, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Renal Dis & Hypertens, Denver, CO 80262 USA. RP Popovtzer, MM (reprint author), Denver VA Med Ctr, Renal Sect 111C, 1055 Clermont St, Denver, CO 80220 USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2003 VL 42 IS 2 AR E5 DI 10.1016/S0272-6386(03)00667-X PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 708FV UT WOS:000184557300036 ER PT J AU Dominitz, JA Selinger, RRE Norman, S AF Dominitz, JA Selinger, RRE Norman, S TI Replacing guaiac-based tests with immunochemical tests in colorectal cancer screening - Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID OCCULT-BLOOD-TESTS C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Dominitz, JA (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 8 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG 1 PY 2003 VL 115 IS 2 BP 154 EP 155 DI 10.1016/S0002-9343(03)00282-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 707RJ UT WOS:000184523400014 ER PT J AU Reeve, JR Green, GM Chew, P Eysselein, VE Keire, DA AF Reeve, JR Green, GM Chew, P Eysselein, VE Keire, DA TI CCK-58 is the only detectable endocrine form of cholecystokinin in rat SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pancreas; radioimmunoassay; blood processing; plasma; molecular forms ID PLASMA; INTESTINE; BLOOD; DEGRADATION; BRAIN AB CCK-58 differs from CCK-8 in patterns of expression of pancreatic secretion of fluid and amylase and gallbladder contraction. These differences have physiological relevance only if CCK-58 release is stimulated by nutrients entering the intestine and if CCK-58 circulates in sizeable amounts. In this study, we report that when radiolabeled CCK-58 is added to rat blood and plasma is formed, there is extensive loss and degradation of the radioactive peptide. Therefore, a new method was developed to minimize loss and degradation of this label. This method recovered >85% of the label with no detectable degradation. Furthermore, the optimized method recovered all unlabeled exogenous cholecystokinin molecular forms in >80% yields. Blood from fasted rats and rats in which cholecystokinin release was stimulated by the trypsin inhibitor camostat contained only CCK-58 (3.5 +/- 0.5 and 17 +/- 1.5 fmol/ml, respectively). Because CCK-58 predominates in the blood, this molecular form should be used in studieson the physiology and pathophysiology of cholecystokinin. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151, Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Harbor Univ Los Angeles Med Ctr, Div Gastroenterol, Torrance, CA 90509 USA. RP Reeve, JR (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151, Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-37482, DK-41301, DK-33850] NR 27 TC 62 Z9 63 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD AUG PY 2003 VL 285 IS 2 BP G255 EP G265 DI 10.1152/ajpgi.00523.2002 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 698TY UT WOS:000184015900002 PM 12686511 ER PT J AU Wei, CC Lucchesi, PA Tallaj, J Bradley, WE Powell, PC Dell'Italia, LJ AF Wei, CC Lucchesi, PA Tallaj, J Bradley, WE Powell, PC Dell'Italia, LJ TI Cardiac interstitial bradykinin and mast cells modulate pattern of LV remodeling in volume overload in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hypertrophy; chymase; angiotensin-converting enzyme ID ANGIOTENSIN-CONVERTING ENZYME; CONGESTIVE-HEART-FAILURE; IN-VIVO; MYOCARDIAL-INFARCTION; RECEPTOR ANTAGONISTS; II FORMATION; DOG HEART; CHYMASE; KININS; INHIBITORS AB In the current study, interstitial fluid (ISF), bradykinin (BK), and angiotensin II (ANG II) levels were measured using cardiac microdialysis in conscious, nonsedated rats at baseline and at 48 h and 5 days after each of the following: sham surgery ( sham, n = 6), sham + administration of ANG-converting enzyme inhibitor ramipril (R, n = 6), creation of aortocaval fistula (ACF, n = 6), ACF + R (n = 6), and ACF + R + BK2 receptor antagonist (HOE-140) administration (n = 6). At 5 days, both ISF ANG II and BK increased in ACF rats (P < 0.05); however, in ACF + R rats, ISF ANG II did not differ from basal levels and ISF BK increased greater than threefold above baseline at 2 and 5 days (P < 0.05). Five days after ACF, the left ventricular (LV) weight-to-body weight ratio increased 30% (P < 0.05) in ACF but did not differ from sham in ACF + R and ACF + R + HOE-140 rats despite similar systemic arterial pressures across all ACF groups. However, ACF + R + HOE-140 rats had greater postmortem wall thickness-to-diameter ratio and smaller cross-sectional diameter compared with ACF + R rats. There was a significant increase in mast cell density in ACF and ACF + R rats that decreased below sham in ACF + R + HOE-140 rats. These results suggest a potentially important interaction of mast cells and BK in the cardiac interstitium that modulates the pattern of LV remodeling in the acute phase of volume overload. C1 Birmingham Vet Affairs Med Ctr, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35233 USA. RP Dell'Italia, LJ (reprint author), Univ Alabama, Dept Med, Div Cardiovasc Dis, 834 MCLM,1918 Univ Blvd, Birmingham, AL 35294 USA. RI Lucchesi, Pamela/E-3558-2011 FU NHLBI NIH HHS [R01 HL 54816, HL 60707] NR 43 TC 27 Z9 27 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 2003 VL 285 IS 2 BP H784 EP H792 DI 10.1152/ajpheart.00793.2001 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 701DN UT WOS:000184153100040 PM 12663259 ER PT J AU Gorin, Y Ricono, JM Kim, NH Bhandari, B Choudhury, GG Abboud, HE AF Gorin, Y Ricono, JM Kim, NH Bhandari, B Choudhury, GG Abboud, HE TI Nox4 mediates angiotensin II-induced activation of Akt/protein kinase B in mesangial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE reactive oxygen species; Rac1; arachidonic acid; protein synthesis ID SMOOTH-MUSCLE-CELLS; NAD(P)H OXIDASE ACTIVITY; JUN NH2-TERMINAL KINASE; PROTEIN-KINASE; NADPH OXIDASE; ARACHIDONIC-ACID; INDUCED HYPERTROPHY; DEPENDENT PATHWAY; RAC1; GROWTH AB ANG II induces protein synthesis through the serine-threonine kinase Akt/protein kinase B (PKB) in mesangial cells (MCs). The mechanism(s) of activation of Akt/PKB particularly by G protein-coupled receptors, however, is not well characterized. We explored the role of the small GTPase Rac1, a component of the phagocyte NADPH oxidase, and the gp91(phox) homologue Nox4/Renox in this signaling pathway. ANG II causes rapid activation of Rac1, an effect abrogated by phospholipase A(2) inhibition and mimicked by arachidonic acid (AA). Northern blot analysis revealed high levels of Nox4 transcript in MCs and transfection with antisense (AS) oligonucleotides for Nox4 markedly decreased NADPH-dependent reactive oxygen species (ROS)-producing activity. Dominant negative Rac1 (N17Rac1) as well as AS Nox4 inhibited ROS generation in response to ANG II and AA, whereas constitutively active Rac1 stimulated ROS formation. Moreover, N17Rac1 blocked stimulation of NADPH oxidase activity by AA. N17Rac1 or AS Nox4 abolished ANG II- or AA-induced activation of the hypertrophic kinase Akt/PKB. In addition, AS Nox4 inhibited ANG II- induced protein synthesis. These data provide the first evidence that activation by AA of a Rac1-regulated, Nox4-based NAD(P) H oxidase and subsequent generation of ROS mediate the effect of ANG II on Akt/PKB activation and protein synthesis in MCs. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, Geriatr Res & Educ Ctr, San Antonio, TX 78229 USA. RP Abboud, HE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM abboud@uthscsa.edu FU NIDDK NIH HHS [DK-43988, DK-55815, DK-33665] NR 46 TC 201 Z9 204 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 2003 VL 285 IS 2 BP F219 EP F229 DI 10.1152/ajprenal.00414.2002 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 697KM UT WOS:000183941900006 PM 12842860 ER PT J AU Marder, SR Glynn, SM Wirshing, WC Wirshing, DA Ross, D Widmark, C Mintz, J Liberman, RP Blair, KE AF Marder, SR Glynn, SM Wirshing, WC Wirshing, DA Ross, D Widmark, C Mintz, J Liberman, RP Blair, KE TI Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; RATING-SCALE; OLANZAPINE; CLOZAPINE; PLACEBO; ANTIPSYCHOTICS; MULTICENTER; PREVENTION; EFFICACY; SYMPTOMS AB Objective: Most controlled studies comparing second-generation and conventional antipsychotics have focused on the acute treatment of schizophrenia. The authors compared symptom outcomes, side effects, and social adjustment in stable schizophrenia outpatients who received 2 years of maintenance treatment with risperidone or haloperidol. Method: This was a 2-year, randomized, double-blind comparison of 6 mg of risperidone versus haloperidol in 63 patients with stabilized DSM-IV schizophrenia. Study patients also received 15 months of standard behavioral skills training or enhanced training with a case manager who promoted patients' use of their skills in the community. Results: The risk of psychotic exacerbations and the risk of leaving the study were similar for both drug treatment groups. However, patients who received both risperidone and the enhanced community-based skills training were more likely to re-main in the study than those in the other treatment groups. Patients demonstrated significant improvement in score on the Brief Psychiatric Rating Scale over time with both medications. There were no between-group differences in cluster scores for thought disturbance, hostile-suspiciousness, and withdrawal-retardation. A significant between-group difference favoring risperidone was found for the anxious-depression cluster. Risperidone resulted in significantly greater reductions in tremor and akathisia and greater improvements in most items on the SCL-90-R. Conclusions: When compared with patients given a low dose of haloperidol, risperidone-treated patients experienced similar improvements in positive and negative symptoms and similar risks of psychotic exacerbations. However, risperidone-treated patients appeared to feel subjectively better, as indicated by less anxiety and depression and fewer extrapyramidal side effects. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Long Beach Vet Affairs Med Ctr, Long Beach, CA USA. RP Marder, SR (reprint author), W Los Angeles VA Hlth Care Ctr, MIRECC-210A,11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. FU NIMH NIH HHS [MH-49573] NR 31 TC 62 Z9 65 U1 3 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2003 VL 160 IS 8 BP 1405 EP 1412 DI 10.1176/appi.ajp.160.8.1405 PG 8 WC Psychiatry SC Psychiatry GA 708AK UT WOS:000184543700008 PM 12900301 ER PT J AU Bishop, MJ O'Donnell, JT Salemi, JR AF Bishop, MJ O'Donnell, JT Salemi, JR TI Mivacurium and bronchospasm SO ANESTHESIA AND ANALGESIA LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 12-16, 2002 CL ORLANDO, FLORIDA SP Amer Soc Anesthesiologists ID LUNG-MECHANICS; RELAXANTS; HISTAMINE C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA 98108 USA. Rush Med Coll, Dept Pharmacol, Chicago, IL 60612 USA. Pharmaconsultant Inc, Palatine, IL USA. RP Bishop, MJ (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Anesthesiol, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 11 TC 4 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 2003 VL 97 IS 2 BP 484 EP 485 DI 10.1213/01.ANE.0000067433.05538.3D PG 2 WC Anesthesiology SC Anesthesiology GA 704RW UT WOS:000184354600032 PM 12873940 ER PT J AU Netscher, DT Eladoumikdachi, F McHugh, PM Thornby, J Soltero, E AF Netscher, DT Eladoumikdachi, F McHugh, PM Thornby, J Soltero, E TI Sternal wound debridement and muscle flap reconstruction: Functional implications SO ANNALS OF PLASTIC SURGERY LA English DT Article ID MCGILL PAIN QUESTIONNAIRE; LATISSIMUS-DORSI MUSCLE; POSTSTERNOTOMY MEDIASTINITIS; CHEST-WALL; STERNOTOMY WOUNDS; PECTORALIS FLAPS; TRANSPOSITION; MANAGEMENT; INFECTIONS; DEFECTS AB The mortality rate for poststernotomy infection, which occurs in as many as 5% of median sternotomy incisions after cardiovascular surgery, was 37.5% until sternal debridement with muscle or omental flap reconstruction became the standard treatment for this postoperative complication and lowered the mortality rate to just more than 5%. There are few reports in the literature of physical functional deficits and long-term outcome resulting from such reconstruction. The authors evaluated two groups of patients who had undergone coronary bypass surgery at least 6 months earlier. One group had no postoperative complications; the other group had developed marked sternal wound infections that required debridement and pectoralis major or rectus abdominis muscle reconstruction. Both groups underwent pectoralis and rectus muscle strength testing, evaluation of pain and ability to perform those activities of daily living that are dependent on pectoral and rectus muscle function, and completed self-assessment questionnaires. Differences between the two groups were significant (p < 0.05) with regard to pain and patient satisfaction with appearance and general functional capacity. Pectoral muscle function and strength were significantly different in patients in whom that muscle was transposed. Rectus muscle strength was not affected by the transposition of a single rectus muscle. Physical morbidity and loss of strength seemed to be related directly to loss of sternal stability stemming from marked infection and debridement rather than from loss of the muscles used in reconstruction. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 30 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD AUG PY 2003 VL 51 IS 2 BP 115 EP 122 DI 10.1097/01.SAP.0000058497.92264.E2 PG 8 WC Surgery SC Surgery GA 714LN UT WOS:000184915900001 PM 12897511 ER PT J AU Etzioni, DA Liu, JH Maggard, MA Ko, CY AF Etzioni, DA Liu, JH Maggard, MA Ko, CY TI The aging population and its impact on the surgery workforce SO ANNALS OF SURGERY LA English DT Article ID GENERAL-SURGERY; RELATIVE VALUES; WORK LOADS; SHORTAGE; SPECIALTIES; PHYSICIANS; MEDICINE; THERES; TRENDS; CARE AB Objective: To predict the impact of the aging population on the demand for surgical procedures. Summary Background Data: The population is expanding and aging. According to the US Census Bureau, the domestic population will increase 7.9% by 2010, and 17.0% by 2020. The fastest growing segment of this population consists of individuals over the age of 65; their numbers are expected to increase 13.3% by 20 10 and 53.2% by 2020. Methods: Data on the age-specific rates of surgical procedures were obtained from the 1996 National Hospital Discharge Survey and the National Survey of Ambulatory Surgery. These procedure rates were combined with corresponding relative value units from the Centers for Medicare and Medicaid Services. The result quantifies the amount of surgical work used by an average individual within specific age groups (<15 years old, 15-44 years old, 45-64 years old, 65+ years old). This estimate of work per capita was combined with population forecasts to predict future use of surgical services. Results: Based on the assumption that age-specific per capita use of surgical services will remain constant, we predict significant increases (14-47%) in the amount of work in all surgical fields. These increases vary widely by specialty. Conclusions: The aging of the US population will result in significant growth in the demand for surgical services. Surgeons need to develop strategies to manage an increased. workload without sacrificing quality of care. C1 VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. RP Etzioni, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 1015 9th St Apt 106, Santa Monica, CA 90403 USA. FU NCI NIH HHS [K08 CA090403] NR 30 TC 252 Z9 259 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 2003 VL 238 IS 2 BP 170 EP 177 DI 10.1097/01.SLA.0000081085.98792.3d PG 8 WC Surgery SC Surgery GA 730MR UT WOS:000185835000003 PM 12894008 ER PT J AU Estes, JD Stolpman, D Olyaei, A Corless, CL Ham, JM Schwartz, JM Orloff, SL AF Estes, JD Stolpman, D Olyaei, A Corless, CL Ham, JM Schwartz, JM Orloff, SL TI High prevalence of potentially hepatotoxic herbal supplement use in patients with fulminant hepatic failure SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 74th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 16-18, 2003 CL MONTEREY, CALIFORNIA SP Pacific Coast Surg Assoc ID ACUTE LIVER-FAILURE; UNITED-STATES; MA-HUANG; INJURY; THERAPIES; INGESTION; PATTERNS AB Hypothesis: The use of potentially hepatotoxic herbal and dietary supplements is highly prevalent in the fulminant hepatic failure (FHF) patient population at our institution, and this subgroup of patients has a worse prognosis. Design: Retrospective case series. Settings: An adult tertiary care university hospital and a Veterans Affairs hospital in Oregon. Patients: All patients referred to the liver transplantation service for FHF from January 2001 through October 2002 (N = 20). We defined FHF as onset of encephalopathy within 8 weeks of onset of jaundice in the absence of preexisting liver disease. All patients underwent investigation for potential causes of liver injury. Potentially hepatotoxic supplements were defined as those with previously published reports of hepatic injury related to their use. Results: Ten patients (50%) were recent or active users of potentially hepatotoxic supplements or herbs; 10 had no history of supplement use. In. the supplement group, 7 patients (35%) had no other identified cause for hepatic failure. Six patients in the supplement group and 2 patients in the nonsupplement group underwent orthotopic liver transplantation. Five patients in each group died. There were no significant differences in transplantation rate (P = .07) or survival (P > .99) between groups. Supplement use alone accounted for the most cases of FHF during this period, exceeding acetaminophen toxicity and viral hepatitis. Conclusions: Herbal and dietary supplements were potential hepatotoxins, in a high proportion of patients with FHF at our institution. Enhanced public awareness of the potential hepatotoxicity of these commonly used agents and increased regulatory oversight of their use is strongly urged. C1 Oregon Hlth Sci Univ, Div Liver Pancreas Transplantat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Orloff, SL (reprint author), Oregon Hlth Sci Univ, Div Liver Pancreas Transplantat, L590,3181 SW Jackson Pk Rd, Portland, OR 97201 USA. NR 37 TC 89 Z9 93 U1 5 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD AUG PY 2003 VL 138 IS 8 BP 852 EP 856 DI 10.1001/archsurg.138.8.852 PG 5 WC Surgery SC Surgery GA 709HB UT WOS:000184618800009 PM 12912743 ER PT J AU Knopp, RH Retzlaff, B Fish, B Walden, C Wallick, S Anderson, M Aikawa, K Kahn, SE AF Knopp, RH Retzlaff, B Fish, B Walden, C Wallick, S Anderson, M Aikawa, K Kahn, SE TI Effects of insulin resistance and obesity on lipoproteins and sensitivity to egg feeding SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE insulin-resistant; obesity; LDL cholesterol; dietary cholesterol ID LOW-CHOLESTEROL ABSORPTION; CORONARY HEART-DISEASE; HIGH BLOOD CHOLESTEROL; DIETARY-CHOLESTEROL; CARDIOVASCULAR-DISEASE; SYNDROME PREDICTS; APOLIPOPROTEIN-B; FOLLOW-UP; A-I; MEN AB Objective - This study was undertaken to determine if insulin resistance without and with obesity influences LDL response to dietary cholesterol and saturated fat. Methods and Results - We fed 0, 2, and 4 egg yolks per day to 197 healthy subjects in a 4-week, double-blind, randomized, crossover design. Subjects were dichotomized on body mass index ( <27.5 and &GE; 27.5 kg/m(2)) and insulin sensitivity (insulin-sensitivity index &GE; 4.2 x 1.0(-4) and <4.2 x 1.0(-4) min(-1) muU/mL), yielding insulin-sensitive (IS, n = 65), insulin-resistant (IR, n = 75), and obese insulin-resistant (OIR, n = 58) subjects. Mean fasting baseline LDL cholesterol (LDL-C) levels were higher in IR and OIR subjects (3.44 +/- 0.67 and 3.32 +/- 0.80 mol/ L) than in IS subjects (2.84 +/- 0.75 mmol/L) (P < 0.001). Progressive triglyceride elevations and HDL-C decreases were seen across the 3 groups. Ingesting 4 eggs daily yielded significant LDL-C increases of 7.8 +/- 13.7% (IS) and 3.3 +/- 13.2% (IR) (both P < 0.05) compared with 2.4 +/- 12.6% for OIR (NS). HDL-C increases were 8.8 +/- 10.4%, 5.2 +/- 10.4%, and 3.6 +/- 9.4% in IS, IR, and OIR, respectively ( all P < 0.01). Conclusions - Insulin resistance without and with obesity is associated with elevated LDL-C as well as elevated triglyceride and low HDL-C. The elevated LDL-C cannot be explained by dietary sensitivity, because the LDL-C rise with egg feeding is less in IR persons regardless of obesity status, probably attributable to diminished cholesterol absorption. The results suggest that dietary management of insulin resistance and obesity can focus more on restricting calories and less on restricting dietary fat. C1 Univ Washington, NW Lipid Res Clin, Div Cardiol, Seattle, WA 98104 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98104 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98104 USA. RP Knopp, RH (reprint author), Univ Washington, NW Lipid Res Clin, Div Cardiol, 325 9th Ave,Box 359720, Seattle, WA 98104 USA. OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR 00037]; NIDDK NIH HHS [DK35816, DK17047] NR 38 TC 58 Z9 59 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2003 VL 23 IS 8 BP 1437 EP 1443 DI 10.1161/01.ATV.0000082461.77557.C7 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 710JQ UT WOS:000184677400022 PM 12816878 ER PT J AU Game, BA Xu, MF Lopes-Virella, MF Huang, Y AF Game, BA Xu, MF Lopes-Virella, MF Huang, Y TI Regulation of MMP-1 expression in vascular endothelial cells by insulin sensitizing thiazolidinediones SO ATHEROSCLEROSIS LA English DT Article; Proceedings Paper CT 61st Scientific Session of the American-Diabetes-Association CY JUN 22-26, 2001 CL PHILADELPHIA, PENNSYLVANIA SP Amer Diabet Assoc DE interstitial collagenase; matrix metalloproteinases; diabetes; PPAR-gamma; gene expression ID ACTIVATED-RECEPTOR-GAMMA; MONOCYTE CHEMOTACTIC PROTEIN-1; TYPE-2 DIABETES-MELLITUS; GENE-EXPRESSION; PPAR-GAMMA; ATHEROSCLEROTIC PLAQUES; IN-VITRO; TROGLITAZONE; LIGAND; ALPHA AB Matrix metalloproteinases (MMPs) have been implicated in the disruption of atherosclerotic plaques that leads to acute coronary events. The present study investigates the effect of thiazolidinediones (TZDs), new antidiabetic drugs, on MMP-1 expression by human vascular endothelial cells. Results show that troglitazone, but not pioglitazone and rosiglitazone, stimulated MMP-1 secretion and mRNA expression in both human umbilical vein and aortic endothelial cells, but had no effect on TIMP-1 and TIMP-2 secretion. Interestingly, troglitazone at high concentrations (greater than or equal to30 mumol/l) inhibited MMP-1 protein synthesis despite a marked stimulation on MMP-1 mRNA. Further studies revealed that troglitazone at higher concentrations inhibits de novo protein synthesis as determined by S-35-methionine/cysteine incorporation, suggesting that the inhibition of MMP-1 synthesis by troglitazone is due to the suppression of total protein synthesis. Finally, our studies showed that high concentrations of troglitazone inhibited the translation initiation factor 4E (eIF4E), but not eIF4G. In summary, the present study demonstrates that insulin sensitizers have different effects on MMP-1 expression, and troglitazone stimulates MMP-1 mRNA expression and protein synthesis at the pharmacological concentrations, but inhibits MMP-1 synthesis at higher doses. This study also suggests that supra-pharmacological concentrations of troglitazone that could be attained in body tissues may inhibit protein synthesis and cause cytotoxicity. Published by Elsevier Ireland Ltd. C1 Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Div Endocrinol Diabet & Med Genet, 114 Doughty St, Charleston, SC 29403 USA. NR 42 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2003 VL 169 IS 2 BP 235 EP 243 DI 10.1016/S0021-9150(03)00165-5 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 717PK UT WOS:000185098400004 PM 12921974 ER PT J AU Davalos, DB Kisley, MA Ross, RG AF Davalos, DB Kisley, MA Ross, RG TI Effects of interval duration on temporal processing in schizophrenia SO BRAIN AND COGNITION LA English DT Article DE schizophrenia; time perception; timing; interval discrimination ID TIME-ESTIMATION; WORKING-MEMORY; PARKINSONS-DISEASE; AUDITORY DURATION; FRONTAL-LOBE; DISCRIMINATION; PERCEPTION; CORTEX; INFORMATION; MASKING AB Introduction: Temporal processing has received scant attention in the literature pertaining to cognitive deficits in patients with schizophrenia. Previous research suggests that patients with schizophrenia exhibit temporal perception deficits on both auditory and visual stimuli. The current study investigated the effects of interval manipulation to (1) replicate the original findings with a larger sample and an increased number of trials (2) assess the degree to which both patients and controls can differentiate temporal changes in a range of experimental interstimulus intervals, and (3) explore whether different interstimulus interval durations pose different levels of difficulty for the patients with schizophrenia. Methods: Participants were asked to decide whether temporal intervals were shorter or longer than standard intervals on a computer-based auditory temporal perception task. The standard interval remained the same duration throughout the various tasks. The interstimulus interval separating the standard and experimental intervals varied in the range of 500, 1000, or 3000ms. Data are presented for a sample of 16 patients with schizophrenia and 15 controls. Results: Data suggest that patients with schizophrenia exhibit deficits in differentiating interval durations across all paradigms compared to their control-group peers on a range of auditory tasks (p <.001). Conclusions: These results are consistent with a general temporal deficit in schizophrenia. However, the roles of medication and localization are also addressed. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80206 USA. RP Davalos, DB (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, 4200 E 9th Ave, Denver, CO 80206 USA. FU NIMH NIH HHS [MH152442, MH56539] NR 53 TC 52 Z9 52 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD AUG PY 2003 VL 52 IS 3 BP 295 EP 301 DI 10.1016/S0278-2626(03)00157-X PG 7 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 712MA UT WOS:000184800400002 PM 12907174 ER PT J AU Targownik, LE Gralnek, IM Dulai, GS Spiegel, BMR Oei, T Bernstein, CN AF Targownik, LE Gralnek, IM Dulai, GS Spiegel, BMR Oei, T Bernstein, CN TI Managemert of acute nonvariceal upper gastrointestinal hemorrhage: Comparison of an American and a Canadian medical centre SO CANADIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week/101st Annual Meeting of the American-Gastroenterological-Association CY MAY 21-24, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Gastroenterol Assoc DE gastrointestinal hemorrhage; hospital length of stay; process of care; rebleeding ID HEALTH-CARE SYSTEM; ACUTE MYOCARDIAL-INFARCTION; UPPER GI HEMORRHAGE; LOW-RISK PATIENTS; UNITED-STATES; TRACT HEMORRHAGE; EARLY DISCHARGE; ENDOSCOPY; RESOURCES; HOSPITALIZATION AB OBJECTIVES: Acute nonvariceal upper gastrointestinal hemorrhage (UGIH) remains a common indication for hospital admission. Differences in the structure, process and outcomes of care in the management of acute nonvariceal UGIH between providers in Canada and the United States have not been previously characterized. The aim of the present study was to compare the structure, process and outcomes of care between a Canadian and an American tertiary care medical centre in the management of acute nonvariceal UGIH. METHODS: Data were collected from identified cases of acute nonvariceal UGIH at the two medical centres over two years. Process measures analyzed included the level of care (intensive care unit [ICU] monitored bed versus unmonitored bed) and hospital length of stay (HLOS). Outcomes assessed included rebleeding, inhospital mortality and readmission and/or death within 30 days of admission. RESULTS: One hundred seventy-five and 83 cases of acute nonvariceal UGIH were identified at the American and Canadian centres, respectively. Cases at the American centre had a lower median HLOS, (2.6 versus 3.9 days, P<0.001) but were significantly more likely to be treated in an ICU or monitored setting (67% versus 16%, P<0.001). There were no significant differences in rates of rebleeding or death in hospital or within 30 days of discharge. CONCLUSIONS: Marked differences exist in the process of care between the Canadian and American medical centres in the management of acute nonvariceal UGIH, despite similar patient severity. Outcomes between the two centres were similar. Minimizing disparity in the process of care of acute UGIH between the two centres may reduce excessive use of resources in the management of acute UGIH without promoting adverse outcomes. C1 Vet Affairs Greater Los Angeles, Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA USA. CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA USA. Univ Manitoba, Fac Med, Dept Internal Med, Gastroenterol Sect,John Buhler Res Ctr, Winnipeg, MB R3E 3P5, Canada. RP Gralnek, IM (reprint author), Univ Manitoba, Fac Med, Dept Internal Med, Gastroenterol Sect,John Buhler Res Ctr, Room 804D,727 McDermot St, Winnipeg, MB R3E 3P5, Canada. FU NCRR NIH HHS [K23 NCRR 1618801] NR 32 TC 10 Z9 10 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0835-7900 J9 CAN J GASTROENTEROL JI Can. J. Gastroenterol. PD AUG PY 2003 VL 17 IS 8 BP 489 EP 495 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 714DG UT WOS:000184896600004 PM 12945010 ER PT J AU Zeliadt, SB Penson, DF Albertsen, PC Concato, J Etzioni, RD AF Zeliadt, SB Penson, DF Albertsen, PC Concato, J Etzioni, RD TI Race independently predicts prostate specific antigen testing frequency following a prostate carcinoma diagnosis SO CANCER LA English DT Article DE prostate carcinoma; recurrence; prostate specific antigen testing; race; surveillance ID RADICAL PROSTATECTOMY; RACIAL-DIFFERENCES; RADIATION-THERAPY; CO-MORBIDITY; CANCER; SURVIVAL; CARE; MEN; RECURRENCE; PATTERNS AB BACKGROUND. The goals of the current study were to describe patterns of prostate specific antigen (PSA) surveillance for prostate carcinoma progression in a community-based cohort of patients and to identify independent clinical and socio-demographic factors that predict the frequency of surveillance. METHODS. Patients diagnosed with localized prostate carcinoma from October 1, 1991 to December 31, 1992 in New Haven and Hartford, Connecticut, were identified. Data were collected through standardized outpatient medical record review. Multivariate statistical methods were used to determine the factors that independently predicted the frequency of surveillance. RESULTS. Six hundred fifty-eight men with localized prostate carcinoma were included in the cohort. Forty-five percent of all patients were tested at least once annually, and 69% were tested at least once every 2 years. Multivariate models indicated that African American men were half as likely as Caucasian men to receive annual testing (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.24-0.97). Men diagnosed at age 70 years or older were 38% less likely to have annual testing than men diagnosed between the ages of 65 and 69 (OR, 0.62; 95% Cl, 0.41-0.94). A higher Gleason score and PSA at presentation also were associated independently with higher rates of annual PSA surveillance. CONCLUSIONS. Postdiagnosis PSA surveillance is common, although not universal. African American men were at significantly greater risk for receiving less frequent testing compared with Caucasian men. This disparity in access to care may explain, in part, previously observed racial differences in survival in prostate carcinoma. Further research is needed to identify the reasons for the racial disparity in PSA surveillance and to design interventions to lessen these differences. (C) 2003 American Cancer Society. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. Univ Connecticut, Sch Med, Urol Sect, Farmington, CT USA. Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Etzioni, RD (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,MP-665, Seattle, WA 98109 USA. FU NCI NIH HHS [CA-88160, CA-92408] NR 33 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2003 VL 98 IS 3 BP 496 EP 503 DI 10.1002/cncr.11492 PG 8 WC Oncology SC Oncology GA 702VU UT WOS:000184246000006 PM 12879465 ER PT J AU Amorosa, VK Isaacs, SN AF Amorosa, VK Isaacs, SN TI Separate worlds set to collide: Smallpox, vaccinia virus vaccination, and human immunodeficiency virus and acquired immunodeficiency syndrome SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID METHYLISATIN BETA-THIOSEMICARBAZONE; COMPOUND 33T57; GAMMA-GLOBULIN; UNITED-STATES; HIV DISEASE; COMPLICATIONS; INFECTION; PROPHYLAXIS; GANGRENOSA; IMMUNITY AB Concerns about the possible release of smallpox by bioterrorists has led to policies that recommend smallpox vaccination of some health care providers, and, in the near future, the vaccine may become available to the general population on a voluntary basis. Both smallpox virus ( variola virus) and the smallpox vaccine ( vaccinia virus) will have a significant impact on people infected with human immunodeficiency virus (HIV). Given that populations with acquired immunodeficiency syndrome and populations with immunosuppressed conditions due to solid organ and bone marrow transplantation were not present in the days when smallpox was prevalent, we will speculate on how smallpox might present in immunodeficient patients, and we will review the adverse events expected from the smallpox vaccine in hosts with HIV infection. C1 Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Isaacs, SN (reprint author), Univ Penn, Dept Med, Div Infect Dis, 502 Johnson Pavil, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [U01 AI048487, AI48487, AI47237, R01 AI047237] NR 39 TC 16 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2003 VL 37 IS 3 BP 426 EP 432 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 705RE UT WOS:000184407900016 PM 12884168 ER PT J AU Giordano, TP Wright, JA Hasan, MQ White, AC Graviss, EA Visnegarwala, F AF Giordano, TP Wright, JA Hasan, MQ White, AC Graviss, EA Visnegarwala, F TI Do sex and race/ethnicity influence CD4 cell response in patients who achieve virologic suppression during antiretroviral therapy? SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2002 CL BARCELONA, SPAIN ID PROTEASE INHIBITOR; INFECTED PATIENTS; COUNTS; GENDER; PREDICTORS; INCREASES; WOMEN; RACE; RASH; RISK AB To determine whether CD4 cell count response to virus suppression during highly active antiretroviral therapy differs according to sex or race/ethnicity, we analyzed data in our observational cohort study for patients receiving their first antiretroviral regimen who experienced virus suppression by 6 months of therapy. In both univariate and multivariate analyses, women had greater CD4 cell count increases, compared with men, as did patients receiving a regimen that did not include a protease inhibitor. Race/ethnicity was not a factor. C1 Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Giordano, TP (reprint author), Houston VA Med Ctr 152, 2002 Holcombe Blvd,Ste 01Y, Houston, TX 77030 USA. OI White, A Clinton/0000-0002-9668-4632 FU NIAID NIH HHS [5 T32 AI07456-10]; NIMH NIH HHS [1 K23 MH67505-1] NR 24 TC 33 Z9 34 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2003 VL 37 IS 3 BP 433 EP 437 DI 10.1086/376638 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 705RE UT WOS:000184407900017 PM 12884169 ER PT J AU Temple, RO McBride, AM Horner, MD Taylor, RM AF Temple, RO McBride, AM Horner, MD Taylor, RM TI Personality characteristics of patients showing suboptimal cognitive effort SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article ID DIGIT RECOGNITION TEST; MILD HEAD TRAUMA; INJURY; MMPI-2; IMPAIRMENT; SEIZURES AB This study examined the relationship between performance on the Portland Digit Recognition Test (PDRT) and the MMPI-2 in a group of veterans who were suspected of having motivation to exaggerate cognitive and/or psychiatric symptoms. Number correct on "easy" trials on the PDRT correlated inversely with MMPI-2 measures of psychopathology, whereas number correct on "hard" trials positively correlated with the same scales. Some individuals performed poorly across both types of PDRT trials and had significant MMPI-2 elevations, whereas others performed poorly only on "hard" PDRT trials and had less extreme MMPI-2 elevations. This study reinforces the need to assess the validity of both cognitive and psychiatric symptom complaints. C1 Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. James A Haley Vet Adm Med Ctr, Tampa, FL 33612 USA. Ralph H Johnson DVA Med Ctr, Charleston, SC USA. RP Temple, RO (reprint author), Brown Univ, Rhode Isl Hosp, 110 Lockwood St,Suite 430, Providence, RI 02903 USA. NR 19 TC 6 Z9 6 U1 3 U2 3 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD AUG PY 2003 VL 17 IS 3 BP 402 EP 409 DI 10.1076/clin.17.3.402.18080 PG 8 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 748DP UT WOS:000186847100012 PM 14704891 ER PT J AU Kahan, BW Jacobson, LM Hullett, DA Ochoada, JM Oberley, TD Lang, KM Odorico, JS AF Kahan, BW Jacobson, LM Hullett, DA Ochoada, JM Oberley, TD Lang, KM Odorico, JS TI Pancreatic precursors and differentiated islet cell types from murine embryonic stem cells - An in vitro model to study islet differentiation SO DIABETES LA English DT Article ID TRANSCRIPTION FACTOR; MOUSE EMBRYOS; BETA-CELLS; INSULIN-II; B-CELL; EXPRESSION; GENE; PROGENITORS; MICE; PREPROINSULIN AB Embryonic stem (ES) cells differentiating in vitro reproduce many facets of early embryonic development, including the expression of developmentally regulated transcription factors and the differentiation of multipotent precursor cells. ES cells were evaluated for their ability to differentiate into pancreatic and islet lineage-restricted stages including pancreatic duodenal homeobox 1 (PDX1)-positive pancreatic precursor cells, early endocrine cell progenitors, and islet hormone-producing cells. Following growth and differentiation in nonselective medium containing serum, murine ES cells spontaneously differentiated into cells individually expressing each of the four major islet hormones: insulin, glucagon, somatostatin, and pancreatic polypeptide. PDX1 immunostaining cells appeared first, before hormone-positive cells had emerged. Hormone-positive cells appeared within focal clusters of cells coexpressing PDX1 and the nonclassical hormone markers peptide YY (YY) and islet amyloid polypeptide (IAPP) in combination with the definitive hormones, characteristic of endocrine cells appearing during early pancreaticogenesis. This system allows the investigation of many facets of islet development since it promotes the appearance of the complete range of islet phenotypes and reproduces important developmental stages of normal islet cytodifferentiation in differentiating ES cell cultures. C1 Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. WiCell Res Inst, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53792 USA. RP Odorico, JS (reprint author), Univ Wisconsin, Univ Wisconsin Hosp & Clin, Sch Med, Clin Sci Ctr H4 756, 600 Highland Ave, Madison, WI 53792 USA. NR 50 TC 100 Z9 112 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 AUG PY 2003 VL 52 IS 8 BP 2016 EP 2024 DI 10.2337/diabetes.52.8.2016 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 705UT UT WOS:000184414200018 PM 12882918 ER PT J AU Haffner, SM Zinman, B Kahn, SE Herman, WH Heise, MA O'Neill, MC Porter, LE AF Haffner, SM Zinman, B Kahn, SE Herman, WH Heise, MA O'Neill, MC Porter, LE CA ADOPT Study Grp TI Differences in the prevalence of the metabolic syndrome between ethnic groups in recently diagnosed Type 2 diabetes in the North American cohort of the ADOPT Study. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Michigan, Ann Arbor, MI 48109 USA. GlaxoSmithKline, King Of Prussia, PA USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 406 BP A144 EP A144 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100406 ER PT J AU Hayashi, T Boyko, EJ McNeely, MJ Leonetti, DL Newell-Morris, L Kahn, SE Fujimoto, WY AF Hayashi, T Boyko, EJ McNeely, MJ Leonetti, DL Newell-Morris, L Kahn, SE Fujimoto, WY TI Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 399 BP A141 EP A141 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100399 ER PT J AU Holman, RR Kahn, SE Heise, MA Porter, LE Freed, MI AF Holman, RR Kahn, SE Heise, MA Porter, LE Freed, MI CA ADOPT Study Grp TI Levels of beta-cell dysfunction and insulin resistance differ between Europeans and North Americans with recently-diagnosed diabetes in the ADOPT study SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Oxford, Diabet Trials Unit, Oxford OX1 2JD, England. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. GlaxoSmithKline, King Of Prussia, PA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 568 BP A198 EP A198 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100568 ER PT J AU Hull, RL Shen, Z Kodama, K Utzschneider, KM Carr, DB Wang, F Kahn, SE AF Hull, RL Shen, Z Kodama, K Utzschneider, KM Carr, DB Wang, F Kahn, SE TI Long term rosiglitazone and metformin treatment reduce the severity of islet amyloid deposition but do not prevent its formation. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed 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 SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 541 BP A188 EP A189 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100541 ER PT J AU Lipsky, BA Norden, C AF Lipsky, BA Norden, C TI Treating infected diabetic foot ulcers: Linezolid is clinically superior to amiopenicillin/beta-lactamase inhibitors (Amino/beta-LI). SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. Pharmacia Corp, Infect Dis, Peapack, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 8 BP A5 EP A5 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100009 ER PT J AU Williams, K Ferrannini, E Bogardus, C DeFronzo, RA Hunt, KJ Garvey, W Reaven, GM Stern, MP AF Williams, K Ferrannini, E Bogardus, C DeFronzo, RA Hunt, KJ Garvey, W Reaven, GM Stern, MP TI A model to identify individuals likely to be insulin resistant. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Texas, Hlth Sci Ctr, Dept Med Clin Epidemiol, San Antonio, TX USA. CNR, Inst Clin Physiol, I-56100 Pisa, Italy. NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Univ Texas, Hlth Sci Ctr, Dept Med Diabet, San Antonio, TX USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Stanford Univ, Sch Med, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 555 BP A193 EP A194 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100555 ER PT J AU Yishak, AA Virella, G Zgibor, J Walsh, M Costacou, T Evans, RW Lopes-Virella, M Kagan, VE Orchard, T AF Yishak, AA Virella, G Zgibor, J Walsh, M Costacou, T Evans, RW Lopes-Virella, M Kagan, VE Orchard, T TI Role of immune complexes, oxidized LDL antibodies and total anti-oxidative reserve in diabetic nephropathy. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 84 BP A32 EP A32 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100085 ER PT J AU Zinman, B Kahn, SE Haffner, SM Herman, W Heise, MA O'Neill, MC AF Zinman, B Kahn, SE Haffner, SM Herman, W Heise, MA O'Neill, MC CA ADOPT Study Grp TI Prevalence and clinical significance of Glutamic Acid Decarboxylase (GAD) antibodies in recently diagnosed Type 2 diabetes in the ADOPT study cohort. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Michigan, Ann Arbor, MI 48109 USA. GlaxoSmithKline, King Of Prussia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 417 BP A148 EP A148 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100417 ER PT J AU Gopal, DV Lieberman, DA Magaret, N Fennerty, MB Sampliner, RE Garewal, HS Falk, GW Faigel, DO AF Gopal, DV Lieberman, DA Magaret, N Fennerty, MB Sampliner, RE Garewal, HS Falk, GW Faigel, DO TI Risk factors for dysplasia in patients with Barrett's esophagus (BE) - Results from a multicenter consortium SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Gastroenterological-Association/Digestive Disease Week CY MAY 16-19, 1999 CL ORLANDO, FLORIDA SP Amer Gastroenterol Assoc DE Barrett's esophagus; COBE; cooperative study of Barrett's esophagus; age; length; prevalence; dysplasia ID COLUMNAR-LINED ESOPHAGUS; ENDOSCOPIC SURVEILLANCE; OBSERVER VARIATION; ADENOCARCINOMA; DIAGNOSIS; CANCER; PREVALENCE; THERAPY; EXTENT AB Studies show Barrett's esophagus prevalence increases with age, while mean length of Barrett's esophagus is unchanged. Few data are available about the relationship between age and length on the development of dysplasia. Our aim was to assess age and length as risk factors for dysplasia. Consecutive patients with Barrett's esophagus were enrolled in a multicenter study establishing a tissue bank of Barrett's esophagus patients 1994 and 1998. Demographics, length of Barrett's esophagus (centimeters), and histology were recorded. Risk factors for dysplasia were assessed, including patient age, gender, and length of Barrett's esophagus. Statistical analysis was performed comparing prevalence of dysplasia ( which included the presence of any carcinoma and high- or low-grade dysplasia) to age and length. In all, 309 patients were studied [ 278 (90%) male and 31 (10%) female]: 5 had adenocarcinoma of the esophagus, 11 had high- grade dysplasia, and 29 had low-grade dysplasia. Patients with Barrett's esophagus without dysplasia were younger than those with dysplasia [62 +/- 0.8 years vs 67 +/- 1.7 years (mean +/- SEM, P = 0.02)]. The risk of dysplasia increased by 3.3%/yr of age. Mean length of Barrett's esophagus in patients with Barrett's alone vs dysplasia was 4.0 +/- 0.2 cm vs 5.4 +/- 0.4 cm (P = 0.003). Patients with Barrett's esophagus length, 3 cm had a significantly greater prevalence of dysplasia compared to length < 3 cm ( 23% vs 9%, P = 0.0001). The risk of dysplasia increased by 14%/ cm of increased length. Multivariate analysis showed age and length to be independent risk factors. In conclusions; prevalence of dysplasia is strongly associated with age and length of Barrett's esophagus. These preliminary results can be used to develop a strategy for screening/surveillance based on age and length of Barrett's epithelium. C1 Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. So Arizona VA Healthcare Syst, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Faigel, DO (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol, PV-310,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Falk, Gary/0000-0002-7143-1436 NR 21 TC 70 Z9 73 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2003 VL 48 IS 8 BP 1537 EP 1541 DI 10.1023/A:1024715824149 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 700HB UT WOS:000184105600016 PM 12924649 ER PT J AU Van Stiegmann, G AF Van Stiegmann, G TI Update of endoscopic band ligation therapy for treatment of esophageal varices SO ENDOSCOPY LA English DT Article; Proceedings Paper CT 3rd International Workshop on Endoscopic Ultrasonography and Advanced Therapeutic Endoscopy CY MAR 07-09, 2003 CL SEOUL, SOUTH KOREA ID RANDOMIZED CLINICAL-TRIALS; METAANALYSIS; PREVENTION; SCLEROTHERAPY; CIRRHOSIS; PROPHYLAXIS; NADOLOL C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Denver Vet Affairs Hosp, Denver, CO 80262 USA. RP Van Stiegmann, G (reprint author), Univ Colorado, Hlth Sci Ctr, 4200 E 9th Ave,Box C-313, Denver, CO 80262 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD AUG PY 2003 VL 35 IS 8 BP S5 EP S8 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 712VQ UT WOS:000184819600026 PM 12929046 ER PT J AU Salinsky, TC Oken, BS Storzbach, T Dodrill, TB AF Salinsky, TC Oken, BS Storzbach, T Dodrill, TB TI Assessment of CNS effects of antiepileptic drugs by using quantitative EEG measures SO EPILEPSIA LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Epilepsy-Society CY DEC 03-05, 2001 CL PHILADELPHIA, PENNSYLVANIA SP Amer Epilepsy Soc DE antiepileptic drugs; electroencephalography; cognition; epilepsy ID EPILEPTIC PATIENTS; HEALTHY-ADULTS; CARBAMAZEPINE; PHENYTOIN; LAMOTRIGINE; PERFORMANCE; GABAPENTIN; FREQUENCY; VALPROATE; RELIABILITY AB Purpose: Antiepileptic drugs (AEDs) can be associated with adverse neurologic effects including cognitive dysfunction. Objective methods for recognizing AED effects on the brain could be valuable for long-term management. We compared quantitative EEG measures and cognitive tests in a group of patients beginning or ending AED therapy. Methods: Subjects included 20 patients beginning AED therapy (AEDon), 12 patients stopping AED therapy (AEDoff), 33 patient controls receiving stable AED therapy (AEDco), and 73 healthy controls (Nco). All subjects underwent structured EEG recording and a cognitive test battery before change in AED dose and again 12-16 weeks later, greater than or equal to4 weeks after the last dose change. Four occipital EEG measures (peak frequency, median frequency, relative theta and delta power) were analyzed. Cognitive test changes were scored by using test-retest regression equations based on the Nco subjects. Wilcoxon tests were used for two-group comparisons. Results: AEDons had a significant decrease, and AEDoffs, a significant increase in the peak frequency of the EEG rhythm, as compared with controls. Results for median frequency and theta power were similar. Change in the EEG peak frequency correlated with an aggregate cognitive change measure (r(2) = 0.71; p < 0.001), individual cognitive measures, and subjective complaints. Of the combined AEDon/AEDoff patients, 58% exceeded the 95% confidence interval for test-retest change in EEG peak frequency. Conclusions: Quantitative measures derived from the occipital EEG are sensitive to AEDs and correlate with AED-related cognitive effects and subjective complaints. Although this correlation does not indicate a direct relation, quantified EEG may be a practical measure of AED impact on the brain. C1 Oregon Hlth Sci Univ, Epilepsy Ctr, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Washington Univ, Epilepsy Ctr, Seattle, WA USA. RP Salinsky, TC (reprint author), Oregon Hlth Sci Univ, Epilepsy Ctr, 3181 SW Sam Jackson Pk Rd CDW 3, Portland, OR 97239 USA. NR 61 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2003 VL 44 IS 8 BP 1042 EP 1050 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 708VG UT WOS:000184590000007 ER PT J AU Latini, R Wong, M Masson, S Staszewsky, L Maggioni, AP Anand, IS Cohn, JN AF Latini, R Wong, M Masson, S Staszewsky, L Maggioni, AP Anand, IS Cohn, JN CA Val HeFT Invest TI Brain natriuretic peptide, but not norepinephrine, predicts improvements in left-ventricular structure and function in patients with chronic heart failure enrolled to Val-HeFT SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 Ist Ric Farmacol Mario Negri, Cardiovasc Res, Milan, Italy. VA Greater LA Healthcare Syst, Los Angeles, CA USA. ANMCO Res Ctr, Florence, Italy. VA Med Ctr, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 34 EP 34 DI 10.1016/S0195-668X(03)93770-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638800119 ER PT J AU Wong, M Chiang, Y Glazer, R Cohn, JN AF Wong, M Chiang, Y Glazer, R Cohn, JN CA Val HeFT Investigators TI Signs and symptoms of heart failure as endpoints for assessing therapeutic response: Val-HeFT data SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 146 EP 146 DI 10.1016/S0195-668X(03)94194-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638800543 ER PT J AU Anand, IS Latini, R Wong, M Masson, S Maggioni, A Hester, A Aknay, N Cohn, JN AF Anand, IS Latini, R Wong, M Masson, S Maggioni, A Hester, A Aknay, N Cohn, JN CA Val HeFT investigators TI Relationship between changes in election fraction, brain natriuretic peptide and norepinephrine over time and the effect of valsartan in Val-HeFT SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 VA Med Ctr, Minneapolis, MN USA. Ist Mario Negri, Milan, Italy. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. ANMCO Res Ctr, Florence, Italy. Novartia Pharmaceut Corp, E Hanover, NJ USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 531 EP 531 DI 10.1016/S0195-668X(03)95589-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638801938 ER PT J AU Behrens, EM Gadue, P Gong, SY Garrett, S Stein, PL Cohen, PL AF Behrens, EM Gadue, P Gong, SY Garrett, S Stein, PL Cohen, PL TI The mer receptor tyrosine kinase: expression and function suggest a role in innate immunity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE apoptosis; phagocytosis; kinase; innate immunity; autoimmunity ID ANTIGEN-PRESENTING CELLS; KILLER T-CELLS; APOPTOTIC CELLS; ACTIVATION; PHAGOCYTOSIS; STIMULATION; CLEARANCE; MICE AB The mer receptor tyrosine kinase mediates phagocytosis of apoptotic cells and modulates cytokine production; it is also required for prevention of systemic autoimmune disease. Using a mer-specific antibody, we have confirmed the presence of mer on macrophages and now report its expression on NK cells, NKT cells, and dendritic cells (DC). We found that DC do not require mer for ingestion of apoptotic cells, as DC from mer-deficient mice phagocytose apoptotic cells normally. Mer was observed in splenic sections on cells outside follicular areas, probably representing DC and macrophages. Mer apparently participates in NKT-cell antigen-induced signaling, as NKT cells from mer-deficient mice evinced much lower cytokine production after in vivo alpha-galactosylceramide stimulation; this defect was intrinsic to the mer-deficient NKT cells. Taken together, these studies show mer expression on cells of the innate immune system. Mer, through its binding of lipid antigens, may not only mediate ingestion of apoptotic cells, but also signal events in NK cells, NKT cells, and DC. C1 Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cohen, PL (reprint author), Univ Penn, 421 Curie Blvd,Room 757, Philadelphia, PA 19104 USA. NR 16 TC 50 Z9 53 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2003 VL 33 IS 8 BP 2160 EP 2167 DI 10.1002/eji.200324076 PG 8 WC Immunology SC Immunology GA 709WC UT WOS:000184648700012 PM 12884290 ER PT J AU Pettus, BJ Bielawski, J Porcelli, AM Reames, DL Johnson, KR Morrow, J Chalfant, CE Obeid, LM Hannun, YA AF Pettus, BJ Bielawski, J Porcelli, AM Reames, DL Johnson, KR Morrow, J Chalfant, CE Obeid, LM Hannun, YA TI The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE(2) production in response to TNF-alpha SO FASEB JOURNAL LA English DT Article DE prostaglandin E-2; inflammation; ceramide; sphingosine; RNA interference; tumor necrosis factor ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; PROGRAMMED CELL-DEATH; FC-GAMMA-RI; EPITHELIAL-CELLS; SPHINGOLIPID METABOLISM; INTESTINAL POLYPOSIS; INHIBITS APOPTOSIS; PHOSPHOLIPASE A(2); ENDOTHELIAL-CELLS AB In this study we addressed the role of sphingolipid metabolism in the inflammatory response. In a L929 fibroblast model, tumor necrosis factor-alpha (TNF) induced prostaglandin E-2 (PGE(2)) production by 4 h and cyclooxygenase-2 (COX-2) induction as early as 2 h. This TNF-induced PGE(2) production was inhibited by NS398, a COX-2 selective inhibitor. GC-MS analysis revealed that only COX-2-generated prostanoids were produced in response to TNF, thus providing further evidence of COX-2 selectivity. As sphingolipids have been implicated in mediating several actions of TNF, their role in COX-2 induction and PGE(2) production was evaluated. Sphingosine-1-phosphate (S1P) induced both COX-2 and PGE(2) in a dose-responsive manner with an apparent ED50 of 100-300 nM. The related sphingolipid sphingosine also induced PGE(2), though with much less efficacy. TNF induced a 3.5-fold increase in sphingosine-1-phosphate levels at 10 min that rapidly returned to baseline by 40 min. Small interfering RNAs (siRNAs) directed against mouse SK1 decreased (typically by 80%) SK1 protein and inhibited TNF-induced SK activity. Treatment of cells with RNAi to SK1 but not SK2 almost completely abolished the ability of TNF to induce COX-2 or generate PGE(2). By contrast, cells treated with RNAi to S1P lyase or S1P phosphatase enhanced COX-2 induction leading to enhanced generation of PGE(2). Treatment with SK1 RNAi also abolished the effects of exogenous sphingosine and ceramide on PGE(2), revealing that the action of sphingosine and ceramide are due to intracellular metabolism into S1P. Collectively, these results provide novel evidence that SK1 and S1P are necessary for TNF to induce COX-2 and PGE(2) production. Based on these findings, this study indicates that SK1 and S1P could be implicated in pathological inflammatory disorders and cancer. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. Univ Bologna, Dept Biol, I-40126 Bologna, Italy. Vanderbilt Univ, Sch Med, Dept Med & Pharmacol, Nashville, TN 37212 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Room 501,Basic Sci Bldg,173 Ashley Ave,POB 250509, Charleston, SC 29425 USA. EM hannun@musc.edu FU NCI NIH HHS [CA77839, CA87584]; NHLBI NIH HHS [HL 07260]; NIDDK NIH HHS [DK48831]; NIGMS NIH HHS [GM62887, GM08716, GM15431, GM43825] NR 58 TC 212 Z9 228 U1 1 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2003 VL 17 IS 11 BP 1411 EP 1421 DI 10.1096/fj.02-1038com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 721YB UT WOS:000185345100033 PM 12890694 ER PT J AU Yang, H Shi, MJ Richardson, A Vijg, J Guo, ZM AF Yang, H Shi, MJ Richardson, A Vijg, J Guo, ZM TI Attenuation of leukocyte-endothelium interaction by antioxidant enzymes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE catalase; superoxide dismutase; leukocyte adhesion; endothelial cells; free radicals ID HUMAN ATHEROSCLEROTIC PLAQUE; LOW-DENSITY-LIPOPROTEIN; NF-KAPPA-B; SUPEROXIDE-DISMUTASE; NITRIC-OXIDE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; TRANSGENIC MICE; DROSOPHILA-MELANOGASTER; CELL-INTERACTIONS AB This report assessed the effect of overexpressing Cu,Zn superoxide dismutase (SOD) and/or catalase on the interaction of mononuclear cells (MNCs) and endothelial cells (ECs). ECs were obtained from the aorta of wild-type mice and transgenic mice overexpressing Cu,ZnSOD and/or catalase. MNCs were obtained from wild-type mice. Treatment of wild-type ECs with CuSO4-oxidized low-density lipoprotein (oxLDL) significantly elevated the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and increased the adherence of MNCs. Overexpression of Cu,ZnSOD and/or catalase in ECs attenuated the adherence of MNCs and the expression of cell adhesion molecules induced by oxLDL. For example, ECs overexpressing Cu,ZnSOD and/or catalase showed significantly less expression of VCAM-1 and ICAM-1 and less number of adherent MNCs than wild-type ECs. Moreover, ECs overexpressing Cu,ZnSOD and catalase in combination showed significantly less expression of VCAM-1 and ICAM-1 and less number of adherent MNCs than those overexpressing either Cu,ZnSOD or catalase alone. These results suggest that combinational overexpression of Cu,ZnSOD and catalase can reduce the expression of cell adhesion molecules and inhibit the adherence of leukocyte to ECs more efficiently than overexpression of Cu,ZnSOD or catalase alone. (C) 2003 Elsevier Inc. C1 Meharry Med Coll, Dept Anat & Physiol, Nashville, TN 37208 USA. Meharry Med Coll, Dept Internal Med, Nashville, TN 37208 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Res Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX USA. RP Guo, ZM (reprint author), Meharry Med Coll, Dept Anat & Physiol, Nashville, TN 37208 USA. FU NCRR NIH HHS [RR03032]; NIA NIH HHS [P30 AG013319, P03 AG13319] NR 44 TC 25 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 1 PY 2003 VL 35 IS 3 BP 266 EP 276 DI 10.1016/S0891-5849(03)00277-6 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 703NG UT WOS:000184285600005 PM 12885588 ER PT J AU Graham, DY Dore, MP AF Graham, DY Dore, MP TI The QUADRATE study: A proposal for a change in the reporting of pharmaceutical supported trials SO GASTROENTEROLOGY LA English DT Letter ID HELICOBACTER-PYLORI INFECTION; QUADRUPLE THERAPY; METRONIDAZOLE; RESISTANCE; EFFICACY; ACHIEVE; CURE C1 VA Med Ctr, Houston, TX 77211 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Med, Inst Internal Med, Sassari, Italy. RP Graham, DY (reprint author), VA Med Ctr, Houston, TX 77211 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2003 VL 125 IS 2 BP 639 EP 639 DI 10.1016/S0016-5085(03)00984-3 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 707VU UT WOS:000184531200062 PM 12891587 ER PT J AU Jensen, DM AF Jensen, DM TI Current diagnosis and treatment of severe obscure GI hemorrhage SO GASTROINTESTINAL ENDOSCOPY LA English DT Review ID WIRELESS-CAPSULE ENDOSCOPY; SMALL-BOWEL ENDOSCOPY; PUSH-TYPE ENTEROSCOPY; TERM FOLLOW-UP; INTRAOPERATIVE ENTEROSCOPY; SMALL-INTESTINE; THERAPY; LESIONS; ORIGIN; YIELD C1 VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Jensen, DM (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Rm 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [M01-RR00865]; NIDDK NIH HHS [DK41301, 1K24 DK02650] NR 63 TC 25 Z9 25 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD AUG PY 2003 VL 58 IS 2 BP 256 EP 266 DI 10.1067/mge.2003.332 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 707VZ UT WOS:000184531700021 PM 12872101 ER PT J AU Hedrick, SC Sales, AEB Sullivan, JH Gray, SL Tornatore, J Curtis, M Zhou, XHA AF Hedrick, SC Sales, AEB Sullivan, JH Gray, SL Tornatore, J Curtis, M Zhou, XHA TI Resident outcomes of Medicaid-funded community residential care SO GERONTOLOGIST LA English DT Article; Proceedings Paper CT 54th Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV, 2001 CL CHICAGO, ILLINOIS SP Gerontol Soc Amer DE long-term care; assisted living; health status ID HOME RESIDENTS; NURSING-HOMES; DEMENTIA; SERVICES; MEMORY AB Purpose: Washington State's initiatives to increase the availability and quality of community residential care presented an opportunity to describe clients entering adult family homes, adult residential care, and assisted living and to identify outcomes of care. Design and Methods: We enrolled 349 residents, 243 informal caregivers, and 299 providers in 219 settings. We conducted interviews at enrollment and 12 months later, and we collected data from state databases. Results: The average resident was a 78 year-old woman reporting dependence in two of six activities of daily living. Residents in adult family homes demonstrated significantly more disability. Seventy-eight percent of residents survived at the 12-month follow-up. In analyses that controlled for differences at enrollment, residents in the three types of settings were very similar in health outcomes at follow-up. Implications: State policies should reflect the wide range of needs of residents seeking care in these settings. Choices among type of setting can be based on the match of needs to individual preferences. C1 VA Puget Sound Hlth Care Syst, HSR&D, Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Calif Dept Hlth Serv, Epidemiol & Evaluat Sect, Maternal & Child Hlth Branch, Sacramento, CA USA. RP Hedrick, SC (reprint author), VA Puget Sound Hlth Care Syst, HSR&D, Ctr Excellence, 152,1660 S Columbian Way, Seattle, WA 98108 USA. OI Sales, Anne/0000-0001-9360-3334 NR 30 TC 19 Z9 19 U1 1 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 2003 VL 43 IS 4 BP 473 EP 482 PG 10 WC Gerontology SC Geriatrics & Gerontology GA 715JE UT WOS:000184967700004 PM 12937326 ER PT J AU Leidholdt, EM Williams, GE McGuire, EL AF Leidholdt, EM Williams, GE McGuire, EL TI A reassessment of radioactive material security in health care and biomedical research SO HEALTH PHYSICS LA English DT Article DE operational topic; radioactive materials; medical radiation; radiation protection AB The medical facilities of the U.S. Department of Veterans Affairs (VA) use radioactive material for health care and biomedical research. In the past, a single level of security for all radioactive material was generally deemed to be adequate. The events of 11 September 2001 prompted a reassessment of security. Based on site visits to VA facilities possessing a range of radioactive material typically used in health care and biomedical research, the VA National Health Physics Program has compiled recommendations for the security of radioactive material. A primary recommendation is to evaluate radioactive material from a risk perspective and use security measures commensurate with risk. The risk evaluation should consider activity, half-life, exposure rate constant, ALI, ease of removal/portability, and dispersibility. We concluded that current security measures are likely adequate for the risks associated with most nuclear medicine departments and biomedical research laboratories. However, for radioactive material of higher risk, particularly multicurie sources of long half-life, the radiation safely staff should consult with police/security experts to determine if additional security measures are warranted. This focus on risk should help optimize resource allocation. We also recommend that security evaluations consider both physical security and personnel security, training of staff with unescorted access to higher-risk radioactive material emphasize security issues, and disposal of higher-risk material not likely to be used. Finally, we note that the goals of security can be in conflict with hazard awareness and hazard communication. C1 US Dept Vet Affairs, VHA Natl Hlth Phys Program, Little Rock, AR 72114 USA. RP Leidholdt, EM (reprint author), US Dept Vet Affairs, VHA Natl Hlth Phys Program, 115HP-NLR,2200 Ft Roots Dr N, Little Rock, AR 72114 USA. EM edwin.leidholdt@med.va.gov NR 15 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2003 VL 85 IS 2 SU S BP S15 EP S19 DI 10.1097/00004032-200308001-00007 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 703WL UT WOS:000184304900004 PM 12865744 ER EF